[Mechanisms leading to muscle degeneration: molecular mechanisms and therapeutical forecasts]. / Dégénérescence programmée de maladies musculaires: aspects moléculaires et previsions thérapeutiques.

In inclusion body myositis (IBM), there is muscular amyloidogenesis and inflammation. A related disorder is due to alterations in the ubiquitin pathway involving the valsolin-containing protein leading to IBM, dementia and Paget's disease. Alteration in the dystrophin glycoprotein complex leads to several muscular dystrophies (MD), and the pathogenesis of dystrophin related MD as well as certain limb girdle MD are discussed. Therapeutic strategies involving inhibition of proteolytic cascades as well as inhibition of a negative regulator of muscle growth (myostatin) are briefly introduced. Finally, molecular aspects of the most common form of adult myopathy, myotonic MD, are discussed. This disease is caused by an aberrant splicing mechanism and interference thereof may be useful in designing therapeutic strategies.

Localization of coxsackie virus and adenovirus receptor (CAR) in normal and regenerating human muscle.

The primary receptor for Adenovirus and Coxsackie virus (CAR) serves as main port of entry of the adenovirus vector mediating gene transfer into skeletal muscle. Information about CAR expression in normal and diseased human skeletal muscle is lacking. C'- or N'-terminally directed polyclonal antibodies against CAR were generated and immunohistochemical analysis of CAR on morphologically normal and regenerating human skeletal muscle of children and adults was performed. In morphologically normal human muscle fibers, CAR immunoreactivity was limited to the neuromuscular junction. In regenerating muscle fibers, CAR was abundantly co-expressed with markers of regeneration. The function of CAR at the neuromuscular junction is currently unknown. Co-expression of CAR with markers of regeneration suggests that CAR is developmentally regulated, and may serve as a marker of skeletal muscle fiber regeneration.

Chronic immune sensory polyradiculopathy: a possibly treatable sensory ataxia.

BACKGROUND: Chronic inflammatory neuropathies can present with a sensory ataxia due to involvement of dorsal root ganglia (DRG) or sensory nerves. Selective inflammatory involvement of sensory nerve roots proximal to the DRG has been postulated. METHODS: The authors identified 15 patients with a sensory syndrome and normal nerve conduction studies. Sensory nerve root involvement was suggested by either somatosensory evoked potential (SSEP) or imaging abnormalities. CNS disease was excluded. RESULTS: All patients had gait ataxia, large fiber sensory loss, and paresthesias, and nine had frequent falls. The disease course was chronic and progressive (median duration 5 years, range 3 months to 18 years). Sural sensory nerve action potential amplitudes were preserved and SSEP abnormalities were consistent with sensory nerve root involvement. Five patients had enlargement of lumbar nerve roots on MRI with enhancement in three. The CSF protein was elevated in 13 of 14 patients tested. Three patients had lumbar sensory rootlet biopsies that showed thickened rootlets, decreased density of large myelinated fibers, segmental demyelination, onion-bulb formation, and endoneurial inflammation. Six patients who required aids to walk were treated with immune modulating therapy and all had marked improvement with four returning to normal ambulation. CONCLUSION: Based on the described clinical features, normal nerve conduction studies, characteristic somatosensory evoked potential (SSEP) abnormality, enlarged nerve roots, elevated CSF protein, and inflammatory hypertrophic changes of sensory nerve rootlet tissue, we suggest the term chronic immune sensory polyradiculopathy (CISP) for this syndrome. This condition preferentially affects large myelinated fibers of the posterior roots, may respond favorably to treatment, and may be a restricted form of chronic inflammatory demyelinating polyradiculoneuropathy.

The effect of aging on postural stability: a cross sectional and longitudinal study.

AIMS OF THE STUDY: Only a good knowledge of the effects of age on postural stability allows differentiating between physiological aging and pathologies leading to its impairment. The aims of this study were to define the posturographic parameters which best reflected the effects of aging on postural stability and to determine the slope of postural stability impairment related to aging. PATIENTS AND METHODS: Postural stability of 50 normal volunteers aged 25-83 years (55.4) was studied with one Kistler force plate. Subjects were asked to stand for 30 s on two-legged stance, eyes open then closed. The center of pressure displacement (COPd) and velocities (COPv), in the antero-posterior (x) and the medio-lateral (z) axis, the sway axis, and the integral of COP displacement vs. time were computed. Eleven subjects were retested at 3 and 6 months to estimate the reliability of posturographic measurements. In addition, 28 subjects aged 25-83 years (60.2) were retested 2.2 years after their first posturographic assessment. RESULTS: COPxv best reflected postural stability impairment with aging. Closure of the eyes increased the variance of the results. This change was higher in subjects more than 60 years old: 0.019-0.157 cm2 s(-2) than in younger ones: 0.011-0.043 cm2 s(-2). Retesting at 3 and 6 months showed a reliability of 79%. According to the cross-sectional part of the study, the slope of postural stability impairment with aging was estimated at 0.0038 cm/s/year. These results were confirmed by the longitudinal part of the study, which showed that COPxv increased from 0.66-0.75 cm/s/year (P = 0.0001) (slope = 0.0041 cm/s/year). CONCLUSION: (1) Measurement of COPxv, on two-legged stance, is a simple and reliable way to assess postural stability. (2) Thanks to both a cross sectional and a longitudinal study, the rate of postural stability impairment due to aging was precisely estimated, which will be useful to help distinguishing between the part of postural stability impairment attributable to aging from the one due to neuro-degenerative diseases.

Endplate dysfunction causing respiratory failure in a patient with prior paralytic poliomyelitis.

A 56-year-old man with late amyotrophic sequelae from poliomyelitis experienced progressive dyspnoea requiring intubation and artificial ventilation in the intensive care unit. Repetitive stimulation studies showed a marked decrement of the trapezius muscle response reversible with edrophonium. Ventilatory function considerably and lastingly improved under anticholinesterase treatment. In the absence of biological evidence for autoimmune myasthenia gravis, it is suggested that a mechanism implying endplate dysfunction related to postpolio syndrome. Repetitive stimulation procedure should be considered in postpolio syndrome patients as some of them may benefit from anticholinesterase treatment.

Subarachnoid hemorrhage: a rare presentation of cerebral venous thrombosis.

Because of its large spectrum of clinical manifestations, diagnosis of cerebral venous thrombosis may be very difficult. Since appropriate treatment influences prognosis, early recognition of this condition is extremely important. We report a subarachnoid hemorrhage as a rare initial manifestation of cerebral venous thrombosis. A 58-year-old woman was admitted with severe headache of sudden onset, neck stiffness, dysarthria, and ataxia. Computed tomography scan showed a subarachnoid hemorrhage in the right posterior fossa. Magnetic resonance imaging coupled with magnetic resonance angiography revealed right transverse/sigmoid sinus thrombosis with hemorrhagic infarction of the right cerebellar hemisphere leading to a pseudotumoral appearance and displacing the fourth ventricle. Anticoagulant treatment resulted in rapid clinical recovery and in resolution of the radiological signs of infarction and of the subarachnoid and subdural hemorrhages.

Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion.

An early sign of human myoblast commitment to fusion is the expression of a non-inactivating delayed rectifier K+ current, I(K(NI)), and an associated membrane potential hyperpolarization. We have isolated the full-length coding region of a human ether-a-go-go K+ channel (h-eag) from myoblasts undergoing differentiation. The h-eag gene was localized to chromosome 1q32-41, and is expressed as a approximately 9 kb transcript in myogenic cells and in adult brain tissue. Forced expression of h-eag in undifferentiated myoblasts generates a current with remarkable similarity to I(K(NI)) indicating that h-eag constitutes the channel responsible for this current in vivo.