Fall-des-Monats

Instructive case studies

A 37-year-old male subject is denied by a casualty insurance to become an insurant due to the argument that he would suffer from epilepsy. Practically, the patient had bilateral tonic clonic seizures at age of 21 and 23 years out of wakefulness, he does not remember a focal onset. One of the seizures manifested at late morning, the other at early evening. There were no triggers such as sleep deprivation, fever or intake of potentially proconvulsant compounds. Family history for epilepsy was unremarkable, there were no hints for other seizure types. Routine and sleep deprivation EEGs were normal as was brain MRI. After the second seizure, the proper diagnosis of epilepsy was made; as there were no hints for focal or generalised epilepsy, it was allocated to be unclassified. Due to significantly increased risk for seizure relapse, antiepileptic drug treatment with levetiracetam was initiated, the maximal daily dose of 1,500 mg was well tolerated. Following the explicit will of the patient, after 2 years of treatment levetiracetam was stopped. Routine EEG at 6 months after withdrawal was still normal.

The question is for how long after the last seizure and for how long after withdrawal of the antiepileptic drug epilepsy formally still persists – for ever? In a position paper from 2014 (Fisher et al. in Epilepsia), the International League Against Epilepsy has cleary defined when epilepsy begins and when it is resolved. A patient has epilepsy after two unprovoked epileptic seizures – as in the current case – or already after one unprovoked seizure, if EEG or MRI findings indicate a significantly increased risk for seizure relapse, i.e. a recurrence risk of more than 60% within the next 10 years. In an individual patient, epilepsy is resolved, if the last seizure manifested at least 10 years ago and if the patient did not take an antiepileptic drug for at least the terminal 5 years.

The current patient has not experienced any epileptic seizures for 14 years, and he has not taken antiepileptic drugs for 12 years. He does not suffer from epilepsy any more. Pragmatically, the patient does not have any restriction in regard to driving, this includes trucks and buses. Thus, the insurance company cannot argue that their refusal is due the fact that the patient (still) has epilepsy. If antecedent epilepsy which is resolved for several years effectively means an exclusion criterium for a casualty insurance statement, needs legal clarification.

A 32-year-old male patient had his first generalized tonic clonic seizures at age of 16 years. Most of the seizures manifested within the first 60 min after awakening. The former EEG demonstrated spike-wave-complexes at a frequency of 3 Hz. This constellation indicates genetic generalized epilepsy (formerly, idiopathic generalized epilepsy), the subsyndrome is epilepsy with grand mal on awakening. The patient was treated with valproic acid at 900 mg daily. This treatment resulted in seizure freedom, the EEG was free of signs of increased neuronal excitability, thus the antiepileptic drug – which was the patient’s wish – was withdrawn after 4 years. In the following 12 years, the patient was seizure-free. Within the context of febrile and probably bacterial bronchitis, the patient suffered from a seizure relapse. He reported spontaneously that due to the infection and associated strong coughing he had poor sleep in the two nights before the seizure. When asked for antibiotic treatment, the patient reported to be administered ampicillin, a derivate of penicilline.

In this constellation, the patient has three triggers that in sum may have resulted in seizure relapse. At first, sleep deprivation is a major trigger for seizures in genetic generalized epilepsy. Secondly, fever is another relevant trigger. Finally, many antibiotics have proconvulsant properties, this in particular accounts for penicilline and its derivates.

In the current case, the EEG was still normal. As the seizure likely was triggered by the three factors mentioned above, there was no need for restarting antiepileptic drug treatment. We informed the patient on the clinical significance of triggers for seizure relapses, in particular massive sleep deprivation and the antibiotics penicilline and its derivates should be avoided. As the seizure relapse occurred after more than 10 years of seizure freedom and triggers were clearly identified, driving restriction is limited to the next 3 months.

A 26-year-old male patient has suffered from epilepsy for the lasts 7 years. Seizures are characterized by impaired awareness and few oral automatisms, duration is 40 sec. On specific questioning, the patient reports some kind of warning sign which he cannot describe very well, but which most likely corresponds to pressuring sensations in the gastric area. The patient is currently treated with 400 mg lacosamide and 10 mg peramapanel. Prior to that, we had already been administered three other anticonvulsants. Seizures frequency is 3-4 per month. Brain MRI demonstrated some cortical alteration which likely corresponds to focal cortical dysplasia.

Due to drug-resistant focal epilepsy, the patient underwent presurgical assessment in our center. At first, video-EEG monitoring was performed with surface electrodes. Three typical seizures were captured, and the seizure onset pattern was seen left temporo-anteriorly. As both seizure semiology and ictal EEG were compatible with a seizure onset zone in left temporo-mesial structures, it became obvious that the cortical alternation in the left parietal lobe likely is not the seizure focus. Cranial MRI and glucose PET were normal, in particular no changes in left temporo-mesial structures were identified. Using subdural strip and grid electrodes, we were able to localize the seizure onset zone in the left hippocampus. The patient underwent anterior temporal lobe resection and since then – after 3 months – has been seizure-free.

Multiple studies on outcome after epilepsy surgery have demonstrated that the identification of a putatively epileptogenic lesion in MRI significantly increases the chance for post-operative seizure freedom. Interestingly, the current case demonstrates that even alterations pointing to focal cortical dysplasia do not necessarily turn out to be the epileptogenic focus. Thus, beyond detailed history taking, recording of at least one typical seizure – by video and simultaneously by EEG – is the prerequisite for successful epilepsy surgery.

A 83-year-old female patient had her first two focal seizures with impaired awareness (previously termed: complex-partial seizure) some weeks ago. CCT demonstrated moderate vascular leukencephalopathy, but the patient did not suffer from clinically relevant cognitive deficits. Two unprovoked epileptic seizures are associated with an increased risk for further seizures, this defines epilepsy and generally presents an indication for antiepileptic drug treatment.

In another hospital, the patient was administered valproic acid, the dose was stepwisely increased to 1,200 mg per day. Timely, the family observed that the patient‘s mental capabilities were significantly impaired. On admission to our hospital, the serum concentration of valproic acid was 130 mg/l (reference: 40 – 100 mg/l). We assumed vaproate encephalopathy and changed the medication to monotherapy with lacosamide 75 twice daily. Within days, the patient’s cognitive impairment normalized.

This case illustrates the limitations of valproic acid. These not only comprise teratogenicity if taken by woman of child-bearing potential, but also the risk of encephalopathy in elderly patients.

Valproic acid is an excellent anticonvulsant in generalized genetic epilepsies (previously termed: idiopathic generalized epilepsy), but these generally do not manifest in the second half of life. In focal epilepsies, this compound has approval but there is a plethora of more suitable drugs; the guidelines of the German Society for Neurology recommend for monotherapy lamotrigine and levetiracetam, but also eslicarbazepineacetate, lacosamide and zonisamide.

In summary, valproic acid should be administered to elderly patients only with caution, new treatment with this anticonvulsant should be avoided at all due to lack of a clear indication and the profile of adverse events.

A 73-year-old male otherwise healthy patient suffered in April 2017 from a first unprovoked tonic clonic generalized seizure. Brain MRI as well as routine and sleep EEG were normal. Thus, this seizure is classified as isolated unprovoked epileptic seizure without significantly increased risk for seizure recurrence. In this constellation, the regular intake of an antiepileptic drug is not recommended.

But the current patient was deeply concerned to suffer a next seizure and asked for an antiepiletic drug. We accepted his request and administered the well-tolerated and efficacious compound lamotrigine in a low dose of 100 mg daily. We informed the patient that – follwing the guidelines for isolated unprovoked seizures – he has to refrain to drive a car on his own for the next 6 months.

At follow-up in October 2017, the patient reported that he increasingly had developed dizziness with lamotrigine which had impaired his quality of life. Therefore, 3 days before the appointment, he had decided on his own to withdraw lamotrigine. On his presentation, dizziness has ceased.

We again informed the patient on the low risk for seizure recurrence in his particular situation. The patient agreed – after the negative experience with lamotrigine – to refrain from taking another antiepileptic drug.

The 6-months driving ban was scheduled to be lifted in October 2017. But we had to inform the patient that after withdrawal of the antiepileptic, he will not be allowed to drive a car on his own for another 3 months.

In summary, after a first unprovoked epileptic seizure with normal EEG- and MRI-examinations, there is no indication for the regular intake of an antiepileptic drug.

A 33-year-old female patient with intellectual disability suffers from epilepsy with complex-partial and former secondary generalized seizures since early childhood. Etiology is unclear, brain MRI demonstrates at most some moderate global cortical atrophy. The patient has a history of taking 10 different antiepileptic drugs, currently she is administered 3,000 mg levetiracetam, 1,800 mg carbamazepine, and 400 mg lacosamide. Despite this triple-therapy, the patient still suffers from 2-3 complex-partial seizures per month. Furthermore, the patient has a most likely cerebellar gait disorder, she complains about unspecific dizziness.

We had the assumption that her complaints are explained by the antiepileptic medication and withdrew carbamazepine step by step. The dose of the two other antiepileptic drugs remained unchanged. Six months later, the patient was admitted for re-assessment. The objective and subjective complaints had ceased, seizure frequeny remained unchanged.

This case nicely illustrates the findings of a long-term study on 148 patients with antiepileptic polytherapy (Poolos et al. 2012 Neurology). This study demonstrates that three antiepiletic drugs administered at the same time are not more efficacious than two substances, but that adverse events are seen more frequently and with more severity. This in particular accounts for co-administration of two or more antiepiletic drugs with concordant mechanisms of action, in this case the sodium channel blockers carbamazepine and lacosamide.

In summary, even patients with difficult-to-treat epilepsy ideally should not be administered more than two antiepileptic drugs simultaneously. In general, withdrawal of further antiepileptic drugs is worthwhile.

A just 18-year-old male patient has epilepsy with likely tonic clonic generalized seizure out of sleep for the last 2 years. The patient does not remember seizure onset, third party observations are not available. At some mornings, the patient remarked strong muscle ache and lateral tongue bites. This constellation does not allow to make another diagnosis than tonic clonic generalized seizures. Until now, the patient had been in out-patient treatment at another center. Brain MRI and routine EEG were normal. In summary, this patient suffers from unclassified epilepsy, seizure onset in sleep may point to focal epilepsy. According to the patient, so far he had not been recommended taking an antiepileptic drug, the rationale behind this remained unclear.

We informed the patient that – after five unprovoked epileptic seizures – he has a high risk (> 80%) for occurrence of further seizures. We further informed him that sleep-bound generalized tonic clonic seizures in particular bear the risk of sudden unexpected death in epilepsy (SUDEP). Eventually, we were able to convince the patient to take an antiepileptic drug. We initiated treatment with levetiracetam at a dose of 500 mg two times daily. At least for the next 6 months, the patient was seizure-free.

In summary, after two unprovoked epileptic seizures, the risk for a third seizure within the next 10 years is more than 60%. According to the current criteria of the International League Against Epilepsy, two unprovoked seizures – due to the high recurrence risk – define epilepsy, generally antiepileptic drug treatment is recommended.

Since his 6th year of life, a 14-year-old male adolescent patient suffers from multiple short (5 to 7 sec) periods with loss of contact. Former EEGs demonstrated generalized 3/sec spike-wave-complexes with maximal amplitude in frontal leads. Back then, the diagnosis of childhood absence epilepsy was made. When absence seizures manifest dozens of times per day, they are termed pyknoleptic absences or pyknolepsy. Some years ago, a US-american double-blind trial figured out that in childhood absence epilepsy ethosuximide still is the most efficient and best tolerated antiepileptic drugs (Glauser et al. 2010, New England Journal of Medicine). From onset of his epilepsy on, our patient was treated with ethosuxumide, absence seizures were well controlled.

At age 14 years, the question arose if the antiepileptic drug can be withdrawn. Childhood absence epilepsy has an excellent prognosis, with beginning of puberty the epileptogenicity markedly decreases. Even without antiepileptic drugs, patients do not suffer any more absences. The current patient and his family have not observed absence seizures for years. We performed a longterm-video-EEG-monitoring for 24 h and did not observe any clinical absence seizures nor any characteristic spike-wave patterns. It is highly likely that this patient will not have further seizures in the future.

This case nicely demonstrates the often benign course of childhood absence epilepsy which in most cases is – depending on age – self-limiting. Thus, in this subsyndrome of generalized genetic epilepsy antiepileptic drug withdrawal in the second decade of life is strongly recommended.

A 38-year-old male patient has suffered from epilepsy for more than 20 years, complex partial seizures lasting 30-40 sec. manifest 4-5 times per month; in the past, he also had generalized tonic clonic seizures. Epilepsy likely is caused by cMRI-proven hippocampal sclerosis on the right. So far, the patient had been treated with six different anticonvulsants, currently he is on 500 mg lamotrigine and 200 mg brivaracetam. In summary, this patient suffers from pharmacoresistant focal epilepsy.

During video-EEG-recording for 7 days, three typical complex partial seizures occurred. In each fit, a stereotyped EEG seizure pattern with onset in anterior temporal leads on the right was seen. This ictal EEG finding corresponds well to a seizure focus in right mesio-temporal structures.

In this constellation, we recommended to the patient resection of right-sided temporal lobe structures, the chance for sustained seizure freedom is 60-70%. However, the patient rejected the operation as he was too afraid of open brain surgery. In his view, ongoing seizures were less incriminatory than the brain operation. In the last 5 years, approximately 20% of patients in our center have rejected epilepsy surgery, after all examinations have been completed and resection of the seizure focus was recommended. Similar rejection rates have been found in studies from the epilepsy centers in Bonn, Bielefeld-Bethel and London.

For some years, in the U.S. a treatment approach is available which uses an intracerebral electrode to apply heat by laser and thus to ablate the epileptogenic focus. The principle is the same as in „open“ surgery – elimination of the seizure focus. The advantage of laser treatment is that the skull does not need to be opened; instead, via a smal borehole a small electrode is placed within the brain. First data have shown that 40-50% of patients with temporal lobe epilepsy become seizure-free with this minimally invasive approach.

Within the next weeks, laser ablation treatment will also be approved and available in Germany. In a collaboration project with the Department of Neurology at the University Magdeburg, we are going to establish this technique as one oft he first centers in Germany. In particular, we will offer this procedure to those patients with epilepsy, who are deeply concerned of „open“ brain surgery and thus reject this treatment option. Thus, we hope that the above mentioned 38-year-old patient agrees on laser ablation in order to get rid of his intractable epilepsy.

A 27-year-old female patient suffers for 12 years from epilepsy with yearly one to two „smaller“ seizures with impaired consciousnes for 30-40 sec. (complex partial seizures) and former „bigger“ seizures with loss of consciousness (generalized tonic clonic seizures). The cause of epilepsy is unknown, thus we made the diagnosis of cryptogenic focal epilepsy. The patient is administered two anticonvulsants, levetiracetam at 2,000 mg and oxcarbazepine at 1,200 mg daily. Except some slight tiredness and subjective concentration deficits, the combination therapy is well tolerated.

For some years, the patient asks if her epilepsy can also be treated with cannabis, she had read about that in the newspapers. Indeed, since spring 2017 in Germany cannabis can be prescribed for multiple chronic disorders, if other treatments were unsuccessful and if the treating physicians thinks that cannabis is a reasonable next treatment option. The insurance companies are compelled to pay for cannabis treatment.

The problem is that we currently do not have evidence that cannabis works in epilepsy. So far, the derivate cannabidiol has mostly been administered to patients (children and adolescents) with severe, special forms of epilepsy. A clinical trial from the US on 200 mostly young patients has demonstrated that cannabidiol reduces seizure frequency by one third.

This study had two flaws. At first, there was no blinded control group receiving placebo (in intractable epilepsies, the placebo effect results in reduction in seizure frequency in the first months in 15-20% of cases). Second, 50% of patients were co-administered clobazam and 30% valproic acid. In both substances, cannabidiol results in a significant increase in serum concentration. Thus, one can not rule out that reduction of seizure frequency with cannabidiol is mainly explained by placebo effect and/or a pharmacokinetic effect.

Against this background, we currently do not recommend treatment with cannabidiol in epilepsy. We also refer to the critical comment by the Germany Society for Epileptology (in German).

Currently, in the US and probably soon in Germany placebo-controlled, double-blinded clincial trials on cannabidiol in epilepsy will be performed. If proven efficacious, cannabidiol – as a number of other anticonvulsant drugs – may be recommended to our patient.

A 35-year-old male patient suffers from difficult-to-treat focal epilepsy since his 17th year of life. Presumably, the cause of epilepsy is a former inflammatory brain disorder. First seizures occurred in the acute phase of his CNS inflammation. Currently, the patient suffers from 3-4 complex partial seizures per month, each preceded by an undetermined aura, and rare grand mal seizures. So far, the patient has been treated with more than 10 different antiepileptic drugs, currently his regimen consists of levetiracetam, lamotrigine and primidone, each in high doses. Though a couple of antiepileptic drugs have been introduced in this patient unsuccessfully, at the end of 2016 we decided to make a treatment trial with perampanel, first aiming at a dose of 6 mg per day. The mechanism of action of perampanel differs from all other antiepileptic drugs, the compound is an inhibitor at the excitatory AMPA receptors.

The patient’s expectations towards perampanel were at best ambiguous, as so many other antiepileptic drugs had failed before. However, surprisingly in the first 3 months of treatment, perampanel resulted in a significant reduction in the frequency of complex partial seizures.

However, under the German law (“Arzneimittelmarktneuordnungsgesetz (AMNOG)“) this antiepileptic drug was classified as having no additional benefit in the treatment of epilepsies. This case illustrates the absurdity of this decision, as in individual cases perampanel definitely has the capacity to clearly improve patients’ seizure disorder. However, due to classification of having no benefit, reimbursement of compounds such as perampanel is on the level of generic drugs like lamotrigine. This does not refund the costs for developing new antiepileptic drugs.

Thus, the producing company Eisai took perampanel off the German market, but the substance still can be obtained via international pharmacies. This patient’s health insurance currently checks if they are going to reimburse the costs for perampanel due to individual efficacy in this patient.

Perampanel – likely due to its different mechanism of action – has proved to be a very successful antiepileptic drug in various European countries and in North America. The case of perampanel clearly illustrates that the current methodology used to assess efficacy within the lines of AMNOG is insufficient. This calls for an urgent need for political action.

A 16-year-old boy suffers from focal epilepsy since his 3rd year of life. Epilepsy is manifesting with sleep-bound hypermotor seizures. He awakes from sleep – somtimes multiple times per night – with marked bilateral, but asymmetric movements of all extremities, consciousness is preserved, duration generally is shorter than 1 min. Every week, seizures occur in three to four nights. The described seizure type points to onset in the frontal lobe, and specifically in the supplementary motor area. 3T-MRI is normal, the patient suffers from cryptogenic partial epilepsy. In the last years, he was administered eight different antiepileptic drugs, current he is on levetiracetam 3,000 mg and lacosamide, 400 mg.

For many years, we spoke to the patient and his parents about the option of epilepsy surgery. When the patient was younger, his parents declined to make a decision for him. Now, the patient himself asked for the prerequisite presurgical diagnostic steps.

In long-term video-EEG with surface electrodes, seizure onset clearly could be seen in the right frontal lobe despite multiple movement artifacts. Interictal PET showed congruent pathology, with hypometabolism in right frontal structures. In a second step, the patient underwent invasive video-EEG monitoring with subdural electrodes covering the supplementary motor area on the right and the interhemispheric fissure. Within a couple of days, we recorded six habitual seizures with onset under four bordering electrodes. Electrical stimulation revealed non-eloquent cortex under these electrodes. With removal of electrodes, cortical structures beneath these electrodes were resected. Since the operation, the patient is seizure-free.

This case illustrates that also in patients with non-lesional frontal lobe epilepsy, resective surgery can be done successfully. However, case series demonstrate that seizure freedom rates are lower compared to temporal lobe or lesional epilepsy. Furthermore, it is highly likely that the patient would have benefited from surgery earlier in his life.

A 69-year-old male patient had a first sleep-bound generalized tonic-clonic seizure 2 years ago. Brain MRI revealed moderate vascular leukencephalopathy, some lacunar lesions were located closely to cortical structures. Routine EEG was normal. In this constellation, it is likely that the microangiopathic cerebral lesions are the cause for this patient’s first seizure. The risk for another epileptic seizure within the next 10 years is approximately 70%, this defines epilepsy, and in the current case focal epilepsy. Due to the high recurrence risk, we recommended to the patient treatment with the antiepileptic drug levetiracetam at 1,000 mg daily, actually this is a secondary prophylaxis. The substance was well tolerated, but after 1 year, the patient asked to stop levetiracetam. We explained to the patient that the risk for another epileptic seizure after withdrawal is above 50%. But still, the patient wanted to stop the antiepileptic drug. At first, he remained seizure free but after 1 year he had a second generalized tonic-clonic seizure out of sleep. After that, the patient himself understood that from now on he has to take an antiepileptic drug, he wanted to restart levetiracetam.

A 25-year-old male patient suffers for 8 years from focal epilepsy characterized by epigastric auras (sensation ascending from the stomach to the throat) and automotor seizures (impaired consciousness with oral automatisms). Frequency of the latter seizure type is 4-5 per month. 1.5 T cranial MRI is normal. Current antiepileptic drug treatment consists of 3,000 mg levetiracetam and 500 mg zonisamide. Previously, the patient was treated with lamotrigine which had to be withdrawn at a dose of 50 mg due to exanthema. In summary, the patient suffers from pharmacoresistant focal epilepsy.

The next management step would be comprehensive evaluation for resective epilepsy surgery aiming at removal of the epileptogenic focus. This evaluation comprises long-term video-EEG-monitoring to record the patient’s habitual epileptic seizures. Furthermore, the patient is applied high-field cranial MRI at 3 T, the additional yield for detection of epileptogenic lesions is 10 to 15%. Also, the patient undergoes extensive neuropsychological testing in order to detect and quantify frontal or temporal lobe deficits. Additional diagnostic tests are performed in dependence on the first findings.

We explained to the patient in detail that after failure of two antiepiletic drugs in high doses sustained seizure freedom with administration of further antiepileptic drugs is highly unlikely. We further explained him the chances and risks of resective surgery, in general the majority of patients clearly benefits from this operation.

However, the patient couldn’t imagine any kind of operation on his brain and thus declined the highly recommended presurgical assessment. As this experience is quite common to us, we systematically assessed for a 6-month-period, how many patients refuse presurgical monitoring and what are the main reasons for refusal. Every second patient with intractable focal epilepsy was recommended presurgical assessment by us, in the other patients seizure frequency and severity was too low. However, 75% of patients who were recommended video-EEG-monitoring – as the current patient – declined that offer. The main reason was some diffuse fear of brain surgery. This survey indicates that eligible patients timely need intensive education on the benefits and potential harms of epilepsy surgery.

In the current patient, at every outpatient visit we will address the topic of surgical treatment of his epilepsy.

A 57-year-old male patient had a first tonic clonic generalized epileptic seizure out of wakefulness without hints for focal onset. The patient was otherwise healthy. Diagnostic tests in another hospital including routine EEG and brain MRI were normal. During an outpatient visit, we attributed the spell to an isolated unprovoked seizure. Due to low seizure recurrence risk, we did not recommend an antiepileptic drug. Following the driving guidelines, the patient was not allowed to drive a car on his own for 6 months after the seizure.

Some days later, the general practitioner made thorough laboratory tests and detected markedly decreased serum magnesium levels (0.29 mmol/l; normal values for adults: 0.7-1.0 mmol/l). In patients without prior epilepsy, magnesium deficiency may be the acute cause of an epileptic seizure, this constellation is termed acute symptomatic seizure. Following the definition of the International League against Epilepsy, serum magnesium levels have to be lower than 0.3 mmol/l to cause and explain an acute symptomatic seizure.

Magnesium blocks the excitatory NMDA receptor in the brain. Is magnesium lacking, this receptor is disinhibited, neuronal excitation is increased. In the extreme, this may result in clinical manifestation of an epileptic seizure.

Thus in the current patient, the seizure was not isolated unprovoked but acute symptomatic. This change in allocation did not result in a different recommendation regarding not administering an antiepileptic drug but regarding driving restrictions. After an acute symptomatic seizure, the patient is not allowed to drive a car on his own for a total of 3 months, if the cause of the seizure is rectified. Even though in the current patient the cause for magnesium deficiency could not be identified, with daily substitution and frequent lab controls the patient now has regular serum concentrations.

This case indicates that there may be very rare acute causes for epileptic seizures. These may impact the risk for seizure recurrence and thus for driving restrictions.

A 42-year-old male patient reports that he had suffered tonic-clonic generalized seizures without focal signs or symptoms in his 22nd, 30th and 36th year of life. All seizures manifested within 60 min. after awakening and were preceded by very short sleep duration and significantly increased alcohol consumption the night before. Interictal EEGs demonstrated generalized 3/s spike-wave-complexes with maximal amplitudes bi-frontally. This patient unequivocally suffers from idiopathic generalized epilepsy, the specific subsyndrome is epilepsy with grand mal on awakening. Due to typical EEG features, the patient is treated since his first seizure with valproate at a dose of 900 mg daily. After 6 years of seizure freedom, the patient now asks for withdrawal of the antiepileptic drug. As all seizures have been triggered (not: caused!) by sleep deprivation and increased alcohol consumption, we assume a rather low recurrence risk after valproate withdrawal, if the well-known triggers can be avoided. The patient himself suggested that – when sleep deprivation and/or increased alcohol consumption can be anticipated – he takes 900 mg valproate for 2 to 3 day in advance. Due to his individually low recurrence risk, we did not generally oppose this pragmatic approach.

We explained to the patient that for 3 months after the last dose of valproate he will not be allowed driving a car. Even more, due to his individual susceptibility, he will not be allowed driving the days after sleep deprivation and increased alcohol intake.

This case demonstrates that in some patients with idiopathic generalized epilepsy seizures only manifest in the context of well-known trigger factors. From the perspective of classification, these still are unprovoked (in contrast to acute-symptomatic) seizures. To avoid misunderstandings, the term “provoked” should be avoided, instead the terms “facilitated” or “triggered” are recommended to describe the circumstances of seizure manifestation.

A 49-year old female patient suffered a first clear generalized tonic-clonic seizure out of wakefulness in the early afternoon. She and a witness did not remember any clinical signs or symptoms that point to partial onset. The relevant question is: what is the risk for occurrence of another unprovoked seizure?

In the emergency room, a brain CT scan was performed which was normal. For sufficient sensitivity, a cerebral MRI scan – following a specific epilepsy protocol with temporal angulation – is required. This was normal as well. Routine EEG and sleep EEG following sleep deprivation were also normal.

In this constellation, there are no hints for an enduring alteration of the brain which increases the probability for another epileptic seizure. Following the most recent definition of epilepsy, the risk for another unprovoked seizure within the next 10 years has to be more than 60 %, thus equalling that after two unprovoked seizures (Fisher et al. 2014 Epilepsia).

We explained to the patient that she has a mildly increased risk for seizure recurrence but that this risk is not that high that by definition she already suffers from epilepsy.

In this regard, there is no indication for antiepileptic drug treatment. The patient is not allowed to drive a car up to 3.5 t on her own for the next 6 months.

If cMRI or EEG would have demonstrated pathological findings, the patient would have an increased risk for seizure recurrence and thus epilepsy.

This case demonstrates the significant relevance to assess recurrence risk after a first unprovoked epileptic seizure.

A 26-year-old female patient suffers at age 18 and 19 years her first and up to now only three generalized tonic clonic seizures. All her seizures manifested within the first 30 min. after awakening in the morning. The patient reported that in those years she had a rather irregular sleep-wake-cycle. EEGs had demonstrated generalized spike-wave-complexes at 3/s. At that time, the correct diagnosis of idiopathic generalized epilepsy had been made. This form accounts for approximately 20% of all epilepsies. The subsyndrome in the current patient is epilepsy with grand mal on awakening.

First choice pharmacological treatment of idiopathic generalised epilepsy is valproic acid. Due to possible malformations and developmental injuries to the embryo during pregnancy (teratogenicity), this drug is generally not administered to female patients with child-bearing potential. The current patient was treated with lamotrigine 100 mg daily, she did not report adverse effects.

Probably due to persisting seizure freedom, the patient did not present in our epilepsy outpatient clinic for 5 years. At age 26, she showed up in our clinic and reported that she had withdrawn lamotrigine some 6 months ago without seizure recurrence. She asked for our advice regarding need for further treatment.

We explained to the patient that idiopathic generalised epilepsies are rather benign conditions with excellent response to pharmacological treatment. In the long run, probability for further seizures decreases. After withdrawal of antiepileptic drugs, more than half of the patients will have seizure recurrence.

As the current patient had a total of only three epileptic seizures and as she has withdrawn the antiepileptic drug based on her own decision, we decided – after 6 months of seizure freedom without pharmacological treatment – to leave her untreated.

This case illustrates that withdrawal of antiepileptic drugs in epilepsy is always an individual decision that considers both biological aspects and patients’ expectations.

A 43-year-old female patient has experienced for 8 years short episodes of 5-10 sec duration with some feeling of pressure in her stomach, this is followed by a rather unspecific sensation affecting the whole body, eventually she feels some tightness of her whole body for another 20 sec. It was not entirely clear, if she is fully conscious during these episodes. Frequency of these episodes is 2-3 / month. At admission to our clinic, the patient was treated with 400 mg zonisamide daily. The patient herself had the perception that her episodes are dissociative seizures. Brain MRI showed hippocampal sclerosis on the left.

To diagnose these episodes correctly, we performed video-EEG-monitoring for 48 h. As it was unclear, if the nature of these episodes was epileptic or dissociative, we withdrew the antiepileptic medication with zonisamide. During video-EEG-monitoring, one habitual episode manifested. The semiological course was as reported previously by the patient. The EEG technician entered the room during the phase with body tightness. At this time point, the patient was completely conscious and reactive. During the feeling of stomach pressure, the EEG demonstrated an ictal seizure pattern with rhythmic theta activity at 6-7 / s. This finding allowed allocating the stomach pressure to an epigastric aura, i.e. a simple partial seizure. We strongly assume that the late behavioral changes with tightness of the whole body are not part of the epileptic seizures, but rather represent a postictal reaction to the aura and the associated discomfort.

After advising the patient on the correct diagnosis, she wanted to remain untreated after prior withdrawal of zonisamide. She expressed that she rather stands the epileptic auras than taking an antiepileptic drugs regularly. We explained to the patient that the hippocampus sclerosis indicates an increased risk for seizure occurrence. Furthermore, we would not be able to exclude that the auras evolve to complex partial seizures with impaired consciousness or even a secondary generalized tonic clonic seizure. The patient decided to take that risk.

As for more than 1 year the patient has only suffered epileptic seizures without impairment of consciousness, she is allowed to drive a car on her own from 3 months after withdrawal of zonisamide.

A 35-year-old male patient suffers for more than 10 years from episodes which let him experience an ascending feeling of fear, he then perfoms actions such as holding both hands in front of his face or lashing about with his left arm. During these episodes, he is awake and fully oriented, he answers questions correctly. In general, duration is 5 min. In addition to these paroxysmal episodes with fear, the patient suffers from a chronic generalized anxiety disorder. So far, a clear diagnostic allocation of these episodes to epileptic or dissociative seizures has not been possible. As frequency of these events was two per month, it has not been possible to capture one of these events by video-EEG-monitoring. The generalized anxiety disorder was treated with pregabaline.

Admission to the Department of Epileptology of our institution aimed to correctly diagnose these events. Some days after admission, the patient experienced the stereotyped ascending feeling of fear. He asked one of the nurses to accompany him into his room. There, at first he was very agitated, he expressed solicitude, he grabbed for the water bottle, he turned around, and re rowed in the air with his left arm. At the same time, he was able to adequately communicate with the nurse. This behaviour rather pointed to a dissociative seizure. But approximately 5 min after onset of this episode, he developed tonic posturing of all extremities which after 20 sec evolved into bilateral clonic movements. Due to the unequivocal grand mal seizure at the end of the episode, for the first time it was possible to ascertain the epileptic origin of these episodes. The initial feeling of fear corresponds to an epileptic aura which lasts a couple of minutes and which eventually – and now for the first time – developed into a tonic clonic generalized epileptic seizure. It remains debatable if the movements during the aura are part of the ictal semiology or if they are rather an unconscious reaction to the epileptic fear aura.

After the correct diagnosis of cryptogenic – brain MRI was normal – partial epilepsy was made, we initiated antiepileptic treatment with lamotrigine.

A 31-year-old male patient is seen regularly in out epilepsy outpatient clinic for more than 10 years. At age 18 years, he suffered a first tonic clonic generalized epileptic seizure early after awakening following a short night with 3 hours of sleep. In the following 13 years, he had another two generalized tonic clonic seizures, both of which occurred after sleep deprivation and directly after awakening. Family history is unremarkable, multiple routine EEGs were normal.

Beyond the epileptic seizures, the patient reported episodes on awakening with complete paralysis with the exemption of tongue and eye movements. This sleep paralysis lasts 1-2 min and is associated with anxiety. So far, these episodes have occurred five times. In addition, the patient reports excessive daytime sleepiness. Polysomnography with multiple sleep latency test revealed SOREM, i.e. sudden onset rapid eye movement sleep.

In this patient, two diagnoses can be made: Firstly, he suffers from epilepsy which likely is idiopathic generalized epilepsy, subsyndrome: epilepsy with grand mal on awakening. Secondly, he suffers from narcolepsy which in this case is characterized by sleep paralysis and striking daytime sleepiness. The diagnosis of narcolepsy was confirmed by the finding of SOREM in the multiple sleep latency test.

Treatment of choice in idiopathic generalized epilepsies is valproic acid. Unfortunately, the current patient developed some unspecific adverse events from this substance. With carbamazepine 900 mg, the patient is seizure-free for the last 3 years. However, this antiepileptic drug is not without problems in idiopathic generalized epilepsies as this sodium channel blocker provides the risk to facilitate occurrence of myoclonic and absence seizures. Gladly, this didn’t occur in this patient. Narcolepsy was treated with modafinil. Since regular administration of this drug, the patient did not experience any more sleep paralyses, excessive daytime sleepiness has improved significantly.

Figures on coincidence of idipathic generalized epilepsies and narcolepsy has not been reported in the literature and genetic similarities have not been demonstrated so far. However, it has to be considered that narcolepsies with a prevalence of 1 in 5,000 is a rather rare condition.

A 67-year-old female patient presents for the first time in our epilepsy outpatient clinic at the Charité in April 2016, she is accompanied by a friend. The patient reports that since her 11th year of life repetitive – often several times per year – stereotyped episodes with some “funny feeling” occur, which she hardly can put into words. Her friend reports that the patient does not react adequately towards external stimuli such as questions or commands. Duration is 1-2 min, no oral or manual automatisms are seen. At onset of seizures in her adolescence, the patient did not dare to talk to her parents about these events. In the further course of her life, the patient has experienced several years without occurrence of these episodes. The patient herself had interpreted these events as “heart attacks”, she has always been something sickish. She had talked multiple times with her general practitioner about these attacks, but he agreed with the patient on cardial events.

In February 2016, one of these episodes occurred in the presence of her adult children. They brought her immediately to the emergency room of a hospital outside of Berlin. The patient was admitted to the department of neurology, and there, these episodes had been judged to be highly suspicious for complex partial epileptic seizures. EEG demonstrated some left temporal slowing but no increased neuronal excitability. Brain MRI was normal. Antiepileptic drug treatment with levetiracetam 2 x 250 mg daily was initiated. Based on the patient’s own and her friend’s description, we did not doubt that these episodes were complex partial seizures and that the patient suffers from cryptogenic partial epilepsy. As we thought that a daily dose of 500 mg levetiracetam is insufficient, we increased the dose to 1,000 mg per day.

Clinical trials on the indigenous population in the Andes have demonstrated that response to the first antiepileptic drug does not differ in patients with long-term frequent seizures compared to new-onset epilepsy. The current patient will present for follow-up in our outpatient clinic in a couple of months which allows to assess a possible treatment success.

A 67-year old male patient suffers form apoplectiform left-sided hemiparesis, predominantly affecting the upper extremity and the face. In the emergency room, the diagnosis of ischemic stroke is made. The patient is admitted to the specialized stroke unit. In the first night, for the first time he suffers a generalized tonic clonic epileptic seizure with a duration of 1 min and postictal confusion for 25 – 25 min. To prevent seizure recurrence, the patient is administered the benzodiazepine clobazam 2 x 10 mg daily, in addition he is treated with 2 x 1,000 mg levetiracetam. Clobazam is withdrawn after a couple of days, levetiracetam is continued while the patient is transferred to a rehabilitation clinic 1 week later.

This patient had an acute symptomatic epileptic seizure. This is defined as seizure manifestation within 7 days of stroke. 70% of all acute symptomatic seizures caused by stroke occur – as the current case – within the first 24 h. Approximately 5% of all patients with ischemic stroke will have an acute symptomatic seizure, in patients with hemorrhages the risk is 8%.

The clinically important question is that of the risk for recurrence of further seizures. For the acute phase, i.e. within the first 7 days of stroke, available data are not reliable. The long-term risk within the next 10 years to suffer a second – then (after more than 7 days from stroke) unprovoked – seizure is 30%. That means that more than two thirds patients with one stroke-related acute symptomatic seizure will never again have an epileptic seizure. Therefore, by definition, an acute symptomatic seizure is not epilepsy as the recurrence risk is too low.

Due to this, there is no need for long-term antiepileptic drug treatment. For the current patient, we recommended to the rehabilitation clinic to withdraw levetiracetam at latest 3 months after stroke. Unfortunately, in clinical practice this does not happen in every case.

A 22-year-old male patient had suffered a first and up to now single generalized tonic-clonic seizure at the age of 11 years. Reports on initial EEGs demonstrated contradictory results with irregular bilateral spike-waves or normal recordings. Cranial MRI was normal. After that index seizure, the patient was treated with valproate, with increasing age the dose was adjusted up to 2,000 mg daily.

When the patient turned to be 18 years, he presented in our epilepsy outpatient clinic for adults. As he had been seizure-free for 7 years and as he had suffered only one seizure, we reduced valproate and – with a further normal EEG – eventually withdrew the antiepileptic.

In the further course, the patient reported new-onset jerks in his legs resulting in falls. On further inquiry, he reported jerks in the upper extremities as well. Jerks only manifested in the first hour after awakening in the morning. Another prerequisite for jerks was a significant reduction of total sleep time to less than 6 h. On nights with conceivably reduced night sleep, he took – on his own decision – 500 mg valproate which completely prevented occurrence of jerks the next morning.

This young patient suffers from juvenile myoclonic epilepsy, myoclonus was suppressed for years by valproate and occurred only after withdrawal of the antiepileptic. Thus, the correct diagnosis could only be made after valproate withdrawal.

Therapeutically, we decided rather pragmatically to continue the path the patient had already taken. If sleep deprivation is foreseeable, he takes 500 mg valpraote the night before. We further recommended to avoid sleep-deprivation and to consume alcohol in moderate amounts only, as excessive alcohol intake may trigger seizures in juvenile myoclonic epilepsy.

… a 38-year-old female patient had suffered in the previous 20 years, not realizing that these were epileptic seizures.

Since 17 years of age, the patient has experienced episodes with an initial perception of familiarity which is followed by short absences. The patient did not attach these –approximately weekly manifesting – episodes too much importance, subjectively these did not have any clinical relevance to her. Also third parties did not have the impression that these episodes presented a relevant medical problem. Due to a concomitant depressive disorder, the patient has started regular psychotherapy 3 years ago. The patient had reported her psychotherapist these “funny” episodes, but the latter attributed those to dissociative (= psychogenic non-epileptic) seizures.

Eventually, the patient presented to a neurologist due to persistent tension-type headache, who transfered the patient under the suspicion of epileptic seizures for further diagnostic procedures and treatment to our epilepsy-center. Just based on the patient’s description of her seizures, we were able to make the diagnosis of partial epilepsy with déjà vu auras and automotor (= complex partial) seizures. A brain MRI was normal, thus etiologically the epilepsy is cryptogenic.

We initiated antiepileptic drug treatment with lamotrigine which – along with levetiracetam – is recommended in the guidelines of the German Neurological Society as first-choice treatment for partial epilepsy. Due to the depressive symptoms, we decided against levetiracetam. With achieving the target dose of 150 mg daily, the patient was free of epileptic seizures.

This case presentation is of interest for two reasons. Firstly, any short-lasting paroxysmal events with alterations of perception and/or absences should be presented to a neurologist, ideally one of those specialized in epilepsy. Secondly, response to new-onset antiepileptic drug treatment after multiple – as in the current case more than 1,000 – epileptic seizures is as good as after 1 or 2 seizures. This also has been demonstrated in a large group of indigenous people with long-lasting untreated epilepsies from the Andes Mountains. Thus, repetitive epileptic seizures in humans don’t render the brain “more epileptic”, as it had been assumed in former times.

A 23-year-old female patient with learning difficulties suffers from partial epilepsy with complex-partial and secondary generalized tonic clonic seizures since early childhood. So far, she was treated with nine different antiepileptic drugs in high doses without beeing seizure-free, this patient’s epilepsy is pharmacoresistant. High-resolution brain MRI did not detect any lesions. In pre-surgical monitoring with scalp EEG recordings, a right hemispheric seizure onset was seen. However, the epileptogenic zone which was aimed to be resected could not be defined. We recommended to the patient and her family invasive EEG recordings with subdural grid electrodes. Similar to other patients, at first the family was unable to decide for the surgical approach. As the patient still suffered from 4 to 5 complex partial seizures per month, we initiated treatment with perampanel in addition to other antiepileptic drugs. With a daily dose of 8 mg, the patient is seizure-free now for 3 years.

In randomized placebo-controlled trials on antiepileptic drugs, only 4 to 8 % of patients become seizure-free, and the duration of such trials commonly is limited to 3 months. But the primary endpoint of these trials is the responder rate, i.e. the fraction of patients with a reduction in seizure frequency as compared to baseline of at least 50 %. Commonly, 30 to 40 % of patients in the verum arm are responders. Prerequisite for approval by the European Medicine Agency (EMA) in London is a significantly higher responder rate in the group of patients treated with the new anticonvulsant compared to the placebo group. This primary endpoint was successfully met by perampanel, and the drug was introduced into the market.

In Germany, in 2011 a law passed the parliament which aims to re-organized the market of pharmaceutical drugs. In addition to the randomized controlled trials as described above and beyond approval by the EMA, the pharmaceutical companies have to prove that the new drug has an additional benefit in comparison to already available drugs. The companies are required to compare the new compound not to placebo but – in a head-to-head fashion – to “older” antiepileptic drugs which are already EMA-approved. These data are not available from international randomized controlled trials, as most study participations were already treated with the comparator in the long course of their epilepsy and therefore can not be included into the studies. On the basis of this law, the German authorities denied an additional benefit of perampanel compared to other anticonvulsants. The pharmaceutical company which produces perampanel has provided the substance for free in the last 2 years. In spring 2016, perampanel will be withdrawn from the German market.

How to explain to the above reported patient, who is seizure-free with perampanel for more than 3 years and who did not have to undergo epilepsy surgery, that the substance has been declared not to have an additional benefit? In this case, this is difficult to place. We now will ask this patient’s and other successfully treated patients’ health insurance company to pay for the costs of this drug when purchased via international pharmacies. Our patient with learning difficulties will definitely not be able to bear the costs on her own.

A 36-year-old male patient suffers from partial epilepsy since his 8th year of life after – at the age of 5 years – he had fallen out of the window resulting in severe traumatic brain injury. Cranial MRI revealed a widespread lesion in the left temporal lobe which also involved frontal lobe structures. Seizure semiology was stereotypical with tonic posturing of the right upper extremity followed by cloni. Frequency was 4 to 5 per month. Following invasive long-term video-EEG with subdural grid electrodes, the seizure focus at the posterior margin of the lesion could be indentified and was resected. Six month after the operation, the patient reported two seizures; he was quite frustrated as the felt the resection to be in vain. On detailed history taking, he said that he had motor signs involving the whole body; this would correspond to tonic clonic generalized seizures. As increase in seizure severity after epilepsy surgery at least was unexpected, we took third party history by a colleague of the patient. She reported that the patient was lying on the floor with jerks of his upper und lower extremities for 2 to 3 min. Motor signs were fluctuating, eyes were closed, and after the end of motor signs the patient was immediately completely reoriented. This description clearly argues for psychogenic non-epileptic seizures.

New-onset psychogenic non-epileptic seizures manifesting after successful epilepsy surgery have recently been described in 4% of patients. Risk factors were female sex and pre-existing psychiatric disturbances.

We explained to the above reported patient our diagnostic appraisal and conveyed within a couple of days a first appointment at our new outpatient clinic for psychogenic non-epileptic seizures, which is part of the Epilespy-Center Berlin-Brandenburg.

A 48-year-old male patient suffers a first generalized tonic clonic seizure, he does not remember any symptoms before loss of consciousness. Head MRI reveals a 2 cm lesion in right amygdala/hippocampus, no enhancement by contrast agent. The most likely diagnosis is ganglioglioma, a benign tumor which probably is carried by the patient for years or even decades. Following the new criteria of the International League against epilepsy, a first generalized tonic clonic seizures and proof of an unambiguous cerebral lesion defines epilepsy, as recurrence risk for further seizures is significantly increased.

On further detailed history taking, the patient reported that since his 30th year of life, i.e. for more than 15 years, he has recurrent episodes of 10 to 15 sec. duration occurring 4 to 5 times per month with some pressure and a feeling of warmth in his stomach, sometimes this sensation “wanders” to the throat. During these stereotyped episodes, he reports to be fully conscious and reactive, bystanders would not notice anything. This semiology is typical for seizure onset in mesio-temporal structures. Twice the patient had contact to a gastroenterologist, gastroscopy had been performed without any findings.

These episodes with abdominal warmth and pressure are undoubtedly epileptic auras, these are by definition simple partial sensory seizures. This type of seizures has no relevant medical significance in itself, but if detected earlier, brain imaging would have been preformed earlier as well. Fortunately, the patient presumably has a benign brain tumor, but a malignant neoplasia would have been possible as well and would have been left undetected.

Antiepileptic pharmacotherapy was initiated with zonisamide at 300 mg daily in a single dose, the patient now has one aura per month. Now, the reason behind the episodes with abdominal pressure has been clarified, the patients tolerates one aura per month, he denies to increase dose of the antiepileptic agent. The presumed ganglioglioma will be controlled by head MRI once per year in regard of general growth and alterations in its structure.

This case nicely demonstrated that the “first seizure” often is not the first seizure, and that detailed history taking is of utmost importance.

A 35-year-old male patient suffers for 8 years from recurrent stereotyped episodes with initial double vision for 2 to 3 min., followed by paresis of facial and then upper extremity musculature, in each case on the right. Duration of paresis is 20 to 30 min., followed by slow recovery over another 10 min. During these episodes, articulation is slurred which obviously is the consequence of right facial weakness. The patient’s wife has video-taped one of these episodes, clearly confirming the specifications. The paroxysmal events are not accompanied or followed by headaches. Frequency is two to three attacks per year. Cranial MRI and EEG examinations were normal.

The patient’s brother and mother suffer from migraine with visual aura, so far both of them did not experience motor deficits in association with headache.

Before the patient presented to us the first time, the diagnosis of transient ischemic attacks was made and a secondary prophylaxis with Aspirin was started. Later another hospital allocated these attacks to focal epileptic seizures. The – assumed – epilepsy was treated with levetiracetam which however was not able to influence occurrence of these episodes.

When the patient presented in our epilepsy outpatient clinic at the Charité for the first time, we again took a detailed history from the patient and his wife regarding these events. The main argument against transient ischemic attacks is the progressive development of motor deficits which is expected to occur suddenly with cerebrovascular accidents. The main argument against focal epileptic seizures is the long duration of the events, epileptic seizures commonly do not last longer than 2 min.

After exclusion of these two differentialdiagnoses, we made the diagnosis of sporadic hemiplegic migraine which shows an atypical course due to lack of headache. We stopped treatment with Aspirin and levetiracetam.

Secondary prophylaxis for recurrent episodes of hemiplegic migraine is lamotrigine which we currently titrate to 150 mg daily.

A 23-year-old man had developed epilepsy with three presumably generalized tonic clonic seizures in the last 4 years, there were no hints for focal seizure onset. Even in detailed history taking, there were no clear hints for binding to the time of day or sleep-wake-cycle. Several routine EEGs and a recent head MRI were normal. So far, the patient was not treated with antiepileptic drugs. On the basis of the previous course of the disease, syndromatically we initially assumed unclassified epilepsy. We performed a long-term video-EEG which was normal. In order to increase diagnostic sensitivity, the patient was put on sleep deprivation. On ward round the next morning, we met the patient sleeping. We woke him up, and within minutes he suffered first severe myoclonus of the upper extremities and the trunk which threw the patient on his back. Three minutes later, repetitive myoclonus developed to a generalized tonic clonic seizure accompanied by an accordant EEG seizure pattern. Thus, during rounding we were able to make the diagnosis of idiopathic generalized epilepsy (subsyndrome: juvenile myoclonic epilepsy), we initiated antiepileptic drug treatment with valproic acid.

This case illustrates that – on the one hand – sleep deprivation is a strong trigger in idiopathic generalized epilepsy and that – on the other hand – wakening or awakening displays a predilection for seizure manifestation in this epilepsy syndrome.

Six months ago, a 10-year-old boy sufferer the first time from two generalized tonic clonic seizures that were preceded by an epigastric aura (feeling of warmth in the upper abdomen that slowly rises to the throat). Brain MRI was normal, thus in another hospital the correct diagnosis of cryptogenic partial epilepsy was made. Antiepileptic drug treatment was started with valproate, the 36-kg boy was put on a target dose of 1,500 mg daily.

With valproate, the boy did not have any further seizures, but his cognition and alertness declinced, his school performance impaired, eventually he appeared to be apathic.

In order to get a second opinion, the boy and his mother presented in our epilepsy outpatient clinic for children and adolscents. Valproate serum concentration was massively elevated at 148 mg/l (upper limit of reference range is at 100 mg/l). The patient was admitted to reduce valproate dose and to eventually switch the anticonvulsant to oxcarbazepine. Yet a couple of days after switching, the patient seemed to be more alert, his school performance can only be assessed in the course of the next weeks or months.

It is correct that after two unprovoked epileptic seizures the risk for next seizures is increased, and antiepileptic drug treatment is recommended. However, the boy suffers from partial epilepsy, and valproate is rather subordinated in that epilepsy syndrome. The actual problem is the rapid dose increase and the too high target dose of valproate in that boy. Serum concentration was not controlled for. Furthermore, epilepsy, anticonvulsant treatment and possibly associated side effects had not been discussed with and explained to the patient and his family. This now has been made good for by neuropediatricians and child neuropsychologists at our institution.

A 29-year-old female patient suffers from idiopathic generalized epilepsy with myoclonic jerks in her upper extremities since her 13th year of life. In addition, she had experienced a total of five generalized tonic clonic seizures after awakening since her 14th year of life. These grand mal seizures commonly are triggered by sleep deprivation the night before. Age at epilepsy onset and both seizure types indicate juvenile myoclonic epilepsy.

Initially, the patient was treated with lamotrigine, but this resulted in an increase of early morning myoclonia. Unfortunately, this is a typical adverse effect of sodium channel blockers. After that, the patient was treated with valproic acid which – in a dose of 1,200 mg daily – resulted in complete seizure freedom for the last 10 years.

The patient now presents with the perspective of becoming pregnant in the forthcoming months. We explained to the patient that pregnancies while treated with valproic acid on the one hand are associated with an increased risk for gross malformations and on the other hand may result in impaired intellectual capabilities of the offspings. Occurrence of both complications is a function of the antiepileptic drug dose.

A recent warning by the European Medicines Agency pointed to the teratogenic effects of valproic acid. It stated that in women who can become pregnant valproic acid may only be administered if other suitable drugs had not been efficacious or had been associated with harmful adverse effects.

We switched the patient from valproic acid to levetiracetam. In idiopathic generalized epilepsy, this antiepileptic drug is not licensed for monotherapy but only for add-on treatment (“off lable use”, i.e. treatment beyond license). Nevertheless, levetiracetam exhibits excellent efficacy in juvenile myoclonic epilepsy. Unfortunately, yet 3 weeks after levetiracetam treatment onset, the patient developed psychiatric adverse effects including anxiety and depressive symptoms. The next antiepileptic drug was topiramate but some weeks later the patient had a generalized tonic clonic seizure – after prior 10 years of seizure freedom. The patient denied further dose increase. In that situation, we recommended to the patient returning to valproic acid. We aimed at a significantly lower dose of 600 mg daily and distributed the dose to four times daily 150 mg. In addition, we administered 5 mg folic acid.

In summary, pregnancies with valproic acid treatment – at best – should be avoided at all. In idiopathic generalized epilepsy, this antiepileptic drug is the most efficacious substance, other drugs are not able to prevent seizure recurrences that reliably. Thus, sometimes it seems impossible to refrain from valproic acid in pregnancies. In these cases, a low maximal daily dose should be sought for in order to prevent damaging – teratogenic – effects on the child.

A 67-year old female patient presents in one of our epilepsy outpatient clinics accompanied by her daughter. The patient reports that since her early school age, i.e. since her 9th year of life, absence seizures have occurred several times per day. Five years later, she suffered her first tonic clonic generalized epileptic seizure. Only at that time point, the correct diagnosis of epilepsy has been made, treatment was initiated with ethosuximide.

One or two years later, the antiepileptic drug was withdrawn, since then the patient has been off medication. The patient and her daughter report that epilepsy in the patient’s primary family, i.e. by her parents and her siblings, has been completely hushed up. Epilepsy was highly disregarded and eventually denied in that family. The daughter later noticed that the patient had recurrent short episodes with unresponsiveness; however, the patient refused to contact a neurologist.

After manifestation of concentration difficulties, the patient eventually presented in our epilepsy outpatient clinic. EEG immediately revealed frequent spike-wave-complexes at 2-3/s lasting up to 3 s. Based on the history and the unequivocal EEG finding, the diagnosis of childhood absence epilepsy was made.

Treatment with 900 mg valproic acid resulted in occurrence of very rare absence seizures, the corresponding EEG showed some single spike-wave-complexes only.

In summary, this case shows on the one hand that epilepsy – in particular in elderly patients – can still be heavily stigmatized. On the other hand, even after hundred thousands of absence seizures, immediate pharmacoresponsiveness is still preserved.

A 16-year-old young man reported almost daily jerks in his arms, that first have occurred 6 months ago. He further said that these sudden lancinating movements originate in his shoulders. These jerks manifest almost always in the early morning in the first 60 min. after awakening. Epileptic seizures with loss or impairment of consciousness were denied. The patient’s mother suffered from a total of five generalized tonic-clonic seizures since the age of 17 years, these seizures also occurred shortly after awakening. She was treated with an antiepileptic drug (AED, name not available) for a couple of years, since age 25 she did not have any more seizures.

The current young man was not treated with an AED so far, as the etiology of his jerks was unclear. We performed longterm video-EEG for 48 h and observed a couple of episodes with the habitual jerks of his upper extremities. While writing on the keyboard of this notebook, he hit the monitor; and while playing chess with his father, he bowled down one of the figures on the board. The corresponding EEG demonstrated generalized discharges with polyspikes followed by a slow wave.

The electroclinical findings with matutinally occurring, lancinating upper extremity myoclonus and polyspike-waves in the EEG allows to make the diagnosis of juvenile myoclonic epilepsy (JME). This form of epilepsy is also termed Janz-Syndrome, as the Berlin-based epileptologist Dieter Janz has worked since the 1950ies extensively on the phenomenology of JME. The condition is characterized by myoclonus of the extremities, some patients additionally suffer from generalized tonic-clonic seizures. JME is a subsyndrome of idiopathic generalized epilepsy (IGE), the etiology is assumed to be based on genetic alterations. Sometimes first-degree family members also suffer from IGE, the mother of the current patient had epilepsy with grand mal on awakening.

Treatment of choice is valproic acid. The patient at first was administered a rather low dose of 600 mg daily. At least in the first week of treatment, the patient was free of myoclonus.

In the last decades, JME patients were thought to require lifelong AED treatment, AED withdrawal was supposed to result almost always in seizure relapse. In the last years, five longterm studies on JME have demonstrated that prognosis in JME is much more favorable than previously thought. In a large number of patients, AED withdrawal beyond the 4th decade of life did not result in seizure recurrence.

A 15-year old male adolescent is admitted to our clinic to clarify if paroxysmal episodes with loss of consciousness and subsequent fall can be attributed to epileptic seizures or to seizures of other origins. Other seizures comprise syncopes or – very rare – cataplectic seizures that are part of narcolepsy. The patient himself was not able to give too many details on the seizures, as he was amnesic for most parts of it.

In our clinic, all patient rooms, corridors, and recreation rooms have fixed video cameras which allow for recording and post-hoc analysis of seizures. At the beginning of this patient’s first seizure in our clinic, he stood at the window of this room drinking some water out of a bottle. After some seconds, his hand holding the bottle slipped downwards, the patient staggered, and eventually fell backwards to the bottom in a flabby manner. Again some seconds later he had a generalized tonic posturing which evolved to bilateral clonic movements. Postictally, the patient is disorientated for another 20 min. In summary, this event unequivocally was an epileptic generalized tonic clonic seizure. In the further course of our diagnostic procedures incl. video-EEG-monitoring, the diagnosis of juvenile myoclonic epilepsy was made. It was somewhat irritating that at the onset of the seizure the muscle tonus was flabby; this rather points to syncope. On the other hand, videographic analyses on induced syncopes in healthy subjects have demonstrated that at the onset the whole body can express a tonic posturing.

This case example may illustrate that single clinical signs are never sufficient to allocate seizures correctly. Rather, the entire clinical scenario has to be considered.

A 32-year-old male patient with massive overweight (140 kg at 178 cm height) underwent an operation with bypass of the stomach 12 months ago. Since then he had suffered from five tonic-clonic generalized epileptic seizures. Prior to seizures, the patient appears to be disorientated, he reports vegetative symptoms such as sweating. After two of these seizures, serum glucose was assessed and was significantly reduced to 40 and 42 mg/dl. Prior to adipositas surgery, the patient never had experienced epileptic seizures.

For clarification of the cause of seizures and for potential treatment, the patient presented in our outpatient clinic. 24-h-video-EEG and cMRI were normal. Following detailed history taking from the patient and his proxies and after critical acclaim of current and former paraclinical findings, we explained to the patient our interpretation. We think that the patient suffers from dumping syndrome after operation for stomach bypass (late dumping). When undigested carbahydrates move too rapidly into the small bowel, they are rapidly absorbed in the intestine resulting in hyperglycemia. This is followed by excretion of insulin, overshoot results in hypoglycemia. This is the pathophysiological basis for our patient’s vegetative symptoms and the subsequent tonic-clonic generalized epileptic seizure. After having explained these interrelations to the patient, he learnt to early identify the onset of hypoglycemic episodes and to immediately treat them with intake of dextrose. Since then no more epileptic seizures have occurred.

In summary, this patient suffers from late dumping syndrome resulting in acute-symptomatic epileptic seizures. Antiepileptic drug treatment is not necessary, as hypoglycemic episodes are now recognized and treated by the patient early. So, he can control and prevent occurrence of epileptic seizures.

A 27-year-old male patient suffered from first epileptic seizures 5 years ago. Seizures were characterized by loss of contact, staring, and swallowing, duration is 1 min. These automotor (= complex partial) seizures initially manifested in wakefulness and in sleep. The patient did not remember an aura preceding seizures from wakefulness, by nature he could not comment on potential auras in seizures from sleep. Two high-quality brain MRIs were normal. This patient suffers from cryptogenic partial epilepsy.

Antiepileptic drug treatment was initiated with lamotrigine, the patient has now been free of seizures from wakefulness with 500 mg daily. The patient’s partner still reports occurrence of 2-3 automotor seizures per year from sleep. The patient himself is amnesic for and thus not distracted by these seizures, he did not follow our recommendation for antiepileptic combination therapy.

The patient owns a driving license since his 18th birthday, he did not drive since his first seizure in the 22nd year of life. He now asks if he is allowed to drive, as for the last 4 years his seizures exclusively manifested in sleep.

We could approve his request. The German driving regulations (November 2009), which apply to most other countries, at first generally prohibit driving in people with epilepsy. But there are exeptions. The most prominent is seizure freedom for more than the last 12 months. In addition, people with seizures occurring exclusively during sleep for more than the last 3 years are allowed – despite continuing seizures – to drive a car themselves. It is presumed that – with unchanged antiepileptic drugs – seizures continue to occur exclusively in sleep and that manifestation from wakefulness is highly unlikely.

Twelve months ago, a 32-year-old male patient suffered a first generalized tonic clonic seizure from sleep. Since then, two further episodes with impaired consciousness and swallowing lasting less than 1 min. have occurred – these are typical clinical signs of an automotor (= complex partial) epileptic seizure. Postictally, the patient was immediately able to speak. EEG – from awakening and sleep – showed right temporal slowing, no increased neuronal excitability. Brain MRI was normal. This patient suffers from cryptogenic partial epilepsy, seizure onset presumably is confined to the right temporal lobe.

We counselled the patient on some basics of epilepsy and recommended – the patient was untreated so far – the regular intake of an antiepileptic drug. The patient was overweight with 105 kg and he asked for a rather uncomplicated treatment regimen. We advised him to take zonisamide (=Zonegran®) that commonly does not result in weight gain but rather has the potential to decrease weight. In addition, the long elimination half-life allows to take the drug once daily.

We told the patient that he has to be free of epileptic seizures for 12 months before he is allowed to drive a car on his own.

At the end of the consultation, the patient asked the question which he had in his mind the preceding weeks: Do epileptic seizures cause irreversible loss of neuronal cells? And does that mean that he has to fear for his cognitive capabilities if further seizures occur? We were able to put his mind at ease and explained to him that current knowledge does not give any hint that “normal” epileptic seizures, lasting less than 2 min., delete neuronal cells. Methodologically, this is difficult to assess. But there are long-term studies covering the brain of people with epilepsy for more than 3 years, and despite frequent epileptic seizures – compared to subjects without epilepsy – no deleterious effects were seen.

Neuropsychological long-term studies covering decades have shown that all people assessed had a slow decline regarding memory, the same was seen in people with epilepsy. The difference was that in average people with epilepsy at onset of the disease had slightly lower memory capabilities – commonly without any consequences in everyday life. These data indicate that slight memory problems in epilepsy – if present at all – are caused by the underlying brain disorder and not by epilepsy or recurrent epileptic seizures. Older antiepileptic drugs may have caused impaired cognition and thus have contributed to this problem. Currently available newer antiepileptic drugs generally do not have this risk.

In summary, epileptic seizures do not cause loss of neuronal cells and do not cause development of memory problems.

A currently 57-year-old female patient suffered first generalized tonic clonic epileptic seizures from wakefulness in her 26th year of life. Partial onset of seizures was not reported. Multiple EEGs and neuroimaging (CT and MRI scans) were normal, the cause of epilepsy remained unclear. In summary, this patient suffers from undetermined epilepsy as the available information does not allow to make the allocation to either a generalized or to a partial epilepsy syndrome.

Initially, the patient was treated with valproic acid, but she gained more than 10 kg of weight. Therefore, treatment was switched to carbamazepine, which was stopped after a couple of years due to unspecific side effects. For the last 15 years, the patient has been treated with lamotrigine, the current daily dose is 2 x 100 mg. The patient feels fine, she does not report any side effects.

As the patient is seizure free for more than 25 years, we discussed with her the possibility to taper and finally withdraw lamotrigine. Her prognosis regarding ongoing seizure freedom is favorable, as EEGs and neuroimaging have always been normal and as she became seizure free with the first antiepileptic drug. The medication has been changed in the meanwhile due to side effects not due to lack of efficacy.

However, the patient refused to stop antiepileptic treatment. The former seizures have been traumatizing and she admits to be afraid of seizure recurrence after lamotrigine withdrawal. Furthermore, she does not have any side effects with this substance.

We can understand this patient’s perspective and do not see any medical problem with continuation of the current lamotrigine treatment regimen.

A 22-year old male patient suffers a first tonic-clonic generalized epileptic seizure. The seizure occurs from wakefulness at midday. Focal onset of this seizure is not reported. In the night before the seizure, sleep duration was shorter than usual. Other clinical seizure forms so far had not occurred. In routine EEG, generalized spike-wave-discharges at 3 Hz with an amplitude maximum in frontal leads were seen. This constellation indicates that the patient has a significantly increased risk for further unprovoked seizures, this defines epilepsy. Due to seizure semiology, the trigger sleep deprivation, and the interictal EEG findings, we allocated the syndrome to idiopathic generalized epilepsy. We initiated pharmacological treatment with the aim to prevent further seizures (that eventually is a secondary prophylaxis), the substance administrated was valproic acid at 2 x 300 mg daily. We informed the patient that he is banned to drive a car himself for the next 12 months.

The former definition of epilepsy demanded occurrence of at least two unprovoked epileptic seizures. The new revised epilepsy definition provides that patients have epilepsy if after the first unprovoked seizure there is an increased risk for further seizures. A structural MRI lesion or interictal epileptic discharges in the EEG indicate such an increased recurrence risk. Patients then need antiepileptic drug treatment. If neuroimaging and EEG are normal, the first unprovoked seizure is not associated with an increased recurrence risk. This is termed as an isolated unprovoked seizure and does not need treatment, the patient is not allowed to drive a car himself for the next 6 months.

The question “Is one seizure epilepsy?” needs to be answered with yes and no, critical is the extent of seizures recurrence risk.

A 42-year old patient with moderately severe mental retardation suffers from partial epilepsy since early childhood. He can not express if his has any auras, but previously frequent automotor (= complex partial) and generalized tonic-clonic (= Grand Mal) seizures occurred. The current antiepileptic treatment regimen comprises phenytoin 350 mg, levetiracetam 2,000 mg and lacosamide 400 mg. One slight automotor seizure occurs once or twice per year. The shared cause for mental retardation and epilepsy is unclear.

The persons taking care of the patient reported that in the previous months gait – with some fluctuations – had been more impaired than before. This probably was caused by relatively high phenytoin serum concentrations between 18 and 25 mg/l.

To optimize pharmacological treatment, the patient was admitted to our specialized ward for patients with epilepsy and additional disability. During the 4-week stay, we reduced phenytoin dose step-by-step and finally stopped this substance. Simultaneously, gait impairment improved obviously. The patient did not suffer from any epileptic seizure up to the following 6 months.

The current case demonstrates that less antiepileptics – in number of substances or in amount of daily dose – often are similarly efficacious compared to more. A large long-term study covering more than 20 years has demonstrated that in difficult to treat epilepsies two antiepileptic drugs are more efficacious than one substance. On the other hand, three agents were not better than two, but the patients – as in the current case – had more side effects.

The 27-year-old female patient presents in the outpatient clinic because she abruptly loses muscle strength when she has to laugh or when she trains intensely at the gym. The muscles of the neck are mostly involved, but her muscles in her arms and legs can also be affected so that objects can fall out of her hands or that she falls to the ground. This complaint has been going on for the past ten years. The frequency with which she loses muscle strength varies with the presence of the appropriate triggers. Additionally, she often feels tired during the day although she sleeps well during the night. It can happen that she suddenly falls asleep for ten or 20 minutes during the day even when she does not feel really tired. Over the past decade she had gained around 65 pounds without changing eating habits, now attaining a body-mass-index of 38.7. She has no further complaints. There is no history of a psychiatric disorder or any other diseases.

Because of the excessive daytime sleepiness and an increased propensity to sleep during the day there is a need for further sleep studies in a sleep laboratory which take place for three days. Polysomnography was entirely normal. The Multiple Sleep Latency Test, performed at 9 and 11 a.m. and at 1, 3, and 5 p.m., showed a pathologically short mean sleep latency of 2.6 min and four sleep onset-REM (= SOREM) with a mean latency of 3.7 min.

The patient’s history and the results from the Multiple Sleep Latency Test allow to establish the diagnosis of narcolepsy with cataplexy (= Narcolepsy type I). Narcolepsy with cataplexy leads to excessive daytime sleepiness, often associated with naps even in the absence of tiredness which mostly last less than 20 minutes. Cataplectic attacks correspond to a sudden loss of muscle tone in emotionally connoted situations (laughter, joy, startle), often in circumscribed parts of the body. The substantial weight gain in our patients also has to be considered as a symptom of narcolepsy with cataplexy due to a positive energy balance.

Almost always narcolepsy with cataplexy is due to orexin-deficiency (orexin = hypocretin), a neurotransmitter exclusively produced in the lateral hypothalamus. Conversely, narcolepsy without cataplexy does not represent orexin-deficiency but should be considered a different disease entity. Mechanisms leading to orexin-deficiency are most likely the result of a topographically selective autoimmunologically induced inflammation in the hypothalamus.

Medical treatment of narcolepsy with cataplexy includes gammahydroxybutyrate to ameliorate cataplectic attacks as well as stimulating substances such as modafinil or methylphenidate. With this therapeutic approach our patient has substantially less cataplectic attacks and also excessive daytime sleepiness has improved. Contrary, her weight gain persists which is why she considers liposuction.

A 22-year-old female patient for the first time presents in our epilepsy outpatient department. Since the age of 16 years, she suffers from regularly occurring seizures that are characterized by loss of contact and non-reagibility as well as prominent oral and manual automatisms. From a semiological point of view, these are typical automotor (= complex partial) epileptic seizures. Frequency is 1-2 per month. Etiology is unclear, at epilepsy onset she had an MRI, but she neither has the images nor the written report. The patient is otherwise healthy, she is working as office clerk.

At presentation in our outpatient clinic, the patient was treated with levetiracetam 2 x 1,500 mg daily. At epilepsy onset, she had been treated with oxcarbazepine, this had had to be tapered after 2 weeks due to significant side effects (details unclear). The patient now presented on her own decision in our clinic asking if her epilepsy could be treated better than now. Her previous doctor had told her, that she can be happy with her current treatment, as other patients with epilepsy are doing worse.

We recommended add-on treatment with lamotrigine and increased dosage step-by-step to 200 mg daily. In case of further seizures, the dosage may be further increased, some patients take up to 800 mg daily without any side effects. In this constellation, the patient has a chance for becoming seizure free of 20-30 %. If further seizures occur with levetiracetam and lamotrigin in high dosages, the patient’s epilepsy is by definition pharmacoresistant. The patient then needs work-up for epilepsy surgery with intensified video-EEG long-term monitoring.

We initiated new neuroimaging with 3 Tesla MRI following a specific epilepsy protocol. In 3 months, the patient presents again in our specialized epilepsy outpatient clinic.

A 7-year-old girl suffers since her 3rd year of life from daily episodes with impaired consciousness, these are accompanied by discrete oral automatisms. Duration of these presumably atypical absence seizures is 15-20 sec. The child additionally suffers from a moderate global developmental disorder, she attends a school for children with special needs. The cause for epilepsy and mental retardation is elusive, cMRT demonstrates some slight global atrophy, cerebrospinal fluid examination is normal.

So far, the girl has been treated with six different antiepileptic drugs. The current treatment regimen with oxcarbazepine and levetiracetam did not result in obvious reduction of seizures frequency.

We discussed with the parents the therapeutic option of ketogenic diet that is well-know in the treatment of epilepsy for more than 80 years. This diet is characterized by high fats and low carbohydrates which lowers the glucose level dramatically. As compensation, the liver converts fat into ketone bodies, thus giving the name of this dietary treatment. The exact mechanism of action is unclear, but eventually frequency of epileptic seizures – in particular in children – is reduced. To be efficacious, ketogenic diet needs to be applied regularly, i.e. day by day. For this purpose, parents and – if suitable – children are taught by specialized diet assistants.

The parents of our young patient agreed on treatment with ketogenic diet and were introduced in preparing food on a ketogenic basis in the Epilepsy-Center Berlin-Brandenburg.

Some days after begin of ketogenic diet, the patient suffers from significantly less seizures. At an outpatient visit one month later, the mother reported one seizure per week. We agreed with the mother to continue this supplementary antiepileptic treatment as long as tolerated by her daughter.

An 18-year-old man suffers from partial epilepsy since early school years. Epilepsy is characterized by 2-3 automotor (= complex partial) seizures per month. In the past years, the patient was treated with four different antiepileptic drugs, however without any significant impact on seizure frequency. His epilepsy was caused by left-sided hippocampal sclerosis, i.e. a scar in mesio-temporal structures.

The patient reported several relevant limitations in his social life, including swimming and obtaining a driving license. In addition, he felt – one year before final school exams – some impairment in his cognitive capacities.

In spring 2013, the patient presented the first time in our epilepsy outpatient clinic. History and MRI finding suggested to timely evaluate the patient for possible epilepsy surgery. Some weeks later, video-EEG-monitoring proved that the patient’s typical seizures originate in left mesio-temporal structures. As video-EEG findings were congruent with MRI pathology, we recommended left anterior temporal lobe resection. We advised the patient that pharmacological antiepileptic treatment presumably will not result in sustained seizure freedom. The patient consented surgery, that was performed 2 weeks later, in May 2013, by our neurosurgical cooperation partners in the Charité.

One year after temporal lobe resection, the patient was re-assessed with multimodal diagnostic tools. He was completely seizure free since the operation, neuropsychology did not detect any deficits following resection.

In spring 2014, that patient successfully made his final school exams, in autumn 2014 he will start to study at university. The patient himself in particular appreciates his independence, he swims on his own and will acquire his driving license in the next weeks.

While pharmacological treatment of epilepsies follows a symptomatic approach, simply preventing or suppressing the next seizures, epilepsy surgery is a causal treatment approach. Temporal lobe resection in patients with hippocampal sclerosis results in seizure freedom in more than 70% of cases. After 2 years of postoperative seizure freedom antiepileptic drugs may be reduced and eventually tapered. If patients with partial epilepsy do not respond to two antiepileptic drugs, evaluation for epilepsy surgery should be considered. The younger the patients are at the time of operation, the better is social outcome.

A 16-year-old young man reported almost daily jerks in his arms, that first have occurred 6 months ago. He further said that these sudden lancinating movements originate in his shoulders. These jerks manifest almost always in the early morning in the first 60 min. after awakening. Epileptic seizures with loss or impairment of consciousness were denied. The patient’s mother suffered from a total of five generalized tonic-clonic seizures since the age of 17 years, these seizures also occurred shortly after awakening. She was treated with an antiepileptic drug (AED, name not available) for a couple of years, since age 25 she did not have any more seizures.

The current young man was not treated with an AED so far, as the etiology of his jerks was unclear. We performed longterm video-EEG for 48 h and observed a couple of episodes with the habitual jerks of his upper extremities. While writing on the keyboard of this notebook, he hit the monitor; and while playing chess with his father, he bowled down one of the figures on the board. The corresponding EEG demonstrated generalized discharges with polyspikes followed by a slow wave.

The electroclinical findings with matutinally occurring, lancinating upper extremity myoclonus and polyspike-waves in the EEG allows to make the diagnosis of juvenile myoclonic epilepsy (JME). This form of epilepsy is also termed Janz-Syndrome, as the Berlin-based epileptologist Dieter Janz has worked since the 1950ies extensively on the phenomenology of JME. The condition is characterized by myoclonus of the extremities, some patients additionally suffer from generalized tonic-clonic seizures. JME is a subsyndrome of idiopathic generalized epilepsy (IGE), the etiology is assumed to be based on genetic alterations. Sometimes first-degree family members also suffer from IGE, the mother of the current patient had epilepsy with grand mal on awakening.

Treatment of choice is valproic acid. The patient at first was administered a rather low dose of 600 mg daily. At least in the first week of treatment, the patient was free of myoclonus.

In the last decades, JME patients were thought to require lifelong AED treatment, AED withdrawal was supposed to result almost always in seizure relapse. In the last years, five longterm studies on JME have demonstrated that prognosis in JME is much more favorable than previously thought. In a large number of patients, AED withdrawal beyond the 4th decade of life did not result in seizure recurrence.

A 28-year old patient suffers from epilepsy with Grand Mal for 5 years. Seizures manifest while awake, but without any further binding to the sleep-wake-cycle. Even purposeful asking did not give hints for focal onset of seizure semiology. Routine and sleep-deprivation EEG were normal as was cerebral MRI. We allocated the condition to unclassified epilepsy, as we did not find evidence for partial or generalized epilepsy. 20% of all epilepsies are unclassified, in some cases the further course of the condition allows to make the syndromatic diagnosis of partial or generalized epilepsy.

The current patient reported 4-5 five Grand Mal annually. Despite this rather high frequency of severe epileptic seizures, the patient declined – from onset of his epilepsy – taking of antiepileptic drugs. He indicated a generally dismissive attitude towards chronically taking medication.

We explained to that patient that the main problem in epilepsy is that seizures generally manifest very sudden and often without any warning. In Grand Mal, uncontrolled falls may result in substantial injuries. We further had to explain him that patients may die during or shortly after a Grand Mal. This sudden unexpected death in epilepsy patients (SUDEP) is likely caused by seizure-related cardial arrhythmias. The most efficient measure to prevent SUDEP is prevention of Grand Mal. Despite our explanations, the patient further declined to take antiepileptic drugs.

Non-adherence towards physicians’ recommendations presents a great challenge, in particular in pharmacotherapy of chronic diseases. In the current case, the patient at least communicated his non-adherence; commonly, the doctor does not know about the irregular or absent taking of antiepileptic drugs.

A 35-year-old female patient suffers from seizures for 10 years. Her disorder commenced during a grievous separation. Seizures are characterized by twitching and beating of all extremities and prominent movements of her trunk and pelvis. These seizures have been diagnosed epileptic 10 years ago. Since then, the patient has regularly taken antiepileptic drugs (at first carbamazepine, now levetiracetam in a dose of 2,000 mg daily). Seizure frequency is 2-3 monthly that is not at all influenced by antiepileptic drugs. The patient herself reports that seizures manifest almost exclusively in situations characterized by stress (e.g. conflicts in her family).

The patient was admitted to the Epilepsy-Center Berlin-Brandenburg by her private neurologist in order to re-assess her seizures due to putative pharmacoresistance.

History already – onset of seizure disorder in the setting of a separation, manifestation of seizures in situations of stress – strongly argues that seizures are not of epileptic but of psychogenic non-epileptic origin. Typical is that seizures occur situational, in contrast epileptic seizures in patients with epilepsy generally manifest unprovoked and unexpected. In a routine EEG, a typical seizure occurred. Semiologically, eyes were closed, motor signs were irregular and undulant. EEG showed movement artifacts, there was no seizure pattern.

We discussed with the patient our diagnostic assessment, levetiracetam was gradually tapered. At the same time, psychotherapy was initiated. The aim was to learn to cope with stressful situations in other ways than permitting development of psychogenic non-epileptic seizures.

Studies have demonstrated that the correct diagnosis of psychogenic non-epileptic seizures is commonly made 7 years after onset. Prior to that patients are administered – with physicians’ assumption of epilepsy – all too often several antiepileptic drugs.

A 43-year-old female patient suffers from partial epilepsy with automotor (= complex partial) seizures for 25 years (seizure frequency, 4-5 per month). Seizures are characterized by impaired consciousness and oral automatisms. Seizures are preceded by epigastric auras. In the past years, the patient was administered eight different antiepileptic drugs that eventually failed to control her seizures. Brain MRI reveals right hippocampal sclerosis that presumably is the cause for the patient’s epilepsy. In pre-surgical assessment, video-EEG-monitoring recorded several habitual seizures with onset pointing to right temporo-mesial structures. As all findings were congruent, we recommended right anterior temporal lobe resection.

However, the patient refused resection, though the chance for post-operative seizure freedom was highly favourable. Reasons for refusal remained elusive.

An analysis from the university hospital Bonn on long-term seizure outcome after epilepsy surgery revealed that in the last 20 years the fraction of patients refusing resection has increased to up to 20% (Bien et al. 2013 JNNP).

We see it as our duty to inform patients explicitly on the risks of injuries and even worse perils accompanying repeated epileptic seizures. These risks significantly overwhelm those of the operative procedure.

A 39-year old female patient with childhood onset epilepsy was admitted to the Epilepsy-Center Berlin-Brandenburg due to intense tiredness, desorientation und impaired speech production. The patient suffers from learning disability, she lives in assisted accommodation. She has partial epilepsy, automotor (= complex partial) seizures with impaired consciousness and oral automatisms are reported to manifest every 2-3 months. The cause of epilepsy is unclear, a cMRT from 2011 is normal.

In the weeks prior to admittance, the patient has slept most of the time und she was almost unable to walk. She was brought onto the ward with a stretcher.

The treatment regimen consisted of five antiepileptic drugs: primidone, carbamazepine, zonisamide, clobazam and valproic acid. On admission, serum concentration of valproic acid was markedly elevated to 130 mg/l (normal range, 40 – 100 mg/l).

The aim of our treatment was to taper some of the antiepileptic drugs without facilitating increase in seizure frequency. Step by step, we reduced and eventually withdrew the substances zonisamide, clobazam and valproic acid. As the patient was administered primidone for more than 30 years, we refrained from withdrawal of this – also potentially sedating – antiepileptic drug due to risk of rebound seizures.

During four weeks of treatment and tapering of antiepileptic drugs in our center, the patient “woke up”, with physiotherapeutic support she re-learned to walk unassisted und she spoke spontaneously. We did not observe increased seizure frequency.

This case demonstrates impressively, that regular review of antiepileptic drug regimen by epilepsy specialists is urgently needed. In this particular patient, all medical troubles – tiredness and incapacity to walk and speak – had to be traced back to overtreatment with five antiepileptic drugs. Generally, even intractable epilepsies should not be treated with more than two antiepileptics. Clinical trials have demonstrated that administration of a third substance does not have any effect on seizure frequency and severity, but significantly increases the risk for non-tolerable side-effects.

A 24-year-old patient reported short episodes with déjà vu for more than 2 years that occur with increasing frequency. In the last weeks, the patient had these episodes daily. His déjà vus are accompanied by smelling perceptions. On inquiry, the patient’s partner reported that déjà vus are followed by episodes with staring, unresponsiveness and slight lip movements. The patient is amnesic for this second part. Now, he suffered the first generalized tonic-clonic seizure. For the first time, this resulted in clinical and additional technical diagnostic procedures. The episodes with déjà vu were classified as epileptic auras evolving to automotor (= complex partial) seizures. Brain MRI revealed a presumably benign tumor in left temporo-mesial structures, representing the cause of this partial epilepsy.

We initiated antiepileptic treatment with levetiracetam, but also high daily doses modified seizure frequency a best modestly. We added lacosamide, the patient is still in dose increase.

A déjà vu (French for “already seen”) is the – often vexing – phenomenonof having the strong sensation that an event currently being experienced has already been experienced in the past. Déjà vus manifest in healthy persons sporadically, the exact neurobiological mechanisms are elusive. In contrast, déjà vus occurring frequently – in particular such as in the current case – in general are manifestations of pathological processes confined to the temporal lobe. As in the current patient episodes with déjà vu unambiguously are followed by automotor seizures, the déjà vu episodes as well are diagnosed to be epileptic. Such episodes are only experienced by the patient himself, they are not seen by witnesses, this defines an epileptic aura.

The benign tumor in the left hippocampus as cause for the patient’s epilepsy does not require resection from a neurosurgeon’s perspective. If the patient does not respond to the second antiepileptic drug and thus fulfils the criteria for pharmacoresistance, the tumor and further parts of the temporal lobe may have to be resected from an epileptologist’s point of view. The overall therapeutic aim is complete seizure freedom.

A 31-year-old female patient has suffered the last 15 years from tonic clonic generalized seizures occurring once yearly. She does not remember if these fits are preceded by subjective or objective behavioral changes that would indicate that these seizures have partial onset. Beyond the Grand Mal, the patient has smaller seizures with some impairment of consciousness since childhood. However, she is unable to further describe this seizure type. Frequency is four to five times per month.

Routine EEG repeatedly shows generalized spike-wave-complexes at 3/s, while reading the patient stumbles indicating a behavioral correlate of the EEG discharges. During long-term-Video-EEG recording, the patient has two semiologically different seizures. On the one hand, a typical tonic clonic generalized seizure without obvious partial onset occurs; EEG shows 3/s spike-wave-complexes at seizure onset. On the other hand, the patient suffers one of the smaller seizures with some loss of contact. This is accompanied by a seizure pattern characterized by rhythmic theta activity confined to left temporal structures. Cranial 3 Tesla MRI (FLAIR sequence) shows a hyperintensive lesion in left temporo-basal structures that probably corresponds to a benign tumor.

In the constellation delineated above, we assume that this patient suffers from both partial and generalized epilepsy. The latter manifests only in Grand Mal, the slight cognitive impairments during generalized EEG discharges are not perceived by the patient. The small seizures, that could have been absence seizures as well, are clinical manifestation of the left temporal seizure pattern. These seizures are slight automotor (= complex partial) seizures and indicate partial epilepsy caused by the left temporal lesion.

On presentation in the Epilepsy-Center, the patient was treated with high dose valproic acid. We added levetiracetam. If automotor seizures continue with this antiepileptic treatment regimen, epilepsy surgery – despite coexisting idiopathic genealized epilepsy – may be discussed perspectively.

A 53-year-old patient was admitted to assess the nature of paroxysmal behavioral changes including movements of the right arm that have occurred for a couple of years. The patient is of South-East-European origin, language barrier impedes adequate history taking. During longterm video-EEG-recording, a typical event occurred. After short pausing, the right hand clenches, evolving to high-frequent shaking of the right upper extremity. After a minute or so, the left arm is involved. During this 2-minute-episode, the eyes are squinted. Semiologically, this event complies with a psychogenic non-epileptic seizure, the EEG does not show a corresponding seizure pattern.

After demonstration of the video to the patient’s son, he confirms that his father’s spells largely look like that in the video.

Seven years before, the patient had already undergone video-EEG-recording in the Epilepsy-Center Berlin-Brandenburg. At that time, a seizure was recorded with initial pausing, evolving to automated movements of the right hand. The eyes are open initially, they are closed in the further course of this seizure. Duration of this light automotor seizure was 1 min. Ictal EEG was characterized by a right anterior temporal seizure pattern.

In direct comparison of the two video sequences, psychogenic non-epileptic seizures – in spite of some semiological similarities – are easily separated from automotor epileptic spells. Based on history as taken from the patient, language barrier does not allow this distinction. Based on third party history as taken from the son, the current paroxysmal behavioral changes seem to be of psychogenic non-epileptic origin. Eventually, we were not able to clarify if automotor epileptic seizures exclusively occurred a couple of years ago or if this seizure type is still present in addition to psychogenic seizures.

Pharmacological antiepileptic treatment with lamotrigine was continued without changes. We recommended behavioral therapy by a psychotherapist in the patient’s native language.

A 72-year-old patient has coffee and cake with his wife and suddenly pauses while eating, the fork does not reach his mouth. The wife describes a staring gaze, the patient is unresponsive for 1-2 min. This episode is not accompanied by motor signs. After the end of this episode, the patient is rapidly reoriented. Therefore, his wife does not take this behavioural change seriously. In the following weeks, such episodes with loss of contact reoccur repetitively – while watching TV, while eating or during conversations. Interestingly, these paroxysmal changes are only observed by his woman, the patient himself is amnesic for these events. After some detours, the patients eventually presents in the outpatient clinic of the Epilepsy-Center Berlin-Brandenburg. Based on the excellent descriptions of the patient’s wife, the episodes are diagnosed as automotor (= complex partial) epileptic seizures. EEG shows mild bilateral temporal slowing but not interictal epileptic discharges. Brain MRI reveals moderate cerebral microangiopathy. We made the diagnosis of partial epilepsy and started antiepileptic treatment with lamotrigine. Three months later, his wife reported that the patient is seizure free.

This case illustrates typical characteristics of epilepsy in the elderly. Automotor seizures are rather subtle, lacking obvious motor signs. The patient does not realize his spells, amnesia is part of the seizures. On making the correct diagnosis, patients regularly respond excellently to antiepileptic drugs. It is important to be familiar with these characteristics as new onset seizures and epilepsies become more likely the older patients are.

An almost 4-year-old boy complains to his parents after every bathing saying “it’s burning, mom it hurts!”. The parents report that in the aftermath their son stares, he has a head version to the right, and a flection of this right arm. The legs become weak and he slumps down. The eyes are open, but the boy cannot speak, duration of the whole episode is 1 min. Thereafter, he is tired and falls asleep. The parents had documented such an event by mobile phone.

Variations of bathing, in particular regarding water temperature, did not stop manifestation of these events.

We performed video-EEG-recording while the boy was bathing in hospital. Here as well, the toddler developed a typical episode. Ictal EEG demonstrated a seizure pattern starting centro-temporally on the left, later under propagation, the whole left hemisphere was involved. The corresponding behavioural changes were the same as described by the parents before. Analysis of chronology of events showed that seizure onset did not correlate with the end of bathing but with hefty towelling (“rubbing”) of the boy by his father. Clinically, the boy suffered from an initial somato-sensory aura (pain) evolving into an automotor seizure.

Thus, we made the diagnosis of “rub epilepsy”, representing a rare form of reflex epilepsies. Trigger zone was the right arm or the right-sided thorax. Cranial MRI was normal. We refrained from antiepileptic drug treatment and recommended the parents a less courageous towelling of their son. Since then, the toddler did not suffer from any further seizures after bathing.

A 49-year-old female patient suffers since puberty from partial epilepsy with eight to nine automotor (= complex partial) seizures per month. Cranial MRI reveals relevant atrophy in mesio-temporal und temporo-lateral structures on the right. The patient suffers from impaired mental development, she is living with her parents. Though her epilepsy is highly intractable against a number of antiepileptic drugs, for many years the patient and her family were opposed towards advanced presurgical assessment.

In autumn 2012, following a couple of further informative discussions, a first video-EEG-monitoring was performed and five of her habitual seizures were recorded. Surprisingly, the EEG seizure pattern was captured first over the left temporal regions, and then with a latency of appr. 10 sec ictal EEG was seen right temporally as well. Thus we were not able to demonstrate congruency between neuroimaging and initial ictal EEG results. We hypothesised that in the current case EEG lateralisation was misleading. Seizure onset was supposed to be confined to right mesio-temporal structures, but ictal activity then at first propagates to the left temporal lobe including temporo-lateral cortex. With some delay, the seizure pattern is then seen in the hemisphere of seizure onset (right), i.e. in termporo-lateral structures.

To confirm this hypothesis, in a next step, we recorded epileptic seizures with help of semiinvasive electrodes placed bilaterally into the foramen ovale that is in close spatial relation to mesio-temporal structures. Thus, we were able to prove that the seizures – as assumed – indeed start on the right side, then propagate to the contralateral hemisphere before they advance to further parts of the right temporal lobe. Now we were able to demonstrate congruency between MRI findings and ictal EEG patterns. On the basis of these findings, we recommended right temporal lobe resection to the patient and her family which was agreed upon.

Since the operation beginning of 2013, the patient is seizure free. In retrospect, the patient said that she should have agreed on presurgical assessment and a potential resection earlier in the course of her epilepsy.

In an otherwise healthy and appropriately developed 14-year-old boy, EEG recording revealed repetitive generalised 3 Hz spike-wave discharges of 3 to 4 s duration. It was unclear if this pattern was just interictal without clinical correlate or if it was an ictal seizure pattern indicating absences. Based on specifications given by the patients himself and his parents it remained elusive if the patient suffered from short episodes with loss of contact. However, this question is of high clinical relevance, as absence seizures require antiepileptic drug treatment while interictal activity does not.

During 24-h longterm-video-EEG recording the above mentioned EEG patterns occurred once to twice per hour. They were not associated with obvious alternations in behaviour. The patient was asked during the EEG discharges to press a pushbutton in response to a tone. He performed this task without any restrictions. We then asked the patient to read loudly from a book while constantly recording the EEG. With occurrence of 3 Hz spike-wave, the patient stumbled while reading, he was unable to continue. Even after the end of generalised discharges, he did not find the correct line on the page where he stopped reading a couple of seconds before.

Thus the reading test proved that the generalised EEG discharges have a clinical correlate characterised by a slight impairment of consciousness. This finding allowed to make the diagnosis of absence epilepsy, and antiepileptic treatment was started with ethosuximide. In a couple of weeks, we will repeat the reading test with EEG recording in order to assess the success of the initiated therapy.

A 42-year-old female patient reports at her first visit in our epilepsy outpatient clinic epigastric sensations occurring paroxysmally for more than 5 years. The sensation is stereotyped, duration is 10 to 20 sec, and frequency is up to three times a week. We specifically asked her if this feeling is accompanied or followed by loss of contact or impaired awareness, but this was denied. As the patient spends a lot of time on her own, there was no chance to get some description from third party. In the last years, she did not seek for medical advice as in daily life these epigastric episodes were not relevant for her.

To further clarify the diagnosis, the patient was admitted for longterm video-EEG to the Epilepsy-Center Berlin-Brandenburg. During 72 h-recording, two episodes with typical symptoms occurred. While the patient was tested by the technician, she was unresponsive for 30 to 40 sec before she returned to normal consciousness. After the seizures, the patient did not remember that she had any other behavioural changes beyond the epigastric sensation. Ictal EEG revealed a seizure in the right temporal structures. Cerebral MRI was normal.

We told the patient that we have made the diagnosis of focal epilepsy that seems to have manifested more than 5 years ago. For all that time, the patient realised the epigastric auras but she was amnesic for the automotor seizures. A study has demonstrated that in the awake state more than half of automotor seizures are not remembered by patients. We assume that the patient frequently develops impaired consciousness following the auras, but does not realise seizures due to ictal amnesia.

We started antiepileptic treatment with levetiracetam, a follow-up appointment in our clinic is pending.

A 57-year-old male patient reports loss of consciousness and subsequent falls when he laughs. One of the falls resulted in nasal bone fracture. These events have occurred for more than 25 years. The more intense he laughs, the more likely he looses consciousness. In the last 12 months, this has happened five times. Family members report that loss of consciousness lasts almost 1 minute, motor signs are lacking, reorientation occurs rapidly.

This information suggests that the events are consistent with syncopes. Accordingly, 24 h-video-EEG-monitoring and head MRI were normal. During echocardiography, manual pressure to the left carotid sinus was accompanied by relevant bradycardia, the patient reported severe dizziness.

In summary, this patient suffers from hypersensitive carotid sinus (“carotid sinus syndrome”). Short-term increased blood pressure – while laughing – results in bradycardia and subsequent syncope. To protect the patient from further syncopes and potential injuries, he promptly will undergo implantation of a cardiac pacemaker.

A 57-year-old lady from Russia with limited German language capabilities was admitted to our Epilepsy-Center in order to clarify if subjective paroxysmal events were of epileptic origin or not. The patient reported nausea and headaches with almost daily frequency. More detailed information was not available, in particular not on the duration of paroxysmal events. Third party history on semiology did not contribute to clarification of diagnosis. On admittance, the patient was treated with 50 mg topiramate and 100 mg lacosamide. Higher dosages were not tolerated, withdrawal of one of these substances resulted in increased frequency of events.

24-h-longterm video-EEG did not detect any seizures, interictal EEG was unremarkable as well. Brain MRI revealed mild vascular leukencephalopathy. We decided to stop both antiepileptic drugs. The following days, while she was still in-patient in our center, the patient did not report any paroxysmal events.

At the evening of the day the patient was discharged from hospital, her daughter observed a seizure with starring, smacking and chewing, and unresponsiveness, duration was 1 min. The patient was amnesic for this seizure, she merely reported headaches. The daughter’s description allowed allocating this event to an epileptic automotor seizure. The patient was started on lamotrigine.

In summary, we assume that the majority of her paroxysmal events characterized by nausea are not epileptic seizures. Nonetheless, the patient unequivocally suffers from additional epileptic seizures. These may be associated with postictal headache, that has been reported by more than one third of patients with epilepsy.

A 41-year-old female patient suffers from intractable epilepsy for more than 15 years. During the seizures she is absent, her husband describes starring, unresponsiveness, as well as chewing and smacking. Duration of seizures is 1 min., frequency is 4-5 monthly. In the past years, the patient had been treated with multiple antiepileptic drugs, at last she was taking three antiepileptics simultaneously.

Longterm video-EEG with scalp electrodes revealed seizure onset in the right temporal lobe, however the seizure onset zone was rather broad. Neuroimaging (MRI) did not show any structural lesion and thus did not help to localise the region of seizure origin. In a second step, EEG was recorded with intracranial electrodes from subdural structures. This diagnostic approach helped to identify the epileptogenic region precisely. Subsequently, parts of the right temporal lobe were resected.

This operation was performed 1 year ago. Since then, the patient did not suffer from any further epileptic seizures. During her visits in our epilepsy outpatient clinic, the patient repeatedly reports that she feels “as newly born”. Currently, she is treated with two antiepileptic drugs, this combination will be continued for at least one more year.

A 37-year-old female patient has suffered for 1 year from suddenly occurring sleep-bound movements of 2 min. durations. The patient herself is amnesic for these episodes. Her partner reports that loud noise – such as ringing of the alarm-clock – commonly preceded sprawling and stretching body movements. The patient was not responsive during these episodes, afterwards she was disoriented for some minutes, usually she fall asleep. In another hospital, the patient was diagnosed to suffer from epilepsy, levetiracetam treatment was initiated. Though, the episodes continued to occur unchanged every other month.

At the Epilepsy-Center Berlin-Brandenburg, video-EEG-telemetry was performed. The patient agreed that loud noise during her sleep was tried to provoke a typical episode. With a 20-sec-delay following striking of a metal bin, the stereotype movements occurred. Diagnostic, however, was not the EEG, but the simultaneously recorded ECG. This demonstrated dramatic cardiac arrhythmia characterised by ventricular tachycardia and torsades de pointes. These disturbances lasted for 2 min., then the ECG returned to regular sinus rhythm.

These investigations helped to make the correct diagnosis of syncopes, the aetiology was noise-induced cardiac arrhythmia. Detailed ECG analysis revealed polonged QT-time, genetic tests demonstrated long-QT-syndrome type II. In the following days, the patient was implanted a cardiac pacemaker in order to protect her from further life-threatening arrhythmias.