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Biomedical subjects

R A Maselli

Publications and source records attributed to R A Maselli.

At least 19 recordsLinked to original sources
PubMed2003

Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2.

OBJECTIVE: To further investigate the basis of abnormal neuromuscular transmission in two patients with congenital myasthenic syndrome associated with episodic ataxia type 2 (EA2) using stimulated single fiber EMG (SFEMG) and in vitro microelectrode studies. METHODS: Two patients with genetically characterized EA2 previously shown to have abnormal neuromuscular transmission by voluntary SFEMG were studied with stimulated SFEMG and anconeus muscle biopsy with microelectrode studies and electron microscopy of the neuromuscular junction. RESULTS: In vivo stimulated SFEMG showed signs of presynaptic failure, with jitter and blocking that improved with increased stimulation frequency. Additional evidence of presynaptic failure was provided by the in vitro microelectrode studies, which showed marked reduction of the end plate potential quantal content in both patients. Of note, the end plate potentials showed high sensitivity to N-type blockade with omega-conotoxin not seen in controls. The ultrastructural studies revealed some evidence of small nerve terminals apposed to normal or mildly overdeveloped postsynaptic membranes, suggesting an ongoing degenerative process. CONCLUSIONS: The authors demonstrated presynaptic failure of neurotransmission in patients with heterozygous nonsense mutations in CACNA1A. The contribution of non-P-type calcium channels to the process of neurotransmitter release in these patients likely represents a compensatory mechanism, which is insufficient to restore normal neuromuscular transmission.

Acetylcholinesterase↗
PubMed2001

Presynaptic congenital myasthenic syndrome due to quantal release deficiency.

OBJECTIVE: To provide clinical, electrophysiologic, and ultrastructural findings in three patients with a presynaptic congenital myasthenic syndrome (CMS). BACKGROUND: Familial infantile myasthenia and paucity of synaptic vesicles are the only two fully characterized CMS. We are describing here three patients with another form of presynaptic CMS characterized by deficiency of the action potential-dependent release without reduction of the spontaneous release of neurotransmitter from the nerve terminal. METHODS: The authors performed electromyography and anconeus muscle biopsies that included intracellular recordings and electron microscopy of the neuromuscular junction in three patients with presynaptic CMS. They also sequenced part of the P/Q-calcium alpha(1)-subunit gene (CACNA1A) and the acetylcholine receptor subunit (AChR) genes in these patients. RESULTS: In these patients there were additional neurologic findings including nystagmus and ataxia. In all three patients the end-plate potential quantal content (m) was markedly reduced but neither the amplitudes nor the frequencies of miniature end-plate potentials were diminished. Ultrastructurally, postsynaptic end-plate folds, nerve terminal size, and synaptic vesicle number were normal but double-membrane-bound sacs containing synaptic vesicles were present in the nerve terminal of all three patients. The screening of reported pathogenic mutations in the CACNA1A and a mutational analysis of AChR subunit genes were negative. CONCLUSION: This form of CMS appears to result only from a deficiency of the quantal release of neurotransmitter that may be due to an abnormal calcium mechanism or impaired endocytosis and recycling of synaptic vesicles.

Adolescent↗
PubMed2000

AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine.

Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive. Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific. In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data.

Adult↗
PubMed1998

Morvan's fibrillary chorea: a paraneoplastic manifestation of thymoma.

Morvan's fibrillary chorea is a rare disease characterised by symptoms which include neuromyotonia, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. The first case of Morvan's fibrillary chorea to be associated with clinical manifestations of myasthenia gravis with thymoma, psoriasis, and atopic dermatitis is reported. Muscle histopathology disclosed chronic denervation and myopathic changes and in vitro electrophysiology demonstrated both presynaptic and postsynaptic defects in neuromuscular transmission. Serum antibodies to acetylcholine receptors, titin, N-type calcium channels, and voltage gated potassium channels were detected. Plasmapheresis, thymectomy, and long term immunosuppression induced a dramatic resolution of symptoms. The association of thymoma with other autoimmune disorders and autoantibodies, and prolonged and sustained remission with chronic immunosuppression, place Morvan's fibrillary chorea on the range of neurological diseases arising as a paraneoplastic complication of cortical thymomas.

Biopsy↗
PubMed1997

End-plate electromyography: use of spectral analysis of end-plate noise.

An automated technique for estimating the channel open time of human end-plate acetylcholine receptors (AChR) is described. The method, which is based on the power spectral analysis of electromyographic end-plate noise, is simple and permits a rapid estimation of the dominant AChR ion channel kinetics. Values of AChR channel open time determined by spectral analysis of end-plate noise in adults (1.23 +/- 0.01 ms at 33 degrees C) were consistently shorter than those estimated from the decay phase of extracellularly recorded miniature end-plate potentials. The channel open time extracted from the end-plate noise compared well with that derived from the analysis of in vitro recorded acetylcholine-induced current noise. Therefore, spectral analysis of end-plate noise may provide a good estimation of the kinetics of the human AChR ion channel. The technique is particularly useful in identifying congenital myasthenic syndromes with altered AChR ion channel function.

Adult↗
PubMed1997

Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study.

Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness. Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases. Muscle biopsies showed variable signs of neurogenic atrophy. In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder. Mechanical ventilation was required in 5 patients. Half of the patients were treated with polyvalent antitoxiin. Prognosis was favorable, though recovery was slow. In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism. High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.

Adult↗
PubMed1997

Fulminant demyelinating neuropathy mimicking cerebral death.

Guillain-Barré syndrome can very rarely present with acute quadripares and cranial nerve involvement resembling a locked-in state. We describe a very unusual case of fulminant neuropathy in a child who was previously exposed to vincristine. The clinical picture resembled brain death; however, electrodiagnostic studies led to the diagnosis of a peripheral neuropathy. Serial electrodiagnostic studies and pathologic findings confirmed demyelination.

Biopsy↗
PubMed1995

Function and ultrastructure of the neuromuscular junction in post-polio syndrome.

We performed a detailed morphological and electrophysiological analysis of the neuromuscular junction in muscle biopsies from 10 patients with post-polio syndrome (PPS). This was done to clarify the basis for the apparent neuromuscular transmission impairment in PPS. In six patients, intracellular microelectrode recordings demonstrated either reduction of amplitudes of miniature end-plate potentials (MEPPs) or decreased quantal content or both. In one patient, reduction of quantal content was only present with prolonged or high-frequency nerve stimulation. In three patients no significant abnormalities were found by the intracellular microelectrode studies. Histologically, atrophy of individual muscle fibers were present in 6 out of the 10 biopsies, but grouped atrophy was not seen. Fiber type grouping suggesting reinnervation was seen in 8 out of the 10 muscle biopsies. Fragmentation and dispersion of the end plate was present in three patients. In two of these patients dispersion of the end plate was associated with an apparent increase of the quantal content. Electron microscopy revealed either normal neuromuscular junctions or small axon termini apposed to normal postsynaptic folds. In summary, variable degrees and different types of failure of neuromuscular transmission were seen in association with histological signs of reinnervation in the muscle biopsies of affected patients. Functional and structural abnormalities of the neuromuscular junction, although very common, were not invariably present and, therefore, they do not appear to be a necessary condition to define the post-poliomyelitic syndrome.

Action Potentials↗
PubMed1994

Pathophysiology of myasthenia gravis and Lambert-Eaton syndrome.

The first part of this article delineates the most important structural and functional bases of neuromuscular transmission under normal conditions. Next, the main effects of myasthenic antibodies at the neuromuscular junction are described. The article emphasizes the role of inflammation as a transient phase proceeding the degenerative changes of the neuromuscular junction observed in myasthenia gravis. The article ends with a discussion of the principal molecular and physiologic changes accounting for the impairment of neuromuscular transmission in Lambert-Eaton Myasthenic Syndrome.

Animals↗