Intravenous levetiracetam in clinical practice--Results from an independent registry.

PURPOSE: Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). METHODS: In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. RESULTS: In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500 mg (range 110-6000 mg) per day. Median age was 66 years (range 0.7-90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. CONCLUSION: In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

Intravenous lacosamide or phenytoin for treatment of refractory status epilepticus.

OBJECTIVES: To compare intravenous phenytoin (PHT) and intravenous lacosamide (LCM) for treatment of status epilepticus after failure of the first and second drug. METHODS: We retrospectively identified patients from a large community hospital in northern Germany who had been diagnosed with SE between August 2008 and December 2010. Patients who had failed to respond to the first two drugs were selected for this analysis. RESULTS: Forty-six patients (23 female, median age 68 years) were identified. LCM was used as third drug in 21 patients (median bolus 400 mg) and PHT in 15 patients (median bolus 1500 mg). Pretreatment was similar regarding substance groups (benzodiazepine as first line, levetiracetam as second line drug) and bolus doses. Status epilepticus was terminated in six patients (40%) of the PHT group and in seven patients (33%) of the LCM group. Four patients (27%) of the PHT group and no patient of the LCM group suffered from a relevant, treatment-related side effect during administration of the third drug. CONCLUSION: Lacosamide and PHT showed similar success rates for treatment of SE when used after failure of benzodiazepines and levetiracetam. However, PHT was associated with relevant side effects that were not seen with LCM.

Intravenous lacosamide for treatment of status epilepticus.

OBJECTIVES: Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. METHODS: We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. RESULTS: Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. CONCLUSIONS: Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Misdiagnosis of epileptic and non-epileptic seizures in a neurological intensive care unit.

OBJECTIVE: The etiological misinterpretation of paroxysmal neurological symptoms frequently causes a delayed treatment or an inappropriate utilization of ICU-capacities. METHODS: In this study, the data of 208 patients admitted to a neurological ICU because of acute transient neurological deficits, loss of consciousness or unclear motor phenomena were retrospectively analyzed. The initial emergency room diagnosis was compared to the final diagnosis and the rate of misdiagnosis was related to the patients' history and diagnostic data. RESULTS: In 13.9%, the emergency room diagnosis of epileptic seizures turned out to be incorrect, whereas in 15.6%, the final diagnosis of epileptic seizures was missed in the emergency room. Factors that were significantly correlated to missing the seizure diagnosis were (i) no prior history of epilepsy, (ii) old age, (iii) multi-morbidity, (iv) pathologic CT-scans demonstrating cerebrovascular lesions, (v) seizure description by non-professionals, (vi) predominantly negative seizure phenomena (aphasia, loss of consciousness, paresis), (vii) lack of tongue-bite lesions.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. OBJECTIVE: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. METHODS: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor "group," covariate "age"). RESULTS: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. CONCLUSIONS: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI.

Frequency of seizures and epilepsy in neurological HIV-infected patients.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. METHODS: The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. RESULTS: Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse. CONCLUSIONS: Seizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group.

Presurgical seizure frequency and tumoral etiology predict the outcome after extratemporal epilepsy surgery.

OBJECTIVE: To examine the predictive value of demographic data for the seizure outcome after extratemporal epilepsy surgery. METHODS: Eightyone patients who underwent resective extratemporal epilepsy surgery were retrospectively studied concerning (a) age at surgery, (b) onset of epilepsy, (c) duration of epilepsy, (d) number of seizures at the time of presurgical evaluation, (d) number of presurgically tested antiepileptic substances and (f) number of seizure types. The data were correlated to the postoperative seizure outcome after two years. RESULTS: 33 patients (40.7%) were seizure free two years after surgery. Univariate and multivariate analysis revealed that both tumor etiology and low presurgical seizure frequency were independently associated with seizure freedom after epilepsy surgery. The recurrence rate in patients with one or more seizures per day was more than two-fold if compared with patients with fewer seizures. The remaining demographic factors did not show a significant association with seizure outcome in our 81 patients. CONCLUSIONS: Fewer than daily seizures prior to surgery and a tumoral etiology independently increase the likelihood of remaining seizure free two years after extratemporal epilepsy surgery.

[Refractory status epilepticus: diagnosis, therapy, course, and prognosis]. / Therapierefraktärer Status epilepticus: Diagnostik, Therapie, Verlauf und Prognose.

Status epilepticus (SE) is a frequent neurological emergency with an annual incidence of 10-20/100,000 individuals. The overall mortality is about 10-20%. Patients present with long-lasting fits or series of epileptic seizures or extended stupor and coma. Furthermore, patients with SE can suffer from a number of systemic complications possibly also due to side effects of the medical treatment. In the beginning, standardized treatment algorithms can successfully stop most SE. A minority of SE cases prove however to be refractory against the initial treatment and require intensified pharmacologic intervention with nonsedating anticonvulsive drugs or anesthetics. In some partial SE, nonpharmacological approaches (e.g., epilepsy surgery) have been used successfully. This paper reviews scientific evidence of the diagnostic approach, therapeutic options, and course of refractory SE, including nonpharmacological treatment.

[Suggestion for a new, patient-oriented epilepsy classification]. / Vorschlag für eine neue patientenorientierte Epilepsieklassifikation.

The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Incidence of seizures in patients with multiple sclerosis treated with intrathecal baclofen.

Oral and intrathecal baclofen (ITB) have been associated with epileptic seizures. The authors observed a higher incidence of epileptic seizures in 99 patients with multiple sclerosis (MS) treated with ITB vs a matched control group (7% vs 1%, p < 0.05). Three patients with MS on ITB developed status epilepticus. Seizures were often associated with additional triggering factors.

Localising and lateralising value of ictal piloerection.

BACKGROUND: Piloerection is a rare clinical symptom described during seizures. Previous reports suggested that the temporal lobe is the ictal onset zone in many of these cases. One case series concluded that there is a predominant left hemispheric representation of ictal cold. The aim of this study is to evaluate the localising and lateralising value of pilomotor seizures. METHODS: Medical records of patients who underwent video electroencephalogram (EEG) monitoring at the Cleveland Clinic between 1994 and 2001 were reviewed for the presence of ictal piloerection. The clinical history, physical and neurological examination, video EEG data, neuroimaging data, cortical stimulation results, and postoperative follow ups were reviewed and used to define the epileptogenic zone. Additionally, all previously reported cases of ictal piloerection were reviewed. RESULTS: Fourteen patients with ictal piloerection were identified (0.4%). Twelve out of 14 patients had temporal lobe epilepsy. In seven patients (50%), the ictal onset was located in the left hemisphere. Four out of five patients with unilateral ictal piloerection had ipsilateral temporal lobe epilepsy as compared with the ipsilateral side of pilomotor response. Three patients became seizure free after left temporal lobectomy for at least 12 months of follow up. An ipsilateral left leg pilomotor response with simultaneously recorded after-discharges was elicited in one patient during direct cortical stimulation of the left parahippocampal gyrus. CONCLUSIONS: Ictal piloerection is a rare ictal manifestation that occurs predominantly in patients with temporal lobe epilepsy. Unilateral piloerection is most frequently associated with ipsilateral focal epilepsy. No hemispheric predominance was found in patients with bilateral ictal piloerection.

Neurosarcoidosis: clinical experience and diagnostic pitfalls.

OBJECTIVE: To describe a group of patients with neurosarcoidosis and to highlight diagnostic difficulties based on current diagnostic criteria. METHODS: The patient database of a general neurological department was searched for patients with established or suspected diagnosis of neurosarcoidosis. Twenty-four patients were identified with definite (n = 3), probable (n = 10) and possible neurosarcoidosis (n = 10). History and clinical, laboratory and imaging data of patients with definite and probable neurosarcoidosis were analyzed. RESULTS: Cranial nerve symptoms were a dominant clinical feature, with the optic nerve being affected most frequently. Cerebrospinal fluid pleocytosis was found in more than half of the patients. Intrathecal IgG synthesis and oligoclonal bands were less frequent. There was a wide array of MRI lesions in both groups. Chest X-ray was false negative in 2 of 5 patients who also underwent a thoracic CT. Therapy with prednisolone was initiated in all patients. After a median of 36 months, 6 of 8 patients with follow-up data of >24 months were still in remission. Aggravation of symptoms required therapy escalation in 2 patients. CONCLUSION: There is a wide range of clinical symptoms and test results in patients with "definite" or "probable" neurosarcoidosis. Because systemic involvement is a crucial diagnostic criterion, extensive medical work-up may be necessary. Prognosis under corticosteroid treatment may be better than previously thought.

[Electric brain stimulation for epilepsy therapy]. / Elektrische Hirnstimulation in der Epilepsietherapie.

Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summary, with the targets and stimulation parameters investigated so far, the effects of electrical brain stimulation on seizure frequency have been moderate at best. In the animal laboratory, we are now testing high-intensity, low-frequency stimulation of white matter tracts directly connected to the epileptogenic zone (e.g., fornix, corpus callosum) as a new methodology to increase the efficacy of DBS ("overdrive method").

Unilateral absence of the basal ganglia plus epilepsy without motor symptoms.

A patient with absence of the basal ganglia and refractory epilepsy without impairment of pyramidal or extrapyramidal motor function is reported. Imaging findings suggest a vascular insult as etiology. Preserved motor function could be explained by neuronal plasticity involving contralateral corticostriatal and pallidothalamic connections and points to a lesion received in early pregnancy.

[Progressive multifocal leukoencephalopathy (PML) in chronic lymphatic leukemia (CLL). Review of the literature and case report]. / Progressive multifokale Leukoenzephalopathie (PML) bei chronisch lymphatischer Leukämie (CLL). Literaturübersicht und Fallbeschreibung.

Progressive multifocal leukoencephalopathy (PML) is an infectious disease of the central nervous system caused by the JC virus. Progressive multifocal leukoencephalopathy represents a reactivation of the JC virus after long-standing immunosuppression. Also, PML plays an important role as an opportunistic infection in patients with AIDS. The average time of survival in patients with PML in combination with chronic lymphatic leukemia (CLL) (n = 17 in the literature) is 4.3 months, and therapeutic options are not established. We report the case of a patient with CLL and PML. Clinical symptoms are slight hemiparesis of the right side, mainly appearing as a disturbance of motor function. In MRI, a typical subcortical lesion was shown, and JC virus DNA was positive in the CSF by PCR. Because of first positive results in treatment of PML in patients with AIDS, therapy with cidofovir was started. After treatment for 16 months, symptoms are stable, the PML-induced lesions in MRI are in regression, and JC virus DNA is not detectable in the CSF.

[Experience with tiagabine in the clinical practice; new insights as to the efficacy and safety profile]. / Erfahrung mit Tiagabin in der Praxis. Neue Aspekte zum Wirkungs- und Sicherheitsprofil.

Tiagabine is a relatively new anticonvulsive agent. Data concerning safety and efficacy come from randomised controlled trials whose relation to everyday clinical practice is poorly defined. We analysed retrospectively the data of 56 patients to whom tiagabine was routinely prescribed in a special clinic. Effect and adverse events were registered according to documentation of routine visits in the outpatient clinic. After a median of 89 weeks, 22 patients (39%) still received tiagabine. All of them noted a reduction in seizure frequency, and eight (14%) became seizure-free. Reasons for stopping the medication were: an increase in seizure frequency, lack of efficacy, tiagabine-associated non-convulsive status epilepticus and sudden and short episodes of mental chang. However, tiagabine seems to be an effective anticonvulsant in clinical practice but should remain in the hands of experienced prescribers until further clarification of possible risk factors for proconvulsive effects.

Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.

PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy.

Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity.

[Homeless men in inpatient psychiatric treatment--a controlled study. 1: Health status and self assessment at intake]. / Wohnungslose Männer in stationär psychiatrischer Behandlung--Eine kontrollierte Studie. Teil 1: Gesundheitszustand und Selbstwahrnehmung bei Aufnahme.

OBJECTIVE: This study examines the objective and the subjectively reported state of health, the social network and the utilisation of mental health services in a representative group of homeless men (n = 50) at time of admission to a psychiatric hospital and compares these results with a control group (matched by diagnosis) of non-homeless men. METHOD AND PATIENTS: The BPRS, the SF-12 Health Survey and a neglection index were administered. The main psychiatric diagnosis (ICD-10) were alcohol addiction (n = 29), drug addiction (n = 13), schizophrenia (n = 7) or personality disorder (n = 1). RESULTS: No differences were found according to sociodemographic basis data, but the homeless group had a smaller social network and less financial resources. There was a higher rate of involuntary admission in the homeless group, less contact to mental health services in the weeks before admission, more psychopathological symptoms and more physical neglection. Self-rating of mental and physical health, however, did not differ significantly. There was a positive correlation between thought disturbance and positive self-rating of mental health. CONCLUSION: The mental and physical health of the homeless patients was markedly worse. Beneath structural barriers symptoms, the extreme distress of their living situation and the decreased insight and motivation for treatment are characteristics of this group of patients which make them difficult to treat.