The spectrum of lower motor neuron syndromes

Abstract

This review discusses the most important lower motor neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom motor neurons (lower motor neuron disease (LMND)) are primarily affected or motor axons and their surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation.MMN is a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence of motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower motor neuron syndromes. For the individual patient, distinction between the various lower motor neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.

Multifocal motor neuropathy

“…The differential diagnosis of MMN includes two different categories of disorders: motor-neuron disease 2,13,14,28,[39][40][41][42][43] and demyelinating neuropathies.…”

“…[4][5][6][7][8][9][10][11] The disorder was thought to be immune mediated, possibly through IgM antibodies that bind gangliosides on human peripheral nerves. 12 The differential diagnosis of MMN includes motor-neuron disease 13,14 and demyelinating neuropathies. [15][16][17] Diagnosis of MMN is supported by the finding of motor but not of sensory abnormalities on nerve-conduction studies.…”

“…The differential diagnosis of MMN includes two different categories of disorders: motor-neuron disease 2, 13,14,28,[39][40][41][42][43] and demyelinating neuropathies. [15][16][17] The first signs and symptoms in MMN can be similar to those in motor-neuron disease, and some patients are initially diagnosed as having amyotrophic lateral sclerosis or lower-motor-neuron disease.…”

Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation

“…Interestingly, postmortem studies showed Bunina bodies, which are common morphological features of PMA and the classic form of ALS. 5,9 Given the rarity of HypoPP and PMA, a chance association of the CACNA1S mutation and this phenotype was unlikely. Furthermore, the daughter of the index patient (III:4, Fig.…”

“…3 Most cases of PMA are linked both clinically and pathologically to amyotrophic lateral sclerosis (ALS). 5,9 Herein we report a patient with familial HypoPP and PMA that had a fatal course. The disorder was associated with the R528H mutation in the calcium channel protein Cav1.1.…”