Natan Gadoth

Cognitive function in idiopathic generalized epilepsy of childhood

This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well‐controlled seizures. Twenty‐four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic‐clonic seizures (GTCS), mean age 14y 4mo, SD 1y 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS) mean age 14y 5mo, SD 1y 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age‐appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non‐verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding nonverbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long‐term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.

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.

Bihemispheric leftward bias in a visuospatial attention-related network.

Asymmetry of spatial attention has long been described in both disease (hemispatial neglect) and healthy (pseudoneglect) states. Although right-hemisphere specialization for spatial attention has been suggested, the exact neural mechanisms of asymmetry have not been deciphered yet. A recent functional magnetic resonance imaging study from our laboratory serendipitously revealed bihemispheric left-hemifield superiority in activation of a visuospatial attention-related network. Nineteen right-handed healthy adult females participated in two experiments of visual half-field presentation. Either facial expressions (experiment 1) or house images (experiment 2) were presented unilaterally and parafoveally for 150 ms while subjects were engaging a central fixation task. Brain regions previously associated with a visuospatial attention network, in both hemispheres, were found to be more robustly activated by left visual field stimuli. The consistency of this finding with manifestations of attention lateralization is discussed, and a revised model based on neural connectivity asymmetry is proposed. Support for the revised model is given by a dynamic causal modeling analysis. Unraveling the basis for attention asymmetry may lead to better understanding of the pathogenesis of attention disorders, followed by improved diagnosis and treatment. Additionally, the proposed model for asymmetry of visuospatial attention might provide important insights into the mechanisms underlying functional brain lateralization in general.

Seizure frequency and characteristics in children with Down syndrome

Seizures have not historically been considered a major component of Down syndrome. We examined the prevalence of epileptic seizures in 350 children and adolescents with Down syndrome evaluated at a regional center between 1985 and 1997. Results showed that 28 patients (8%) had epileptic seizures: 13 (47%) partial seizures; 9 (32%) infantile spasms, and 6 (21%) generalized tonic-clonic seizures. In the infantile spasm group, there was no relationship between the initial electroencephalogram (EEG) pattern and response to treatment or long-term seizure control, or between type of pharmacologic treatment (valproic acid, adrenocorticotropic hormone or both) and clinical remission, EEG normalization or long-term seizure control. Neurodevelopmental outcome was poor despite good seizure control in the infantile spasm group. This regional study reinforces the relative association of seizures and Down syndrome. A prospective study including a national/international registry with emphasis on developmental assessment and long-term follow up is warranted.

Do men with pseudotumor cerebri share the same characteristics as women? A retrospective review of 141 cases

Objective To determine whether males with pseudotumor cerebri (PTC) differ from females by clinical presentation, risk factors, and outcome. Methods The medical records of patients diagnosed with PTC or idiopathic intracranial hypertension (IIH) in two major university hospitals were obtained. Diagnostic criteria, clinical features, presence of obesity, mode of treatment, and outcome were tabulated. Results A total of 134 patients (18 males and 116 females) fulfilled the Dandy diagnostic criteria for PTC. Females and males shared similar clinical features and outcome. There was a substantial difference between the groups regarding body weight. The majority of females (77.8%) were considered significantly overweight, compared to 25% of the males. Conclusion Pseudotumor cerebri in males is relatively rare. The clinical features are identical to those found in females. The fact that the majority of the male patients had a normal body weight may indicate that increased body weight does not play a major role in causing PTC in men, whereas it is an established major risk factor in women.

Epidemiology of idiopathic intracranial hypertension in Israel.

Objectives To determine the incidence, demographic, and clinical features of Pseudo Tumor Cerebri (PTC)/Idiopathic Intracranial Hypertension (IIH) in Israel. Materials and Methods The chairpersons of all neurology and ophthalmology departments in Israel were asked to complete questionnaires regarding patients diagnosed with PTC/IIH from 1998 through 1999. Each questionnaire contained details regarding patients age, sex, country of birth, age at diagnosis, weight, height, presence of obesity, and the results of lumbar puncture, brain computed tomography, magnetic resonance imaging, and/or magnetic resonance venography. Results Ninety-one patients with PTC/IIH were diagnosed during the years 1998 to 1999. Eighty-five (93.4%) patients were females and six (6.6%) patients were males. The calculated incidence of PTC/IIH in the Israeli general population was 0.57 to 0.94 per 100,000 persons, with incidences of 1.82 per 100,000 for women and 0.034 per 100,000 for men. The incidence for women during the childbirth years was 4.02 per 100,000. The female to male ratio was higher than previously reported for Western countries. Conclusions Although the population of Israel is a mixture of people originating from Eastern and Western countries, the incidence of PTC/IIH was found to be similar to that of Western countries. This finding is an additional support to the notion that PTC/IIH is more common in obese populations.

Clinical and polysomnographic characteristics of 34 patients with Kleine-Levin syndrome.

There is only scant information on sleep characteristics and long‐term follow‐up in patients with Kleine–Levin syndrome (KLS). This study describes the clinical course, results of polysomnography and long‐term follow‐up in a relatively large group of patients with KLS. During the years 1982–97, we encountered 34 patients (26 males and eight females) with KLS. We were able to obtain the original polysomnographs from 28 males and four females. In 25 patients, data regarding their present state of health were obtained. Fourteen agreed to be present at a detailed interview and examination while 11 gave the information by phone. The mean age at onset was 15.8 ± 2.8 years and the mean diagnostic delay, 3.8 ± 4.2 years. The mean duration of a single hypersomnolent attack was 11.5 ± 6.6 days. The main abnormal findings extracted out of 35 polysomnographs obtained from 32 patients during and/or in‐between attacks included: decreased sleep efficiency, and frequent awakenings from sleep stage 2. All 25 patients reported present perfect health, with no evidence of behavioral or endocrine dysfunction. In adolescents with periodic hypersomnia, the diagnosis of KLS should be explored. Sleep recordings during a hypersomnolent period will often show frequent awakenings from sleep stage 2. The long‐term prognosis is excellent.

Multiple sclerosis in children

Multiple sclerosis (MS) is traditionally the domain of adult neurologists due to its characteristic presentation during early adult life. Although descriptions of infants with MS appeared in the beginning of the last century and the first autopsy was described even earlier, it was not until 1980 that childhood onset MS was recognized and subsequently well characterized. In spite of this, the awareness of pediatricians and pediatric neurologists to the occurrence of MS especially in infants and young children is still unsatisfactory. It is not infrequent that a meticulous, time consuming and costly search for metabolic and degenerative disorders other that MS is initiated before the diagnosis of MS is considered. This leads to a significant diagnostic and therapeutic delay in many young patients. Moreover, when the presentation is acute and characterized by confusion, seizures, CSF pleocytosis following a viral infection, a diagnosis of meningoencephalitis will be frequently reached. In this review, updated data on frequency, epidemiology, some special clinical and radiological features of childhood onset MS, outcome and treatment will be briefly discussed with the purpose of alerting physicians to the possibility of the occurrence of MS even in infants and young children.

Machado-Joseph disease: correlation between the clinical features, the CAG repeat length and homozygosity for the mutation.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a CAG trinucleotide repeat in the MJD1 gene located on 14q32.1. We confirmed that the CAG expansion caused MJD in a Yemenite Jewish family and demonstrated that most of the clinical variation among members of this family was due to the genotype of the affected individuals. Six patients who presented with an early onset (25 years) and severe disorder were found to be homozygous for the CAG expansion. Among 5 heterozygotes for the CAG expansion older than 40 years, one had neurological symptoms from the age of 45, while the others were asymptomatic. In one of the heterozygotes, no neurological symptoms were present when last examined at the age of 66. Homozygosity for the MJD1 mutation was the main cause of variability in this large family, however, other factors clearly played a role in the expression of the gene. We could demonstrate that homozygote sibs with similar expansion in both alleles had significant differences in disease severity. Gender did not affect the clinical expression in this family.

Encephalopathy in compensated hashimoto thyroiditis: A clinical expression of autoimmune cerebral vasculitis

A young girl with compensated Hashimoto thyroiditis suffered from progressive encephalopathy while euthyroid. Seizures and mental abnormalities responded excellently to corticosteroids only, supporting the view that encephalopathy could be the clinical manifestation of autoimmune cerebral vasculitis.