New onset status epilepticus in older patients: Clinical characteristics and outcome.

PURPOSE: We here evaluated (1) the differential characteristics of status epilepticus (SE) in older (≥60 years) compared to younger adults (18-59 years). In particular, we were interested in (2) the proportion and characteristics of new onset SE in patients with no history of epilepsy (NOSE) in older compared to younger adults, and (3) predictive parameters for clinical outcome in older subjects with NOSE. METHODS: We performed a monocentric retrospective analysis of all adult patients (≥18years) admitted with SE to our tertiary care centre over a period of 10 years (2006-2015) to evaluate clinical characteristics and short-time outcome at discharge. RESULTS: One-hundred-thirty-five patients with SE were included in the study. Mean age at onset was 64 years (range 21-90), eighty-seven of the patients (64%) were older than 60 years. In 76 patients (56%), SE occurred as NOSE, sixty-seven percent of them were aged ≥60 years. There was no age-dependent predominance for NOSE. NOSE was not a relevant outcome predictor, especially regarding age-related subgroups. Older patients with NOSE had less frequently general tonic clonic SE (GTCSE; p=0.001) and were more often female (p=0.01). Regarding outcome parameters and risk factors in older patients with NOSE, unfavourable outcome was associated with infections during in-hospital treatment (0.04), extended stay in ICU (p=0.001), and generally in hospital (p<0.001). CONCLUSION: In our cohort, older patients represented the predominant subgroup in patients with SE. Older patients suffered more often from non-convulsive semiology and had a less favourable short-time outcome. NOSE was not a predictive outcome parameter in older patients. Data suggest that avoiding infections should have a priority because higher infection rates were associated with unfavourable outcome.

Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Adjunctive retigabine in refractory focal epilepsy: Postmarketing experience at four tertiary epilepsy care centers in Germany.

PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure-freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve.

[ALS and frontotemporal dementia - case report and review of the literature]. / ALS und frontotemporale Demenz - Fallbericht und Literaturübersicht.

The occurrence of cognitive decline in amyotrophic lateral sclerosis (ALS), especially in the form of frontotemporal dementia (FTD), has been described previously. Recent molecular biology and histopathology data suggest that both ALS and FTD may share common pathological pathways and may present two phenotypes of the same proteinopathy. The underlying pathophysiological mechanism may be defective RNA- and DNA-modulation, mediated by the proteins TDP43 and FUS. These findings are suggestive of a new disease category of TDP43-proteinopathies, which include ALS, FTD and overlap syndromes. While about half of the FTD cases are associated with TDP43-deposits, tau is found in the other half. A significant clinical overlap to other tauopathies exists here as well, for instance with corticobasal degeneration. In this paper, we present a case report and review the clinical spectrum and current pathogenetic concepts of FTD.

[Concussive convulsions: seizure or no seizure?]. / Kommotionelle Konvulsionen: Epileptischer Anfall oder nicht?

Convulsions following traumatic brain injury (TBI) represent a diagnostic and therapeutic challenge. They can be differentiated into late (> 7 days after TBI), early (1 - 7 days after TBI), immediate (within the first 24 h after TBI), and impact seizures (within seconds after TBI). Some authors suggest that most impact seizures are non-epileptic in origin and hence coined the term "concussive convulsions" for benign impact seizures. Early and late post-traumatic seizures frequently indicate structural brain damage and transition to chronic, post-traumatic epilepsy. The data for impact seizures or concussive convulsions is less clear: only a small percentage of impact seizures is associated with structural brain damage and the development of post-traumatic epilepsy, rather the majority of cases are benign and associated with an excellent prognosis. Here, we present a case report as a starting point for pathophysiological and clinical considerations regarding convulsions that start within seconds after TBI.

Developmental stutter in a patient with callosal agenesis disappears during steroid therapy.

A 10-year-old left-handed girl with a developmental stutter and agenesis of the corpus callosum with associated hydrocephalus ceased stuttering immediately upon initiation of steroid therapy for colitis. Steroid taper resulted in a recurrence of the stutter and resumption for treatment of recrudescent colitis caused its disappearance again. Baseline agenesis of the corpus callosum with hydrocephalus and the patient's course in the face of the known effects of steroids on white matter lend support to the hypothesis that stuttering reflects anomalous dominance and/or atypical interhemispheric connectivity, as evidenced by the fact that presumed alterations of white matter tracts affected speech rhythms/stuttering.

Visual evoked potentials in dyslexics and normals: failure to find a difference in transient or steady-state responses.

We measured transient and steady-state checkerboard contrast-reversal visual evoked potentials (VEPs) in ten dyslexics, five patient controls, and 11 normals over a range of contrasts and luminances. Latency, amplitude, and phase measurements failed to distinguish the responses of dyslexics from those of normals or patient controls. Decreases in luminance or contrast resulted in an increased latency of the transient VEP in all groups, but these changes also did not distinguish the responses of dyslexics from those of the controls. Response variability was similar in dyslexics and normals, but was increased in subjects with attention deficit-hyperactivity disorder (ADHD). Performance on standardized psychometric testing did differentiate the dyslexics from controls, but did not correlate with VEP responses.

Sex differences in learning abilities and disabilities.

Boys more often than girls are affected by all the cognitive developmental disorders of childhood. Differences in the etiology of learning disabilities as well as general sex differences in learning styles in boys versus girls may explain the male preponderance in the prevalence of learning disabilities. The effects on learning of hormonal sex differences, maturation rate differences, and differences in frequency of perinatal brain injury will be discussed.

Double disconnection effects resulting from infiltrating tumors.

Patients with left hemisphere lesions deep in parietal or parietal-occipital regions close to the lateral ventricles have been reported to have impaired performance on left ear speech stimuli in dichotic listening tests. This loss has been termed "paradoxical" because it presents at the ear ipsilateral to the lesion. Two patients with infiltrating tumors which involved the corpus callosum demonstrated that effect, but also demonstrated right ear extinction on a complex-pitch discrimination test that required right hemisphere processing. Since the side at which the impairment will be demonstrated depends upon the type of test used, the term "paradoxical extinction" does not clearly describe this phenomena. It is suggested that the so-called paradoxical loss is better referred to as callosal extinction.

Arthrogryposis multiplex congenita in an infant with posterior agenesis of the corpus callosum.

A term male infant with arthrogryposis multiplex congenita and agenesis of the corpus callosum is described. Physical examination revealed multiplex dysmorphic features and fixed joints. A muscle biopsy showed type II fibers to be more than 12% smaller than type I fibers, consistent with the diagnosis of fiber type disproportion. The CT scan disclosed absence of the posterior corpus callosum and moderate atrophy of the cerebellar hemispheres. The pathogenetic mechanism for the muscle (and thus joint) abnormalities of this infant is discussed with respect to a central etiology.