Depression and anxiety disorders in patients with multiple sclerosis: association with neurodegeneration and neurofilaments.

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.

Depression and anxiety disorders in patients with multiple sclerosis: association with neurodegeneration and neurofilaments

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.

d-serine levels in Alzheimer's disease: implications for novel biomarker development.

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-ß oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-ß/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

[Multiple sclerosis: clinical and laboratorial correlation]. / Esclerose múltipla: correlação clínico-laboratorial.

The clinical and demographic characteristics of 86 Brazilian patients with clinically definite multiple sclerosis (MS) were compared to the cerebrospinal fluid (CSF) findings. The disease course was relapsing-remitting in 71% and chronic progressive in 29% of the cases. The IgG index was increased in 76% in the chronic progressive status and 46% and 49% during the bout and remission, respectively (p < 0.005). Only 36% of the MS patients using corticosteroids had increased IgG index, in comparison to the 64% of the patients without immunosupressive treatment. Oligoclonal IgG bands were detected in the CSF of 77% and 88% of the MS corticosteroids users and non-users, respectively. The quantitative study of intrathecal synthesis of IgG contributes to demonstrate the immunological differences between the two forms of MS, the relapsing-remitting and the chronic progressive. The treatment with corticosteroids decreases quantitatively the intrathecal synthesis of IgG but not the presence of oligoclonal bands.

Multiple sclerosis in Brazil. Analysis of cerebrospinal fluid by standard methods.

The demonstration of intrathecal IgG synthesis has been used as an important laboratory parameter to support the diagnosis of multiple sclerosis (MS). The Committee for European Concerted Action for Multiple Sclerosis has recommended a protocol for the assessment of intrathecal IgG synthesis. We applied this methodology to determine the cerebrospinal (CSF) profile of 128 Brazilian patients with MS. We detected hypercytosis lower than 35 cells/mm3 in 97%, protein lower than 80 mg/dl in 99%, normal blood-CSF barrier function in 76%, increased IgG local production around 53% and oligoclonal IgG bands by isoelectric focusing in 85% of the definite MS patients. The diagnostic accuracy of the quantitative analysis was lower than the qualitative. The detection of oligoclonal bands was especially important in the cases of normal quantitative assays of IgG. In addition, we found a lower frequency of inflammatory reaction in CSF in our MS cases, in comparison to some European studies.