[Progressive asymmetrical peripheral neuropathy of both legs in a 64-year-old man].
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B-Lymphocytes↗
Biomedical subjects
G Said
Publications and source records attributed to G Said.
Axonal regrowth through collagen tubes bridging the spinal cord to nerve roots.
The capacity of central nervous system (CNS) axons to elongate from the spinal cord to the periphery throughout a tubular implant joining the ventral horn of the spinal cord to an avulsed root was investigated in a model of brachial plexus injury. The C5-C7 roots were avulsed by controlled traction and the C6 root was bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder containing or not containing an autologous nerve segment, or an autologous nerve graft. Nine months later, the functionality and the quality of the axonal regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and histological examination of the gap area. A normal electromyogram of the biceps was observed in all animals where the C6 root was bridged to the spinal cord. The mean average amplitude of the motor evoked potentials was comprised between 17.51 +/- 12.03 microV in animals repaired with a collagen cylinder, and 27.83 +/- 22.62 microV when a nerve segment was introduced in the tube. In nonrepaired animals spontaneous potentials reflecting a muscle denervation were observed at electromyography. Retrograde labelling indicated that a mean number of 58.88 +/- 37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a tube versus 78.38 +/- 62.11 when a nerve segment was introduced in the channel, and 97.25 +/- 56.23 in nerve grafting experiments. Analyses of the repair site showed the presence of numerous myelinated regenerating axons. In conclusion, our results indicate that spinal cord neurons can regenerate through tubular implants over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve grafting experiments. The combination of an implant and a nerve segment did not significantly increase the regeneration rate.
Animals↗
Painful proximal diabetic neuropathy: inflammatory nerve lesions and spontaneous favorable outcome.
Proximal diabetic neuropathy is a disabling neuropathy that occurs predominantly in non-insulin-dependent diabetic patients over the age of 50. Inflammatory lesions have been found in nerve biopsy specimens of diabetic patients with severe proximal neuropathy or with other patterns of multifocal neuropathy. Some of these patients respond dramatically to treatment with corticosteroids or with other immunomodulators. In this article we report on our findings in 4 additional patients with painful proximal diabetic neuropathy and different patterns of inflammatory nerve lesions whose condition improved spontaneously shortly after performance of a nerve biopsy, without additional treatment.
Aged↗
Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's disease.
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Adult↗
Necrotizing peripheral nerve vasculitis.
Necrotizing vasculitis of the type in polyarteritis nodosa is a treatable cause of neuropathy. The diagnosis must be confirmed histologically by demonstration of characteristic arterial lesions in nerve and muscle biopsy specimens. Ischemic neuropathy which results from occlusion of nerve arteries in polyarteritis nodosa also occurs as a consequence of inflammatory arterial lesions in other connective tissue disorders, in some infectious neuropathies and in patients with malignant lymphomas. Patients with vasculitic neuropathy may also present with isolated peripheral neuropathy.
Adrenal Cortex Hormones↗
Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease: evidence for association of a DRD2 allele.
We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white. To complete the study of the DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients, who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms, similar allelic frequencies were present in familial, sporadic PD and control patients. In contrast, at the DRD2 locus, the overall allelic distribution was significantly different in the sporadic PD (p < 0.01) and in the familial PD groups (p < 0.05), each was compared with the controls. The odd ratios were significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with respective values of 1.84 (95% CI, 1.23-2.74) and 2.83 (95% CI, 1.32-6.08). Individuals who were homozygous for allele 3 were 2.3 times more frequent in the sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and MAOB, might be a genetic determinant of PD in the population tested.
Alleles↗
[Multifocal motor neuropathies with conduction blocks. 39 cases].
Clinical, biological and electrophysiological features from a cohort of 39 multifocal motor neuropathies with conduction blocks (NMM with CB) have been studied. There were 29 males and 10 females with an average of 47.3. At the first evaluation, the mean duration of the symptoms was of 8 years with extremes between 1 and 28. Pain and paresthesias were present in respectively 10 and 18 p. 100 of the patients. Fasciculations and cramps were observed in more than 2/3 of the cases. Three patients had tremor at rest. Upper limb muscular weakness was the predominant initial symptom (84.6 p. 100). The weakness always affected distal and unilateral muscles. Radial and cubital nerve distribution are mainly affected and in half of the cases an unilateral motor deficit in the lower limb was associated. Muscle atrophy was frequent (74 p. 100) and rapidly developed in the first 2 years. Reflexes were decreased or absent in 64 p. 100. In 78 p. 100 of cases, biological study showed normal serum immunoelectrophoresis and CSF. IgM anti-GM1 antibodies were found in 24/36 patients. Very high titres were found in 5 cases. All patients had CB in upper limbs. The preferential localizations of the CB were equally at the median and ulnar nerves. Only 7 patients had CB localized to the lower limbs. In many cases, marked reduction of the motor amplitude prevented the detection of CB, marked reduction of the motor amplitude prevented the detection of CB. Moderate fibrillation potentials were found in 28 p. 100 of patients. Giant muscular unit potentials were frequent (21/39). F-waves in nerve with CB were always abnormal with marked increased latencies. Late responses sometimes seemed to be repeater F-waves. Axon reflexes were detected in 5 cases. The late responses abnormalities could precede the block. Clinical, biological and electrophysiological described arguments could may distinguish NMM with CB from motor neuron disease and relate them to the group of chronic demyelinating neuropathies.
Adult↗
[Peripheral neuropathy caused by thallium poisoning].
A 20-year-old man developed over three weeks a sensory and painful neuropathy associated with diffuse alopecia. There was motor weakness, and superficial and deep hypoesthesia of the inferior limbs. Deep tendon reflexes were normal. Electrophysiological study mainly showed axonal motor neuropathy. This patient was admitted six weeks after the first symptoms. The clinical picture suggested thallium poisoning, which was confirmed by thallium concentrations in plasma, urine, hair and nails. After search, thallium was identified in a rat poison.
Adult↗
Peripheral neuropathy in polyarteritis nodosa.
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Female↗
Ultrastructural immunolabelling of amyloid fibrils in acquired and hereditary amyloid neuropathies.
Both acquired and familial amyloid neuropathies carry a poor prognosis. In addition, amyloid is sometimes difficult to visualise in nerve biopsy specimens, and the pathogenesis of nerve lesions is still a matter of controversy. In order to learn more on the subject, we studied nerve specimens from seven patients with proven amyloid neuropathy by ultrastructural immunocytochemistry in order to better understand their pathogeny and to evaluate the reliability of the method for detection of amyloid antigens in the endoneurium. An indirect immunolabelling technique using protein A-gold complex (pA-g) was applied. Polyclonal antisera against human IgG, IgM, lambda and kappa light chains and prealbumin were assayed. Amyloid fibrils were labelled in six of seven cases: in four cases with anti-transthyretin (TTR) antibodies and in two with anti-lambda light chain antibodies. The type of immunolabelling correlated with the biochemical type of the amyloidosis as defined by TTR gene analysis and serum immunoelectrophoresis. The amyloid fibrils and gold labelling were always located in the endoneurial space. No intracellular deposit or labelling was found. The immunolabelling was highly specific, gold particles being detected only near to amyloid fibrils with no background gold labelling. Ultrastructural immunolabelling with pA-g could be used for detection of amyloid in progressive axonal neuropathy of unknown origin, with important therapeutic implications.
Adult↗
Diabetic neuropathy: an update.
Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The usual pattern is a distal symmetrical sensory polyneuropathy, associated with autonomic disturbances. Less often, diabetes is responsible for a focal or multifocal neuropathy affecting cranial nerves, especially oculomotor nerves, and roots and nerves innervating proximal muscles of the lower limbs. Metabolic abnormalities due to hyperglycaemia, lack of insulin and their consequences and ischaemic phenomena secondary to diabetic microangiopathy account for nerve lesions.
Diabetic Neuropathies↗
Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly. A retrospective review of 100 consecutive patients.
Peripheral neuropathy is an important factor of disability in the elderly. In order to learn more on the usefulness of intensive evaluation of patients over 65 years of age with subacute or chronic disabling peripheral neuropathy, we reviewed the clinical and nerve biopsy findings of the last 100 patients of this age group who suffered from a peripheral neuropathy severe enough to justify performance of a nerve biopsy for a diagnostic or prognostic purpose. Normal nerve biopsy findings led to the diagnosis of lower motor neuron disease in three patients and pointed to lesions of the spinal roots in six other patients. Necrotizing arteritis was demonstrated in the biopsy specimens of 23 patients, and non-necrotizing vasculitis in five. In five additional patients the diagnosis of vasculitic neuropathy was kept in spite of non-contributive biopsy findings. In two diabetic patients who had a multifocal neuropathy the biopsy also revealed the presence of vasculitis. Thus 35% of the patients included in this series had one form or another of vasculitic neuropathy. Fourteen patients had a chronic inflammatory demyelinating polyneuropathy. In 11 patients the neuropathy was associated with monoclonal gammopathy, which was benign in nine and associated with malignant plasma cell dyscrasia in two. Among the six patients with diabetes mellitus, two patients who presented with a multifocal neuropathy were found to have vasculitis in the nerve specimen; in the others the biopsy was performed because of uncommonly severe pains or motor involvement due to an extremely severe diabetic neuropathy. Six patients suffered from a long-lasting disability secondary to a drug-induced neuropathy. The remaining 15% had neuropathies of different origin, including amyloidosis, lepromatous leprosy, carcinomatous neuropathy and alcoholic neuropathy. Six patients had a mild, non-progressive or slowly progressive axonopathy of unknown origin, ageing of the peripheral nervous system may have played a role in its development. Our findings show that vasculitis is an important and treatable cause of disabling neuropathy in the elderly and that the proportion of patients with severe neuropathy of unknown origin is small.
Aged↗
Vasculitis and peripheral neuropathy.
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Antibodies, Antineutrophil Cytoplasmic↗
Detection of Mycobacterium leprae in nerve lesions by the polymerase chain reaction.
A simple procedure is described for the detection of Mycobacterium leprae by the polymerase chain reaction in nerve biopsies sectioned with a cryostat and then treated with proteinase K. All samples from lepromatous leprosy patients and the majority of samples from paucibacillary cases yielded positive results. This approach may be useful for differentiating between leprosy and other inflammatory neuropathies.
Adult↗
[Guillain-Barré syndrome: morphological lesions and their relations with clinical manifestations].
Acute demyelinization of the peripheral nervous system is a characteristic feature of Guillain-Barré syndrome. Lesions of the spinal roots predominate with more or less diffuse multifocal peripheral demyelinization. Inflammatory lesions of the distal peripheral nervous system are less common. Segmentary demyelinization of nerve fibers accompanying inflammatory lesions show characteristic penetration of macrophages within a normal appearing myelin sheath. The myelin on the segments concerned is rapidly destroyed by phagocytosis and removed with the macrophages. Once the debris has been removed, the axons are remyelinized after proliferation of the Schwann cells. In monophasic cases, the entire processes occurs over a 2-3 week period allowing remyelinization and rapid functional recovery. In prolonged cases, flare-ups of demyelinization, non remyelinization or damage to the axons can retard recovery. The mechanism and impact of axon damage which accompanies demyelinization at various degrees and which may predominate in certain cases, is discussed here.
Axons↗
Peripheral neuropathy with necrotizing vasculitis in rheumatoid arthritis. A clinicopathologic and prognostic study of thirty-two patients.
OBJECTIVE: To examine the clinicopathologic features of the noncompressive neuropathies in rheumatoid arthritis (RA). METHODS: We studied 32 patients with RA and peripheral neuropathy whose nerve and/or muscle biopsy specimens exhibited necrotizing vasculitis. Morphologic analysis of nerve specimens included light and electron microscopy studies and teased fiber preparation. Survival was evaluated, and the prognostic values of clinical, biologic, and pathologic features were assessed by Cox proportional hazards model. A prognostic assessment based on the significant variables was devised to estimate the probability of survival of any individual patient. RESULTS: Epi- and/or perineurial vasculitis was observed with the same frequency in the 17 patients with sensory and motor deficit and the 15 patients with sensory neuropathies and was associated with axonal degeneration of an average of 77.7% of the nerve fibers. The mean followup was 7.2 years, and the overall survival rate at 5 years was 57%. A full prolonged remission of the vasculitis was observed in 53% of the patients; relapse occurred in 25%. The factors correlated with mortality, in decreasing order of significance, were clinical cutaneous vasculitis (P = 0.0003), neuropathy affecting 3 or 4 limbs (P = 0.03), and depressed level of C4 (P < 0.05). The prognostic assessment indicated a wide range of 5-year probabilities of survival, from < 1% to 93%. CONCLUSION: Necrotizing vasculitis is responsible for the different patterns of noncompressive neuropathies in RA, including mononeuritis multiplex and distal symmetric sensory or sensorimotor neuropathy. Cutaneous vasculitis, multifocal neuropathy, and depressed C4 level were the 3 independent variables which best predicted mortality. We propose a prognostic assessment according to these variables, to stratify patients to receive more aggressive or less aggressive therapy.
Adult↗
Haplotype analysis of French, British and other European patients with familial amyloid polyneuropathy (met 30 and tyr 77).
Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder originally and most frequently described in Portugal. The usual constituent amyloid fibril protein is transthyretin (TTR) and the most frequent mutation in the TTR gene associated with FAP (including all Portuguese cases) is that at position 30 (met 30). Three different TTR haplotypes have been described in association with the met 30 mutation in European patients. We studied the haplotypes of 27 families (24 French, 2 British and 1 Greek) with FAP met 30 by analysing three polymorphisms in introns of the TTR gene. We also studied 6 families (2 British, 3 French and 1 Spanish) with FAP tyr 77. There were two main haplotypes in French patients with FAP met 30, one most commonly seen in the French families of Portuguese descent which was the same haplotype as previously described in Portuguese patients (haplotype I) and another haplotype (III) detected in most informative French families not of Portuguese origin. The age of onset of symptoms was consistently later in French than in Portuguese patients and in patients with haplotype III as the disease-associated haplotype rather than haplotype I. British and French patients with the tyr 77 mutation had different haplotypes. The most likely explanation of these findings is multiple founders of both mutations.
Amyloid Neuropathies↗
A clinical and genetic study of familial cases of Parkinson's disease.
We assessed a group of patients with a family history of Parkinson's disease (PD) in order to see if they differed clinically from sporadic cases and to study their genetic characteristics. Index cases were selected on the basis of clinically typical PD, and at least one affected relative. Fourteen families including 110 first degree and 40 second degree relatives were ascertained. A total of 31 individuals (17 females and 14 males) were found to be affected. This group was compared for selected clinical parameters to 31 age matched patients with sporadic PD. No statistical difference was found between the two groups. In familial cases, both the clinical parameters studied and the course of the disease varied within and between families, as observed in sporadic cases. The genetic transmission was compatible with an autosomal dominant model. The total segregation ratio of 0.25 suggested an incomplete penetrance, which increased with age, from 0 below the age of 30 to 0.43 over the age of 70. Age at onset was earlier in children than in their parents in the 8 multigeneration kindreds studied (mean difference 26 +/- 4.6 years, p = 0.01), whereas it was identical within a generation (mean difference 4.7 +/- 5.7 years, p = 0.1). Although we cannot exclude an ascertainment bias, our results are compatible with an anticipation phenomenon, which deserves further studies for confirmation.
Adult↗