The question of whether primary lateral sclerosis (PLS) is a nosological entity distinct from amyotrophic lateral sclerosis (ALS) has been the subject of controversy since it was first described in the nineteenth century. PLS has been defined as a rare, non-hereditary disease characterized by progressive spinobulbar spasticity, related to the selective loss of precentral pyramidal neurones, with secondary pyramidal tract degeneration and preservation of anterior horn motor neurones. In the recent clinical literature, the frontier between ALS and neurodegenerative disease remains poorly defined. We studied 20 patients with a diagnosis of PLS. We carried out a variety of tests in order to determine the presence of a more diffuse neurodegenerative process. We also performed a longitudinal electrophysiological evaluation. Our clinical, electrophysiological and pathological investigations provide evidence that the disease has a heterogeneous clinical presentation and that degeneration is not restricted to the central motor system.

Primary lateral sclerosis (PLS) has been defined as rare, and the neuropsychological changes remain poorly defined. We studied 20 patients with a diagnosis of PLS. We carried out an extensive psychometric testing including a general assessment (memory, language, attention, visual-constructional ability and praxis) and a more specific assessment of prefrontal and premotor cortex functions in order to characterize the neuropsychological profile of the patients compared to matched controls, and explore executive functions and premotor cortex functions. None of the PLS patients was demented but they all presented memory deficits reflecting an executive dysfunction. All patients but three had signs of premotor and/or prefrontal cortex deficits. The cognitive impairment in PLS, specifically related to a frontal lobe dysfunction, seems qualitatively similar to ALS. Our results suggest a patchy distribution of cortical involvement in PLS but it remains difficult to draw any definite conclusion as to the spatio-temporal progression of the disease into the different regions of the frontal lobe.

Our objective was to assess the spectrum and clinical associations of cognitive impairment in French patients with ALS, and determine the effect of cognitive impairment on survival in this population. One hundred and thirty-one patients were enrolled in a cross-sectional cohort study of neuropsychological test performance. ANOVA and χ(2) tests assessed differences in clinical characteristics between impaired and unimpaired patients; multiple regression determined which features contributed most strongly to cognitive status, and Cox models compared survival. Fifty-three patients (40%) were categorized as cognitively impaired based on test performance. Thirteen (10%) patients had frontotemporal dementia (FTD) clinically; all scored in the moderate to severely impaired range on testing. Impaired patients had less education (p = 0.001), and severely impaired patients were more likely to have bulbar onset than unimpaired patients (p < 0.001). Severe cognitive impairment predicted shorter survival (p = 0.007), even when controlled for motor severity (p = 0.001). In summary, 10% of a consecutive series of French ALS patients had overt dementia and 40% were cognitively impaired by neuropsychological testing. We conclude that lower education level and possibly bulbar-onset ALS were associated with impairment. As in other causes of dementia, higher education attainment may protect against clinical cognitive deterioration in ALS. French patients with severe cognitive impairment have shorter survival time.

Considering the few studies published on the psychopathology of ALS patients, we carried out a preliminary study evaluating depression, anxiety, emotional reactions and coping strategies in such patients. Twenty-seven ALS patients were included and evaluated using a semi-structured interview, after which they were asked to complete a questionnaire. The rater asessed the DSM-IV criteria for a major depressive episode, dysthymia and generalized anxiety, using the MADRS scale for depression, the Covi anxiety scale and the Depressive Mood scale. Subsequently, patients completed the Ways of Coping checklist. Patients were neither anxious nor depressed. Patients whose diagnosis was recent (less than six months) presented greater emotional deficit. Patients younger than 50 years of age used problem focused strategies more frequently. Those having received the diagnosis in the preceeding six months used emotion focused strategies significantly more often.The absence of characterized depression and anxiety confirmed results of the literature. The significance of this study is found in the observation of specific emotional reactions present in the first six months following diagnosis disclosure. The results show that it is useful to continue the affective evaluation of these patients and to undertake longitudinal studies starting at the time of diagnosis disclosure.