Esther Kahana

Acute transverse myelitis Incidence and etiologic considerations

There have been few population-based studies of acute transverse myelitis (ATM). Therefore, incidence and population selectivity of this disorder in different regions is not well known. Data on all Jewish patients with ATM throughout Israel were collected for the period 1955 through 1975. Based on 62 patients who satisfied rigid diagnostic criteria, the average annual incidence rate was 1.34 per million population. No significant difference in incidence was noted between European American-born and Afro/Asian-born populations. There was no significant seasonal or annual fluctuation in frequency. In 37% of the patients, a history of infection prior to ATM was reported, more commonly among younger patients. ATM rarely evolved into multiple sclerosis. More than one-third of the patients with ATM made a good recovery; in another one-third recovery was only fair; 14 patients failed to improve and 3 died. If other population-based studies of ATM were undertaken, comparison with our results might shed further light on the causes of this disorder.

Mutation of the Prion Protein in Libyan Jews with Creutzfeldt–Jakob Disease

BACKGROUND Creutzfeldt-Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease--10 Libyan Jews from Israel and 1 Libyan Jew from Italy--to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. METHODS The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. RESULTS The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G----A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt-Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt-Jakob disease. CONCLUSIONS The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt-Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt-Jakob disease is a true dominant disorder.

Amyotrophic lateral sclerosis. A study of its presentation and prognosis

SummaryAll identified Israeli patients with amyotrophic lateral sclerosis (ALS) with onset of the disease from 1959 through 1975 (n=318) were evaluated clinically. Most of our patients (63%) presented with weakness; only 10% presented with atrophy and 3% with fasciculations. In 31% of the cases, the onset of the disease was focal and 22% of the patients presented with bulbar signs, but only 6 patients presented with emotional lability (pseudo-bulbar). Twelve per cent of the patients presented with muscle cramps, pain or paraesthesia. Atypical signs such as motor cranial nerve lesion, dementia, sphincter disturbance and deep sensation loss are discussed. A relatively high proportion of our patients suffered from malignant tumour, but with no association with any specific tumour. The median survival time was 3 years. Patients with onset of their disease with bulbar signs had a shorter life expectancy (2.2 years): Twenty nine per cent of our patients survived for more than 5 years and 16% for more than 10 years.

Creutzfeldt-Jakob Disease: Focus among Libyan Jews in Israel

A countrywide search for Creutzfeldt-Jakob disease in Israel disclosed 29 cases with onset between 1963 and 1972. Incidence in various ethnic groups varied in the narrow range of 0.4 to 1.9 per million population except among Jewish immigrants from Libya, among whom the incidence was 31.3 per million. An extraordinary excess of Creutzfeldt-Jakob disease exists in this ethnic group.

Migration and risk of multiple sclerosis

A study of multiple sclerosis (MS) frequency among immigrants to Israel revealed that those from Afro-Asian countries, where MS is rare, had a low prevalence of MS, while European immigrants had a relatively high prevalence of the disease. On the other hand, native-born Israelis had a high rate of the disease, like European immigrants, regardless of the region of origin of their forebears. Age-specific incidence rates plotted for different age-at-immigration cohorts and based only on the most rigidly defined cases suggested that Afro-Asians who immigrated very early in life had rates similar to European immigrants. Among immigrants who came to Israel at an older age, Europeans had higher age-specific incidence rates of MS than Afro-Asians. Although the number of patients available for analysis in the youngest age-at-immigration cohort was small, and the age groups for which specific incidence rates could be plotted were still few, the results indicated that migration modifies risk only among those who migrate early, before adolescence. Over the next decade, as this immigration cohort ages, the validity of this result can be verified. If correct, it would mean that MS can be acquired in the brief interval between infancy and preadolescence.

Cerebral multiple sclerosis.

AMONG THE MOST DIFFICULT FORMS of multiple sclerosis (MS) to diagnose are those that include cerebral signs and symptoms such as hemiparesis, hemianopia, psychosis, and convulsions. Although the latter signs are welldocumented manifestations of MS,I their occurrence in a given case may raise doubts about the diagnosis unless the signs occur together with other disseminated neurological signs and a history of remissions and exacerbations is elicited. In the present study, the frequency with which cerebral signs occurred in a nationwide series of MS patients ascertained in Israel is reported. In addition, certain clinical factors were examined to determine if they were associated with increased risk of the cerebral form of MS.

Outcome of infants with unilateral Sturge‐Weber syndrome and early onset seizures

Patients with Sturge‐Weber syndrome often present with seizures during the first year of life. Currently, only patients with clinically significant seizures who do not respond to medical treatment are candidates for early epileptic surgery. However, a delay of surgical treatment may result in cognitive deterioration. We studied the correlation between parameters and outcome of seizures to re‐examine the criteria for early epilepsy surgery. We performed a retrospective chart review combined with telephone interviews of parents of all Israeli infants with unilateral Sturge‐Weber syndrome and early onset seizures, and we examined whether age of seizure onset and seizure intensity were correlated with cognitive level and the degree of hemiparesis at follow‐up. We recruited a total of 15 patients with unilateral Sturge‐Weber syndrome and early onset seizures, five of whom underwent epilepsy surgery. The mean follow‐up period of all the patients was 15 years: six patients had normal intelligence, four had borderline cognitive level, three had mild mental retardation* and two had moderate mental retardation. Eight of the ten non‐operated patients still experience seizures at follow‐up. Cognitive delay was significantly correlated with seizure intensity in the early period, but not with the age of seizures onset, the degree of hemiparesis, or the presence of ongoing seizures. We conclude that high seizure intensity in young patients with Sturge‐Weber syndrome is a prognostic marker for mental deterioration.

Detection of 14-3-3 protein in the CSF of genetic Creutzfeldt-Jakob disease

The 14-3-3 protein, a protein involved in signal transduction, is present in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and not in patients with other dementing diseases. We show here that this is also true for patients with E200K CJD, but not for healthy carriers of the mutation.

Multiple sclerosis frequency in Israel's diverse populations.

Background: Israel has served for almost half a century as a site for epidemiologic studies of multiple sclerosis (MS). Its small geographic size, well-equipped, accessible, and subsidized health facilities, trained physicians, detailed census data, and a National MS Register, maintained since 1960, offer advantages for accurate determinations of MS frequency in its diverse populations. Method: The authors calculated age-specific prevalence of MS in Israeli-born Jewish inhabitants, immigrant Jews from Europe/America and from North Africa/Asia, Israeli-born Christian and Moslem Arabs, Druze, and Bedouins. Results: Prevalence rate of MS per 105 population on June 30, 2000, for each of these groups in the order listed was 61.6, 53.7, and 27.9 for the Jewish groups and 35.3, 14.7, 10.9, and 17.3 for the non-Jewish groups. Three tiers in MS prevalence were apparent. The highest rates were in Israeli-born Jews and in Jewish immigrants from Europe/America (significantly higher in the former than the latter). Jewish immigrants from African/Asian countries and Christian Arabs had intermediate MS rates (significantly lower than in the first two groups but not significantly different from each other). Moslem Arabs, Druze, and Bedouins had the lowest rates of MS (significantly lower than in the intermediate group but not significantly different from each other). Conclusion: Diverse ethnic groups living in the same geographic area may have significantly different frequencies of MS.

Do Creutzfeldt‐Jakob disease patients of Jewish Libyan origin have unique clinical features?

A focus of Creutzfeldt-Jakob disease is present in Israel among Jews born in Libya. The present study examines the clinical features in this particular group of patients. In a country-wide study of Creutzfeldt-Jakob disease, we identified 114 patients; 49 were Libyan immigrants, and 65 (three of whom had Libyan ancestors) were born in other countries. The clinical presentation and evolution of the disease is very similar in patients born in Libya and others without Libyan ancestors, but it tends to be more classical in the Libyan patients, with higher frequency of myoclonic jerks and periodic EEG and a progressive course of shorter duration. The Libyan patients tend to complain more often of headache, which is most probably an ethnic expression for depression and loss of concentration. There was no difference between the familial and nonfamilial cases.