Pseudodominant Friedreich's ataxia with phenotypic heterogeneity

Objective - A family with a clinically heterogeneous progressive ataxia in two generations is presented. Methods - Having eliminated mutations within the known dominant spinocerebellar ataxia genes, the family was investigated for expansion at the Friedreich's gene. Results - The affected members (father, son and daughter) were homozygous for the mutation at the Friedreich's gene, while the unaffected (the mother and her sister) were heterozygous. Conclusion - This pseudodominant form of Friedreich's ataxia should be considered in families with an apparently autosomal dominant progressive ataxia in conjunction with sensory neuropathy and pyramidal signs. © 2007 The Authors

Symptomatic focal mononeuropathies in diabetic patients: Increased or not?

The aim of this study was to investigate whether symptomatic mononeuropathies are more frequent in diabetic patients without symptoms of acute or subacute polyneuropathy than in the general population.For this purpose, six hundred and forty two consecutive outpatients with various acute symptomatic mononeuropathies (radial, ulnar or peroneal neuropathy, Bell's palsy or carpal tunnel syndrome) without symptoms of acute or subacute polyneuropathy were studied. The results showed that in 522 patients with symptomatic carpal tunnel syndrome (CTS) and in 38 patients with Bell's palsy, the rate of diabetes was 7.7% and 10.5%, respectively. These rates do not differ significantly from the anticipated frequency of diabetes in the general population. On the other hand, in 18 patients with radial neuropathy at (or distally to) the spiral groove, in 41 patients with ulnar neuropathy and in 23 patients with peroneal neuropathy at the fibular head, the respective rates were 27.8%, 12.2 % and 30.4%. These rates are significantly higher than those anticipated according to the frequency of diabetes in the general population. The findings of the present study indicate that only focal limb neuropathies due to acute external compression are more frequent in diabetic patients

Migraine with aura: Segregation analysis and heritability estimation

A genetic study was performed in a group of 60 migraine patients and their first-degree relatives as well as in a group of sex- and age-matched controls. Segregation analysis showed that multifactorial inheritance seems to be the most probable mode of genetic transmission. Heritabilities were estimated according to the sex of probands and relatives. Our findings favor multifactorial inheritance, but the contribution of a major gene can not be excluded

Spinal muscular atrophy: DNA fragmentation and immaturity of muscle fibers

The presence of apoptotic fibers and the embryonic proteins desmin and vimentin were investigated in muscle biopsy specimens from patients with spinal muscular atrophy (SMA). Apoptosis was studied in 24 cases of SMA by means of in situ end labeling of nuclear DNA fragmentation using TUNEL staining and immunohistochemistry. Apoptotic nuclei were observed in 54.1% of the cases, and desmin and vimentin positive fibers were found in the majority of cases. A significant negative correlation was observed between the number of apoptotic nuclei and the duration of the disease, as well as between the number of desmin and vimentin positive fibers and the age of onset. These findings indicate that apoptosis, although probably a secondary phenomenon following denervation, plays a role in the progress of spinal muscular atrophy. © 2007 Elsevier GmbH. All rights reserved

Platelet monoamine oxidase activity in subjects tested for Huntington's disease gene mutation

Monoamine oxidase activity (MAO) has been related to neuronal damage, since the oxidative deamination of biogenic amines produces free radicals that may enhance oxidative stress. Elevated enzyme activities in brain (MAO-A and MAO-B forms) and in platelets (MAO-B form) have been reported in several degenerative diseases, indicating that MAO activity may be involved in the disease progression. We estimated platelet MAO activity in a group of 59 patients (34 males) with HD, 20 subjects (7 males) at risk, and 29 (14 males) healthy subjects with positive family history for HD, categorized according to clinical features and the number of CAG repeat units (CAG-RN) at the Huntington gene. A group of 64 subjects (36 males) with negative family history for HD served as controls. In contrast to some previous studies, platelet MAO activities in both male and female patients (CAG-RN 40 to 62) with overt symptomatology, were not different compared to same sex control subjects. Subjects at risk (CAG-RN 39 to 52), though, showed significantly lower activities compared to same sex patients or controls. MAO activities seem to increase with disease progression, and tend to be higher in patients with dementia. The increases may be an epiphenomenon of disease pathology, but the possibility that an increase in the expression of the enzyme precedes the onset of the disease and contributes to enhanced oxidative stress should be considered in future longitudinal studies as a possible mechanism that accelerates disease progression

Co-segregation of huntington disease and hereditary spastic paraplegia in 4 generations

INTRODUCTION: Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. REPORT OF THE CASES: We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. CONCLUSIONS: The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons. Copyright © 2011 by Lippincott Williams &Wilkins