Sporadic lower motor neuron disease with adult onset: classification of subtypes

Abstract

The discovery of the genetic basis of hereditary lower motor neuron disease (LMND) and the recognition of multifocal motor neuropathy as a distinct clinical entity necessitate a new classification of LMND. To this end, we studied the clinical and electrophysiological features of 49 patients with sporadic adult-onset LMND in a cross-sectional study. Disease duration was more than 4 years to exclude the majority of patients with amyotrophic lateral sclerosis. Based on the pattern of weakness, we identified three groups: 13 patients with generalized weakness (group 1); eight patients with symmetrical, distal muscle weakness (group 2); and 28 patients with non-generalized asymmetrical weakness of the arms in most patients (group 3). Group 3 could be subdivided into patients with weakness in predominantly the distal (group 3a) or the proximal (group 3b) muscle groups, both with disease progression to adjacent spinal cord segments. Distinctive features of group 1 were an older age at onset, more severe weakness and muscle atrophy, lower reflexes, greater functional impairment, more widespread abnormalities on concentric needle EMG, respiratory insufficiency and serum M-protein. In groups 2 and 3, concentric needle EMG findings also suggested a more widespread disease process. Retrospectively, the prognosis of sporadic adult-onset LMND appears to be favourable, because clinical abnormalities were still confined to one limb in most patients after a median disease duration of 12 years. We propose to classify the patients in the different subgroups as slowly progressive spinal muscular atrophy (group 1), distal spinal muscular atrophy (group 2), segmental distal spinal muscular atrophy (group 3a) and segmental proximal spinal muscular atrophy (group 3b). The described clinical phenotypes may help to distinguish between different LMND forms.

MR-Pathologic Comparison of the Upper Spinal Cord in Different Motor Neuron Diseases

“…All ALS patients met the revised El Escorial criteria of definite ALS (www.wfnals.org/guidelines/1998elescorial/elescorial1998.htm). In the LMND group, all patients fulfilled the criteria for LMND with adult onset according to Van den Berg-Vos et al [1]; in 3 of them, survival motor neuron gene deletions were detected. In all LMND patients, upper and lower limbs were affected.…”

“…Defined types of motor neuron diseases (MND) differ in clinical, electrophysiological, genetic and histopathological findings, but phenotype differentiation often fails to reflect the distinct neuropathological pattern of vulnerability [1, 2]. Furthermore, besides marked changes in lower motor neurons, electrophysiological and neuropathological investigations can show corticospinal tract (CST) abnormalities and dorsal column alterations of the spinal cord in MND.…”

Classification of Phenotype Characteristics in Adult-Onset Spinal Muscular Atrophy

“…Furthermore, all patients were evaluated with respect to the body mass index, possible deformities, and screened for psychiatric and/or cognitive abnormalities. According to Van den Berg-Vos et al [9], the muscle groups were divided into upper, middle and lower cervical or lumbosacral limb regions. Each limb region consisted of two or three myotomes.…”

“…Due to the mainly sporadic occurrence of adult LMND, genetic investigations were reserved to large families so far [8]. In 2003, Van den Berg-Vos et al [9] published a proposal for a classification based on clinical and electrophysiological characteristics with respect to time course, based upon investigations in 49 adult LMND patients. The authors established three main groups: group 1, characterized by generalized weakness; group 2, characterized by symmetrical, distal muscle weakness; group 3, characterized by nongeneralized asymmetrical weakness of the arms or legs.…”

Signs of MRI affection of brain in сlassical Amyotrophic Lateral Sclerosis patients

“…Simon et al и R.M. Van den Berg-Vos et al [36,42]. Поражение шейного и пояснично-крестцового регионов в сочетании с вовлечением бульбо-псевдо-бульбарного региона у 9 больных с БАС было про-анализировано нами отдельно (см.…”