PLS or ALS?
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Weill Cornell Medical Center. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: The clinical presentation of PLS and ALS are similar, and it may be difficult to distinguish them early in the course.
Sources: Tartaglia MC et al. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2007;64;232-236.
Mezzapesa DM, et al. Whole-brain and regional brain atrophy in amyotrophic lateral sclerosis. AJNR Am J Neuroradiol. 2007; 28:255-259.
Can one, early on, differentiate primary lateral sclerosis (PLS) from amyotrophic lateral sclerosis (ALS)? To address this question, retrospective review of PLS (n = 43) and ALS (n = 661) patients seen at the Motor Neuron Disease Clinic at the University of Western Ontario, between 1990-2006, was undertaken. El Escorial and Pringle (Brain 1992;115;495-520) diagnostic criteria were used to classify ALS and PLS patients, respectively. All patients underwent nerve conduction studies and electromyography, and PLS was diagnosed only in the absence of lower motor neuron abnormalities on electrodiagnostic studies. Patients were evaluated for a myriad of symptoms and signs, including dysarthria, dysphagia, fasciculations, cramping, weakness, wasting, dementia, and parkinsonism. Concomitant illness was also assessed, including HIV, diabetes, epilepsy, malignancy, and cardiac, thyroid, rheumatologic, respiratory, and autoimmune disease. Statistical analysis included Mann-Whitney tests and logistic regression.
No significant gender difference was seen between the 2 groups. ALS onset was later than PLS, 59 vs 54 years, respectively (P = 0.009). At presentation, stiffness was the only symptom significantly (p < 0.001) more frequent in PLS (47%) compared to ALS (4%). At follow up, PLS patients rarely developed muscle wasting (2%), and their survival was significantly longer (11.2 vs 3.8 years, P < 0.001). Bulbar dysfunction was significantly more frequent in ALS than PLS (88% vs 74%, P = 0.01). Parkinsonism, cerebellar and sensory abnormalities were rare in both groups. Trauma was more often a historical feature of PLS than ALS, 19% vs 8% (P < 0.05), but the only medical condition significantly associated with either disease was autoimmune disorders, seen in 5 PLS vs 1 ALS patient (P = 0.002). Over 16 years of follow up, ALS survival was 33%, compared to 89% in PLS (P < 0.001). Less than 3% of motor neuron disease patients have PLS and spasticity is the only presenting sign significantly more common in PLS than ALS. If wasting has not developed in such patients by 3 years after onset, PLS rather than ALS is the likely diagnosis.
Commentary
Although primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are considered diseases of the motor neuron, there is evidence to suggest that the neuropathology of ALS extends beyond the motor system. Clinical, neuropsychological, and brain magnetic resonance (MR) studies, the latter using specific software to estimate brain atrophy and voxel-based morphometry to indicate selective volumetric loss, were performed on 16 patients who satisfied El Escorial criteria for ALS. None demonstrated clinically evident dementia, behavioral impairment, or personality change. All underwent cognitive evaluation including memory, language, and attention tests, encompassing concentration and processing speed as well. Depression was assessed using the Beck Depression Inventory. Nine healthy subjects served as controls. Statistical analysis included the Fisher Exact Test, nonparametric Mann-Whitney U test, and multivariate logistic regression.
None of the patients were depressed. Among the neuropsychological tests, only the Symbol Digit Modality test was significantly worse in ALS patients compared to healthy controls. Mini mental status testing was done, including Spinnler Prose Memory test, verbal fluency, and Brown-Peterson Interference tests were no different between the groups. MR whole brain measures were comparable between controls and ALS patients. Brain parenchymal fraction was slightly but significantly (P = 0.012) lower in the latter, correlating with the presence of cognitive impairment rather than ALS, with gray-matter volume-loss bilaterally in several frontal and temporal regions, slightly more on the right. In light of recent associations between ALS and fronto-temporal dementias (tauopathies), ALS may indeed be a neurodegenerative disease that is more extensive than previously thought.
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