Autonomic nervous system disorders in multiple sclerosis.

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS), which also affects the autonomic nervous system (ANS). Manifestations of MS in the ANS include urological, sexual, gastrointestinal, cardiovascular, and thermoregulatory disorders as well as increased fatigue. These problems are common yet are often underestimated due to the non-specificity of the symptoms and the limited evaluation of the ANS in the usual clinical practice. Most of these symptoms seem to be related to localized lesions in the CNS. However, the mechanisms by which these disorders are caused in MS have not been fully investigated, thus preventing any focused etiological treatment. The most common disorders of the ANS in MS represent a challenge for clinicians due to the variability of the clinical picture and our minimal data on their diagnosis and treatment. Early diagnosis and initiation of individualized treatment regimens, often in need of multiple approaches, seem to yield the best results in managing ANS dysfunction in MS patients.

Is may be Time to Update the Current Definitions of the Types of Multiple Sclerosis.

Since 1996, a debate regarding the cause of disability in Multiple Sclerosis (MS) and the accuracy of the current definitions of MS types has not subsided. Recently, many researchers presented evidence supporting that relapses are a significant causative factor of the increased disability in multiple sclerosis (MS), primarily, but not exclusively, indicating that the disease's progression, which is independent of any relapse activity, plays a significant role in the patient's deterioration mainly in adult MS cases, and this gradually becomes the principle pathway with which disabilities compound in MS patients. We propose an updated definition of the types of MS, highlighting the central role of the disease's progression.

A probable role of copper in the comorbidity in Wilson's and Creutzfeldt-Jakob's Diseases: a case report.

BACKGROUND: To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson's and Creutzfeldt-Jakob disease (CJD), linked through copper. CASE PRESENTATION: A 44-year-old male with a history of inherited Wilson's disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson's disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14-3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient's CSF, using the RT-QuIC method, which has a 99.4-100% specificity for CJD, made the diagnosis of CJD highly probable. CONCLUSION: This is the first report of Wilson's and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD.

Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer's disease.

Background Alzheimer's disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid ß 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%. Recently, we found that CSF amyloid ß precursor-like protein-1 (APLP1) and neuronal pentraxin receptor (NPTXR) are promising biomarkers of AD. The aim of the present study is to validate CSF APLP1 and NPTXR as biomarkers of AD severity. Methods APLP1 and NPTXR concentrations were measured in the CSF of patients with mild cognitive impairment (MCI) (n = 14), mild AD (n = 21), moderate AD (n = 43) and severe AD (n = 30) using enzyme-linked immunosorbent assays (ELISAs). Results CSF APLP1 and NPTXR were not associated with age or sex. CSF APLP1 was not different between any of the AD severity groups (p = 0.31). CSF NPTXR was significantly different between MCI and mild AD (p = 0.006), mild and moderate AD (p = 0.016), but not between moderate and severe AD (p = 0.36). NPTXR concentration progressively declined from MCI to mild, to moderate and to severe AD patients (p < 0.0001, Kruskal-Wallis test). CSF NPTXR positively correlated with the Mini-Mental Status Examination (MMSE) score (p < 0.001). Conclusions NPTXR concentration in CSF is a promising biomarker of AD severity and could inform treatment success and disease progression in clinical settings.

Does cognitive dysfunction correlate with neurofilament light polypeptide levels in the CSF of patients with multiple sclerosis?

OBJECTIVE: To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive dysfunction in MS. METHODS: This observational case-control study included patients with MS. CSF levels of NfL were determined using enzyme-linked immunosorbent assay. Cognitive function was measured with the Brief International Cognitive Assessment for MS (BICAMS) battery and Paced Auditory Serial Addition Test (PASAT3), standardized to the Greek population. RESULTS: Of 39 patients enrolled (aged 42.7 ± 13.6 years), 36% were classified as cognitively impaired according to BICAMS z-scores (-0.34 ± 1.13). Relapsing MS was significantly better than progressive forms regarding BICAMS z-score (mean difference [MD] 1.39; 95% confidence interval [CI] 0.54, 2.24), Symbol Digit Modality Test score (MD 1.73; 95% CI 0.46, 3.0) and Greek Verbal Learning Test (MD 1.77; 95% CI 0.82, 2.72). An inversely proportional association between CSF NfL levels and BICAMS z-scores was found in progressive forms of MS (rp = -0.944). CONCLUSIONS: This study provides preliminary evidence for an association between CSF NfL levels and cognition in progressive forms of MS, which requires validation in larger samples.