Iftah Biran

Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family

Abstract.Background: Frontotemporal dementia with parkinsonism linked to chromosome 17q21–22 (FTDP-17) is an autosomal dominant tauopathy manifested by a variable combination of personality changes, cognitive decline and hypokinetic-rigid movement disorder. Significant clinical and pathological heterogeneity of FTDP-17 is related in part to more than 20 different pathogenic mutations identified in the tau gene. Among others, the P301S mutation has been previously reported in three families of European and one of Japanese origin presenting with different clinical phenotypes. Objectives To report a three-generation family of Jewish-Algerian origin with FTDP-17 due to the P301S tau mutation. Methods: Clinical, neuropsychological and neuroimaging evaluation of 3 patients, tau genotyping, and pathological study of the proband. Results: The 3 affected family members had a fairly stereotyped clinical course with early personality changes from their late 30s followed within a period of 1–2 years by a progressive cognitive and motor deterioration eventually leading to a state of akinetic mutism or death 3–5 years after the initial symptoms. The main clinical manifestations included severe dementia and hypokinetic-rigid movement disorder associated with supranuclear gaze impairment, pyramidal signs and frontal release signs. Brain imaging disclosed a variable degree of frontotemporal atrophy, ventriculomegaly and regional cerebral hypoperfusion or glucose hypometabolism. Frontal lobe biopsy in the proband revealed weak tau immunoreactivity in a few cortical neurons, in rare neurites and in some glial cells with no neurofibrillary tangles. Molecular DNA analysis identified a P301S mutation in exon 10 of the tau gene. Conclusions: The observed clinical features further expand the reported P301S phenotype and confirm a more aggressive course of the disease than in the other known tau mutations.

Lack of hemispheric localizing value of the palmomental reflex

I read the article by Gotkine et al.1 with great interest. They concluded there was no significant association between the side of the reflex and the side of hemispheric lesion in patients with unilateral reflexes and the unilateral lesions. We are interested in palmomental reflex (PMR) in various neurological disorders and are routinely performing this test. In my experience, there is no significant correlation between the side of positive reflex and the pathognomonic site. I would like to ask the authors to clarify a few points. If 89% of …

Spinal Cord Involvement in Uncomplicated Herpes Zoster

ABSTRACT We prospectively evaluated herpes zoster patients during the acute phase of the disease for central nervous system involvement. Of 24 patients with spinal zoster, 13 (54%) had spinal cord abnormality, which was asymptomatic in 12 of the 13. Age but not lack of acyclovir treatment was associated with such involvement. In all but 2, neurological involvement resolved within 6 months. Although the mechanism responsible for the neurological abnormalities is unknown, findings may support the hypothesis that zoster is associated with spread of viral infection into the spinal cord and therefore support the possibility that zoster is due to active viral replication in the ganglion.

Increased severity over generations of Charcot-Marie-Tooth disease type 1A

BackgroundCharcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene. This mutation is not modified during inheritance.ObjectivesWe set forth to test the hypothesis that in a subgroup of CMT1A patients there is clinical anticipation, namely an increase in disease severity over generations.MethodsThirty-nine CMT1A mutation-positive patients in 16 families and 23 parent-offspring pairs were evaluated. This included 14 families with 2 generations and 2 families with 3 generations. Age of presentation was assessed by interviewing the patients and clinical severity was measured using the CMT neuropathy score (CMTNS).ResultsIn 21/23 parent-child pairs and 14/16 families, there was an earlier age of presentation in children of genetically affected parents. The mean age of onset in the progeny was 12.61 years compared to 41.22 years in the parent generation, (p < 0.001).Mean severity in the younger generation was slightly higher than that of the parent generation. When corrected for the age difference, the trend for a worse phenotype in the younger generation became statistically significant (p < 0.02,Wilcoxon signed rank test).ConclusionsOur findings suggest that in a subgroup of CMT1A patients there is an increase in clinical severity over generations. The mechanism responsible for this observation remains unknown. Our findings should be validated on a larger cohort of CMT1A families.

Category specific dysnomia after thalamic infarction: a case-control study.

Category specific naming impairment was described mainly after cortical lesions. It is thought to result from a lesion in a specific network, reflecting the organization of our semantic knowledge. The deficit usually involves multiple semantic categories whose profile of naming deficit generally obeys the animate/inanimate dichotomy. Thalamic lesions cause general semantic naming deficit, and only rarely a category specific semantic deficit for very limited and highly specific categories. We performed a case-control study on a 56-year-old right-handed man who presented with language impairment following a left anterior thalamic infarction. His naming ability and semantic knowledge were evaluated in the visual, tactile and auditory modalities for stimuli from 11 different categories, and compared to that of five controls. In naming to visual stimuli the patient performed poorly (error rate>50%) in four categories: vegetables, toys, animals and body parts (average 70.31+/-15%). In each category there was a different dominating error type. He performed better in the other seven categories (tools, clothes, transportation, fruits, electric, furniture, kitchen utensils), averaging 14.28+/-9% errors. Further analysis revealed a dichotomy between naming in animate and inanimate categories in the visual and tactile modalities but not in response to auditory stimuli. Thus, a unique category specific profile of response and naming errors to visual and tactile, but not auditory stimuli was found after a left anterior thalamic infarction. This might reflect the role of the thalamus not only as a relay station but further as a central integrator of different stages of perceptual and semantic processing.

Coital headaches induced by amiodarone

Coital headache or headache associated with sexual activity as classified by the International Classification of Diseases , revision 101 are characterized by abruptly appearing headaches occurring just before or at orgasm.2 It can be secondary to a structural lesion such as a vascular malformation, but is usually of a benign nature. The pathophysiology of benign coital headache is not clear, though an association with migrainous headache is noted.2,3⇓ Coital headache as a side effect of pharmacologic agents and chemical compounds has been reported with other medications such as birth control pills.3 Here we report a case of coital headache induced by amiodarone therapy. A 52-year-old, right-handed man presented to our …

Now dear, I have a headache! Immediate improvement of cluster headaches after sexual activity

The precise pathogenesis of cluster headaches is unknown, but a hypothalamic generator has been postulated as the cause of the disorder.1 In two patients with typical cluster headaches, sexual activity alleviated the episodes. This association may shed some light on the pathogenesis and treatment of this incapacitating disorder. Patient 1 : A 61-year-old, previously healthy man presented with excruciating, left-sided orbital headaches appearing in bouts that lasted for 10 weeks. The pain occurred nightly at around 22:00 h, and was associated with ipsilateral ptosis, lacrimation and rhinorrhoea. Neurological examination and brain imaging were normal and he was diagnosed with cluster headaches, according to International Headache Society (IHS) criteria.2 The headaches always lasted for 90–150 min, except for instances when the patient had sexual intercourse, which at the point of orgasm resulted in instant dramatic improvement in the pain, with complete relief always being achieved within several minutes and no recurrence until the next evening. Orgasm occurred on six occasions between 5–30 min after the onset of the episode …