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To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.

Introduction Mitochondrial trifunctional protein deficiency (MTPD) is a long-chain fatty acid oxidation disorder characterized by co-existence of rhabdomyolysis episodes and peripheral neuropathy. Two phenotypes are described: generalized mitochondrial trifunctional protein deficiency (gMTPD) and isolated long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency (iLCHADD) that is always associated with the c.1528G>C mutation. Peripheral neuropathy of MTPD is commonly described in children as axonal, length-dependent and sensorimotor. Objectives To report clinical and electrophysiological features of four independent adult MTPD patients with peripheral neuropathy. Results Onset of the disease was characterized in all patients by rhabdomyolysis episodes occurring during childhood preceded by severe hypoglycemic episodes in three patients. Peripheral nerve involvement manifesting as sensory ataxia appeared later, during adolescence or adulthood. In all cases, electroneuromyogram showed no length-dependent sensory potentials decrease characteristic of sensory neuronopathy (“ganglionopathy”). All patients harbored at least one c.1528G>C mutation. Discussion We describe MTPD as a newly hereditary etiology of sensory neuronopathy in adults, specifically in patients with c.1528G>C mutation. MTPD should be screened for by performing plasma acylcarnitines in patients with chronic sensory neuronopathy and additional suggestive features such as exercise intolerance or retinopathy .

Background and purpose Charcot-Marie-Tooth (CMT) 1C due to mutations in LITAF/SIMPLE is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with PMP22 mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP). Methods Charcot-Marie-Tooth 1C patients were followed-up in referral centres for neuromuscular diseases or were identified by familial survey. All CMT1A and HNPP patients were recruited at the referral centre for neuromuscular diseases of Pitie-Salpetriere Hospital. Results Two phenotypes were identified amongst 18 CMT1C patients: the classical CMT form ('CMT-like', 11 cases) and a predominantly sensory form ('sensory form', seven cases). The mean CMT neuropathy score was 4.45 in CMT1C patients. Motor nerve conduction velocities in the upper limbs were significantly more reduced in CMT1A than in CMT1C patients. On the other hand, the motor nerve conduction velocity of the median nerve was significantly lower in CMT1C compared to the HNPP group. Distal motor latency was significantly more prolonged in CMT1A patients compared to the CMT1C and HNPP groups, the latter two groups having similar distal motor latency values. Molecular analysis revealed five new LITAF/SIMPLE mutations (Ala111Thr, Gly112Ala, Trp116Arg, Pro135Leu, Arg160Cys). Conclusions Our study delineates CMT1C as mostly a mild form of neuropathy, and gives clinical and electrophysiological clues differentiating CMT1C from CMT1A and HNPP. Delineating phenotypes in CMT subtypes is important to orient molecular diagnosis and to help to interpret complex molecular findings.

Some patients within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) have distal acquired demyelinating symmetric (DADS) neuropathy, usually associated with anti-myelin-associated-glycoprotein (MAG) IgM monoclonal gammopathy. The aim of this retrospective study was to investigate patients with DADS neuropathy without anti-MAG antibodies, and study their response to immunotherapy.Patients were selected on the basis of (i) 'Definite CIDP' according to the EFNS/PNS Guideline criteria, (ii) The presence of disproportionately prolonged motor latencies resulting in a terminal latency index (TLI) ≤ 0.25 in at least two motor nerves and (iii) The absence of anti-MAG antibodies on ELISA. Response to immunotherapy was defined as persistent improvement by at least one point on the INCAT disability score.Data from 146 CIDP patients were analysed, and 10 patients were included. Six had clinically pure sensory neuropathy, and four had sensorimotor neuropathy. Ataxia was present in nine patients, generalized areflexia in seven and postural tremor in two. Five of the 10 patients had abnormal sensory potentials only in the upper limbs. An associated condition was found in nine patients: two chronic lymphocytic leukaemias, four IgG monoclonal gammopathies (one associated with non-Hodgkin's lymphoma) and two IgM monoclonal gammopathies of unknown significance. Patients were mostly improved with intravenous immunoglobulin (IVIg), corticosteroids, plasma exchanges, or a combination thereof.DADS neuropathy without anti-MAG antibodies is more likely to be considered a variant of CIDP. In addition, such patients should be systematically investigated for an associated haematological or immunological condition.

Cryoglobulinemic neuropathies caused by hepatitis C virus are frequent and may have severe clinical outcomes. The aim of this study was to clarify the clinical and anatomical correlations of these neuropathies.Between 1992 and 2007, 22 consecutive patients with cryoglobulinemic neuropathies caused by hepatitis C virus were retrospectively included. Patients were evaluated clinically, electrophysiologically and underwent a neuromuscular biopsy. The group of patients with vasculitis on nerve biopsy was compared with the group without vasculitis.All the neuropathies were axonal with 11 polyneuropathies and 11 mononeuropathies multiplex. The seven patients with medium-sized vasculitis on the nerve biopsy presented an acute sensorimotor mononeuropathy multiplex in six cases (85%), with ischemic conduction block in three cases (42%) and wallerian degeneration in four cases (57%). Among the four patients with small-sized vasculitis, two had a mononeuropathy multiplex (50%) without conduction block (0%) and with wallerian degeneration in one case (25%). The 11 patients without vasculitis (nine lymphocytic perivascular infiltrates and two non inflammatory biopsies) had a polyneuropathy in eight cases (72%) without conduction block and wallerian degeneration (0%). The type of neuropathy was different in the group of patients with vasculitis compared with the group without vasculitis. The neuropathies with vasculitis were significantly different with more frequent mononeuropathies multiplex (p0.05), acute early stage (p0.01), disability (p0.05) and wallerian degeneration (p=0.01).Among hepatitis C patients with cryoglobulinemia, neuropathies with small-sized vasculitis show a pattern between severe mononeuropathies multiplex with medium-sized vasculitis and moderate polyneuropathies with lymphocytic perivascular infiltrates. In cryoglobulinemic vasculitis with hepatitis C, the severity of the neuropathy depends on the nature of the cellular inflammation and the size of the vessel involvement.

If a sensory neuropathy appear from an autoimmune disease, it was important to precise the type with clinical and electrophysiological characteristic features (distal symmetric polyneuropathy, chronic inflammatory demyelinating polyneuropathy, Sensory mononeuritis multiplex, sensory neuronopathy, small-fiber neuropathy). The type of neuropathy have an influence on the complementary explorations. It was very important to determine the mechanism between the neuropathy and the autoimmune disease for the treatment. We present a young patient with systemic lupus erythemathosus and sensory neuropathy. This case illustrates this diagnosis strategy.

Although the diagnosis of spondyloenchondrodysplasia (SPENCD) can only be made in the presence of characteristic metaphyseal and vertebral lesions, a recent report has highlighted the pleiotropic manifestations of this disorder which include significant neurological involvement and variable immune dysfunction. Here we present two patients, one of whom was born to consanguineous parents, further illustrating the remarkable clinical spectrum of this disease. Although both patients demonstrated intracranial calcification, they were discordant for the presence of mental retardation, spasticity and white matter abnormalities. And whilst one patient had features consistent with diagnoses of Sjogren syndrome, polymyositis, hypothyroidism and severe scleroderma, the other patient had clinical manifestations and an autoantibody profile of systemic lupus erythematosus. These cases further illustrate the association of SPENCD with immune dysregulation and highlight the differential diagnosis with Aicardi-Goutieres syndrome and other disorders associated with the presence of intracranial calcification. Undoubtedly, identification of the underlying molecular and pathological basis of SPENCD will provide important insights into immune and skeletal regulation.

Multifocal motor neuropathy is a well described condition characterized by slowly progressive, predominantly distal, asymmetric limb weakness and wasting, predominantly in the arms within an anatomical distribution of individual motor nerves, with minimal or no sensory involvement.The aim of this retrospective study was to look for a significant reduction of the amplitude of sensory potentials in a cohort of 21 patients with defined multifocal motor neuropathy according to the Workshop Report criteria [Workshop Report, 2001. 79th ENMC International Workshop. Multifocal motor neuropathy 14-15 April 2000, Hilversum. The Netherlands. Muscle Nerve 11, 309-314], within a follow-up of at least 3 years.Thirteen patients (62%) (Group 1) had a reduction of the amplitude of at least one sensory potential, of whom four patients had abnormalities of two or more sensory potentials, while eight patients (Group 2) had no abnormality. No significant differences were found for gender, age at onset, number of involved motor nerves, CSF protein count, presence/absence of anti-GM1 serum antibodies and response to IgIV between the two groups.This study underlines the difficulty in defining criteria for multifocal motor neuropathies capable of distinguishing them from other chronic acquired demyelinating polyneuropathies, and mainly from multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, also called Lewis-Sumner's syndrome.

Hypohidrosis is a classic feature of Fabry disease; in contrast, hyperhidrosis has only been rarely described. The aim of the study is to characterise the baseline descriptive data on hyperhidrosis (frequency, age at onset, sex ratio and outcome with and without enzyme replacement therapy) in hemizygous male and heterozygous female patients with Fabry disease. We describe case histories of five patients with Fabry disease and hyperhidrosis seen at three different centres. We have also analysed a cohort of 21 paediatric patients in the UK and a large European cohort of patients enrolled in the Fabry Outcome Survey (FOS). Five patients (three female, two male) with hyperhidrosis were originally identified, although each had additional symptoms related to Fabry disease. The age at onset of hyperhidrosis was less than 18 years in four cases. In the cohort of 21 paediatric patients (12 female, nine male), one female had hyperhidrosis; the age at onset of this symptom was 11 years. In the FOS cohort, 66 of 714 patients with Fabry disease had hyperhidrosis (44 of 369 females, 11.9%; 22 of 345 males, 6.4%). The female predominance was observed in seven of nine countries from which data were analysed. Hyperhidrosis is an increasingly recognised feature of the Fabry disease phenotype. It is more prevalent in females than in males and often appears in childhood or adolescence. The efficacy of enzyme replacement therapy on this recently recognised symptom should be assessed.

Lumbosacral plexopathy is the equivalent in the lower limbs of neuralgic amyotrophy (also known as Parsonage-Turner syndrome) in the upper limbs. It is well-known in patients with diabetes mellitus, when it is known as Bruns-Garland syndrome.We report the case of a 47-year-old woman who developed a unilateral neuropathy of the leg, neither radicular nor truncal in origin. The slow continuous improvement was not affected by any of the treatments administered.Lumbosacral plexopathy is characterized by intense pain in one or both legs, associated with motor and sensory deficits. Recovery is usually slow (6 to 36 months) and often incomplete. The electrodiagnostic examination shows important acute motor and sensory axonal loss, characterized by denervation and low-amplitude sensory action potential. Treatment generally combines analgesics with narcotic agents, neuropathic pain medication, short-term corticosteroids, and rehabilitation. In the most severe cases, long-term corticosteroids and other immunosuppressive agents may be required. This diagnosis cannot be reached until all other radicular, plexal and truncal origins have been ruled out.

We report the clinical features of two unrelated patients, a 51-year-old woman and a 54-year-old man, presenting proximal myopathy with lipomatosis. In both patients, muscle biopsies showed numerous ragged-red fibers. Molecular analysis were performed with denaturating gradient gel electrophoresis (DGGE) on muscle, blood, hair, buccal and urinary cells. The A8344G mutation of the tRNA-lysine gene of the mitochondrial DNA was detected in all tissues at high levels (more than 80 p cent). None of the patients had a contributive family history, and signs of central nervous system involvement were absent. These observations confirm that lipomatosis may be encountered in mitochondrial disorders and is tightly associated with the A8344G mutation.

Peripheral neuropathy has been widely reported in patients with monoclonal gammopathy (MG), more frequently immunoglobulin M (IgM) or IgG than IgA. Nevertheless, it remains unclear whether this association has clinical or pathogenic relevance. In order to clarify the possible role of IgG/IgA MG in neuropathy, we studied the clinical and electrophysiological features of 15 consecutive patients with polyneuropathy and IgG/IgA-MG, and compared them to those of 40 patients with polyneuropathy associated with IgM-MG, previously reported. Nine middle-aged patients (60%) had a chronic progressive or relapsing demyelinating polyneuropathy (DP) that was clinically and electrophysiologically indistinguishable from classic chronic inflammatory demyelinating polyneuropathy (CIDP) and frequently responded to immunosuppressive treatments, both characteristics supporting a dysimmune process. Six older patients (40%) had a chronic axonal distal polyneuropathy similar to the so-called chronic cryptogenic sensory polyneuropathy: there was no clear relationship with the MG in these patients and the response to immunosuppressive treatments was poor. Several features allowed us to distinguish between polyneuropathies associated with IgG/IgA-MG (IgG/IgA-PN) considered together and polyneuropathies associated with IgM-MG (IgM-PN). In the first group, the proportion of patients with a predominantly sensory clinical picture (27%) was less than that in the second group (75%), and there were fewer changes in nerve conduction studies. In addition, we found that the nine patients with DP associated with IgG/IgA-MG (IgG/IgA-DP) differed from the 31 with DP associated with IgM-MG (IgM-DP): clinical and electrophysiological studies clearly showed that the demyelinating pattern was more heterogeneous in IgG/IgA-DP than in IgM-DP. The spectrum of polyneuropathies associated with IgG/IgA-MG is heterogeneous, including DP, which is similar to classic CIDP, and axonal polyneuropathy, in which the pathogenic role of the MG remains elusive. In addition, IgG/IgA-DP differ from IgM-DP on clinical and electrophysiological grounds, suggesting probable different physiopathological mechanisms.

Peripheral neuropathy is a common feature of many vasculitic syndromes. In some patients, the neuropathy may be the sole manifestation of vasculitis.A 74-year-old lady complained of pain and weakness of the lower limbs. In her history, we noted right optic neuritis, monoclonal gammopathy and dyslipidemia treated by fenofibrate. Clinical examination showed proximal muscle strength deficit of lower limbs, with quadriceps femoral muscles atrophy. Muscle stretch reflexes were absent. There was no deficit in light touch and pain sensation, but proprioception was impaired. There was electromyographic evidence of myopathic impairment with abnormal spontaneous activity. Amplitude of the sensory action potentials was mildly reduced. Laboratory tests were normal. Fenofibrate was stopped, but the clinical symptoms increased. Four months later, another electrophysiological study showed a very reduced amplitude of sensory action potentials. Myopathic impairment was less severe. Nerve biopsy showed inflammation and necrosis of nerve arteries, which lead to the diagnosis of necrotizing vasculitis. A corticosteroid treatment was done. Six months later, clinical and electrophysiological improvement clearly appeared.Histological lesions of vasculitis confined to the peripheral nervous system are those of classic polyarteritis nodosas. There is no systemic involvement nor biological abnormalities, which strengthens the role of nerve and muscle biopsy. The prognosis is good after corticosteroid treatment, which is not the case with systemic vasculitis.

Meningo-radiculitis is the most common peripheral nerve system involvement of Lyme disease. We report the observation of a 73 year-old woman presenting a subacute multiple mononeuropathy and a severe inflammatory syndrome. Diagnosis of Lyme disease was confirmed by a lymphocytic meningitis with positive serologic results in the cerebrospinal fluid. Nerve biopsy showed inflammatory cells spreading along the endoneurium. This case report emphasizes that Lyme disease may present as a multiple mononeuropathy mimicking a vasculitic neuropathy.

To study characteristics of peripheral neuropathies associated with hepatitis C virus infection.A study of two groups of four patients with peripheral neuropathy and infected with hepatitis C virus, and a literature review.We observed four cases of peripheral neuropathy in patients with hepatitis C virus infection with persistent negativity of mixed cryoglobulinemia, and with no purpura, rheumatoid factor, or low C4 level. Neuropathy improved with treatment in three patients between 8 and 28 months after treatment was begun. We report four other observations of peripheral neuropathy with mixed cryoglobulinemia. Worsening of peripheral neuropathy was observed 2 to 13 weeks after initiation of interferon alpha despite improvement of hepatic parameters. After stopping interferon, peripheral neuropathy worsened (one case), stabilized (one case), or improved (two cases).In patients infected with hepatitis C virus, peripheral neuropathy can be due to mixed cryoglobulinemia, periarteritis nodosa, and perhaps hepatitis C virus itself as suggested by our first observations. Low doses of interferon alpha may worsen peripheral neuropathy in patients with mixed cryoglobulinemia, as suggested in our later observations.

Juvenile dermatomyositis does not have, unlike the adult form, a paraneoplastic character.We report the case of a 12-year-old girl who has a typical dermatomyositis complicated by the appearance of very aggressive lesions of lobular panniculitis predominating in the lower limbs. Their refractory character to different treatments (in particular corticosteroids, chloroquine, dapsone, methotrexate, azathioprine, intravenous immunoglobulins and ciclosporin A) will finally lead to the diagnosis of subcutaneous T-cell lymphoma. This will be complicated by a macrophagic activation syndrome leading to death despite chemotherapy.The occurrence of panniculitis during a dermatomyositis should lead to the search for a subcutaneous T-cell lymphoma, especially if the lesions are locally aggressive and refractory to usual treatments, which permits an early chemotherapy.

The thoracic outlet syndrome (TOS) encompasses various clinical entities affecting the neurovascular bundle crossing the thoracic outlet. Unfortunately, this term often proves to be confusing because many of these entities have little in common beyond their known or presumed lesion site. Neurogenic TOS (true TOS) is caused by compression of the lower trunk in the brachial plexus, the cervical ribs or fibrous band. This syndrome is extremely rare. We consider that this neurological form of TOS is a clearly defined neurological syndrome. We report 10 patients with true TOS. All were females. Stating the onset was difficult because symptoms were progressive and insidious. Pain was the most frequently reported symptom. Sensory deficit was slight or absent. All patients showed unilateral severe atrophy of the thenar muscles. Wasting and weakness developed later. A reduced amplitude of ulnar and median compound muscle action potential associated with a normal amplitude of median sensory nerve action and a reduced amplitude of ulnar sensory nerve action potential were indicative of a chronic axon loss in the lower trunk of the brachial plexus. In all cases, we performed medial antebrachial cutaneous sensory nerve action potential, a C8-T1 innervated nerve. The absence of the medial antebrachial cutaneous sensory nerve action potential in 9 patients and a reduction in amplitude of 50 p. 100 compared to the unaffected side in the other patient, indicated the diagnostic value of this easy and reproductible test. It confirmed a C8-T1 post-ganglionic radicular lesion or a lower brachial plexus neuropathy. Radiography showed a rudimentary bilateral cervical rib or an elongated C7 transverse process in all cases. Surgery was performed in the affected side in 7 patients and in each case the lower part of the brachial plexus was found to be stretched and angulated over a fibrous band, which was removed. Pain was relieved after 1 to 4 weeks. A minimal motor improvement was observed after one year. Electrophysiological results were unchanged.

A new type of inflammatory myopathy of unknown etiology has recently been described in France. The myopathy, called macrophagic myofasciitis, had never been described in the literature.In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993. The first 22 cases are described.The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each). Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%). Electromyographic recordings showed the existence of myopathy (35%). Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering. The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes. Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy.A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France. Diagnosis is based on muscular biopsy. Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'études et de recherche sur les maladies musculaires acquises) are in progress.

We report clinical and neurophysiological characteristics of six patients (five women and one man) presenting a pure motor bilateral asymmetric proximal and distal weakness in the setting of radiation therapy for Hodgkin's lymphoma in four cases, carcinoma of the uterus in one, and cancer of the ovary in one. Motor deficit, amyotrophy, cramps, fasciculations and tendinous areflexia were confined to the lower limbs in five patients and to the upper limbs in one. No sensory or sphincter disturbance was noted. The progression of the disease was slow with sometimes secondary stabilization. In some patients, CSF showed a slight increase in protein content with no cell. Blood and MRI medullary examination were normal. Delay between radiation therapy and onset of neurological symptoms range from 6 to 24 years (mean 15). Neurophysiological findings suggest ventral roots proximal conduction blocks. We found an increase F-waves latency, a complete distal palsy contrasting with persistent muscle action potential after distal stimulation, in most of the patients; and an evidence of a conduction block between the erb point and the cervical roots using magnetic stimulation in the patient with upper limbs involvement. Mechanisms and sites of nerve radiation injury remains still unclear. These data could indicate, as it was already reported, a proximal damage involving predominantly the motor roots.

We report 6 patients with true neurogenic thoracic outlet syndrome. All were female and presented unilateral severe atrophy of the thenar muscles. Pain in the affected upper limb was frequently reported, but sensory deficit was slight or absent. Reduced amplitude of ulnar and median compound muscle action potential associated with a normal amplitude of median sensory nerve action potential (SNAP) and a reduced amplitude of ulnar SNAP was indicative of a chronic axon loss in the lower trunk of the brachial plexus. The absence of the medial antebrachial cutaneous SNAP in 5 patients and a reduction in amplitude compared to the unaffected side in the other patient indicated a C8-T1 postganglionic radicular lesion or a lower brachial plexus neuropathy. Radiography showed a rudimentary bilateral cervical rib or an elongated C7 transverse process in all cases. Surgery was performed, and in each case the lower part of the brachial plexus was found to be stretched and angulated over a fibrous band, which was removed. Pain was relieved after 1-4 weeks, but at 1 year, there was only minimal motor improvement and the electrophysiological results were unchanged.

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.

Charcot-Marie-Tooth (CMT) disease is the most frequent inherited peripheral motor and sensory neuropathy characterised by chronic distal weakness with progressive muscular atrophy and sensory loss of the distal extremities. The dominant form of the disease is genetically heterogeneous but only one locus has been identified on chromosome 8q13-q21.1 for autosomal recessive CMT. By homozygosity mapping in a large Algerian kindred, we have assigned a second locus for autosomal recessive CMT to chromosome 5q23-33. Linkage analysis demonstrated that the same locus is involved in a second Algerian family with a demyelinating CMT. Haplotype reconstruction and determination of the minimal region of homozygosity restricts the candidate region to a 4 cM interval.