Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. OBJECTIVES: To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. METHODS: In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. RESULTS: Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. CONCLUSION: Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics.

Clinical and electroencephalographic findings in acutely ill adults with non-convulsive vs convulsive status epilepticus.

BACKGROUND: Non-convulsive status epilepticus (NCSE) indicates a change in the mental state with no motor manifestations, being a clinical expression of prolonged epileptiform activity. In contrast to convulsive status epilepticus (CSE), no unified treatment recommendations have been proposed so far. We were interested to review the clinical and encephalographic characteristics in hospitalized patients with NCSE and CSE and compare their treatment and outcome. PATIENTS AND METHODS: The electroencephalographic recording records of adult patients with electrographic status epilepticus were retrieved. Patients' clinical records were then analyzed. RESULTS: Fifty-three patients with CSE and 25 patients with NCSE were identified. Background diseases, neuroimaging findings and complications were similar in CSE and NCSE. Anoxia was a more frequent etiological factor only for myoclonic SE. Patients with CSE presented more often with coma. The number of drugs used for treatment was similar, but anesthetics drugs were administered more frequently in patients with CSE. The 30-day mortality rate was higher in myoclonic SE and generalized tonic-clonic SE, but the outcome on discharge in terms of survival and recovery was comparable between CSE and NCSE. CONCLUSIONS: The results of the present study show that the clinical parameters of NCSE in acutely ill patients do not substantially differ from those of patients with CSE. Moreover, despite more severe mental changes and the need for more anesthetic drugs for treatment of CSE, the final outcome did not differ between both groups. This might indicate that NCSE in acutely ill patients should be regarded as seriously as CSE.

Outcome of lamotrigine treatment in juvenile myoclonic epilepsy.

OBJECTIVES: To determine the response rate of patients with juvenile myoclonic epilepsy (JME) to lamotrigine (LTG) and identify predictive factors for treatment response. MATERIAL AND METHODS: Medical records of 62 patients with JME were reviewed for demographic, clinical, and EEG parameters. We determined clinical response to LTG and compared LTG responders with non-responders. RESULTS: There were 35 LTG responders (56%) and 27 non-responders (44%). JME patients without generalized tonic clonic seizures (GTCS) responded better to LTG (P = 0.04). Valproic acid (VPA) failure because of adverse events rather than lack of efficacy (P = 0.069) and delay in diagnosis (P = 0.07) showed a tendency toward good response to LTG. CONCLUSIONS: LTG should be considered a drug of first choice for JME patients without GTCS. LTG as second-line treatment after VPA failure seems more appropriate for those patients whose reason for VPA failure is poor tolerability rather than lack of efficacy.

Epilepsy syndrome-associated balance dysfunction assessed by static posturography.

PURPOSE: To compare subclinical balance dysfunction in patients with various epilepsy syndromes with apparently healthy subjects. METHODS: Twenty-seven patients with localization-related epilepsy (LRE), 19 with primary generalized epilepsy (PGE), who had no subjective complaints of impaired balance and no abnormal neurologic findings on examination, and 22 apparently healthy subjects, underwent static posturography using the Posture Scale Analyzer (PSA) system. RESULTS: Sway index was higher in patients compared to healthy subjects in all tests, significant for single leg stance (p=0.005). Patients with PGE had a higher sway index compared to patients with LRE in six of the tests, also significant for single leg stance (p=0.027). This difference was not affected by the type of AED treatment or disease duration. CONCLUSION: Posturography can improve balance function assessment in patients with epilepsy, demonstrate subclinical impairment in seemingly asymptomatic patients, and further characterize balance deficits in different epilepsy syndromes.

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Autosomal recessive form of periventricular heterotopia.

BACKGROUND: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant inheritance pattern. OBJECTIVE: To classify cortical malformation syndromes associated with PH. METHODS: Analyses using microsatellite markers directed toward genomic regions of FLNA and to a highly homologous autosomal gene, FLNB, were performed on two pedigrees to evaluate for linkage with either filamin gene. RESULTS: Two consanguineous pedigrees with PH that suggest an autosomal recessive inheritance pattern are reported. MRI of the brain revealed periventricular nodules of cerebral gray matter intensity, typical for PH. Seizures or developmental delay appeared to be a common presenting feature. Microsatellite analysis suggested no linkage to FLNA or FLNB. CONCLUSIONS: Autosomal recessive PH is another syndromic migrational disorder, distinct from X-linked dominant PH. Further classification of these different syndromes will provide an approach for genetic evaluation.

Evidence for genetic heterogeneity supports clinical differences in congenital myasthenic syndromes.

Congenital myasthenic syndromes (CMS) define a diverse group of disorders, all of which compromise neuromuscular transmission. Symptoms can be present at birth or appear during childhood, and can range in severity. Both autosomal dominant and recessive forms exist, and a number of clinical subtypes have been described. The cause of many cases of CMS has been traced to mutations in the genes for the acetylcholine receptor (AChR) subunits, previously mapped to chromosomes 2 and 17. Recently, an additional form of CMS known as familial infantile myasthenia (FIM) was linked to chromosome 17p. The gene for FIM has not yet been identified. We examined the DNA from 5 families of Iranian Jewish origin (6 affected individuals) who have been diagnosed with a phenotypically unique form of CMS. Four of the families are consanguinous, and all families originate from the same geographical region, thus it is highly likely that they would carry the same ancestral CMS mutation. We examined these families for linkage to the regions on chromosomes 2 and 17 containing the AChR subunit genes, and to the region on 17p to which FIM was localized. Our data excludes linkage to these regions, suggesting that the clinical differences seen among patients with CMS correlate with locus heterogeneity, and that a defect in a different gene is responsible for the CMS in these patients.

Stimulus-sensitive seizures in postanoxic coma.

PURPOSE: To describe four patients with stimulus-sensitive seizures and myoclonus following severe hypoxic-ischemic injury. METHODS: In 22 months, four adult patients with myoclonus, generalized tonic-clonic, and clonic seizures following tactile stimulation were identified. EEG and hospital records were reviewed. RESULTS: EEGs showed bursts of generalized spike and polyspike activity following tactile stimulation associated with the clinical seizures. No cerebral activity was present between the epileptiform bursts. At times, prolonged periods of suppression were recorded. All patients failed to respond to antiepileptic drugs and died. CONCLUSIONS: Stimulus-sensitive seizures and myoclonus following anoxia are associated with poor clinical outcome. The presence of seizures and myoclonus in conjunction with epileptiform discharges on EEG confirms that post-anoxic myoclonus is an epileptic state.

Triphasic waves in a psychiatric population: a retrospective study.

In a retrospective study of 15.326 EEGs performed from 1983 to 1992 in a psychiatric institute, 83 EEGs (62 patients-13 men and 49 women ranging in age from 59 to 90 years, with a mean age of 74 years) had triphasic waves (TWs). All 62 patients were awake, though they were often confused. Most (n = 56) had dementia, usually severe; 15 also had delirium. There were six nondemented patients (age range, 59-79 years, with a mean age of 67 years). Infrequent etiologies included neuroleptic malignant syndrome (n = 1) and hepatic encephalopathy (n = 1); in four, the cause was uncertain, although all were receiving lithium. EEG features analyzed included frequency of background rhythms, distribution of the TWs, periodicity, and epileptiform abnormalities. Background rhythms were slow in all but seven patients (mean, 6.2 +/- 1.7 [SD] Hz). TWs were maximal posteriorly in 47 patients and anteriorly in six and were diffuse in nine. Neuroimaging studies showed prominent posterior abnormalities in only one case. Periodicity was prominent in four patients; in two the TWs were maximal anteriorly. Interictal epileptiform activity was present in six, a history of seizures in eight, and myoclonus in four. TWs are uncommon in a psychiatric population; they occur primarily in elderly, severely demented patients. They are usually associated with background slowing, are often maximal posteriorly, and occasionally are periodic.

Linear intracerebral calcification after depth electrode implantation.

We report linear calcifications along the trajectories of previously implanted depth electrodes in 2 patients. A 20-year-old man and a 38-year-old woman with medically intractable complex partial seizures (CPS), underwent bilateral frontal and mesiotemporal depth electrode implantation as part of their epilepsy surgery workup. Brain computed tomography (CT) at that time was normal (except for cerebrellar atrophy in one case). One patient had a left anterotemporal lobectomy (ATL), and the other declined operation. Subsequent CT scans showed linear calcifications 1-2 cm long in the occipital lobes (unilateral in 1 and bilateral in the other) that followed the trajectories of the temporal depth electrodes. This finding remained unchanged at latest follow-up (2-2.5 years), and no new pathology has appeared on subsequent scans. No abnormalities of calcium metabolism were detected. Review of all available CT scans of our patients with a history of previous depth electrode implantation showed no additional similar cases. We believe this is the first report of intracerebral calcifications after depth electrode implantation.

Single fiber EMG in a congenital myasthenic syndrome associated with facial malformations.

Six patients with a newly described genetic syndrome in Iraqi and Iranian Jews of congenital myasthenia associated with facial malformations were studied with voluntary and stimulation single fiber EMG (SFEMG). Voluntary SFEMG revealed abnormal jitter in all patients in both extensor digitorum communis (EDC) and orbicularis oculi (OOC) muscles, though much smaller in the clinically unaffected EDC. SFEMG study of OOC muscle by axonal stimulation at rates from 1 to 48 Hz showed the most increased jitter at the highest stimulation frequencies in the majority of end-plates, one-third of which showed maximal jitter at intermediate rates. These results may suggest a postsynaptic abnormality as the underlying cause for the neuromuscular transmission defect, and demonstrate the usefulness of SFEMG in the diagnosis of congenital myasthenia.

X-linked mental retardation with bilateral clasped thumbs: report of another affected family.

A Sephardi Jewish family is reported in which the two brothers had mental retardation, lower limb spasticity and bilateral clasped thumbs anomaly. This X-linked recessive disorder has only been reported twice. We believe this syndrome comprises a distinct entity among the X-linked mental retardation syndromes.

Mitochondrial abnormalities in oculopharyngeal muscular dystrophy.

A family with oculopharyngeal muscular dystrophy (OPMD) is described. Histological and histochemical studies of muscle biopsy showed nonspecific myopathic changes; no "ragged-red" fibers were seen. Electron microscopy demonstrated bizarre large mitochondria with abnormal cristae, but no intranuclear inclusion bodies. Our findings are compatible with the possibility that OPMD is a heterogeneous syndrome, and may be a manifestation of mitochondrial myopathy.

Treatment of porphyric convulsions with magnesium sulfate.

We report a 16-year-old girl with acute intermittent porphyria who had abdominal pain, generalized tonic-clonic and simple partial seizures, and inappropriate antidiuretic hormone secretion. Because most antiepileptic drugs are contraindicated in porphyria, she was treated with magnesium sulfate i.v. Soon after starting treatment, seizures stopped, returned, and then again responded in several trials with discontinuation and reinstitution of i.v. magnesium sulfate. Our experience encourages the use of magnesium sulfate for treatment of seizures in patients with porphyria.

The value of sleep recording in evaluating somnambulism in young adults.

Somnambulism (SOM) is a benign childhood sleep disorder which may persist until young adulthood. The diagnosis relies heavily on the history, and no polysomnographic (PSG) criteria have yet been defined. The present study attempts to evaluate the role of whole-night polysomnographic recording in the investigation of SOM. The PSG records of 24 sleepwalkers, 18-25 years old, and 12 age-matched controls, were analysed. Sleepwalkers had remarkably more epochs containing hypersynchronous delta waves (HSD) (59.6 +/- 60.1 vs. 1.7 +/- 3.2; P less than 0.0001), a higher proportion of HSD/total time spent in stage 3-4 (24.9 +/- 21.1% vs. 1.1 +/- 2.0%, P less than 0.0002), and more stage 3-4 sleep interruptions (8.4 +/- 5.7 vs. 3.7 +/- 1.7, P less than 0.004). They also tended to have a larger proportion of their sleep time in stage 3-4 (30.6 +/- 11.7% vs. 22.6 +/- 6.8%; P less than 0.07). Although their sensitivity and specificity have yet to be more fully investigated, these seem to be quantitative, easy-to-use variables which may characterize adult SOM and may aid in its proper diagnosis.

Cogan's syndrome complicated by lacunar brain infarcts.

Cogan's syndrome, nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction, is an uncommon disease of young adults, probably a manifestation of vasculitis. A 32 year old woman with this syndrome developed a thalamic syndrome with amnesia and dysphasia due to lacunar infarcts.

Extracranial metastases of medulloblastoma in adults: literature review.

A consecutive series of 30 cases of extracranial medulloblastoma metastases in adults is analysed. The majority of the patients were males with a 3:1 male/female ratio. Bone was the most frequent site of metastases in adults (77%) and children (78%), followed by lymph nodes (33%) in both children and adults. Lung metastases were more common in adults (17%), but liver metastases occurred more frequently in children (15%). Possible routes of spread and development of metastases are discussed, with special emphasis on the role of shunts in tumour seeding. Distant extracranial metastatic spread of medulloblastoma occurs at the rate of 7.1%. Mean interval between operation of the primary tumour and the discovery of metastases was shorter in children (20 months) than in adults (36 months). Survival after the discovery of metastases was also shorter in children (5 months) than in adults (9.5 months). Shunts were associated with an earlier appearance of metastases and with a poorer prognosis. A detailed review of the literature of 119 cases of medulloblastoma with extracranial metastases is provided.

Congenital myasthenia associated with facial malformations in Iraqi and Iranian Jews. A new genetic syndrome.

Fourteen Jewish patients from 10 families of either Iraqi or Iranian origin with congenital myasthenia had associated facial malformations which included an elongated face, mandibular prognathism with class III malocclusion and a high-arched palate. Other common features were muscle weakness restricted predominantly to ptosis, weakness of facial and masticatory muscles, and fatigable speech; mild and nonprogressive course; response to cholinesterase inhibitors; absence of antibodies to acetylcholine receptor; decremental response on repetitive stimulation at 3 Hz but no repetitive compound muscle action potential in response to a single nerve stimulus. This newly recognized form of congenital myasthenia with distinctive ethnic clustering and associated facial malformations is transmitted as an autosomal recessive disorder. The facial abnormalities may be secondary to the neuromuscular defect or may be primary and unrelated. Further studies are needed to elucidate the defect in neuromuscular transmission responsible for the pathogenesis of this syndrome.