Atypical Motor Neuron Disease and Related Motor Syndromes

Abstract

There is an imperative need for the early diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) in the current era of emerging treatments. When evaluating the patient with ALS/MND, the neurologist must consider a number of other motor neuron disorders and related motor syndromes that may have clinical features resembling ALS/MND. The revised Airlie House-El Escorial diagnostic criteria have been established through the consensus of experts meeting at workshops. However, by definition, using these criteria a patient is likely to have fairly advanced disease at the time of a definitive ALS/MND diagnosis. The reasons for the difficulty in making an early ALS/MND diagnosis are several. No surrogate diagnostic marker currently exists for ALS/MND. ALS/MND at its onset is heterogeneous in clinical presentation, its clinical course is variable, and several clinical variants are recognized. In addition, certain motor syndromes, such as monomelic amyotrophy, postpolio muscular atrophy, and multifocal motor neuropathy, can clinically mimic ALS/MND. Therefore, not only may the diagnosis of ALS/MND be clinically missed in the early stages, but worse, the patient may be wrongly labeled as having ALS/MND. The diagnosis of ALS/MND requires a combination of upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Motor syndromes in which the deficit is restricted to the UMN or LMN through the entire course of the disease are described as atypical MND in this review. Approximately 5% of patients with ALS/MND have overt dementia with a characteristic frontal affect. ALS/MND with parkinsonism and dementia is rare outside the western Pacific region. The clinical course of motor disorder in these overlap syndromes does not differ from that in typical ALS/MND.

Incidence of ALS in Lombardy, Italy

“…Although this diagnostic category may be largely represented by progressive muscular atrophy (PMA) and there are reports defining pure sporadic lower motor neuron disease as a separate nosographic entity, 15 still PMA can be considered as part of the spectrum of ALS because neurophysiologic and pathologic studies detect pyramidal tract involvement in patients with LMN signs, 16,17 and ubiquinated inclusions (typical ALS findings) have been found in most PMA cases. 17 In addition, patients with familial ALS carrying different superoxide dismutase-1 mutations present at the onset with a LMN phenotype 18,19 and are included in the revised El Escorial categories as clinically definite familial, laboratory-supported ALS.…”

Predictors of delay in the diagnosis and clinical trial entry of amyotrophic lateral sclerosis patients: A population-based study

“…Neurophysiological and autopsy studies demonstrated that the pyramidal tracts are often affected in patients with LMN syndromes [18,19] and ubiquinated inclusions typical of ALS have been found in most PMA cases in a recent report [19]. Familial cases carrying superoxide dismutase-1 mutations frequently present LMN phenotype at onset [20,21].…”

Subclinical Sensory Involvement in Monomelic Amyotrophy

“…6 The pattern of muscle weakness in our patient is also typical of MA, which is characterized most frequently by involvement of the C8/T1 myotomes. 3,7,9,10 The weakness is restricted to the single presenting extremity in most cases, but a small number of patients have milder involvement of the contralateral limb clinically, electrodiagnostically, and/or by imaging studies. 5,7,9,11 Neuroimaging of some patients with MA may reveal focal cord atrophy or lack of the normal cervical enlargement.…”