Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins. In addition to the 16 mutations described previously, we report 19 novel mutations. These data indicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support the wide heterogeneity of molecular defects in this rare disease.

[Dropped head syndrome: diagnostic discussion apropos of 3 cases]. / Syndrome de la tête tombante: discussion diagnostique à propos de 3 cas.

We report three cases presenting mainly with neck extensor weakness, or dropped head syndrome, revealing respectively myasthenia gravis, amyotrophic lateral sclerosis and non-inflammatory neck extensors myopathy. We discuss the different diagnosis of this rare syndrome and this late onset localized myopathy of unknown etiology.

[Critical study of electrophysiologic techniques for exploration of carpal tunnel syndrome]. / Etude critique des techniques électrophysiologiques d'exploration du syndrome du canal carpien.

Carpal tunnel syndrome is the most frequent entrapment neuropathy. Nerve conduction studies and electromyography are useful to appreciate the localization and the degree of nerve involvement, and help to the therapeutic management. Various electrophysiological procedures may be used and are reviewed. For each of them, positive (sensitivity and specificity) and negative points (technical difficulties, errors and false positive) are reported. A guideline is proposed.

Modelization of motor nerve conduction velocities for Charcot-Marie-Tooth (Type-1) patients. CMT-France Network.

Charcot-Marie-Tooth (CMT) type-1 (CMT1) neuropathy is characterized by peripheral nerve demyelination and has been divided into several subtypes. The most frequent among these, subtype 1A, is related to a microduplication of the region p11.2 of chromosome 17. This region contains the PMP-22 gene which is involved in peripheral nerve myelination. Since motor nerve conduction velocity (MNCV) is closely related to nerve myelination, we compared type-1A patient MNCVs versus non-A CMT1 patient MNCVs, in 57 CMT1A patients and 21 non-A type-1 patients. Patients with the 17p11.2 duplication have MNCVs that are significantly more reduced (about 20 m/s) compared to patients without the 17p11.2 duplication (about 30 m/s). This study also permits a model of the MNCV in the median nerve (MedMNCV) of CMT1 patients, with age, gender and molecular status as parameters. Furthermore, in order to help clinicians to diagnose subtypes of CMT1 patients, the probability for type 1A is modeled as a function of MedMNCV only.

DNA analysis as a tool to confirm the diagnosis of asymptomatic hereditary neuropathy with liability to pressure palsies (HNPP) with further evidence for the occurrence of de novo mutations.

We performed DNA analysis in four families with hereditary neuropathy with liability to pressure palsy (HNPP). An interstitial deletion of the 17 p11.2 region was found in typically affected patients as well as in as yet asymptomatic patients. The opportunity for an individual genotyping permitted to ascertain a de novo deletion in one clinically affected case with no relevant familial history. DNA analysis thus becomes the most sensitive tool in diagnosing HNPP, since potentially affected patients may lack either informative familial history, or clinical symptoms or even suggestive EMG or histopathological data (tomaculas).

Fine mapping of randomly distributed multiple deletions of mitochondrial DNA in a case of chronic progressive external ophthalmoplegia.

Multiple deletions of mitochondrial DNA have been detected by Southern blotting in the skeletal muscle of a 42-year-old woman with chronic progressive external ophthalmoplegia. A PCR method, using several combinations of primers covering the whole mtDNA as well as sequence analysis, disclosed the wide spectrum of these multiple deletions differing in size, location and sequence at the breakpoint junction. Most involved the major region between the two replication origins. However, three deletions affected the minor region and lacked either the light strand origin of replication or the heavy strand promoter. These data suggest an impairment of mtDNA replication leading to illegitimate recombination and extensive damage of mtDNA.

Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families.

Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases involving the abnormal function of ion channels. This group of muscle diseases also comprises hyperkalemic periodic paralysis and paramyotonia congenita, both sodium-channel diseases, and myotonia congenita, a chloride-channel disorder. HypoPP is characterized by acute attacks of muscle weakness concomitant with a fall in blood potassium levels. We recently localized the hypoPP locus (hypoPP1) to chromosome 1q31-32, in an interval where the alpha 1 subunit of the dihydropyridine receptor calcium channel (CACNL1A3) also maps. Subsequently, deleterious mutations in the voltage-sensor segment S4 were found, establishing the dihydropyridine receptor CACNL1A3 as the causative gene for hypoPP. In this paper, we report the study of 16 hypoPP families of Caucasian origin. We found only two mutations--Arg528His and Arg1239His--that cosegregated with hypoPP, each in half of the families. Analysis of the clinical characteristics of both groups of families demonstrated that incomplete penetrance is a distinctive feature of the Arg528His mutation. Using dinucleotide repeats contained within or close to the dihydropyridine receptor gene, in conjunction with evidence of a de novo Arg1239His mutation, we show that a founder effect is unlikely to account for the two predominant mutations.

Carpal tunnel syndrome in Mucopolysaccharidoses. A report of four cases in child.

Carpal tunnel syndrome (CTS) is very uncommon in childhood. Sixty-five cases are reported in the literature, principally due to metabolic diseases. In Mucopolysaccharidoses, prospective studies (Wraith and Alani, 1990) found a bilateral CTS in about 90%. We report four cases of Mucopolysaccharidoses, diagnosed on clinical and biological data (two cases of Hurler disease, and two cases of Hunter disease), in children aged less than five years. Each child had claw hands, without thenar atrophy. Median nerve conduction studies and electromyography confirm the CTS. Motor and sensory nerve conductions are normal in other nerves. Concentric needle studies show in two cases, on abductor pollicis brevis, spontaneous activities as repetitive discharges, fasciculations and multiplets. Median nerve stimulations reveal responses with late potentials during 70 ms due to reinnervation. The physiopathology of those carpal tunnel syndromes is discussed.

[Hereditary myasthenic syndromes with late onset. Value of electrophysiological tests]. / Syndromes myasthéniques héréditaires à révélation tardive. Intérêt des explorations électrophysiologiques.

A myasthenic syndrome was diagnosed in 3 female patients aged 37, 47 and 56 years. The symptoms were first noticed in childhood, and at 16 and 25 years. Respectively weakness and atrophy of finger extensor muscles were present in all patients. In 2 of them scapular and cervical muscles were involved. Weakness was markedly increased by cold in every patient. Similar symptoms were noted in first degree relatives in all cases. Single nerve stimulus elicited a repetitive compound muscle action potential in hand muscles. Repetitive nerve stimulation induced a myasthenic decrement in finger extensor muscles. SFEMG studies demonstrated increased jitter with frequent blockings. Genetic, clinical and electrodiagnostic data were consistent with the hypothesis of the so-called "Slow-Channel" myasthenic syndrome. As 2 of these patients were considered to have "unknown myopathy" the use of careful nerve stimulation tests is advocated in such cases.

[Surgical applications of anatomical variations of the median nerve at the wrist]. / Applications chirurgicales des variations anatomiques du nerf médian au poignet.

After a brief report of median nerve anatomy at wrist, authors describe terminal variations of its distribution. Classic description of five terminal sensitive and motor median nerve branches is not constant. Many anatomic variations have been reported and so many, classifications proposed. Lantz' classification is useful, it may be divided in four groups. Other anatomic variations concern cutaneous palmar nerve branch and different nervous anastomosis. Advantage of this anatomic study is incidence of variations on surgical access of carpal tunnel. Those nervous variations of median nerve at wrist are frequent, unknown and wrong indexed and may be so many "anatomic traps" for surgeon.

[Lambert-Eaton syndrome and small cell cancer. Etiopathogenic considerations apropos of 2 cases]. / Syndrome de Lambert-Eaton et cancer à pétites cellules. Considérations étiopathogéniques à propos de deux observations.

The authors report two cases of Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma. Following the observations, the clinical diagnosis of this syndrome is considered. We discuss the autoimmune pathogenesis and the relation between paraneoplastic syndrome and small cell cancer. This syndrome is caused by autoantibodies that block the voltage-dependent calcium channels at motor nerve terminals. Small cell carcinoma cells appear to express calcium channels, suggesting that autoantibody production may be triggered by tumor calcium channels determinants. The autoimmune paraneoplastic syndrome theory refers to cross-antigenicity.

[Paralysis of abdominal muscles caused by Lyme disease]. / Paralysie des muscles larges de l'abdomen due a une maladie de Lyme.

A 67-year old patient with meningoradiculitis due to Borrelia Burgdorferi presented with unilateral trunk dysesthesias and severe asymmetrical abdominal distension. The causes of abdominal wall paralysis are reviewed.

[Neurological complications caused by gold salts. Nosologic report apropos of a case]. / Complications neurologiques des sels d'or: discussion nosologique à propos d'un cas.

Gold therapy is responsible for many neurological complications. We report a case presenting with the clinical and electrophysiological characteristics of neuromyotonia, polyradiculoneuritis and Morvan's fibrillary chorea. The various neurological complications of gold therapy and the possible relationships between these different syndromes are discussed.

Neurophysiological explorations in cervicobrachial neuralgia.

The various electrophysiological techniques which can be used in cervicobrachial neuralgia and their respective advantages and limitations are described. Beside the conventional electromyography and electrostimulation techniques, the indications for radicular motor and somesthetic evoked potentials are discussed.

[Electrophysiologic data on myasthenic syndromes of the Lambert-Eaton type. A series of 23 cases]. / Données électrophysiologiques dans les syndromes myasthéniformes de type Lambert-Eaton. A propos d'une série de 23 cas.

The electrophysiological data of 23 adult patients with Lambert-Eaton myasthenic syndrome (LEMS) have been reviewed. Lung carcinoma was disclosed in 17. In six cases with an EMG follow-up ranging between one and 17 years no carcinoma was detected. The results of repetitive nerve stimulation test (RNS) were not statistically different between the 2 groups. Low CMAP ulnar amplitude was present in all patients (mean: 1.7 mV). Decremental response at low rate of stimulation (3 Hz) was present in 17/20 (means: 30%). An abnormal incremental response at high rate of stimulation was present in all cases (mean: 826%). The authors emphasize the interest of a 50 Hz stimulation for 4 s. Increase of the 'F-wave' amplitude was noticed in some cases. Electrophysiological changes suggestive of an associated mild neuropathy were noticed in eight patients but H-reflex was present in 3/3 cases. SFEMG abnormalities were found in 6/6 cases. In one case, stimulated SFEMG showed more blockings and an increased jitter with low rate of stimulation. In one case the electrical pattern of RNS could be misinterpreted as myasthenia gravis in one tested muscle only. The author's results suggest that CMAP amplitude and RNS test could be used to appreciate the short-term improvement of LEMS with treatment and in some cases for the long-term follow-up.

[Suprascapular nerve entrapment at the spinoglenoid notch]. / Syndrome canalaire du nerf sus-scapulaire dans le défilé spino-glénoïdien.

The suprascapular nerve passes through the spinoglenoid notch with a risk of entrapment. This results in distal nerve lesion characterized by isolated paralysis of the infraspinatus muscle and, most often, by shoulder pain. We report 7 clinical and electromyographical cases of pure infraspinatus muscle paralysis. The value of the electrodiagnosis, which demonstrated prolonged suprascapular distal nerve latencies (over 5 milliseconds) in the infraspinatus muscle affected while latencies were normal in the supraspinatus muscle, is emphasized. Mechanical factors were associated with paralysis in 5 cases. Compressive synovial cysts were found in 2 patients operated upon. Surgical enlargement of the spinoglenoid notch regularly and rapidly relieves pain and sometimes helps in recovery of the infraspinatus muscle.

[Lambert-Eaton syndrome: clinical and electrophysiological study of 18 cases associated with lung cancer]. / Syndrome de Lambert-Eaton: étude clinique et électrophysiologique de 18 cas associés à un cancer du poumon.

The clinical and electrophysiological data of 18 consecutive adult patients with paraneoplastic Lambert-Eaton myasthenic syndrome (LMES) have been reviewed. The cancer associated with LEMS was small-cell lung carcinoma (SCLC) in 15 cases and epidermoid lung carcinoma in 3 cases. The main clinical neurological features were proximal lower limb weakness (100%), depressed tendon reflexes (94%) and dryness of the mouth (66%). The results of repetitive nerve stimulation (RNS) were not statistically different in the paraneoplastic LEMS group and in a group of 6 LMS patients in whom no carcinoma had been detected. Low-amplitude compound muscle action potential (CMAP) was present in all cases; decremental response at low stimulation rates was present in 13/15 cases. An abnormal incremental response at high stimulation rates was observed in all cases. A close correlation between CMAP amplitude and clinical condition was found in 4 cases during the long-term follow-up. In one patient the RNS electrical pattern could be misinterpreted as myasthenia gravis in only one muscle tested. We underline the usefulness of a 50 Hz stimulation during 4 seconds to establish the diagnosis unequivocally, and that of post-exercise facilitation in routine detection among an SCLC population. Our results suggest that CAMP amplitude and RNS test could be used to evaluate the short-term improvement of LMS under treatment and, in some cases, for the long-term follow-up. The infraclinical axonal neuropathy detected in 8 patients probably was another associated autoimmune paraneoplastic complication.