Categories
Multiple sclerosis Neuroinflammation Neurosarcoidosis

How does CSF analysis distinguish MS from neurosarcoidosis?

Distinguishing neurosarcoidosis from multiple sclerosis based on CSF analysis: A retrospective cohort study.

Arun T, Pattison L, Palace J.

Neurology 2020 (online ahead of print)

Abstract

Objective: 

To characterize a cohort of patients with neurosarcoidosis with particular focus on CSF analysis and to investigate whether CSF values could help in distinguishing it from multiple sclerosis (MS).

Methods: 

This retrospective cohort study enrolled 85 patients with a diagnosis of neurosarcoidosis (possible, probable, or definite). CSF total protein, white cell count, and angiotensin-converting enzyme levels were measured. CSF and serum oligoclonal immunoglobulin G (IgG) patterns were analyzed with the use of odds ratios and binary logistic regression.

Results: 

Eighty patients had a probable (nonneural positive histology) or definite (neural positive histology) diagnosis of neurosarcoidosis. Most frequent findings on MRI were leptomeningeal enhancement (35%) and white matter and spinal cord involvement (30% and 23%). PET scan showed avid areas in 74% of cases. CSF analysis frequently showed lymphocytosis (63%) and elevated protein (62%), but CSF-selective oligoclonal bands were rare (3%). Serum ACE levels were elevated in 51% of patients but in only 14% of those with isolated neurosarcoidosis. Elevated CSF ACE was not found in any patient.

Conclusions: 

Large elevations in total protein, white cell count, and serum ACE occur in neurosarcoidosis but are rare in MS. The diagnostic use of these tests is, however, limited because minimal changes may occur in both. MS clinical mimics in neurosarcoidosis are not common, and intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is rare in neurosarcoidosis but occurs in 95% to 98% cases of MS. We suggest caution in making a diagnosis of neurosarcoidosis when intrathecal oligoclonal IgG synthesis is found.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): differential diagnosis

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MRI scan. NIH Image Gallery on Flikr. https://www.flickr.com/photos/nihgov/30754695411

Categories
Stroke

Is thrombolysis beneficial when time of stroke onset is unknown?

Efficacy and safety of thrombolytic therapy for stroke with unknown time of onset: a meta-analysis of observational studies.

Zhu RL, Xu J, Xie CJ, Hu Y, Wang K.

J Stroke Cerebrovasc Dis 2020 (Epub ahead of print).

Abstract

BACKGROUND:

Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies available for patients with known-onset stroke (KOS). Whether rt-PA treatment would improve functional outcomes in patients with stroke with unknown time of onset (UTOS) is undetermined, we aimed to systematically assess the efficacy and safety of thrombolysis for UTOS patients in this meta-analysis.

METHODS:

A systematic literature search of Medline, Embase, and Cochrane Library was conducted. We considered the relevant data comparing thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients or thrombolyzed UTOS patients versus thrombolyzed KOS patients. Treatment efficacy and safety were measured according to modified Rankin Scale scores of 0-2 (mRS 0-2), and the presence of spontaneous intracerebral hemorrhage (SICH) or mortality at 90 days respectively.

RESULTS:

A total of 11 studies with 2581 patients meeting the inclusion criteria were included in the meta-analysis. All the patients had an ischemic lesion that was assessed by imaging including computed tomography or magnetic resonance imaging. Among these studies, 6 compared the thrombolytic efficacy in thrombolyzed UTOS patients with that in nonthrombolyzed UTOS patients (mRS 0-2: odds ratio [OR] =1.76, 95% confidence interval [CI] 1.11-2.81, P = .02), and 8 studies compared thrombolyzed UTOS patients with thrombolyzed KOS patients (mRS 0-2: OR = 0.87, 95% CI 0.66-1.15, P = .33). The incidence of SICH and mortality at 90 days had no difference between thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients and thrombolyzed UTOS patients versus thrombolyzed KOS patients (all P > .05).

CONCLUSIONS:

Data from observational studies suggest that thrombolysis for unknown time of onset stroke UTOS had significantly favorable outcomes at 90 days compared with nonthrombolyzed patients.

This paper is cited in the neurochecklist:

Thrombolysis: clinical use

By Marvin 101 – Own work, CC BY-SA 3.0, Link

Abstract link

Categories
Multiple sclerosis

Does breastfeeding influence the risk of postpartum MS relapses?

Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis.

Krysko KM, Rutatangwa A, Graves J, Lazar A, Waubant E.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Multiple sclerosis (MS) relapses may be increased in the postpartum period, and whether breastfeeding is associated with reduction in the risk of postpartum relapses remains controversial.

METHODS

PubMed and Embase were searched for studies assessing the association between breastfeeding and MS disease activity published between January 1, 1980, and July 11, 2018, as well as reference lists of selected articles.

RESULTS:

The search identified 462 unique citations, and 24 (2974 women) satisfied eligibility criteria and were included, of which 16 were included in the quantitative meta-analysis. The pooled summary odds ratio for the association of breastfeeding with postpartum relapses was 0.63 (95% CI, 0.45-0.88; P = .006) compared with a reference of nonbreastfeeding. Pooled adjusted hazard ratio across 4 studies that reported this finding was 0.57 (95% CI, 0.38-0.85; P = .006). There was moderate heterogeneity (I2 = 48%), which was explained by variable prepregnancy relapse rate, postpartum follow-up duration, and the publication year. A stronger association was seen in studies of exclusive rather than nonexclusive breastfeeding, although both demonstrated an association. Studies were rated at moderate and serious risk of bias, with concern for residual confounding, although sensitivity analysis including only moderate quality studies was consistent with a protective outcome of breastfeeding.

CONCLUSIONS:

These findings suggest that breastfeeding is protective against postpartum relapses in multiple sclerosis, although high-quality prospective studies to date are limited and well-designed observational studies that aim to emulate a randomized trial would be of benefit.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): poor prognostic factors

Mothers from Eastern Ukraine attend Training on Breastfeeding. UNICEF Ukraine on Flickr. https://www.flickr.com/photos/unicefua/17063692941

Abstract link

Categories
Vascular

Is dabigatran as effective as warfarin for cerebral vein thrombosis?

RE-SPECT CVT Study Group. Safety and efficacy of dabigatran etexilate vs dose-adjusted warfarin in patients with cerebral venous thrombosis: a randomized clinical trial.

Ferro JM, Coutinho JM, Dentali F, et al;

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.

METHODS:

RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.

INTERVENTIONS:

Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks.

RESULTS:

In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).

CONCLUSIONS:

This trial found that patients who had cerebral vein thrombosis anticoagulated with either dabigatran or warfarin had low risk of recurrent venous thromboembolic events, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT.

This paper is cited in the neurochecklist:

Cerebral vein thrombosis (CVT): anticoagulant treatment

By MarinaVladivostokOwn work, CC0, Link

Abstract link

 

Categories
Neuroinflammation

How effective is stem cell transplantation for NMO?

Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica. 

Burt RK, Balabanov R, Han X, et al.

Neurology 2019; 93:e1732-e1741.

Abstract

OBJECTIVE:

To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) could be a salvage therapy for neuromyelitis optica spectrum disorder (NMOSD).

METHODS:

Thirteen patients were enrolled in a prospective open-label cohort study (11 NMOSD aquaporin-4-immunoglobulin G [AQP4-IgG]-positive, 1 NMOSD without AQP4, and 1 NMOSD AQP4-IgG-positive with neuropsychiatric systemic lupus erythematosus [SLE]). Following stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim, patients were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2, rATG (thymoglobulin) given IV at 0.5 mg/kg on day -5, 1 mg/kg on day -4, and 1.5 mg/kg on days -3, -2, and -1 (total dose 6 mg/kg), and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. AQP4-IgG antibody status was determined by Clinical Laboratory Improvement Amendments-validated ELISA or flow cytometry assays. Cell-killing activity was measured using a flow cytometry-based complement assay.

RESULTS:

Median follow-up was 57 months. The patient with coexistent SLE died of complications of active lupus 10 months after HSCT. For the 12 patients with NMOSD without other active coexisting autoimmune diseases, 11 patients are more than 5 years post-transplant, and 80% are relapse-free off all immunosuppression (p < 0.001). At 1 and 5 years after HSCT, Expanded Disability Status Scale score improved from a baseline mean of 4.4 to 3.3 (p < 0.01) at 5 years. The Neurologic Rating Scale score improved after HSCT from a baseline mean of 69.5 to 85.7 at 5 years (p < 0.01). The Short Form-36 health survey for quality of life total score improved from mean 34.2 to 62.1 (p = 0.001) at 5 years. In the 11 patients whose baseline AQP4-IgG serostatus was positive, 9 patients became seronegative by the immunofluorescence or cell-binding assays available at the time; complement activating and cell-killing ability of patient serum was switched off in 6 of 7 patients with before and after HSCT testing. Two patients remained AQP4-IgG-seropositive (with persistent complement activating and cell-killing ability) and relapsed within 2 years of HSCT. No patient with seronegative conversion relapsed.

CONCLUSION:

Prolonged drug-free remission with AQP4-IgG seroconversion to negative following nonmyeloablative autologous haematopoietic stem cell transplant warrants further investigation.

This paper is cited in the neurochecklist:

Neuromyelitis optica (NMO): treatment

By FnaqOwn work, CC BY-SA 4.0, Link

Abstract link

Categories
Vascular malformations

Is stereotactic radiosurgery beneficial for cerebral cavernous malformations?

Stereotactic radiosurgery for cerebral cavernous malformations: a systematic review.

Poorthuis MHF, Rinkel LA, Lammy S, Al-Shahi Salman R.

Neurology 2019; 93:e1971-e1979.

Abstract

OBJECTIVE:

The efficacy of stereotactic radiosurgery (SRS) for the treatment of cerebral cavernous malformations (CCMs) is uncertain, so we set out to quantify clinical outcomes after SRS for CCM and compare them to microsurgical excision or conservative management.

METHODS:

We searched Ovid Medline and Ovid EMBASE from inception until June 1, 2018, for peer-reviewed publications describing clinical outcomes after SRS for ≥10 people with CCM in cohorts with or without a comparison group treated with neurosurgical excision or conservative management. Two reviewers independently extracted data from the included studies to quantify cohort characteristics and the incidence of the primary outcome (death attributable to CCM or its treatment) and secondary outcomes (incident nonfatal symptomatic intracerebral hemorrhage [ICH] and incident nonhemorrhagic persistent focal neurologic deficit [FND]). We assessed whether comparative studies showed a dramatic association (meaning the conventionally calculated probability comparing 2 differently managed patient groups from the same population was <0.01 with a rate ratio greater than 10).

RESULTS:

We included 30 cohort studies involving a total of 1,576 patients undergoing SRS for CCM. Four nonrandomized studies compared SRS to other treatment strategies, but did not demonstrate dramatic associations. During a median follow-up of 48 (interquartile range 35-62) months after SRS, the annual incidences (95% confidence interval) of outcomes were death 0.18% (0.10-0.31), ICH 2.40% (2.05-2.80), FND 0.71% (0.53-0.96), and the composite of death, ICH, or FND 3.63% (3.17-4.16). Outcomes did not differ by CCM location or type of SRS.

CONCLUSION:

After stereotactic radiosurgery for cerebral cavernous malformations, the annual incidences of death, intracerebral haemorrhage, and focal neurologic deficit are <5% and seem comparable to outcomes without SRS. A randomized trial of SRS for CCM is needed.

This paper is cited in the neurochecklist:

Cerebral cavernous malformations (cavernomas): non-surgical treatments

By Karlo J Lizarraga and Antonio AF De Salles – https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-469, CC BY 2.5, Link

Abstract link

Categories
Neurochecklists updates

Video: getting a handle on neurology

Neurochecklists is a comprehensive and practical neurology database.

It is an easy to use handy and searchable reference tool.

This short video shows how neurochecklists gives you a handle on neurology.

Categories
Parkinson's disease

Does Parkinson’s disease increase the risk of stroke?

Does Parkinson’s disease increase the risk of cardiovascular events? A systematic review and meta-analysis.

Alves M, Caldeira D, Ferro JM, Ferreira JJ.

Eur J Neurol 2020; 27:288-296.

Abstract

BACKGROUND AND PURPOSE:

The impact of Parkinson’s disease (PD) on the risk of cardiovascular disease is poorly known. The aim was to systematically review observational studies evaluating the association between PD and cardiovascular events.

METHODS:

MEDLINE through PubMed, the Web of Science and Cochrane Central Register of Controlled Trials with conference proceedings were searched from inception to 4 July 2019. Two reviewers independently selected studies comparing cardiovascular events between Parkinson’s disease and control groups. Ischaemic stroke, myocardial infarction and cardiovascular mortality were the outcomes of interest. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. The study protocol was registered at PROSPERO: CRD42017076527.

RESULTS:

Eleven studies were included: nine cohort studies and two case-control studies. PD was associated with a significantly increased risk of stroke (nine studies: OR 1.66, 95% CI 1.19, 2.34; I2  = 50%). No significant differences were detected regarding myocardial infarction risks (eight studies: OR 1.15, 95% CI 0.72, 1.83; I2  = 76%) nor cardiovascular mortality risks (seven studies: OR 1.11, 95% CI 0.85, 1.45; I2  = 47%) in PD patients.

CONCLUSIONS:

The best evidence available showed an association between Parkinson’s disease and increased risk of stroke. The risk of myocardial infarction and cardiovascular mortality was not different in PD and non-PD individuals.

This paper is cited in the neurochecklist:

Parkinson’s disease (PD): cognitive and ischaemic features

By Mikael Häggström, based on image by Andrew Gillies/User:Anaru – Derivative of File:Basal ganglia circuits.png, CC BY-SA 3.0, Link

Abstract link

Categories
Multiple sclerosis

How long can the pre-symptomatic phase of MS last?

Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis.

Bjornevik K, Munger KL, Cortese M, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.

OBJECTIVE:

To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.

METHODS:

Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.

RESULTS:

Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).

CONCLUSIONS:

The levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): non-modifiable risk factors

By GerryShaw – Standard tissue culture and immunofluorescencePreviously published: Unpublished, CC BY-SA 3.0, Link

Abstract link