Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.
 ...
PMID:The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study. 48 11

The mean percentage of linoleate to total fatty acids in phosphatidylcholine and lysophosphatidylcholine fractions of serum phospholipids from neuropathic patients with HMN (hereditary motor neuropathy, also called distal type of progressive muscular atrophy), HMSN-I and HMSN-II (two types of peroneal muscular atrophy), and FA (Friedreich's ataxia) was reduced by approximately 10--20% (P less than 0.001). On the other hand, the mean percentage of nervonic acid in sphingomyelin was elevated by 9--20%. No significant difference was observed in phosphatidylethanolamine between neuropathic patients and control subjects. The mean concentration of phosphatidylcholine and sphingomyelin was also significantly reduced in neuropathic patients (except in HMN and HMSN-III). A significant correlation between endogenous 2-linoleoyl-sn-glycerol-3-phosphocholine and cholesteryl linoleate synthesis in vitro suggests that the decreased activity of phosphatidylcholine acyltransferase (EC 2.3.1.43; LCAT) in neuropathic patients is influenced by the fatty acid composition of their lipoprotein substrate. Furthermore, the reduction of phosphatidylcholine and of cholesteryl linoleate synthesis in vitro in neuropathic patients was affected by age and sex. It is unlikely that the reduced linoleate level in serum phosphatidylcholine for most, possibly all, of the inherited neuropathies studied here reflects a specific biochemical disorder. Possibly it reflects a more generalized biochemical alteration common to inherited neuropathy. One possibility is that biosynthesis of new membrane in axonal regeneration, segmental remyelination and Schwann cell hyperplasia may reduce the serum linoleate pool.
 ...
PMID:Lipid abnormalities in hereditary neuropathy. Part 2. Serum phospholipids. 65 Feb 57

An electrophysiological study, comprehensive of peripheral sensory and motor conduction velocity (SCV, MCV), motor cortical stimulation (CS), median nerve somatosensory evoked potentials (SSEPs), brainstem evoked potentials (BAEPs) and sural nerve biopsy, was performed on 100 hereditary ataxia patients: 48 with Friedreich's ataxia (FA), 18 with Early Onset Cerebellar Ataxia (EOCA) and 34 with Autosomal Dominant Cerebellar Ataxia (ADCA). An early "peripheral" and "central" sensory impairment was observed in FA probably due to axonal loss and not related to disease severity or duration. On the contrary, BAEP and CS findings suggested a progressive involvement of the auditory and motor pathways. The presence of a non progressive sensory neuropathy allowed a distinction of EOCA patients in two groups: with and without peripheral neuropathy. The clinical and genetic heterogeneity was confirmed by the variability of evoked potential results. The ADCA patients showed the mildest degree of electrophysiologic abnormalities with an involvement of the peripheral pathways, both sensory and motor, more frequent than the central ones.
 ...
PMID:[Clinical and electrophysiological findings in various hereditary sensory neuropathies]. 129 78

Fine structural alterations of Schmidt-Lanterman incisures (SLI) were investigated in a series of 242 unselected sural nerve biopsies that had been examined for diagnostic purposes. The series included cases with Friedreich's ataxia, HSAN I, HMSN I-III, HMSN VI, tomaculous neuropathy, metachromatic leukodystrophy, ceroidlipofuscinosis, dysproteinemic neuropathies, and myotonic dystrophy, in addition to several neuropathies less-specifically classified as either of a predominantly demyelinating, axonal, or neuronal type. The following classification of SLI alterations is proposed: (A) abnormal inclusions; (B) changes in shape and dimension; and (C) modes of disintegration. Abnormal inclusions comprised membranous whorls, uniform and pleomorphous lysosome-like bodies, and accumulation of granular substances at the site of the major dense line, or granular deposits at the site of the intraperiod line of the myelin sheath. Variations of incisural shape and dimension included folding, dilatation, and pocket formation (compartmentalization). Disintegration at incisures comprised a fine, vesicular and a gross, vacuolar type. Various combinations of these changes were observed. The most frequent change consisted of membranous whorls, detected in SLI of 89 biopsies. They were most prominent in chloroquine neuropathy where they occurred in SLI as well as in the adaxonal and abaxonal cytoplasm of Schwann cells. Compartmentalization of the myelin sheath at incisures associated with formation of myelin loops was a frequent feature in myotonic dystrophy. It is concluded, that changes of incisural ultrastructure are sensitive indicators of human neuropathies offering clues to the type of the underlying pathomechanism.
 ...
PMID:Fine structural evaluation of altered Schmidt-Lanterman incisures in human sural nerve biopsies. 155 44

Fourteen patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon reflexes (EOCA) were examined and compared with 11 patients with Friedreich's ataxia (FA). The mean age of onset in EOCA was 15.9 +/- 6.0 yrs (FA: 14.0 +/- 5.7 yrs). Annual progression rate and the percentage of patients who were wheelchair-bound was lower in EOCA as compared with FA, although the difference did not reach statistical significance. The latency until becoming wheelchair-bound, however, was significantly longer in EOCA than in FA. The segregation ratio in EOCA was significantly lower than 0.25. Clinically, EOCA and FA patients presented with a progressive cerebellar syndrome. Associated symptoms, such as muscle wasting, sensory disturbances, foot deformity, scoliosis and electrocardiographic abnormalities were encountered less frequently in EOCA than in FA patients. The electrophysiological findings in EOCA were variable and pointed to axonal degeneration in peripheral nerves and central pathways. Posturographic measurements revealed a higher incidence of anteroposterior sway direction in EOCA as compared with FA, suggesting a cerebellar type of ataxia in EOCA. Eleven out of the 14 EOCA patients had cerebellar atrophy in MRI. The characteristic MRI finding in FA was upper cervical cord shrinkage and only minor atrophy of the cerebellum. The demonstration of cerebellar atrophy in the majority of EOCA patients supports the view that EOCA is distinct from FA. It is uncertain, however, whether EOCA is a homogenous disease entity or a group of phenotypically similar syndromes.
 ...
PMID:Early onset cerebellar ataxia with retained tendon reflexes. Clinical, electrophysiological and MRI observations in comparison with Friedreich's ataxia. 188 66

Hereditary motor and sensory neuropathies (HMSN) comprise a heterogeneous group of disorders. Since phenotypic manifestations are similar in most families, classification is based on differences in the mode of inheritance, onset and progression of the disease, nerve conduction velocity and nerve biopsy findings. Autosomal dominant, autosomal recessive, X-dominant and X-recessive forms, substantial intrafamilial differences, intermediate forms and the combination of neuropathies with spinocerebellar degeneration within one and the same sibship have been described. On the basis of selected own cases it is demonstrated that there is a broad spectrum of functional and structural abnormalities depending on the progression of the disease and on the site of nerve studied (proximal or distal part). Both the neuronal and hypertrophic variants begin with axonal degeneration of the dying back type followed by segmental demyelination and variable degrees of hypertrophic Schwann cell proliferation. Constantly, posterior columns of the spinal cord reveal fiber loss. Since the molecular basis of the different forms remains to be clarified it seems to be of greater interest to underline common features than to separate seemingly different nosological entities. It is suggested that the latter are partly the result of a selection of cases with a variable severity. Evidently, the syndrome of myatrophic ataxia comprises apart from "pure" HMSN with unsignificant degenerations of posterior columns and "pure" Friedreich's ataxia with mild peripheral nerve fiber loss intermediate forms.
 ...
PMID:[The nosological situation of hereditary motor and sensory neuropathies (HMSN, Charcot-Marie-Tooth disease, neural muscular atrophy)]. 228 21

This paper examines the topography of neuronal degeneration in the central nervous system of the dystonia musculorum (dt) mutant mouse, revealed by selective silver impregnation, specific histochemical staining and electron microscopy. Neuronal lesions have been observed exclusively in the spinal cord, the medulla and the anterior lobe of the vermis. In the spinal cord, axonal degeneration was maximal among large and medium-sized primary sensory fibers, whereas thin caliber primary afferents were unaffected, with the exception of those containing acid phosphatase activity. In regions of laminae VI to VIII that receive numerous degenerative primary afferents, neurons undergoing different phases of degeneration (chromatolysis, lipid accumulation, dark shrunken necrosis) were constantly found. Most of the latter belonged to spinocerebellar neurons, owing to the presence of fiber degeneration in both spinocerebellar tracts and mossy fiber degeneration in the anterior vermal lobe. In the medulla only axonal degeneration was observed and was confined to three fiber systems: the dorsal column pathway, the sensory trigeminal fibers (both from the trigeminal ganglion and from the mesencephalic trigeminal nucleus), and the spinocerebellar fibers entering the cerebellum through the inferior and superior cerebellar peduncles. This study also suggests a simple pathophysiological mechanism for the onset and the progression of the degeneration: dystonic gene action would affect perinatally specific classes of sensory receptors, producing the degeneration of the nerve terminals and, progressively, the cell death of the sensory ganglion cells at their origin. This retrograde death, which results in the massive and early deafferentation of spinocerebellar neurons, would provoke, trans-neuronally, the impairment of these second order sensory neurons and the progressive degeneration of the spinocerebellar system. The close resemblance of the neuropathology of the mutant mouse to Friedreich's ataxia (the commonest form of human degenerative ataxic disorders) allows one to suppose that the dystonic mouse may be an optimal animal model for studying the genetic basis and the pathophysiological mechanisms of this form of human ataxia.
 ...
PMID:Pathologic changes in the CNS of dystonia musculorum mutant mouse: an animal model for human spinocerebellar ataxia. 321

Neuro-ophthalmological assessment, including red-free light retinography, in conjunction with simultaneous visual evoked potential (VEP) and pattern electroretinogram (PERG) recordings were performed in 10 Friedreich's ataxia patients: 9 patients showed marked VEP abnormalities. Moderate PERG amplitude reduction, with normal latencies, was related to mild and scattered fiber loss revealed by red-free light retinography. The initial part of the visual pathways does not seem to be the main site of electrophysiological abnormalities as demonstrated by the greater extent and relative independence of VEP versus PERG alterations. Primary axonal degeneration of the optic nerve and tracts cannot account for all features of VEP abnormalities, thus implying some dysfunction in succeeding visual structures as well.
 ...
PMID:Visual involvement in Friedreich's ataxia: PERG and VEP study. 322 18

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.
 ...
PMID: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. 345 14

The changes in evoked potentials following median and tibial nerve stimulation in nine patients with clinically defined Friedreich's ataxia are reported and discussed. The response originating in the brachial plexus (Erb's point potential) was absent or reduced in amplitude with no prolongation of peak latency, and the response generated in the cauda equina (N18) was absent in all cases. Conduction time from the brachial plexus to cervical spine and medulla oblongata was normal, whereas the central conduction time (N13a/N20, N13b/N20) was delayed. There was moderate to marked attenuation of the primary cortical response to median nerve stimulation. In one patient N20 disappeared during the course of the disease as opposed to the persisting subsequent negative wave, the latter thus simulating a very marked delay in the primary cortical response. Accordingly the cortical response to tibial nerve stimulation, which was only present in two patients and was markedly delayed, might represent a later potential with the primary response absent. The findings are consistent with neuropathological descriptions of a dying back neuropathy with primary axonal degeneration concerning the 1st order sensory neuron. In addition there is evidence either of delayed conduction in 2nd and 3rd order sensory neurones or of abnormal synaptic transmission.
 ...
PMID:Somatosensory evoked potentials following median and tibial nerve stimulation in patients with Friedreich's ataxia. 367 95


1 2 3 4 5 6 7 Next >>