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Clinical features that distinguish PLS, upper motor neuron–dominant ALS, and typical ALS

From the Departments of Neurology (P.H.G., I.B.K., H.M., L.P.R.) and Biostatistics (B.C.), Columbia University, New York, NY.

Address correspondence and reprint requests to Dr. Paul H. Gordon, Fédération des Maladies du Système Nerveux, Centre Référent Maladie Rare SLA, Hôpital de la Pitié-Salpêtrière, 47-83, Boulevard de l’Hôpital, 75651 Paris, France Paul.gordon{at}psl.aphp.fr

Objective: To determine how clinical features at the first evaluation and in follow-up can be used to suggest a diagnostic outcome for patients with only upper motor neuron (UMN) signs at disease onset.

Methods: We reviewed the records of 34 patients (9 primary lateral sclerosis [PLS], 15 UMN-dominant amyotrophic lateral sclerosis [ALS], and 10 randomly selected control patients with ALS) seen in 1984–2007. Analysis of variance F tests for continuous variables and ² tests for categorical variables analyzed differences in baseline data among the diagnostic categories. Linear and generalized mixed effects models assessed the relation between examination data and diagnostic group over time.

Results: At first examination, the lowest score of the weakest muscle (p < 0.001), the site of onset (p = 0.041), and time to evaluation (p = 0.05) discriminated between eventual diagnostic group; patients with PLS were stronger, slower in progressing, and more likely to have limb onset than the other groups. Strength 4 on any muscle was associated with the diagnosis of ALS (p = 0.0001), but not PLS. Across all visits, muscle strength (p = 0.003), ALS Functional Rating Scale score (p = 0.009), and vital capacity (p = 0.026) predicted group assignment. UMN-dominant and ALS groups had more weight loss (p = 0.004), even when controlled for dysphagia (p = 0.021) and muscle atrophy (p = 0.009), and patients with ALS were more likely to have hyporeflexia (p = 0.001).

Conclusions: Features at baseline most suggestive of eventual lower motor neuron signs were focal muscle weakness or bulbar onset. Later, weight loss, reduced forced vital capacity, and limb weakness predicted lower motor neuron dysfunction. We suggest that patients with only upper motor neuron signs have periodic evaluations of strength, weight, forced vital capacity, Amyotrophic Lateral Sclerosis Functional Rating Scale score, and EMG, because a change in any can signal the imminent development of lower motor neuron signs.

ALS = amyotrophic lateral sclerosis; ALSFRS-R = ALS Functional Rating Scale; FVC = forced vital capacity; LMN = lower motor neuron; MMT = manual muscle testing; MRC = Medical Research Council; MRS = magnetic resonance spectroscopy; PLS = primary lateral sclerosis; UMN = upper motor neuron; UMN-D = upper motor neuron dominant.

Supplemental data at www.neurology.org

Supported by a grant from MDA Wings Over Wall Street.

Disclosure: Dr. Mitsumoto has received one-time honoraria for serving on advisory boards from the following pharmaceutical companies: Knopp, Avanir, NeuralStem, and Otsuka. He has received grants from NIH, the Muscular Dystrophy Association, and Knopp, Avanir, and Teva pharmaceutical companies to support clinical trials and clinical research.

Received December 9, 2008. Accepted in final form March 2, 2009.