[Can treatment with anesthetic anticonvulsive drugs worsen outcome in status epilepticus?] / Kann der Einsatz anästhetisierender Antikonvulsiva beim Status epilepticus das Outcome verschlechtern?

BACKGROUND AND OBJECTIVES: Nowadays, there is an ongoing discussion about the risks and benefits of anesthetic treatment concerning outcome in status epilepticus (SE). Therefore, we performed a retrospective database analysis to examine the influence of treatment with anesthetic drugs and narcosis in SE on mortality and disability. METHODS: All treatment episodes of SE at the Department of Neurology of the University of Rostock between 01 January 2000 and 31 December 2009 were evaluated. SE severity before treatment, mortality, and disability at discharge were taken into account. RESULTS: Of 167 treatment episodes of SE, 34 included treatment with anesthetic anticonvulsive drugs and narcosis. In the treatment episodes with use of anesthetic anticonvulsive drugs and narcosis, there was a more than twofold increased risk for death compared to the other treatment episodes. However, due to sample size this difference was not significant (p = 0.09). Cardiopulmonary complications were the cause of death in 4 of 5 patients dying during treatment episodes with anesthetic anticonvulsive drugs and narcosis. At discharge, disability as measured with the Modified Rankin Scale was higher in patients treated with anesthetic anticonvulsive drugs and narcosis than in the others (p = 0.03). A subgroup analysis revealed that especially in patients with nonconvulsive SE with impaired consciousness treatment with narcosis was associated with a higher rate of new deficits or mortality (p = 0.012). CONCLUSIONS: Especially when considering narcosis for treatment of nonconvulsive SE, risks and benefits should be carefully weighed. When treating SE with anesthetic drugs and narcosis, everything has to be done to avoid cardiopulmonary complications.

[Efficacy of Epileptological Consultation After Initially Unsuccessful Antiepileptic Medication]. / Behandlungsergebnisse durch eine spezialisierte epileptologische Betreuung nach einem ersten erfolglosen Therapieversuch bei Menschen mit Epilepsie.

OBJECTIVE: At least 25 % of patients with epilepsy do not achieve seizure freedom with their first antiepileptic medication. The aim of this study is to make a contribution to discussions on the efficacy of further antiepileptic medications in achieving seizure freedom for at least one year or reduction of seizure frequency of more than 50 % for more than one year. METHODS: All patients who presented between January 1, 2009 and July 1, 2013 to the epileptological outpatient consulting service of the University of Rostock with at least one seizure in the previous year despite taking at least one antiepileptic medication were evaluated. Outcome was assessed according to the data available on July 1, 2014. RESULTS: 70 patients (35 f/35 m) aged 43.6 years on average (SD 16.7) with active epilepsy, who had taken 3.7 antiepileptic drugs on average (SD 2.8) before the first presentation to our service, were counseled on further antiepileptic treatment options. On average, 1.96 (SD 1.8) antiepileptic drugs were introduced in the therapy. At the last visit to our service, 15.7 % of the patients were seizure free for more than one year and 45,6 % of the patients had a reduction of seizure frequency of at least more than 50 %. CONCLUSION: With specialized epileptological counseling, substantial improvement in seizure frequency can be achieved in about 60 % of patients with epilepsy after failure of the initial antiepileptic drug.

[Perampanel in the treatment of a patient with glioblastoma multiforme without IDH1 mutation and without MGMT promotor methylation]. / Perampanel in der Behandlung eines Patienten mit Glioblastoma multiforme ohne IHD-1-Mutation und ohne MGMT-Promotor-Methylierung.

Malignant gliomas like glioblastoma multiforme (GBM) release glutamate which causes excitotoxic death to surrounding neurons, thereby vacating room for tumor expansion. We report the case of a patient with GBM treated with the AMPA receptor blocker Perampanel (PER) in combination therapy for partial seizures. Histological work-up of a biopsy showed the tissue of a GBM without mutation of the isocitrate dehydrogenase 1 (IDH1) and without promotor methylation of the O6-methylguanine-DNA methyltransferase (MGMT). In a group of patients with IDH 1 wild type and non-methylated MGMT a median survival of 199 days after surgery (i. e. 6.5 months) was described. Our patient lived about one year longer. PER rendered our patient seizure-free for at least the last seven months of his life. It was well tolerated and did not increase the toxicity of temozolomide. When choosing an antiepileptic drug (AED) for the treatment of seizures in patients with malignant brain tumors, the efficacy, the tolerability and perhaps possible effects on tumor progression of the AED should be taken into account.

[Anticonvulsant therapy for brain tumour-related epilepsy]. / Antiepileptikabehandlung bei Hirntumor-bedingten epileptischen Anfällen.

The lifetime risk of patients with brain tumours to have focal epileptic seizures is 20-80%. Based on current evidence the management of tumour-related seizures does not differ substantially from that applied to epilepsies from other aetiologies. Therefore, the choice of an anticonvulsant is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumour-related epilepsy; this corresponds with the recommendation of the German guidelines on the treatment of focal seizures of any aetiology. Based on current evidence, the prophylactic prescription of long-term antiepileptic drugs in brain tumour patients who have not presented with seizures is not justified. Because of the high risk of recurrence, however, antiepileptic treatment should be strongly considered after a single brain tumour-related seizure.

[Experience with levetiracetam in the treatment of status epilepticus]. / Erfahrungen mit Levetiracetam in der Behandlung des Status epilepticus.

Non-convulsive status epilepticus and epilepsia partialis continua are common epileptic conditions for which straightforward recommendations based on controlled randomised trials for treatment of therapy refractory courses are lacking. Therefore in these conditions sometimes antiepileptic drugs that are not approved by governmental authorities for the treatment of status epilepticus (SE) are used. Here we review all case reports and case series concerning the treatment of SE with levetiracetam (LEV), that had been listed in pub-med up to December 12th 2011. Additionally we analysed abstracts and papers in peer reviewed journals, that were listed in the references of the primarily reviewed papers. Furthermore we looked for LEV treatments in papers on the use of lacosamide (LCM) in SE. LEV was given in dosages ranging from 500 mg to 9000 mg per day. Side effects were especially sedation and irritability. Estimated on the basis of the case series the overall success-rate of LEV in terminating status epilepticus may be set in a range between 53.7% and 58.1%. Therefore LEV may be a useful alternative for the treatment of SE when the approved drugs are contraindicated or when these drugs have been taken without success.

[Combination therapy for epilepsy]. / Kombinationstherapie bei Epilepsie.

Use of Monotherapy is acknowledged as the standard anticonvulsant therapy although no more than about 65% of patients become seizure-free with a single antiepileptic drug. Therefore, up to 50% of patients with epilepsy are treated at least intermittently with more than one antiepileptic drug. The percentage of patients achieving complete seizure control with combination therapy after ineffective monotherapy is small. Monotherapy and combination therapy are not always contrary to each other; many anticonvulsants have different modes of action and are effectively a combination therapy in one drug. Combinations of anticonvulsants with differing mechanisms of action are called "rational polypharmacy". A superior efficacy of these combinations over combinations of anticonvulsants with identical or similar mechanisms of action have not been proved by randomised trials. Add-on trials with lacosamide and the combination of lamotrigine and valproic acid, however, suggest a superior tolerability and/or efficacy of combinations with differing mechanisms of action. Treatment with drug combinations should take into account, above all, efficacy and safety, interactions, and costs of each antiepileptic drug as well as comorbidity.

Recurrent aphasic status epilepticus after prolonged generalized tonic-clonic seizures versus a special feature of Todd's paralysis.

Postictal aphasia may be a feature of Todd's paralysis or the presentation of aphasic nonconvulsive status epilepticus (NCSE). We describe a 74-year-old woman with three episodes of aphasic status epilepticus after prolonged generalized tonic-clonic seizures. In the first episode, the NCSE was not definitively diagnosed, but an increase in the epileptic medication led to resolution of the epileptic activity within 2 weeks. During the second episode, NCSE was terminated within 7 days under intensified antiepileptic treatment. In the third episode, phenytoin treatment led to intoxication and resulted in further treatment on an intensive care unit. The patient required several months to recover from this episode. NCSE in the elderly is difficult to recognize, especially when it presents as a prolonged postictal deficit like aphasia. Once diagnosed it has to be treated carefully, because in the elderly, aggressive treatment strategies may be associated with a high risk of adverse events.

[Cognitive deficits and psychiatric disorders in patients with new-onset epilepsy]. / Kognitive Defizite und psychiatrische Störungen in Frühstadien epileptischer Erkrankungen.

From a theoretical point of view it may be hypothezised that cognitive deficits are not uncommon in patients with new-onset epilepsy since causative brain lesions, genetic influences and interictal epileptic activity are likely to exist even before the first unprovoked seizure. We reviewed the literature concerning cognitive deficits in genetically determined epilepsy-syndromes and studies on cognitive and psychiatric deficits in patients with new-onset epilepsy. In several animal models hints of memory deficits or learning disorders even before the manifestation of epileptic seizures were found. Some learning disorders showed characteristics of the human attention-deficit-hyperactivity-disorder. In familial frontal epilepsies specific associations between cognitive deficits as well as psychiatric syndromes and certain mutations were described. Cognitive deficits in adult patients with new-onset epilepsy were described several times with regard to delayed recall in verbal memory, selective attention and psychomotor performance. Depression and suicide attempts were increased before the first seizure. In childhood cognitive deficits were regarded as causative factors for behavioral problems, which sometimes were even found before the first recognized seizure. Verbal memory deficits at the onset of epilepsy seemed to be a risk factor for the development of a therapy refractory course. But on the basis of the published data it is impossible to state whether cognitive deficits after a first unprovoked seizure in adulthood indicate an increased risk of recurrent seizures apart from the results of MRI and EEG studies.

[Research and quality control at a neuropsychiatric epilepsy clinic]. / Wissenschaft und Qualitätssicherung auf einer neuropsychiatrischen Epilepsiestation.

Quality management in German health care services is demanded by law. If a monitoring of treatment results using scientifically established scores is performed as a part of quality management, the data may also be used for research on the course and the outcome of chronic disease and even for basic research. Using a multimodal therapy monitoring on a neuropsychiatric ward for patients with refractory epilepsy it could be shown that comprehensive treatment strategies were able to enhance cognitive abilities, mood and coping-strategies. The introduction of selective serotonin reuptake inhibitors (e. g. citalopram, sertraline) did not result in an increased burden of seizures. Interesting for understanding the multiple causes of depression was the finding that folic acid serum levels in the lower normal range or below were associated with a higher risk of depressive mood.

[On the value of neuropsychological short tests in epileptology]. / Zur Wertigkeit neuropsychologischer Kurztests in der Epileptologie.

Cognitive deficits are common in patients with epilepsy refractive to therapy and have considerable influence on the quality of life in this group of patients. Therefore, neuropsychological investigations should play an important role in the comprehensive evaluation of patients with chronic epilepsy. The aim of this study was to examine whether a reliable screening for cognitive deficits in these patients may be reduced to the assessment of two bedside tests. In a prospective study we analyzed the results of 40 patients with epilepsy refractive to therapy subjected to a 45-min neuropsychological screening battery and compared them with the results of a short battery consisting of two bedside tests. Using the screening battery as the gold standard, the short battery had a sensitivity of 50% and a specificity of 100%. Changing the criteria for pathological results in the short battery, sensitivity could be raised to 81.25% but specificity fell to 50%. Therefore, bedside tests instead of longer neuropsychological testing cannot be recommended as a screening method for cognitive deficits in patients with chronic epilepsy.

[Influence of age at onset, age and duration of illness on cognitive abilities in patients with refractory epilepsy]. / Der Einfluss von Erkrankungsalter, Lebensalter und Krankheitsdauer auf die kognitiven Leistungen bei Patienten mit therapierefraktärer Epilepsie.

This retrospective study was performed as part of the controversial discussion whether increasing cognitive deficits in patients with refractory epilepsy are mainly an effect of normal aging or caused by epilepsy related noxious events during the course of an intractable epilepsy. Neuropsychological data and information about the course of the disease from 146 patients with refractory epilepsy were available. There were significant correlations between the age at onset and premorbid intelligence, duration of disease and fluid intelligence and age and difference between premorbid intelligence and fluid intelligence as a measure of cognitive deterioration. Discussing these results we conclude that beneath a clear effect of normal aging on cognitive deterioration there is probably a small effect of the refractory course of the epilepsy, which might be mediated by the number of seizures. Additionally we would like to encourage early cognitive screening and rehabilitation programmes for patients with epilepsy to minimize the effect of the age of onset on the level of education or premorbid intelligence.

The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

BACKGROUND: Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. OBJECTIVE: This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. METHODS: We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. RESULTS: There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. CONCLUSIONS: Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

Possible oxcarbazepine interaction with cyclosporine serum levels: a single case study.

We studied the influence of an add-on medication with oxcarbazepine on the cyclosporine trough level in a kidney transplant recipient with pharmacoresistant epilepsy. Two weeks after the beginning of the trial we observed a decrease of the cyclosporine trough and the Na serum levels. Both could be corrected by a small-dose reduction of oxcarbazepine, an augmentation of the cyclosporine dosis, and oral sodium chloride substitution. After this episode the cyclosporine trough and the Na serum levels remained stable. Seizure frequency was reduced by 95%. The influence of oxcarbazepine on the cyclosporine serum level has to be studied carefully in other patients after transplantation before the use of oxcarbazepine can be recommended in patients with an immunosuppressive medication with cyclosporine. Our data suggest that oxcarbazepine may be an effective drug with tolerable side effects in this group of patients.

Increased V/D-ratio in lumbosacral SEP's as a new electrophysiological measure of spasticity.

STUDY DESIGN: Open-label, prospective study. OBJECTIVE: To establish the amplitude-ratio of V-response and D-response (V/D-ratio) as a new measure of spasticity, comparing the motor effect of the H-reflex to the sensoric input. METHODS: In 13 legs of seven patients with spasticity and in four legs of patients without central nervous system disease, maximal M-response and maximal H-reflex were recorded. Lumbosacral SEP's were recorded with the same stimulus parameters as the maximal H-reflex. H/M-ratio and V/D-ratio were compared to the increased muscle tone. RESULTS: The H/M-ratio and the V/D-ratio in legs with spasticity differed significantly from the H/M-ratio and the V/D-ratio in normal legs. But only the V/D-ratio was higher in legs with moderately or highly increased muscle tone than in legs with slightly increased muscle tone. CONCLUSION: The V/D-ratio increases in spasticity and shows an even closer relationship to increased muscle tone than the H/M-ratio.

The effects of therapy on spasticity utilizing a motorized exercise-cycle.

UNLABELLED: F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in patients receiving pharmacological antispastic therapy as well as in those having physiotherapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of the therapy with a motorized exercise-cycle, which moves the legs of paraplegic patients in a way similar to cycling. Ten F-waves were recorded immediately before and after the therapy with a motorized exercise-cycle in 70 legs of 35 patients with spastic paraparesis. Mean F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after therapy than before. CONCLUSION: The antispastic effect of the therapy with a motorized exercise-cycle may be documented by a decrease of F-wave-amplitude parameters.

Effects of physiotherapy on F-wave-amplitudes in spasticity.

F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in spasticity and pharmacological antispastic therapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of physiotherapy. Ten F-waves were recorded immediately before and after physiotherapy in 42 legs of 21 patients with spastic paraparesis due to multiple sclerosis. Mean F-wave amplitude, maximum F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after physiotherapy than before. Therefore the antispastic effect of physiotherapy is documented by a decrease of F-wave-amplitude parameters.

Early cognitive impairment in multiple sclerosis detected by a screening with a vocabulary-test.

Vocabulary deficits in multiple sclerosis patients do not fit to the concept of subcortical dementia usually applied to describe cognitive impairment in multiple sclerosis. In a screening of young patients with a vocabulary test a significant correlation was found between the age at the onset of symptoms and the score in this test. This may lead to an explanation of vocabulary deficits recently described as results of a slowed language acquisition caused by subcortical lesions in early multiple sclerosis.