Diffusion tensor imaging abnormalities in photosensitive juvenile myoclonic epilepsy.

BACKGROUND AND PURPOSE: Multiple structural white matter abnormalities have been described in patients with juvenile myoclonic epilepsy (JME). In the present study, the question of whether microstructural variations exist between the two subgroups of JME, with and without photoparoxysmal responses (PPR positive and negative), was addressed using diffusion tensor imaging. METHODS: A selection of 18 patients (eight PPR positive) from a tertiary epilepsy center diagnosed with JME and 27 healthy controls was studied. The following regions of interest were investigated: the ascending reticular activating system, lateral geniculate nucleus, genu of the internal capsule, ventromedial thalamus and inferior cerebellar peduncle. RESULTS: Widespread white matter microstructural abnormalities in JME and in particular in PPR positive cases were identified. PPR positive patients demonstrated increased fractional anisotropy in the ascending reticular activating system and ventromedial thalamus compared to PPR negative patients and healthy controls. Reduced fractional anisotropy of the lateral geniculate nucleus was observed in the entire JME group compared to healthy controls. CONCLUSIONS: Several microstructural variations between PPR positive and negative JME patients have been identified. Our findings highlight the pivotal role of the thalamus in the pathophysiology of primary generalized seizures and suggest that thalamo-premotor connections are both an essential part of epileptic networks and important in the pathogenesis of photosensitivity.

Epilepsy in the elderly: restrictions, fears, and quality of life.

OBJECTIVES: Due to demographic change and high incidence of epilepsy in elderly, the number of elderly with epilepsies is increasing. However, only few studies investigated the impact of epilepsy on quality of life (QoL). We investigated how epilepsy affects different aspects of QoL dependent on the age of the patients and the age of onset of epilepsy. MATERIALS AND METHODS: In a multicenter, cross-sectional study, three patient groups were recruited from five centers: Group A1: 45 elderly (≥65 years.) with late onset of epilepsy (≥65 years), group A2: 51 elderly (≥65 years.) with early-onset, long-lasting epilepsy (≤50 years), group B: 41 young adults (≤50 years) with epilepsy. Statistical analysis of differences between groups was performed using generalized linear models. RESULTS: Elderly with late-onset epilepsy (group A1) had a significantly lower seizure frequency, were treated with less anti-epileptic drugs (AEDs), and reported a better tolerability of AED treatment, but had more comorbidities compared with groups A2 and B. After adjusting for seizure frequency, tolerability of AEDs and comorbidity, young adults (group B) reported the highest overall QoL, whereas patients of group A1 and A2 did not differ significantly. Epilepsy-related fears, especially fears of stigmatization, were significantly higher in elderly with long-lasting epilepsy compared with groups A1 and B. CONCLUSION: Seizure-related variables, tolerability of AEDs and comorbidity have a stronger impact on QoL and on restrictions due to epilepsy than age, age at onset of epilepsy or duration of epilepsy. However, some results indicate group-specific patterns of impairment and epilepsy-related fears.

Epilepsy in the elderly: comparing clinical characteristics with younger patients.

The prevalence and incidence of epilepsies in elderly is high. Due to demographic development, the portion of elderly patients with epilepsy will continue to rise over the next decades. In this study, we aimed to investigate seizure semiology, etiology, comorbidity, and therapy in elderly patients dependent on onset of epilepsy and in comparison with younger patients. In a prospective multicentre study, 202 epilepsy patients were included in a consecutive manner and subdivided into three groups (group A1: >65 years, onset of epilepsy after the age of 65 years; group A2: >65 years with early onset epilepsy, seizure onset before the age of 50 years; and group B: <50 years with epilepsy). Clinical data with respect to epilepsy, seizures, comorbidity, etiology, and anti-epileptic drug (AED) therapy were assessed using a questionnaire developed especially for these patient groups and filled out by the physicians. The clinical profile with regard to etiology, postictal conditions, and comorbidities clearly depends on the age of the patients and age of onset of epilepsy. Patients with an epilepsy onset after 65 years need lower doses of AEDs, gain better seizure control and have more concomitant diseases than younger patients or elderly epilepsy patients with early-onset epilepsy.

Thrombocytopenia during levetiracetam therapy.

A 64-year-old patient with symptomatic epilepsy developed thrombocytopenia during treatment with levetiracetam (LEV). As no other medical reason could be evaluated, a medication side effect was postulated. The only new drugs were valproic acid (since 3 weeks) and levetiracetam (since 3 days). After valproic acid medication was ended, thrombocytopenia did not improve and even worsened further. Finally levetiracetam administration was ended and trombocytopenia resolved rapidly and completely within few days.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

A case of hippocampal laminar necrosis following complex partial status epilepticus.

Cortical laminar necrosis (CLN) is a metabolic injury pattern usually observed after cerebral hypoxia, hypoglycemia, or ischemia. We report serial magnetic resonance imaging findings in a patient with complex partial status epilepticus (SE) developing a band-like, T1-hyperintense lesion consistent with CLN along the surface of the left hippocampus without concurrent other causes of CLN. This observation suggests a direct pathogenetic link between SE and CLN involving combined damage to neurons and glia.

On the psychopathology of unilateral temporal lobe epilepsy.

Personality adjustment of patients with unilateral temporal lobe epilepsy (TLE) was investigated in the light of special characteristics of the epilepsy process, psychosocial stressors, and the cognitive status of the patients. Thirty-seven patients with medically intractable unilateral temporal lobe epilepsy (16-55 years of age; 20 right temporal and 17 left temporal foci) were examined with standardized personality inventories (FPI, STAI, IPC, TSK) supplemented by a rating scale evaluated by the neuropsychologist (GEWLE). Patients with left temporal lobe epilepsy were characterized by increased emotional dependency, less externally judged composedness, increased depressive drive and mood, increased nervousness, increased search for information and exchange of disease experience, and greater tendency to persevere (P < 0.05). Cognitive status and psychosocial status did not significantly differ. The evaluation of personality adjustment contributes to the lateralization of the epileptogenic focus and reveals interesting patterns in the preoperative diagnostic puzzle, and in addition provides a strategy to individualize psychotherapeutic strategies.

Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors causing intractable epilepsy.

OBJECTIVE: Dysembryoplastic neuroepithelial tumors (DNT) are relatively benign brain lesions that often cause medically intractable epilepsy. There is mounting evidence that multidrug transporters such as P-glycoprotein (P-gp) or multidrug resistance-associated proteins (MRP) play an important role in the development of resistance to antiepileptic drugs (AED). MATERIAL AND METHODS: In the present study, we examined the expression of several multidrug transporters in 14 cases of DNT. The peritumoral brain tissue as well as 9 cases of arteriovenous malformations (AVM) served as controls. P-gp, MRP2, MRP5 and breast cancer resistance protein (BCRP) expression was evaluated qualitatively and quantitatively using immunohistochemistry. RESULTS: All transporters were overexpressed quantitatively in DNT, but each revealed a different labeling pattern. P-gp and BCRP were predominantly located in the endothelium of brain vessels. MRP5 was detected primarily in endothelial cells, but notably also in neurons. The expression of P-gp, MRP2 and MRP5 was low in AVM, whereas BCRP demonstrated strong staining. Examination of MDR1 gene polymorphisms revealed no correlation with P-gp expression whereas the MRP2 exon 10 G1249A polymorphism was associated with different MRP2 labelling. CONCLUSIONS: Our results show that multidrug transporters are overexpressed in DNT. This finding supports the view that several of these transport proteins may play an important role in the mechanisms of drug resistance in epileptic brain tissue.

Serum neuron-specific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures.

PURPOSE: To evaluate the discriminative power of serial, simultaneous determinations of serum neuron-specific enolase (NSE), prolactin (PRL) and creatine kinase (CK) in differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES). METHODS: Prospective measurement of the three markers after 44 single seizures (32 ES and 12 PNES) during continuous video-EEG monitoring at seven different sampling points. RESULTS: Patients with ES had a significantly greater increase in PRL at 10, 20, 30 min, 1 and 6 h. The sensitivity for elevated NSE and CK was low. PRL showed a higher sensitivity. However, the corresponding positive predictive value was lower than in CK and NSE. Additionally, PRL had the lowest specificity of all parameters. CONCLUSIONS: The limited discriminative power of PRL, CK, and NSE calls into question if these markers are helpful in differentiating PNES and ES.

Bilateral hypoglossal nerve injury following the use of the laryngeal mask without the use of nitrous oxide.

Hypoglossal nerve injury is a rare complication of anaesthesia airway management in adults. Until now the use of nitrous oxide for anaesthesia supposedly contributed to this complication. We present a case of bilateral hypoglossal nerve injury following the use of a laryngeal mask airway without the use of nitrous oxide. At the conclusion of 3 h of surgery in extreme side rotation, a 15-year-old boy of 88 kg could not extend his tongue beyond his teeth. An MRI confirmed the absence of pharyngeal haematoma and the absence of thrombosis of the basilar artery. We conclude that even when patients have no medical history and nitrous oxide is not being used, prolongation of the operation in an extreme position might increase the risk of major complications with a laryngeal mask.

Oxcarbazepine in focal epilepsy and hepatic porphyria: a case report.

PURPOSE: Despite the development of new antiepileptic agents (AEDs), the therapy of epilepsies along with hepatic porphyrias remains difficult. Most AEDs such as carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) may precipitate clinically latent porphyria by inducing hepatic metabolism and increasing hepatic heme synthesis. Actually, only gabapentin (GBP), an AED without any hepatic metabolism, is known as a potential therapy for partial seizures in patients having hepatic forms of porphyria. METHODS: We present the case of a 28-year-old man with porphyria cutanea tarda (PCT) who has had pharmacoresistant epilepsy with complex partial and secondarily generalized seizures since early childhood. Despite having undergone several AED therapies over the years, no seizure-free interval had been observed. Only CBZ could cause a seizure reduction, but this treatment had to be discontinued as an elevation of the transaminases as well as pruritus and erythema were noted. The patient was then started on oxcarbazepine (OCBZ), a ketoanalogue of CBZ similar in its pharmacologic mechanism as well as its clinical use, but which, in contrast to CBZ, has only a low hepatic induction of microsomal enzymes. A final maintenance dose four times higher than that of CBZ was prescribed. RESULTS: In the follow-up, the patient stopped having seizures, and his liver functions became normal. CONCLUSIONS: It can be concluded that OCBZ can successfully be administered to patients with hepatic porphyria and focal epilepsy who did not respond to treatment with GBP.

Influence of valproate monotherapy on platelet activation and hematologic values.

PURPOSE: Valproate (VPA) has been linked to coagulation disturbances, with both impaired and exaggerated clotting, which has been attributed to an effect of VPA on platelets or hemostatic proteins. Additional thrombocytic function testing may help to identify patients at risk of increased bleeding caused by platelet dysfunction. METHODS: We evaluated the influence of VPA on hematologic routine values and platelet activation by using immunostaining and flow cytometry in 30 patients receiving long-term VPA therapy and in 30 controls. RESULTS: The fraction of activated platelets was similar in both groups; however, the general extent of platelet activation was significantly lower in the patient group, with considerable interindividual variability. In addition, patients had a significantly lower platelet count, prolonged thrombin time, and higher mean corpuscular hemoglobin. CONCLUSIONS: Our data confirm the previously reported hematologic changes caused by VPA and additionally suggest that VPA impairs procoagulatory thrombocytic function, which is reflected by reduced platelet activation and increased thrombin time. Possible mechanisms of VPA-platelet interaction are discussed.

[Dissociative stupor--differential diagnosis of coma following injury]. / Dissoziativer Stupor--eine Differentialdiagnose des Komas nach Unfällen.

Two cases are described in which a dissociative stupor originating from conversion neurosis simulated a coma following a sustained trauma. At first both patients showed no response to being addressed or to pain stimuli. They presented an upward eye gaze deviation, cardiorespiratory functions were stable. Following extensive diagnostic procedures revealing no organic cause for the clinical symptoms, the diagnosis of a hysterical consciousness disorder was stated. Symptoms of conversion neuroses include lacking call response, gait disorder, seizure-like conditions and strength diminution in one or more extremities. In these cases suspicious facts are the absence of injuries (for example by falling down or tongue bite during a dissociative attack), eye gaze deviation and the phenomenon that, when the patient's arm is raised above the head and let fall, it never hits the face but glides down beside the body.

Ictal and interictal ECD-SPECT for focus localization in epilepsy.

Forty-one ECD (Technetium-99m-ethyl cysteinate dimer) SPECT investigations were undertaken in the course of a presurgical diagnostic work-up in 23 patients with pharmacoresistant focal epilepsy. In 21 patients, both an ictal and interictal SPECT were conducted. In the patients receiving ictal SPECT the tracer was injected between 7 and 30 s after the seizure onset. Of the interictal SPECTs 17 of 23 showed focal hypoperfusion which was consistent in 17 cases (74%) with the area of the electrophysiological focus (EF) and 6 patients had a normal interictal SPECT. Of the ictal SPECTs 18 of 21 (86%) showed regional hyperperfusion, 18 of them in the same location as the EF. Ictal SPECT showed a hypoperfusion similar to that in interictal SPECT in another 3 patients. In these cases seizure duration was short (28-54 s), so that the tracer reached the brain postictally. Our results show that ictal ECD-SPECT is an effective method for demonstrating an epileptogenic focus. Possible reasons for false-negative ictal SPECT results are discussed.

[Prognostic factors and clinical outcome in symptomatic focal epilepsies]. / Prognostische Faktoren und klinischer Verlauf bei symptomatischen fokalen Epilepsien.

Successful drug therapy for symptomatic focal epilepsy is often difficult to achieve. The aim of our study was to determine predictors of seizure-free versus therapy-resistant courses of epilepsy. To accomplish this, we evaluated clinical data obtained early in the course of focal symptomatic epilepsy to determine which factors best determine the probability of therapeutic success. This retrospective study included 70 patients who were treated at the Neurology Clinic, University of Greifswald, between 1984 and 1992. Inclusion criteria were: Clear clinical diagnosis, a minimum of 3 years follow up in our epilepsy outpatient clinic, therapy with standard anticonvulsant drugs, and good compliance. We distinguished between patients who were seizure-free for at least two years and those who were not. 22 patients (31.4%) were seizure-free, whereas 48 patients (68.6%) remained resistant to pharmacotherapy. Prognostic factors for seizure-free outcome were: Focal grand mal seizures as the only seizure type ever experienced by the patient, the occurrence of only one type of seizures during the course of the illness, the occurrence of only nocturnal seizures, few grand mal seizures before starting an effective anticonvulsant therapy, no previous status epilepticus, and the remission of focal epileptic EEG patterns during effective drug therapy.