Rating neurologic impairment in multiple sclerosis

Kurtzke, John F.

doi:10.1212/wnl.33.11.1444

Cited by 13,452 publications

(8,871 citation statements)

References 11 publications

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“…The EDSS is the most widely used disability measure in MS studies; a higher score denotes more severe disability 22. The SDMT is a measure of processing speed, one of the most‐commonly affected cognitive domains in MS; lower scores indicate more impaired processing speed 23.…”

Section: Methodsmentioning

confidence: 99%

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Nourbakhsh

Bhargava

Tremlett

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children.MethodsParticipants with pediatric‐onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox‐proportional hazard models were used.ResultsUsing global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota‐derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota‐derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4–34%) and 32% (95% CI: 16–44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk.InterpretationTrp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.

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Section: Methodsmentioning

confidence: 99%

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Nourbakhsh

Bhargava

Tremlett

et al. 2018

Ann Clin Transl Neurol

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“…However, very little is known about CSF UA levels in NMOSDs. Therefore, we performed a hospitalized‐based study to investigate CSF UA levels in NMOSD patients and analyzed the correlation between CSF UA levels and clinical characteristics involving disease duration, disease disability assessed by the Expanded Disability Status Scale (EDSS) score (Kurtzke, 1983), and blood–brain barrier (BBB) integrity.…”

Section: Introductionmentioning

confidence: 99%

Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Shu

Zhang

et al. 2016

Brain and Behavior

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IntroductionPrevious studies have shown that serum uric acid (UA) modulates outcomes of neurological diseases, although little is known about cerebrospinal fluid (CSF) UA levels in neuromyelitis optica spectrum disorders (NMOSDs).MethodsCerebrospinal fluid and serum UA levels were measured in samples from 68 patients, including NMOSDs during relapse (n = 38) and controls with noninflammatory and non‐neurodegenerative diseases (CTLs, n = 30). Correlation analysis was performed between CSF UA and clinical characteristics, serum UA, and blood–brain barrier integrity in NMOSDs.ResultsCerebrospinal fluid UA levels in NMOSDs were significantly higher than in CTLs (p = .002), while serum UA differences between NMOSDs and CTLs were not statistically significant. In NMOSDs, CSF UA levels were significantly higher in patients with an impaired blood–brain barrier than in patients with an intact one (p < .001), and significantly higher in longer disease duration than in shorter disease duration patients (p = .002). CSF UA levels were also significantly higher in active patients upon MRI than in inactive patients (p < .001), and significantly higher in patients with brain lesions than without brain lesions (p = .024). CSF UA was significantly associated with the serum UA levels (r = .454, p = .002), disease duration (r = .383, p = .018), and blood–brain barrier index (r = .805, p < .001), but did not correlate with age, gender, annualized relapse rate, duration, or severity of NMOSD. Multiple regression analysis demonstrated that CSF UA was independent of the blood–brain barrier index (β = .765, p < .001) and serum UA levels (β = .01, p = .019) in NMOSDs.ConclusionsCerebrospinal fluid UA levels were elevated in NMOSD patients during relapse, and were likely modified by serum UA levels and blood–brain barrier integrity.

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“…CombiWISE10 is a sensitive, continuous composite scale developed and optimized by machine learning that ranges from 0 to 100 and combines EDSS,11 Scripps NRS,12 25 foot walk, and nondominant hand data for nine hole peg test. CombiWISE slope was calculated from linear regression equations for patients with more than 3 CombiWISE data points.…”

Section: Methodsmentioning

confidence: 99%

Pharmacodynamic effects of daclizumab in the intrathecal compartment

Komori

Kósa

Stein

et al. 2017

Ann Clin Transl Neurol

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ObjectiveIt was previously demonstrated that daclizumab therapy normalizes cellular cerebrospinal fluid (CSF) abnormalities typical of multiple sclerosis (MS) in the majority of treated patients. However, CSF cells represent only the mobile portion of intrathecal immune responses. Therefore, we asked whether daclizumab also reverses compartmentalized inflammation and if not, whether residual inflammation correlates with clinical response to the drug.MethodsForty MS patients treated with an intravenous or subcutaneous injection of daclizumab were followed for up to 16 years in two open‐label clinical trials. MRI contrast‐enhancing lesions (CELs), clinical scales, and CSF biomarkers quantified residual disease.ResultsRapid decreases in CELs, sustained throughout the observation period, were observed with daclizumab treatment. Daclizumab therapy induced modest but statistically significant (P < 0.0001) decreases in CSF levels of T‐cell activation marker CD27 and IgG index. Interleukin 2 (IL‐2) CSF levels increased from baseline levels during treatment, consistent with reduced IL‐2 consumption by T cells, as a consequence of daclizumab's saturation of high‐affinity IL‐2 receptors. CSF levels of IL‐12p40, chitinase‐3‐like protein‐1 (CHI3L1), chemokine C‐X‐C motif ligand 13, and neurofilament light chain (NFL) were also significantly reduced by daclizumab. Among them, inhibition of CHI3L1 correlated with inhibition of NFL and with lack of disease progression.InterpretationThese observations confirm daclizumab's direct pharmacodynamics effects on immune cells within central nervous system tissues and identify inhibition of CSF biomarkers of myeloid lineage as a stronger determinant of reduction in clinical MS activity than inhibition of biomarkers of adaptive immunity.

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Rating neurologic impairment in multiple sclerosis

Cited by 13,452 publications

References 11 publications

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Pharmacodynamic effects of daclizumab in the intrathecal compartment

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