Prevalence and epidemiology of stroke in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). OBJECTIVE: To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients. METHODS: Systematic review and meta-analysis of registry-based and cohort studies. RESULTS: Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3-4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97-3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8-4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2-1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27-3.41) and ICH (RR: 2.31; 95% CI 1.04-5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9-24.7%) for dyslipidaemia, 18.2% (95% CI 5.9-35.3%) for hypertension and 5.4% (95% CI 2.1-10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (ß = - .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0-5) attenuation of the risk of AIS. CONCLUSION: The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience.

BACKGROUND: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. METHODS: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. RESULTS: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. CONCLUSIONS: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To assess whether statins (3­hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). APPROACH: A systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. RESULTS: We identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-ß. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.901.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.364.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-ß were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. CONCLUSIONS: We detected no benefit from statin treatment as add-on to IFN-ß in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.

Primary Sjögren's syndrome (pSS)-related cerebellar ataxia: a systematic review and meta-analysis.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates of the exocrine glands, particularly the salivary and lacrimal glands, resulting in oral and ocular dryness. pSS has been linked to various neurological manifestations, including cerebellar dysfunction. We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related cerebellar ataxia. METHODS: A systematic literature search in the PubMed database was performed and 19 papers were eligible to be included in this paper. RESULTS: The pooled prevalence of cerebellar ataxia in pSS is estimated to be 1.5% (95% CI 0.3-6.8%). pSS patients with cerebellar involvement have a female-to-male ratio of 6:1. Although most of the patients are adults in their fifth decade of life when diagnosed, cases of children with pSS and cerebellar involvement have been reported. Typical cerebellar ataxia related to pSS manifests with vermian dysfunction, namely gait ataxia and/or cerebellar speech. Cerebellar ataxia due to pSS may also mimic degenerative cerebellar ataxia, especially when the onset is progressive. CONCLUSIONS: The diagnostic approach to a patient with cerebellar ataxia of unknown etiology should include evaluation for an underlying pSS. A thorough history and clinical examination, antibody testing, brain MRI imaging and/or MRS of the cerebellum will assist in establishing the diagnosis. Setting up a joint neuro-rheumatology clinic can be valuable given that rheumatic and neurological diseases share comorbidities.

Bilateral non-bifurcating carotid arteries in a patient with recurrent cerebrovascular events.

INTRODUCTION: Among congenital anomalies of the carotid artery circulation, the presence of a non-bifurcating carotid artery is extremely rare. Relevant cases with unilateral non-bifurcating carotid artery have scarcely been described in the literature. After extensive literature review, only one case with asymptomatic bilateral non-bifurcating carotid arteries associated with persistent proatlantal artery was identified. METHODS: We present the case of a 40-year-old man with recurrent cerebrovascular events presenting non-bifurcating carotid arteries bilaterally. RESULTS: A 40-year-old man presented in the emergency department with a transient ischemic attack. Past medical history included prior ischemic stroke of unknown etiology in the distribution of the left middle cerebral artery, untreated hyperlipidemia and tobacco use. Complete work-up in order to identify the underlying mechanism of the patient's recurrent cerebrovascular events was negative, except for the finding of non-bifurcating carotid arteries bilaterally, associated with an extensive intracranial anastomosing arterial network. Long-term antiplatelet therapy and statins were administered as secondary stroke prevention therapy. DISCUSSION: Previous reports suggest that non-bifurcating carotid arteries may be associated with atherosclerotic plaque formation in symptomatic cases due to shear stress, tortuosity or other local factors. However, in the absence of atherosclerosis, the pathogenic association of bilateral non-bifurcating carotid arteries with cerebrovascular events remains questionable, but may be considered when other stroke etiologies are excluded.

Cervical duplex ultrasound for the diagnosis of giant cell arteritis with vertebral artery involvement.

Giant cell arteritis (GCA) is a systemic inflammatory arteriopathy of medium and large-sized arteries, predominantly affecting branches of the external carotid artery. Ischemic stroke has been reported in 2.8-7% of patients diagnosed with GCA. The majority of ischemic strokes may involve the posterior circulation as a result of vertebral and/or, less frequently, of basilar artery vasculitis. Prompt diagnosis is crucial since high-dose corticosteroid treatment is highly effective in preventing the occurrence or recurrence of ischemic complications, including posterior circulation ischemic stroke in cases with vertebrobasilar involvement. Cervical duplex sonography (CDS) of the temporal arteries is a powerful diagnostic tool with high sensitivity and specificity for the diagnosis of GCA. In cases with clinical suspicion or a temporal artery ultrasonographic confirmation of GCA, a detailed evaluation of the cervical, axillary, and intracranial arteries with CDS and transcranial-duplex-sonography, respectively, should be part of the ultrasound examination protocol. Specifically, signs of extracranial vertebral artery wall inflammation ("halo" sign) and focal luminar stenoses may be accurately depicted by ultrasounds in high-risk patients or individuals with ischemic stroke attributed to GCA. In this review, we present three cases of GCA and posterior circulation ischemic complications that were initially evaluated with comprehensive neurosonology protocol and were promptly diagnosed with GCA based on the characteristic "halo" sign in the temporal and vertebral arteries. In addition, we discuss the relevant literature concerning the utility of CDS for the early diagnosis of GCA, focusing on the subtype with extracranial arterial involvement, particularly that of the vertebral arteries.