J.-F. Hurtevent

Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q)

Objective: To report a family with X-linked Charcot-Marie-Tooth disease (CMTX) with proven connexin 32 (Cx32) mutation associated with deafness. Methods: Twelve members of a CMTX family were examined clinically. Electromyography and sensory and motor conduction studies were performed in three men, two women, and a 7-year-old boy. Audiometric testing was carried out in the three men, one woman, and an 8-year-old girl. Molecular genetic analysis was performed in six men and five women. Results: The three men and the 7-year-old boy had the usual sensorimotor deficit and pronounced reduction of motor nerve conduction velocity. A 15-year-old boy was asymptomatic and had only areflexia. The women had impairment of vibratory sensation and slight slowing of nerve conduction velocities. Sensorineural deafness was observed in the three men and in an 8-year-old girl without any motor or sensory deficit. Molecular genetic analysis revealed a new missense mutation located in codon 142 of the Cx32 gene leading to the substitution of an arginine by a glutamine. Conclusion: CMTX due to Cx32 mutations often shows interfamilial and intrafamilial phenotypic variation, which is also the hallmark of this family. The sensorineural deafness observed in this family suggests that Cx32 could play an important role in the auditory pathway.

Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene

Axonal forms of Charot-Marie-Tooth disease, either dominantly or recessively inherited, are clinically and genetically heterogeneous. We describe the clinical and electrophysiological characteristics of an axonal autosomal recessive form of Charot-Marie-Tooth disease in a French family, associated with a new mutation of the ganglioside-induced differentiation-associated protein-1 gene (GDAP1). Two sisters, born to non-consanguineous parents, presented severe proximal and distal sensorimotor deficit, areflexia, pes cavus, scoliosis and vocal cord and diaphragm paralysis. They lost ambulation in the third decade and since then they have been wheelchair bound. Nerve conduction studies were consistent with an axonal neuropathy. Clinical and electrophysiological examination of their parents and their brother was normal. Genetic analysis revealed a homozygous thymidine deletion at nucleotide position 558 resulting in a frameshift at codon 186 and a stop codon at position 205. This axonal form of Charot-Marie-Tooth disease associated with a new GDAP1 mutation is recessively inherited and is characterized by a severe phenotype, since patients become wheelchair bound in the third decade, and present vocal cord and diaphram paralysis, which may be missed as they had no respiratory symptoms until the third decade.

Visual evoked potentials study in chronic idiopathic inflammatory demyelinating polyneuropathy

BACKGROUND The frequency of the association between chronic demyelinating inflammatory polyneuropathy (CIDP) and central nervous system (CNS) demyelinating lesions is probably underestimated. OBJECTIVE To investigate the occurrence of combined central and peripheral demyelination in CIDP patients and to correlate visual evoked potential (VEP) abnormalities with CNS demyelinating lesions, observed on brain magnetic resonance imaging, and antibodies against glycolipids. METHODS Nerve conduction studies, brain MRI and antibodies against glycolipids were prospectively studied in 17 patients who fulfilled the diagnostic criteria proposed for CIDP (Cornblath DR, Asbury AK, Albers JW, Feasby TE, Hahn AF, McLeod JG, Mendell JR, Parry GJ, Pollard JD, Thomas PK. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology, 1991;41:617-618). VEPs were performed in each case before and after 6 months treatment with either intravenous immunoglobulins (IVIG) or steroids. RESULTS Eight patients (47%) had increased latencies in at least one eye or showed increased interocular latency difference. Four patients (23%) presented a significant high signal intensity on T2-weighted brain MRI images. Of these 4 patients, 3 had prolonged VEP latency. Two patients with delayed VEP latency had antibodies against GM1, and SGLPG and anti-sulfatides, respectively. One patient with normal VEPs also had antibodies to GM1. VEP results were not significantly modified after treatment, either with steroids or IVIG. CONCLUSION This study confirmed the high frequency of abnormal VEPs in CIDP patients, and found that they are poorly correlated with CNS demyelinating lesions and antibodies against glycolipids. The VEP abnormalities of these patients may be explained by the susceptibility to immune-mediated damage of both the peripheral nervous system and the optic nerve.

A simple functional marker to predict the need for prolonged mechanical ventilation in patients with Guillain-Barré syndrome

IntroductionPatients suffering from Guillain-Barré syndrome (GBS) may frequently develop an acute respiratory failure and need ventilatory support. Immune therapy using plasma exchange or immunoglobulins has modified the natural course of the disease and by decreasing the length of the plateau phase, may induce a rapid improvement in ventilatory function. However a substantial proportion of patients still require prolonged mechanical ventilation (MV) and tracheotomy. The present study was designed to search for simple functional markers that could predict the need for prolonged MV just after completion of immune therapy.MethodsWe analyzed the data collected in a cohort of patients with GBS admitted to the intensive care unit (ICU) of our university hospital between 1996 and 2009. Demographic, clinical, biological and electrophysiologic data, results of sequential spirometry, and times of endotracheal intubation, tracheotomy, and MV weaning were prospectively collected for all patients. Sequential daily neurological testing used standardized data collection by the same investigators all along the study period. Results were compared by single and multiple regression analysis at admission to ICU and at the end of immune therapy, according to the need and duration of MV (≤ or > 15 days).ResultsSixty-one patients with severe GBS were studied. Sixty-six percent required MV (median length: 24 days). The lack of foot flexion ability at ICU admission and at the end of immunotherapy was significantly associated with MV length > 15 days (positive predictive value: 82%; odds ratio: 5.4 [1.2 - 23.8] and 82%; 6.4 [1.4 - 28.8], respectively). The association of a sciatic nerve motor conduction block with the lack of foot flexion at the end of immunotherapy was associated with prolonged MV with a 100% positive predictive value.ConclusionsIn patients admitted to ICU with Guillain-Barré syndrome and acute respiratory failure, the lack of foot flexion ability at the end of immune therapy predicts a prolonged duration of MV. Combined with a sciatic motor conduction block, it may be a strong argument to perform an early tracheotomy.

The first European family with tibial muscular dystrophy outside the Finnish population

We report the first European tibial muscular dystrophy (TMD) family outside the Finnish population. Clinical examination showed late onset distal leg myopathy similar to the description of TMD. A molecular genetic study was made owing to the very recent TMD linkage findings on chromosome 2q31. All five clinically affected patients segregated a specific haplotype for the locus, whereas two unaffected patients had different haplotype. The results of this family without Finnish ancestors show that TMD exists outside the Finnish population.

Phrenic nerve palsy as a feature of chronic inflammatory demyelinating polyradiculoneuropathy

We report four patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who presented with phrenic nerve palsy, which was unilateral in two instances. The two patients with bilateral phrenic nerve involvement required mechanical ventilation. After treatment with intravenous immunoglobulins (IVIg) or steroids, the sensorimotor deficit and respiratory parameters improved in three patients, but the fourth patient remained ventilator dependent and died from pulmonary infection. Although rare, phrenic nerve palsy may be a feature of CIDP and may be responsive to treatment with IVIg or steroids. Muscle Nerve 27: 497–499, 2003

Maladie de Parkinson, camptocormie et myosite focale paraspinale

Resume Introduction La camptocormie, definie comme une inclinaison majeure du tronc sur le bassin cedant en decubitus, est reconnue comme une complication rare mais classique de la maladie de Parkinson. Observation Nous rapportons le cas d’un patient âge de 49 ans qui developpa progressivement un syndrome parkinsonien akineto-rigide et tremulant, et une camptocormie. L’imagerie par resonance magnetique des muscles dorso-lombaires, l’electromyogramme et la biopsie musculaire confirmerent l’existence d’une myosite focale paraspinale lateralisee a gauche. Discussion Plusieurs cas publies recemment permettent de decrire un tableau clinique coherent dont ce sujet est representatif : patients de sexe masculin, plutot jeunes, arrives au stade des fluctuations motrices, traites par agoniste et L-Dopa, installant en 1 an un tableau severe, tres invalidant et non modifie par les traitements anti-parkinsoniens. Conclusion Des etudes systematiques seront necessaires pour expliciter le lien qui peut unir ces differents processus pathogeniques a priori si eloignes.

Immunological profiles determine neurological involvement in Sjögren's syndrome

BACKGROUND Up to 68% of patients with primary Sjögrens syndrome (pSS) undergo neurological complications, and evidence for distinct immunological subgroups is emerging. We sought to determine systemic and immunological profiles associated with neurological manifestations. METHODS 420 patients fulfilling the 2002 American-European pSS criteria were retrospectively analyzed. Neurological manifestations were diagnosed through clinical, biological, electrophysiological, and imaging findings. Biographical, clinical, and laboratory data were compared. RESULTS Within 93 (22%) patients with neurological manifestations, peripheral and central nervous systems were involved in 66% and 44%, respectively. Raynauds phenomenon, cutaneous vasculitis, renal involvement, and cryoglobulinemia were associated with sensorimotor neuropathy and mononeuritis multiplex (p<0.05). Conversely, pure sensory neuropathy occurred without extraglandular manifestation, and without anti-Ro/SSA antibodies (p<0.05). All neurological manifestations were associated with increased use of corticosteroids and immunosuppressive drugs (p<0.05). CONCLUSIONS In pSS, patients with sensorimotor neuropathies and pure sensory neuropathies have distinct extraglandular and immunological profiles.

A new case of autosomal dominant myotonia associated with the V1589M missense mutation in the muscle sodium channel gene and its phenotypic classification

We report a phenotype associated with the Val1589Met substitution in SCN4A gene in a French family which would be better classified as paramyotonia congenita. The proband was a 48-year-old woman, who described muscle stiffness and occasional flaccid weakness, both symptoms being induced by exercise, cold and heat. Severe muscle stiffness affected facial, oropharyngeal and limb muscles leading to transient paralysis of these muscles. One sister, two nephews and the son of the proband had similar symptoms. Molecular analysis of the muscle sodium channel gene (SCN4A) by nucleotide sequencing revealed a G-to-A transition of cDNA nucleotide at position 4765 predicting a substitution of methionine for valine at position 1589. This shows that the Val1589Met mutation in the SCN4 gene may cause different phenotypes, either potassium-aggravated myotonia or paramyotonia congenita. Familial or individual factors other than the missense mutation per se influence the expression of the disease in sodium channel disorders.

Congenital myopathy with central cores and fingerprint bodies in association with malignant hyperthermia susceptibility.

A 26-year-old man had proximal weakness in the shoulder and the pelvic girdle since infancy. His sister, aged 16 years, presented a similar phenotype with more pronounced pelvic weakness. His muscle biopsy showed dense non-reducing inclusions which had a lamellar pattern at the ultrastructural level. These structures showed the typical features of fingerprint inclusions which were widely distributed in the fibers. Several central cores and other structural changes such as Z-line streaming were also observed. In view of the central cores, the male patient was investigated for malignant hyperthermia susceptibility. After exposure to halothane or caffeine, unusual intense contractures were observed on fiber preparations. The coexistence of central cores associated with fingerprint inclusions is suggestive of mixed congenital myopathy, which is in our case associated with malignant hyperthermia susceptibility.