Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.

BACKGROUND: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. OBJECTIVE: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. METHODS: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). RESULTS: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. CONCLUSIONS: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.

Humoral immune activation in amyotrophic lateral sclerosis patients.

There is evidence that immunological factors may involved in the pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Few studies to date have explored the status of the humoral immune response in patients with ALS. We examined the presence of humoral immune activation in ALS patients, serum immunoglobulins (IgG, IgA and IgM) levels were measured in 36 patients with ALS and 35 normal controls. Serum IgG, IgM and IgA levels were not significantly different in our ALS patients compared with the control group (P=ns). No correlations of serum IgG, IgM and IgA concentrations with duration, severity of the disease or the clinical form of onset (bulbar or spinal) were found in our ALS patients. Our results do not suggest a humoral immune activation in ALS patients. This does not exclude that immunological mechanisms may be involved in ALS pathogenesis.

Proinflammatory cytokines in serum and cerebrospinal fluid of CIDP patients.

INTRODUCTION: Little is known about the role of cytokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin (IL)-12 and IL-15 are the major growth and differentiation factors for Th-1 cells and IL-17 is a marker of Th-17 cell expansion and activation, a high proinflammatory new subset of T cells that induce severe autoimmunity. PATIENTS AND METHODS: We measured by enzyme-like immunosorbent assay serum and cerebrospinal fluid (CSF) levels of IL-15, IL-12, and IL-17 in 24 patients with CIDP and 12 patients with other non-inflammatory neurological disorders and serum levels in 16 healthy subjects. RESULTS: We found a positive association of CSF IL-12 (P = 0·012) with CIDP presence (P<0·001). CONCLUSIONS: Our findings suggest that IL-12 may be involved as potential marker of immune activation in CIDP. The increase in its levels in CSF may be a marker of initiation of Th-1 cell-mediated immunity.

Prevalence of major depression in ALS: comparison of a semi-structured interview and four self-report measures.

This study aimed to compare prevalence estimates of current major depression obtained with a semi-structured interview and four frequently used self-report depression severity measures in a sample of amyotrophic lateral sclerosis (ALS) patients. Thirty-seven ALS patients (56.8% males) aged 37-80 years (mean 62.0 ± 10.7) without respiratory insufficiency or dementia were studied during hospitalization or on a follow-up visit. SCID-IV interview as well as self-report Hospital Anxiety and Depression Scale (HADS), ALS Depression Inventory (ADI), Center for Epidemiological Studies-Depression scale (CES-D) and Beck Depression Inventory (BDI-I) were administered. Kappa coefficients of diagnostic agreement between various instruments were calculated. Results showed that 37.8% of patients had a lifetime diagnosis of depression and in 13.5% depression followed ALS onset. Percentages of patients 'diagnosed' with current major depression were: 21.6% (SCID-IV), 16.7% (HADS-D ≥ 11), 16.2% (ADI ≥ 29), 25% (CES-D ≥ 24) and 24.3% (BDI-I ≥ 16). High kappa values were recorded between CES-D, BDI-I and SCID-IV as well as between HADS-D and ADI. CES-D, BDI-I and SCID-IV gave the highest prevalence estimates of current major depression in ALS patients and were in poor agreement with estimates based on HADS and ADI; it is suggested that this is possibly because the former give a far greater emphasis on physical symptoms of depression than the latter.

Interleukin-15 and interleukin-12 are elevated in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

BACKGROUND: There is evidence that immunological factors may be involved in pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). Interleukin (IL)-15 and IL-12 are proinflammatory cytokines produced by activated blood and glial cells. They promote T cell differentiation and proliferation. PATIENTS AND METHODS: We measured by ELISA serum and cerebrospinal fluid (CSF) levels of IL-15 and IL-12 in 21 patients with ALS and 19 patients with other noninflammatory neurological disorders (NIND) studied as a control group. IL-15 and IL-12 serum and CSF levels were also correlated with duration of the disease, the disability level determined using the revised ALS Functional Rating Scale and the clinical subtype of the disease onset in patients with ALS. RESULTS: IL-15 and IL-12 serum levels were higher in patients with ALS as compared with patients with NIND (p = 0.014 and p = 0.011, respectively). IL-15 and IL-12 CSF levels were also increased in patients with ALS (p = 0.011 and p = 0.005, respectively). IL-15 and IL-12 levels were not correlated with disease duration, disability scale or clinical subtype of the disease onset in ALS patients. CONCLUSIONS: Our findings suggest that these molecules may be involved in the pathogenic mechanisms acting as potential markers of immune activation in ALS.