1/16. Atypical friedreich ataxia phenotype associated with a novel missense mutation in the X25 gene.We describe two sisters with early onset gait ataxia, rapid disease progression, absent or very mild dysarthria and upper limb dysmetria, retained knee jerks in one, slight to moderate peripheral nerve involvement, and diabetes. Molecular analysis showed that they are compound heterozygotes for GAA expansion and a novel exon 5a missense mutation (R165P). This mutation appears to be associated with an atypical but not milder friedreich ataxia phenotype.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
2/16. Very late-onset friedreich ataxia despite large GAA triplet repeat expansions.BACKGROUND: Most patients with friedreich ataxia (FRDA) have abnormal GAA triplet repeat expansions in both X25 genes. The size of the GAA expansion in the shorter of the 2 expanded alleles correlates significantly with parameters of clinical severity and is inversely related to the age at onset. OBJECTIVES: To describe the clinical and molecular genetic findings in a patient with very late-onset FRDA and to review the literature. PATIENT AND methods: A 58-year-old white woman with mild progressive gait disturbance of 15 years' duration whose examination revealed mild incoordination was analyzed for mutations in the X25 gene. A combination of long-range polymerase chain reaction and genomic Southern blot analyses were used to identify GAA expansions in intron 1 of the X25 gene. To uncover evidence of somatic variability in triplet repeat length, dna isolated from several tissue samples was similarly analyzed. Single-strand conformational polymorphism analysis was used to screen for mutations spanning the entire coding sequence of frataxin and all intron-exon junctions of the X25 gene. RESULTS: dna isolated from blood leukocytes revealed GAA triplet repeat expansions in both X25 genes, which were estimated to contain 835 and 1200 repeats. Similar expansions were detected in dna isolated from lymphoblasts, fibroblasts, buccal cells, and sural nerve, with estimated mean ( /- SD) lengths of the shorter and longer expansions being 854 ( /-69) and 1283 ( /-72) triplets, respectively. A review of reported cases of late-onset friedreich ataxia (25-39 years) and very late-onset friedreich ataxia (> or =40 years) demonstrated that this is the first instance of a patient presenting with very late-onset FRDA despite carrying more than 800 GAA repeats in both expanded X25 alleles. CONCLUSIONS: This unique case of very late-onset FRDA highlights a limitation in our ability to accurately predict the phenotype in FRDA based solely on the size of the GAA expansion. Other genetic or environmental factors may significantly modify disease severity in FRDA.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
3/16. friedreich ataxia with minimal GAA expansion presenting as adult-onset spastic ataxia.Around a quarter of friedreich ataxia (FA) patients, despite being homozygous for GAA expansion within the FRDA gene, show atypical presentations. Our aim is to describe the case of three brothers with long-term follow-up suffering from late onset FA manifested with spastic ataxia. The three patients belong to a family with occipital dysplasia (OD) and Chiari I malformation previously reported by us. We have carried out serial examinations since 1977. Electrophysiological and neuroimaging studies, and molecular genetic analyses of hereditary ataxias are available in all three patients. Onset of symptoms occurred between 25 and 35 years. The clinical picture consisted of progressive spastic gait, truncal and limb ataxia, dysarthria, nystagmus, hyperreflexia with knee and ankle clonus and extensor plantar response, and mild hypopallesthesia. Ages at present vary between 50 and 59. One patient is wheelchair-bound but the other two are able to walk with support. Leaving OD aside, skeletal anomalies are not prominent. All three patients showed cardiomyopathy. MR imaging revealed atrophy of the cerebellum and spinal cord. Motor and sensory nerve conduction velocities were normal. Central conduction time of both motor and sensory pathways was delayed or unobtainable. All three patients were homozygous for the GAA expansion, the smaller expanded allele ranging between 131 and 156 repeats. Four heterozygotic carriers were detected among non-ataxic relatives including one with OD; furthermore, an asymptomatic OD patient showed normal genotype. We conclude that adult onset spastic ataxia is a distinctive FA phenotype associated with minimal GAA expansion. This phenotype represents a new cause of selective distal degeneration of central sensory axons. The present concurrence of OD and FA reflects coincidental cosegregation of two different inherited disorders.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
4/16. Auditory neuropathy in friedreich ataxia. A report of two cases.friedreich ataxia (FA) is a hereditary neurodegenerative disease with autosomical recessive inheritance. The purpose of this paper is to present two cases of FA with auditory neuropathy, demonstrated by Otoacoustic emissions (OAE) and brainstem auditory evoked potentials (BAEP). The patients were two adolescent girls. Both patients underwent behavioral pure-tone audiometry, BAEP, OAE, motor nerve conduction measurement, and magnetic resonance image studies. Both girls showed at least five of nine clinical criteria for FA. They also showed abnormal BAEP and normal OAE indicating auditory neuropathy. One patient showed normal thresholds on behavioral pure-tone audiometry, whereas the other patient showed a mild sensorineural hearing loss. In one case there was absence of peripheral caloric vestibular response, and electronystagmographic abnormalities compatible with cerebellar dysfunction. Cochlear function as assessed by OAE had not been reported previously in cases of FA. We conclude that auditory neuropathy should be considered in patients diagnosed as FA. Furthermore, BAEP and OAE should be included in the diagnostic routine in these patients.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
5/16. Bathing trunk naevus and neurofibromatosis type 1: a unique association of Friedrich's ataxia.A 15-year-old male presented with history of progressive instability of gait for last 6 months. General examination revealed multiple subcutaneous nodules all over the body. There was a large pigmented naevus over the lower back area along with a subcutaneous bosselated swelling over right arm. Neurological examination revealed features of gait ataxia. Plantar reflexes were extensor on both sides. skin biopsy from the pigmented naevus showed features of melanocytic naevus. Electrophysiological studies of both common peroneal and sural nerves revealed features of axonal neuropathy. With the above clinical and laboratory findings a diagnosis of neurofibromatosis type 1 accociated with bathing trunk naevus and Friedrich's ataxia was entertained.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
6/16. A 71-year-old male with 4 decades of symptoms referable to both central and peripheral nervous system.May 2005. Combined demyelination of the central and peripheral nervous system is an uncommon disorder and has been referred to by many appellations. We present the case of a 71-year-old man with a progressive nervous system disorder beginning in his 30s. The diagnosis in life was unclear, but had over the years been variously considered to be guillain-barre syndrome (GBS), friedreich ataxia, or multiple sclerosis (MS). At autopsy old CNS demyelination consistent with MS was found as well as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with onion bulb formation in hypertrophic nerves. Microscopic examination showed some onion bulb formation in the CNS as well as in peripheral nerves. The nosology of these disorders is discussed and relevant animal models briefly reviewed.- - - - - - - - - - ranking = 2keywords = nerve (Clic here for more details about this article) |
7/16. multiple system atrophy with neuronal intranuclear hyaline inclusions. Report of a case and review of the literature.A 31/2-year-old girl presented with frequent falls. She had an unsteady gait, delayed behavioural development absent tendon reflexes and in the legs decreased strength tone and equivocal plantar responses. She then developed ataxia, nystagmus, choreoathetosis, cranial nerve palsies, diminished strength and tone in the arms, sensory deficit in the limbs and autonomic nervous system dysfunction. She became progressively less responsive and succumbed at the age of 63/4 years. Examination of the central, peripheral and autonomic nervous system showed ubiquitous neuronal intranuclear hyaline inclusions and neuronal loss in several sites.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
8/16. Non-hereditary multiple telangiectasias of the central nervous system. Report of two clinicopathological cases.We describe 2 clinicopathological cases of non-hereditary multiple telangiectasias of the nervous system. In the first case, the general course of the disease was characterized by spells over a period of 7 years and the major lesions successively involved cranial nerves, spinal cord and brain. Neuropathological examination showed both ischemic and hemorrhagic changes. Systematized degenerative changes were found and were similar to those observed in spinocerebellar heredodegenerations (Friedreich's ataxia). In the second case, the 3 years of evolution were characterized by spells of the encephalitic type only. A review of the literature indicates the rarity of this kind of disease, the usual localization of capillary malformations and the clinical polymorphism (epilepsy, strokes, multifocal syndromes masquerading as multiple sclerosis). The pathogenesis of pathological changes is discussed.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
9/16. Is the sensory neuropathy in ataxia-telangiectasia distinguishable from that in Friedreich's ataxia? Morphometric and ultrastructural study of the sural nerve in a case of Louis Bar syndrome.The bioptical morphometric and ultrastructural study of sural nerve in a 17-year-old boy with ataxia-telangiectasia (AT) is reported. Our findings include a loss of fibers, particularly of large ones, axonal degenerative changes, Schwann cell inclusions of various type, and rare signs of primary demyelination. Teased-fiber study showed paranodal myelin enlargements, segmental demyelination, shortening, and/or variability of internodal length. This picture is similar to that in Friedreich's ataxia (FA), although they differ in degree and time of onset. A correct neuropathologic diagnosis of AT cannot be made on the basis of sural nerve biopsy alone.- - - - - - - - - - ranking = 6keywords = nerve (Clic here for more details about this article) |
10/16. coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.Abnormalities of the heart are a frequent and possibly ubiquitous problem in patients with Friedreich's ataxia, but their pathogenesis is unclear. Postmortem findings are reported from the hearts of three patients with Friedreich's ataxia who died of congestive heart failure and atrial arrhythmias. Particular attention was paid to the following: the large and small coronary arteries, the nerves and ganglia, the conduction system, and the histological and cellular features of the cardiomyopathy. There were pleomorphic nuclei and focal fibrosis and degeneration throughout each heart including the conduction system. There were distinctive abnormalities of both large and small coronary arteries, and focal degeneration of nerves and ganglia. These observations suggest a mosaic concept for the pathogenesis for the cardiomyopathy of Friedreich's ataxia that involves the interplay of molecular faults, cardiomyopathy, cardioneuropathy, and coronary disease.- - - - - - - - - - ranking = 2keywords = nerve (Clic here for more details about this article) |
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