Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression.

BACKGROUND: To date there are no biomarkers with proven reliability as a measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS. METHODS: Thirty-seven consecutive patients with ALS, 25 with chronic inflammatory demyelinating polyneuropathy and 21 with other neurodegenerative diseases were evaluated. CSF NFL levels were assayed by two-site solid-phase sandwich ELISA. In patients with ALS, neurological status was assessed by the revised ALS Functional Rating Scale (ALSFRS-r) and the Medical Research Council scale, and the progression of the disease was evaluated using the 'diagnostic delay' and the 'progression rate'. RESULTS: Cerebrospinal fluid NFL levels were higher in ALS cases than in controls (P < 0.0001). Using receiver operating curve analysis, an optimal NFL cut-off of 1981 ng/l discriminated between patients with ALS and neurological controls, with a sensitivity of 78.4% and specificity of 72.5%. Multivariate logistic regression confirmed the association between CSF NFL levels and the presence of ALS (age and sex adjusted odds ratio for ALS 8.9; 95% CI 3.1-25.8; P < 0.0001). In ALS, CSF NFL negatively correlated with the diagnostic delay (P < 0.0001) and the ALSFRS-r (P = 0.014) and positively with the progression rate (P < 0.0001). CONCLUSIONS: High CSF NFL levels were found in patients with ALS, reflecting the burden of neurodegeneration. The significant relation between CSF NFL levels and disease progression suggests that NFL may be a useful marker of disease activity and progression in ALS.

Serum and CSF anti-GM1 antibodies in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

High titers of antibodies directed against gangliosides, especially GM1, are found in the serum of patients with a variety of polyneuropathies, including those of the inflammatory type. We assayed anti-GM1 IgG and IgM levels in the serum and cerebrospinal fluid (CSF) of 23 patients with Guillain-Barré syndrome (GBS) and 10 with chronic inflammatory demyelinating polyneuropathy (CIDP) to investigate whether this immune response may also be localized within the intrathecal compartment and correlate with clinical parameters such as time interval since disease onset, disability score, preceding infectious episodes, and GM1 therapy. When compared to the control group, anti-GM1 IgG was increased in the serum of 39% of GBS and 10% of CIDP patients, whereas anti-GM1 IgM was elevated in 17% of GBS and none of the CIDP patients. In both patient groups, however, anti-GM1 antibody levels were more frequently elevated in CSF than paired sera: they belonged to the IgG class in 48% of GBS and 50% of CIDP patients, and to the IgM class in 48% of GBS and 55% of CIDP patients. In the GBS group, anti-GM1 IgM serum levels inversely correlated with time elapsed between sample collection and onset of disease (P < 0.05), whereas serum anti-GM1 IgG levels positively correlated with the loss of functional ability (P < 0.005). Increased anti-GM1 antibodies in GBS serum were not associated with clinical or serological evidence of infectious antecedents nor with previous GM1 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrathecal IgG synthesis in multiple sclerosis: comparison between isoelectric focusing and quantitative estimation of cerebrospinal fluid IgG.

Isoelectric focusing of CSF and serum IgG followed by crossed immuno isoelectric focusing and direct immunofixation as well as quantitative assay of IgG and albumin were performed in 64 clinically definite multiple sclerosis patients. Intrathecal IgG synthesis was calculated according to the CSF IgG index and de novo CNS IgGsyn. Isoelectric focusing showed abnormal IgG fractions i CSF indicating increased intrathecal synthesis of oligoclonal IgG in 99% of patients. Only 62% and 70% of multiple sclerosis patients showed values of CSF IgG indices and de novo CNS IgGsyn higher than in controls. Increased intrathecal IgG synthesis was indicated more frequently by de novo CNS IgGsyn in patients with a normal CSF IgG index than by the CSF IgG index in patients with normal de novo CNS IgGsyn. All patients with blood CSF barrier damage had increased de novo CNS IgGsyn, but only 40% had an increased CSF IgG index. Isoelectric focusing seemed to be a more sensitive method to detect an increased intrathecal oligoclonal IgG synthesis than quantitative methods. Identification of abnormal IgG fractions can be performed easily and with more reproducible results by direct immunofixation than by crossed immuno isoelectric focusing. The formula for de novo CNS IgGsyn seemed more sensitive and less influenced by blood-CSF barrier damage than the CSF IgG index to detect increased intrathecal IgG synthesis in multiple sclerosis patients. No correlation was found between the CSF IgG pattern or amounts and age, duration, clinical course or therapy of the disease.