Peroneal muscular atrophy: Part 1. Clinical and electrophysiological study

doi:10.1016/0022-510X(83)90172-7

Journal of the Neurological Sciences

Volume 61, Issue 3, October–November 1983, Pages 389-399

https://doi.org/10.1016/0022-510X(83)90172-7 Get rights and content

Abstract

144 patients with the clinical syndrome of peroneal muscular atrophy or Charcot-Marie-Tooth disease were studied. Thirteen were recognized as the spinal form of the disease since all had normal motor nerve conduction velocity and sensory nerve action potential. The remaining patients could be classified according to their values of motor conduction velocity for the median nerve. Two main groups were therefore identified: 55 patients whose nerve conduction was below 30 m/s belonged to group I, which corresponds to the previously reported hypertrophic form or hereditary motor sensory neuropathy (HMSN) type I. Sixty-four patients whose nerve conduction was above 40 m/s belonged to group II which corresponds in the majority of cases to teh neuronal form of HMSN type II. Twelve patients could not be classified since the motor nerve conduction velocity for median nerve ranged between 30 and 40 m/s. These could belong to either of the two main groups or might form an intermediate group, the existence of which is discussed. Clinical genetic and electrophysiological features of the two main groups are discussed and compared.

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Classifications of neurogenetic diseases: An increasingly complex problem
2016, Revue Neurologique
Citation Excerpt :
Based on electrophysiological findings, Dyck and Lambert [5,6] distinguished demyelinating from axonal forms. This dichotomy relies on the motor conduction velocity of the median nerve: cases where the velocity is > 38 m/s are regarded as “axonal”, while those < 38 m/s are classified as “demyelinating”; subsequently, an “intermediate” form was identified in patients with conduction velocities between 30 and 40 m/s [7,8]. The demyelinating forms are the most common (constituting around two-thirds of cases).
Neurodegenerative disorders represent a wide group of diseases affecting the central and/or peripheral nervous system. Many of these disorders were described in the 19th century, but our genetic knowledge of them is recent (over the past 25 years). However, the continual discovery of disease-causing gene mutations has led to difficulties in the classification of these diseases. For this reason, our present proposals for updating and simplifying the classification of some of these conditions (Charcot–Marie–Tooth diseases, distal hereditary motor neuropathies, hereditary sensory and autonomic neuropathies, hereditary spastic ataxias, hereditary spastic paraplegias and hereditary spastic ataxias) are expounded here.
Neurophysiological approach to disorders of peripheral nerve
2013, Handbook of Clinical Neurology
Citation Excerpt :
The conduction velocity is mostly in the 15–30 m/second range, and very severely reduced motor and sensory conduction velocities, below 12 m/second, should raise the suspicion of Dejérine–Sottas syndrome (CMT1B or 3), which in some cases occur in connection with mutation of P0. Occasionally CMT1 patients have conduction velocities > 38 m/second and there may be considerable variation even within the same families (Bouche et al., 1983; Gherardi et al., 1983; Kaku et al., 1993a). The conduction slowing is seen from the age of 3–5 years and does not progress significantly after 5 years of age (Garcia et al., 1998).
Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables.
Conventional electrophysiological methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed.
An essential role of MAG in mediating axon-myelin attachment in Charcot-Marie-Tooth 1A disease
2013, Neurobiology of Disease
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CMT1A leads to distal weakness, atrophy and sensory loss caused by degeneration of motor and sensory axons (Krajewski et al., 2000). Demyelination precedes the occurrence of clinical symptoms that correlate with axonal degeneration (Berciano et al., 1989; Bouche et al., 1983; Garcia et al., 1998; Nicholson, 1991). CMT1A is caused by duplication of the DNA region encoding the peripheral myelin protein 22 (PMP22) or by a point-mutation within this gene (Patel et al., 1992; Roa et al., 1991; Suter et al., 1992).
Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy caused by the duplication of the PMP22 gene. Demyelination precedes the occurrence of clinical symptoms that correlate with axonal degeneration. It was postulated that a disturbed axon–glia interface contributes to altered myelination consequently leading to axonal degeneration. In this study, we examined the expression of MAG and Necl4, two critical adhesion molecules that are present at the axon–glia interface, in sural nerve biopsies of CMT1A patients and in peripheral nerves of mice overexpressing human PMP22, an animal model for CMT1A. We show an increase in the expression of MAG and a strong decrease of Necl4 in biopsies of CMT1A patients as well as in CMT1A mice. Expression analysis revealed that MAG is strongly upregulated during peripheral nerve maturation, whereas Necl4 expression remains very low. Ablating MAG in CMT1A mice results in separation of axons from their myelin sheath. Our data show that MAG is important for axon–glia contact in a model for CMT1A, and suggest that its increased expression in CMT1A disease has a compensatory role in the pathology of the disease. Thus, we demonstrate that MAG together with other adhesion molecules such as Necl4 is important in sustaining axonal integrity.
Non-fortuitous dynamin II mutation-related association: Neutropenia and Charcot-Marie-Tooth disease
2012, Revue Neurologique
La maladie de Charcot-Marie-Tooth (CMT) est une neuropathie héréditaire sensitivomotrice, correspondant à un groupe hétérogène sur les plans clinique et moléculaire. De nombreux gènes peuvent être en cause imposant une étude moléculaire. Nous rapportons un cas original de CMT associée à une neutropénie chronique chez un patient porteur d’une mutation K562del du gène de la dynamine 2 (DNM2) et présentant, par ailleurs, une atteinte cognitive précoce. L’existence de manifestations associées, et notamment une neutropénie, peut orienter l’étude moléculaire au cours du CMT.
Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a genetically and clinically heterogeneous group of disorders of the peripheral nervous system. Mutations in multiple genes are currently known. We report an original case of CMT associated with chronic neutropenia in a patient with a K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with alterated cognitive function. Associated manifestations may guide molecular study.
Current status on electrodiagnostic standards and guidelines in neuromuscular disorders
2011, Clinical Neurophysiology
Citation Excerpt :
In the interpretation of a NCS one should be aware of a grey zone, i.e. an area where a nerve abnormality is proven but a distinction between demyelination and axonal loss can not be made either due to the nature of the pathophysiological process or to problems inherited in the electrodiagnostic method. This was evidenced in studies of patients with peroneal muscular atrophy classified by biopsy, where an overlap in motor CV or DML in some cases were seen between the axonal and demyelinating types (Bouche et al., 1983; Buchthal and Behse, 1977). The main reason for the difficulty in discriminating primary demyelination from primary axonal loss is that conduction slowing, in addition to involvement of myelin or Schwann cells in demyelinating neuropathy, can also be caused by secondary loss of fast conducting, large-diameter fibres in axonal neuropathy.
The aim of this review is to present the status of electrodiagnostic standards and guidelines in neuromuscular disorders. Electrodiagnostic guidelines are developed on the background of medical technology assessment, wherefore a short presentation of medical technology assessment is given covering: (1) Evidence-based medicine, i.e. “to do the right thing”, describing practice parameters and the STARD initiative which introduces evidence-based medicine in electrodiagnostic medicine, (2) Continuous quality improvement, i.e. “to do the thing right”, describing variation among laboratories in methods and interpretation of tests, and the need for medical audit and implementation of electrodiagnostic guidelines, (3) Outcome studies, i.e. “is it worthwhile to do the right thing right?”. In electrodiagnostic medicine there are very few outcome studies.
Standards and guidelines described in the literature for different neuromuscular disorders are presented, often as figures or tables. These cover guidelines developed in detail for CIDP by expert consensus multicentre groups by AAN, INCAT, EFNS/PNS and for other inflammatory demyelinating neuropathies are described, as well as guidelines differentiating between demyelinating pathophysiology and axonal loss by motor and sensory nerve conduction studies.
Furthermore, electrodiagnostic guidelines for ALS as detailed in the El Escorial, the modified El Escorial and the recent supplementary Awaji criteria are described and presented in a comprehensive table. Only few electrodiagnostic guidelines are published for nerve entrapment, cervical radiculopathy and neuromuscular transmission failure whereas none are known for myopathy. If no electrodiagnostic criteria for a given disorder exist, criteria for the electrodiagnostic examination are described if present.
It is concluded that future research is needed in order to develop more electrodiagnostic guidelines in neuromuscular disorders by international expert consensus groups. Such research should use an evidence-based medicine approach and medical technology assessment and include continuous quality development and outcome studies.
Charcot-Marie-Tooth disease
2009, Presse Medicale
La maladie de Charcot-Marie-Tooth (CMT) est une neuropathie héréditaire sensitivomotrice et l’une des maladies héréditaires du système nerveux les plus fréquentes.
Le phénotype clinique est relativement homogène dominé par un déficit moteur et une amyotrophie de topographie distale, d’installation progressive qui débutent et prédominent aux muscles péroniers.
Deux formes principales de CMT sont distinguées par les données électrophysiologiques et pathologiques : la forme démyélinisante et la forme axonale. Plus de 20 formes génétiques sont à l’heure actuelle identifiées et d’autres gènes et loci restent encore à découvrir, démontrant une grande hétérogénéité et une multiplicité des mécanismes physiopathologiques du CMT. La classification des différentes formes se fonde sur le mode de transmission autosomique dominant, autosomique récessif ou lié à l’X et sur la nature démyélinisante, axonale ou encore « intermédiaire » de la neuropathie.
Les formes dominantes sont dominées par le CMT1A, dû à une duplication ou une mutation ponctuelle de la PMP22, et par le CMTX, dû à une mutation de la connexine 32.
Les formes autosomiques récessives sont plus fréquentes en Afrique du nord et sont dominées par les mutations de GDAP1 et de la lamine A/C, leurs phénotypes sont habituellement plus sévères.
L’hétérogénéité génétique grandissante rend plus complexe le diagnostic génétique qui ne peut se concevoir sans une stratégie diagnostique basée d’une part sur la classification des formes génétiques et d’autre part sur les particularités phénotypiques et la fréquence des gènes responsables dans la population étudiée.
Charcot-Marie-Tooth (CMT) disease, also known as peroneal muscular atrophy or hereditary motor and sensory neuropathy, is among the most frequent hereditary disorders of the nervous system.
The relatively homogeneous clinical phenotype involves mainly progressive weakness and wasting of distal muscles; it starts and predominates in the peroneal muscles.
Electrophysiological and pathology data distinguish two principal forms of CMT: demyelinating and axonal. More than 20 distinct genetic subtypes have been identified to date and other new loci and genes remain to be discovered, thus demonstrating wide genetic heterogeneity and a number of different pathophysiological mechanisms. The classification of these different forms is based on both the mode of inheritance — autosomal dominant, recessive or X-linked — and the neuropathy type — demyelinating or axonal or “intermediate”.
The principal dominant forms are CMT1A, due to a duplication or point mutation in the PMP22 gene, and CMTX, due to mutations in the connexin 32 gene. Autosomal recessive forms are more frequent in North Africa. The most common involve mutations of GDAP1 or lamin A/C and generally lead to more severe phenotypes than the dominant forms.
The great genetic heterogeneity necessitates a strategy for genetic diagnosis. It is based in part on the classification of the different genetic forms and in part on the phenotypic particularities and the frequency of the responsible genes in the population under study.

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Peroneal muscular atrophy: Part 1. Clinical and electrophysiological study

Abstract

J. Neurol. Sci.

J. Neurol. Sci.

J. Neurol. Sci.

J. Neurol. Sci.

Electromyographic studies in peroneal muscular atrophy

Arch. Neurol. (Chic.)

Clinical and electrodiagnostic features of Charcot-Marie-Tooth syndrome

Acta Neurol. Scand.

Peroneal muscular atrophy and related disorders, Part 1 (Clinical manifestations as related to biopsy findings, nerve conduction and electromyography)

Brain

The peroneal muscular atrophy syndrome — Clinical, genetic, electrophysiological and nerve biopsy studies, Part 1 (Clinical genetic electrophysiological findings)

J. Genet. Hum.

Inherited neuronal degeneration and atrophy affecting peripheral motor, sensory, and autonomic neurons