scholarly journals Does CSF pleocytosis have a predictive value for disease course in MS?

2019 ◽  
Vol 6 (5) ◽  
pp. e584 ◽  
Author(s):  
Itay Lotan ◽  
Felix Benninger ◽  
Rom Mendel ◽  
Mark A. Hellmann ◽  
Israel Steiner

ObjectiveMS is a demyelinating CNS disorder with a spectrum of clinical patterns regarding course and prognosis. Although several prognostic factors are considered in the initial evaluation of patients, biological markers defining the disease course and guiding treatments are currently lacking. It is unknown whether patients with CSF pleocytosis differ in regard to symptoms, disease course, and prognosis from those without. The aim of this study was to evaluate whether CSF pleocytosis during the initial presentation has an impact on the clinical course and progression of MS.MethodsWe retrospectively evaluated patients attending the MS Clinic at Rabin Medical Center between January 1999 and January 2016 who underwent lumbar puncture (LP) at disease presentation, considering CSF cell count, clinical diagnosis (clinically isolated syndrome [CIS] and relapsing-remitting MS [RRMS]), annualized relapse rate (ARR), paraclinical findings (imaging, CSF oligoclonal bands, and evoked potentials), and disease progression, expressed by the Expanded Disability Status Scale (EDSS).ResultsOne hundred fourteen patients (72 females) underwent LP at disease presentation (RRMS: n = 100, CIS: n = 14). Age at diagnosis was 32.4 ± 12.2 years, and the follow-up time was 9.4 ± 3.8 years. Forty-six patients showed a pleocytic CSF (≥5 cells per μL). Compared with patients with <4 cells per μL, patients with pleocytosis had a higher ARR (0.60 ± 0.09 vs 0.48 ± 0.04; p = 0.0267) and a steeper increase (slope) in the EDSS score throughout the follow-up period (correlation coefficient: r2 = 0.04; p = 0.0251).ConclusionsCSF pleocytosis may be considered a biological unfavorable predictive factor regarding disease course and progression in MS.

2021 ◽  
Vol 3 (3) ◽  
pp. 366-376
Author(s):  
Lorenzo Tonetti ◽  
Federico Camilli ◽  
Sara Giovagnoli ◽  
Vincenzo Natale ◽  
Alessandra Lugaresi

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.


2002 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
M Liguori ◽  
M G Marrosu ◽  
N Milani ◽  
...  

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.


2018 ◽  
Vol 89 (10) ◽  
pp. A18.3-A18
Author(s):  
Lim H ◽  
Whittam D ◽  
Jackson E ◽  
Williams N ◽  
O’Connell D ◽  
...  

BackgroundThe association of N-methyl d-aspartate receptor-antibodies (NMDAR-Abs) and encephalitis is now well recognised. MethodsRetrospective review of frequency of diagnosis and outcomes in encephalitis with NMDAR-Abs identified at the Walton Centre between 2012–2017.ResultsNMDAR-Abs were detected in 29/1131 (3%) of sera and/or CSF samples. Of 20 (69%) patients with encephalitis, 50% were identified in the last two years. Median onset age was 34(17–75) years and 60% (12/20) were female. Median symptom duration before diagnosis was 24(2–720) weeks between 2012–2015, improving to 14(1–96) weeks between 2015–2016. Five patients (25%) had an infectious prodrome (one prior HSV-1 encephalitis). Psychiatric/cognitive symptoms, seizures, and movement disorders were present in 80% (16/20), 70% (14/20), and 55% (11/20) of patients respectively. Three patients had ovarian teratomas.Electroencephalograms were abnormal in 65% (15/23) and MRI brain in 37% (7/19) patients. Unmatched intrathecal oligoclonal bands and CSF pleocytosis were present in 31% (5/16) and 60% (15/25) of samples respectively. Immunotherapy was beneficial in 73% (11/15) of patients. Two patients died (sepsis and multi-organ failure) and two improved spontaneously. At a median follow-up of 9 (5–180) months, 69% (11/16) of patients had an mRS ≤2. ConclusionAlthough the recognition of NMDAR-Ab encephalitis has improved, there is still a significant delay to diagnosis. The majority of patients have good outcomes.


2001 ◽  
Vol 7 (6) ◽  
pp. 359-363 ◽  
Author(s):  
M Tintoré ◽  
A Rovira ◽  
L Brieva ◽  
E Grivé ◽  
R Jardí ◽  
...  

Aim of the study: To evaluate and compare the capacity of oligoclonal bands (OB) and three sets of MR imaging criteria to predict the conversion of clinically isolated syndromes (CIS) to clinically definite multiple sclerosis (CDMS). Patients and methods: One hundred and twelve patients with CIS were prospectively studied with MR imaging and determination of OB. Based on the clinical follow-up (conversion or not conversion to CDMS), we calculated the sensitivity, specificity accuracy, positive and negative predictive value of the OB, and MR imaging criteria proposed by Paty et al, Fazekas et al and Barkhof et al. Results: CDMS developed in 26 (23.2%) patients after a mean follow-up of 31 months (range 12-62). OB were positive in 70 (62.5%) patients and were associated with a higher risk of developing CDMS. OB showed a sensitivity of 81%, specificity of 43%, accuracy of 52%, positive predictive value (PPV) of 30% and negative predictive value (NPV) of 88%. Paty and Fazekas criteria showed the same results with a sensitivity of 77%, specificity of 51%, accuracy of 57%, positive predictive value of 32% and negative predictive value of 88%. Barkhof criteria showed a sensitivity of 65%, specificity of 70%, accuracy of 69%, PPV of 40% and NPV of 87%. The greatest accuracy was achieved when patients with positive OB and three or four Barkhof's criteria were selected. Conclusions: We observed a high prevalence of OB in CIS. OB and MR imaging (Paty's and Fazekas' criteria) have high sensitivity. Barkhof's criteria have a higher specificity. Both OB and MR imaging criteria have a high negative predictive value.


2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.


2015 ◽  
Vol 21 (8) ◽  
pp. 1013-1024 ◽  
Author(s):  
J Kuhle ◽  
G Disanto ◽  
R Dobson ◽  
R Adiutori ◽  
L Bianchi ◽  
...  

Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.


2013 ◽  
Vol 20 (6) ◽  
pp. 733-738 ◽  
Author(s):  
Michelle H Cameron ◽  
Mary Fitzpatrick ◽  
Shannon Overs ◽  
Charles Murchison ◽  
Jane Manning ◽  
...  

Background: In short-term trials, dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS). The tolerability and effects of dalfampridine-ER in clinical practice have not been reported. Objectives: The objective of this paper is to determine the clinical tolerability and effects of dalfampridine on walking and community participation. Methods: All patients at the Portland VA Medical Center prescribed dalfampridine-ER over one year completed the Timed 25-Foot Walk (T25FW), Multiple Sclerosis Walking Scale-12 (MSWS-12), Two-Minute Timed Walk (2MTW), and Community Integration Questionnaire (CIQ) at baseline and follow-up clinic visits. Ongoing use and measures over one year were analyzed. Results: A total of 39 patients (mean age 56.5 years, mean disease duration 19.5 years, 82% male, 38% relapsing–remitting MS, 62% progressive MS) were prescribed dalfampridine-ER. Twenty-four (62%) continued to take dalfampridine-ER. At initial follow-up, all measures improved significantly from baseline (T25FW: –2.7 s, p = 0.004; 2MTW: 41 feet (ft), p = 0.002; MSWS12: –11, p < 0.001; CIQ: 1.2, p = 0.003). At one year, walking endurance and self-perceived walking were still significantly improved (2MTW: 33 ft, p = 0.03; MSWS-12: 5.9, p = 0.007). Conclusions: Dalfampridine-ER was associated with short-term improvements in walking speed and community participation, and sustained improvements in walking endurance and self-perceived impact of MS on walking for one year. Our study supports the utility of this medication in late MS.


2007 ◽  
Vol 13 (8) ◽  
pp. 1033-1037 ◽  
Author(s):  
A.M. Bamer ◽  
K. Cetin ◽  
D. Amtmann ◽  
J.D. Bowen ◽  
K.L. Johnson

Determining multiple sclerosis (MS) clinical course is important in research and clinical practice. However, many patients do not know their clinical course, limiting the option to use self-report in research studies including surveys. In order to address this, we developed a self-report item to be used in self-administered mailed surveys displaying graphically the courses of MS. The validity of this item was then evaluated by comparing physician-assessed disease clinical course to patient response on the self-report item on 94 of 99 consecutive patients seen in an MS specialty clinic. Kappa statistics were calculated comparing self-assessed versus physician-assessed MS clinical course for the four common MS clinical courses (κ=0.45) and for relapsing remitting versus other courses (κ=0.62) indicating substantial agreement. Subsequent administration of the item by mail to 1371 individuals with MS in Washington and Montana determined that while most individuals responded as intended to the item, persons with less than a high school education ( P=0.009) or over the age of 60 ( P = 0.002) were significantly more likely to leave the item blank. It appears that this item may be used to obtain a rough estimate of MS clinical course in research using self-report surveys where physician assessments are impractical. Multiple Sclerosis 2007; 13: 1033—1037. http://msj.sagepub.com


Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2089-2105 ◽  
Author(s):  
Anne Kerbrat ◽  
Charley Gros ◽  
Atef Badji ◽  
Elise Bannier ◽  
Francesca Galassi ◽  
...  

Abstract Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P &lt; 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P &lt; 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P &lt; 0.0001), brainstem (r = 0.45, P &lt; 0.0001) and spinal cord (r = 0.57, P &lt; 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.


2020 ◽  
Vol 7 (4) ◽  
pp. e719 ◽  
Author(s):  
Erik Ellwardt ◽  
Leoni Rolfes ◽  
Julia Klein ◽  
Katrin Pape ◽  
Tobias Ruck ◽  
...  

ObjectiveTo provide first real-world experience on patients with MS treated with the B cell–depleting antibody ocrelizumab.MethodsWe retrospectively collected data of patients who had received at least 1 treatment cycle (2 infusions) of ocrelizumab at 3 large neurology centers. Patients' characteristics including premedication, clinical disease course, and documented side effects were analyzed.ResultsWe could identify 210 patients (125 women, mean age ± SD, 42.1 ± 11.4 years) who had received ocrelizumab with a mean disease duration of 7.3 years and a median Expanded Disability Status Scale score of 3.75 (interquartile range 2.5–5.5; range 0–8). Twenty-six percent of these patients had a primary progressive MS (PPMS), whereas 74% had a relapsing-remitting (RRMS) or active secondary progressive (aSPMS) disease course. Twenty-four percent of all patients were treatment naive, whereas 76% had received immune therapies before. After ocrelizumab initiation (median follow-up was 200 days, range 30–1,674 days), 13% of patients with RRMS/aSPMS experienced a relapse (accounting for an annualized relapse rate of 0.17, 95% CI 0.10–0.24), and 5% of all patients with MS experienced a 12-week confirmed disability progression. Treatment was generally well tolerated, albeit only short-term side effects were recorded, including direct infusion-related reactions and mild infections.ConclusionsWe provide class IV evidence that treatment with ocrelizumab can stabilize naive and pretreated patients, indicating that ocrelizumab is an option following potent MS drugs such as natalizumab and fingolimod. Further studies are warranted to confirm these findings and to reveal safety concerns in the longer-term follow-up.Classification of evidenceThis study provides Class IV evidence that for patients with MS, ocrelizumab can stabilize both treatment-naive and previously treated patients.


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