The calcium homeostasis and the membrane potential of cultured muscle cells from patients with myotonic dystrophy.

Using the fluorescence indicator, quin2, we compared the cytoplasmic Ca2+ concentration ([Ca2+]i) of cultured myotubes obtained from control subjects and myotonic dystrophy (MyD) patients. In Ca2(+)-free buffer the [Ca2+]i of the cultured MyD muscle cells was not significantly different from that of the control cells. In the presence of 1 mM external Ca2+ the cultured MyD muscle cells showed a significantly higher [Ca2+]i, which was due to the influx of Ca2+ through voltage-operated nifedipine-sensitive Ca2+ channels. In the presence of external Ca2+, MyD myotubes did not respond to acetylcholine, whereas control myotubes showed a transient increase in [Ca2+]i after addition of acetylcholine. This increase was inhibited by the addition of nifedipine. The differences in Ca2(+)-homeostasis between cultured MyD muscle cells and control cells were not due to differences in the resting membrane potential or the inability of the MyD cells to depolarize as a response to acetylcholine. Therefore, cultured MyD muscle cells exhibit altered nifedipine-sensitive voltage-operated channels which are active under conditions in which they are normally present in the inactive state, and which are unable to respond to depolarization caused by acetylcholine.

Familial progressive vestibulocochlear dysfunction.

A kindred is presented in which several members had complaints of head movement-dependent oscillopsia due to acquired vestibular areflexia in combination with progressive hearing loss. History was noncontributory for other neurologic or otologic diseases (including infectious diseases) or use of neuro-ototoxic drugs. The pedigree suggests autosomal dominant inheritance.

Autosomal recessive form of hereditary motor and sensory neuropathy type I.

We studied pathologic changes in sural nerve biopsies from four patients with probable autosomal recessive (AR) hereditary motor and sensory neuropathy (HMSN) type I with a median motor nerve conduction velocity greater than 10 m/sec, comparing them with the pathologic features in autosomal dominant (AD) HMSN type I. The four recessive and two sporadic cases showed segmental demyelination. However, the classic onion bulbs of concentric Schwann cell processes, which occur in AD type I, were rare; many axons, also of a smaller size, were surrounded by onion bulbs of basal laminae. Schwann cells of the myelinated and unmyelinated types were involved in these onion bulb formations. Patients with HMSN type I who have many basal lamina onion bulbs should be considered as having AR inheritance.

Allelic heterogeneity in hereditary motor and sensory neuropathy type Ia (Charcot-Marie-Tooth disease type 1a).

The most frequently found mutation in autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) is a large duplication on chromosome 17p11.2 containing probes VAW409R3, VAW412R3, and EW401. We investigated a family with severe features of HMSN I, and demonstrated the absence of this duplication by a quantitative analysis of the hybridization signals of VAW409R3 and VAW412R3. Linkage analysis, however, revealed linkage with probe VAW409R3a (lod score, 3.22), which demonstrates the existence of allelic heterogeneity within the HMSN Ia locus. These findings have implications for clinical practice and for investigating the identity of the HMSN Ia gene.

Dantrolene sodium does influence the second-wind phenomenon in McArdle's disease. Electrophysiological evidence during exercise in a double-blind placebo-controlled, cross-over study in 5 patients.

Five patients with McArdle's disease entered a double-blind, placebo-controlled, cross-over study of dantrolene sodium. None of the patients experienced beneficial effect of dantrolene sodium medication. Each patient performed 2 exercise tests. Surface EMG during exercise tests without medication showed a temporary increase in EMG activity during the adaptation phase. Quite unexpectedly however, in view of the negative clinical results, this electrophysiological manifestation of muscle fatigue during the adaptation phase diminished or disappeared in all patients investigated when dantrolene sodium was used.

Hereditary vestibulo-cochlear dysfunction and vascular disorders.

A family is described with a progressive autosomal dominant vestibulocochlear dysfunction resulting in a Dandy syndrome, head movement dependent oscillopsia and hearing loss. The history was negative for other neurological or otological diseases (including infectious diseases) or use of neuro-ototoxic drugs, except for a high incidence of vascular disorders (hypertension, stroke, and heart infarction).

Hereditary neuropathy with liability to pressure palsies: a clinical, electroneurophysiological and morphological study.

Clinical, electroneurographic and myographic studies were performed on 99 patients of 13 families having hereditary neuropathy with liability to pressure palsies (HNPP) and on 116 relatives. Diagnosis was confirmed in all families by a nerve biopsy of the index case. Large focal myelin thickenings (tomacula) were found in nerve biopsies of affected persons, whether or not pressure palsies had occurred. By using three electroneurographical parameters it was possible to discriminate between asymptomatic patients and unaffected relatives. Complaints sometimes mentioned in literature as being associated with HNPP such as low back pain, brachialgia and short lasting paraesthesia are not related to HNPP. The hereditary transmission is autosomal dominant with total penetration but variable expression.

In vitro contraction test for malignant hyperthermia in patients with unexplained recurrent rhabdomyolysis.

A few cases of non-anaesthetic-induced rhabdomyolysis in humans, predisposed to malignant hyperthermia (MH), have been described in literature. We studied a group of 6 consecutive patients with unexplained and recurrent attacks of rhabdomyolysis with the test used to determine susceptibility to MH, the in vitro contraction test (IVCT). The results of the IVCT showed 5 of these 6 patients to be MH susceptible. In cultured muscle cells from one of these patients a disturbed calcium homeostasis could be demonstrated. The relation between MH and recurrent rhabdomyolysis is discussed.

Early morphological features in dominantly inherited demyelinating motor and sensory neuropathy (HMSN type I).

Seventeen cases of dominantly inherited demyelinating motor and sensory neuropathy (HMSN type I) with infantile onset were studied. Not only clinical and electrophysiological data, but also the g ratio (axon diameter to fibre diameter), considered to be a distinguishing feature between HMSN type I and HMSN type III, showed overlap. Morphological and morphometrical investigations already revealed a lack of small and large diameter myelinated axons at an early stage, and a demyelinating process most active in early childhood followed later by axonal loss. It was concluded that the histopathology of HMSN type I cannot be sufficiently explained by axonal atrophy with secondary demyelination.

An autosomal dominant type of congenital muscular dystrophy.

A family with an autosomal dominant type of congenital muscular dystrophy (CMD) will be reported. In general, an autosomal recessive mode of inheritance is accepted for CMD. In 1980, Kalyanaraman et al reported another family with an autosomal dominant CMD with possible involvement of the central nervous system (CNS). Our report concerns a father and daughter suffering from CMD without CNS involvement. The histological findings, especially some mitochondrial abnormalities in the muscle biopsy were remarkable.

Cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a familial sterol storage disease based on an inborn error of metabolism involving bile acid synthesis. Predominant clinical features are a chronic progressive neurological syndrome, mental deterioration, bilateral cataract and xanthomas. The presence of xanthomas usually leads to the diagnosis, and the reverse is probably also true: without xanthomas the diagnosis will often not be made. CTX may therefore be less rare than commonly thought, and the incidence of xanthomas in CTX may be overestimated. Four cases without xanthomas among the presenting symptoms are described, and the relevance of xanthomas in CTX is discussed.

Increased daytime sleepiness and snoring--obstructive sleep apnea syndrome caused by webbing of the soft palate.

A case report is presented of a man with increased daytime sleepiness and snoring due to an obstructive sleep apnea syndrome caused by webbing of the soft palate narrowing the velopharyngeal aperture. The diagnosis obstructive sleep apnea syndrome was confirmed by polysomnography. After uvulopalatopharyngoplasty there was a marked objective and subjective improvement of patient's complaints. The authors stress the importance of sleep monitoring in patients with excessive daytime sleepiness and snoring. Otorhinolaryngologic examination is necessary in patients with obstructive sleep apnea syndrome to search for anatomic abnormalities of the oropharynx.

Sensory axonopathy in hereditary distal spinal muscular atrophy.

A girl of 14 year is presented with a distal spinal muscular atrophy (SMA) with autosomal recessive inheritance. The technical findings are in agreement with the diagnosis. Light microscopical examination of sural nerve biopsy, including teased fiber studies and morphometry, showed no abnormalities. Electron microscopical investigation however demonstrated axonal pathology. The question arises if distal SMA is a distal axonopathy mainly of motor nerves, but to some extent also of sensory nerves.

Oculopharyngodistal myopathy with early onset and neurogenic features.

Some clinical variants of oculopharyngeal dystrophy are known; a rare form is described in this article: the early-adult form of oculopharyngodistal myopathy. The diagnosis was made in 2 patients ((brother and sister) on the grounds of extensive clinical, biochemical and morphological (microscopical, histochemical and submicroscopical) investigations. Although oculopharyngeal dystrophy is generally considered to be a purely myogenic condition, in one of our patients some neurogenic indications were found (EMG and biopsy). The general picture, however, was that of a myopathy with the characteristic morphological signs of oculopharyngeal dystrophy in the skeletal musclebiopsy.

Congenital fibre type disproportion.

Four children with congenital fibre type disproportion were described. It was shown that their type 1 fibres were at least 12% smaller than the type 11 fibres. There was no increase in the terminal innervation ratio (TIR), but a decreased number of terminal knobs was observed in the biopsy of one child. The distribution of fibre types in the biopsy of another child bears out the notion that the abnormalities as seen in the biopsy can be traced back to the spine.

Muscle cramp as a feature of neuromuscular disease. Five neuromuscular disorders, accompanied by frequent muscle cramps.

Five case reports of neuromuscular disorders, presenting with frequent muscle cramps are discussed. Clinical diagnosis and pathophysiologic concepts are highlighted.