Stroke phenotype in cannabis users among young adults with ischemic stroke.

BACKGROUND AND PURPOSE: Incidence of ischemic stroke in young adults has been steadily increasing over the past 20 years. One hypothesis to explain this phenomenon is the increase in the use of illicit drugs, including cannabis. However, the mechanisms and the clinical presentation of ischemic stroke associated with cannabis use are unclear. The objective of this study was to describe the phenotype of ischemic stroke in cannabis users compared to nonusers among a population of young adults with a first-ever ischemic stroke. METHODS: Patients aged 18-54 years consecutively hospitalized in a university department of neurology for a first-ever ischemic stroke from January 2017 to July 2021 were included. Drug use over the past year was assessed by a semistructured interview, and the stroke phenotype was described using the ASCOD classification. RESULTS: A total of 691 patients, including 78 of 691 (11.3%) cannabis users, were included. Cannabis use was independently associated with potential A1 (odds ratio [OR] = 3.30, 95% confidence interval [CI] = 1.45-7.5, p = 0.004) and uncertain A2 (OR = 13.1, 95% CI = 2.89-59.4, p < 0.001) atherosclerotic cause of stroke after adjustment for vascular risk factors including tobacco and other drug use. Moreover, the association of atherosclerosis and cannabis use was significant for frequent (OR = 3.13, 95% CI = 1.07-8.6, p = 0.030) and daily cannabis use (OR = 4.43, 95% CI = 1.40-13.4, p = 0.008), but not for occasional use. CONCLUSIONS: We found a significant, independent, and graded association of cannabis use with the atherosclerotic stroke phenotype.

Leptomeningeal enhancement on post-contrast FLAIR images for early diagnosis of Susac syndrome.

BACKGROUND: Leptomeningeal enhancement (LME) is a key feature of Susac syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted images (T1-WI). OBJECTIVE: As post-contrast fluid-attenuated inversion recovery (FLAIR) may be more sensitive, our aim was to assess LME in SuS on this sequence. METHODS: From 2010 to 2020, 20 patients with definite SuS diagnosis were retrospectively enrolled in this multicentre study. Two radiologists independently assessed the number of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the interrater agreement was calculated. RESULTS: Thirty-five magnetic resonance imagings (MRIs) were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WI in 19 patients. In terms of patients, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (17/17 (100%) vs. 15/19 (79%), p < 0.05). In terms of sequences, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (19/19 (100%) vs. 16/25 (64%), p < 0.005). LME was disseminated at both supratentorial (19/19) and infratentorial (18/19) levels on post-contrast FLAIR, contrary to post-contrast T1-WI (3/25 and 9/25, respectively). Interrater agreement was excellent for post-contrast FLAIR (κ = 0.95) but only moderate for post-contrast T1-WI (κ = 0.61). CONCLUSION: LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.

Migraine and large artery atherosclerosis in young adults with ischemic stroke.

INTRODUCTION: Migraine is a risk factor for ischemic stroke, but the mechanisms of stroke associated with migraine are debated. The aim of this study was to investigate the association between migraine and large artery atherosclerosis (LAA) in young adults with ischemic stroke. METHODS: Patients aged between 18 and 54 years consecutively treated for first acute ischemic stroke in a university hospital stroke unit between January 2017 and December 2019 were included in this cross-sectional study. Migraine status was systematically assessed by the same headache specialist. Stenotic and nonstenotic LAA of extracranial and intracranial cerebral arteries were evaluated and graded using the ASCOD (atherosclerosis, small-vessel disease, cardiac pathology, other causes, dissection) criteria. We adjusted the association between migraine and LAA for traditional risk factors. RESULTS: A total of 415 patients were included (mean age [standard deviation], 43.9 [8.7] years; 258/415 [62.2%] men). Migraine with aura (MWA) was diagnosed in 76 patients, and migraine without aura (MWoA) in 68 patients. Patients with migraine had fewer traditional cardiovascular risk factors. Stenotic LAA (10/144 [6.9%] vs. 42/271 [15.5%]; p < 0.001) and LAA of any grade (35/144 [24.3%] vs. 138/271 [50.9%]; p < 0.001) were significantly less frequent in patients with migraine than in patients without migraine, respectively. Multivariable analysis adjusting for age, sex, overweight, tobacco use, hypertension, diabetes, and hyperlipidemia showed a negative association between migraine and LAA of any grade (odds ratio [OR] = 0.44, 95% confidence interval [CI: 0.254-0.78], p = 0.005). This negative association was found for both MWoA (OR = 0.42, 95% CI [0.204-0.88], p = 0.020) and MWA (OR = 0.47, 95% CI [0.228-0.96], p = 0.037) compared to no migraine. CONCLUSION: In this study of young adults with ischemic stroke, migraine had a negative association with LAA. This negative association was independent of traditional vascular risk factors and was found for both MWA and MWoA.

Insular functional connectivity in migraine with aura.

INTRODUCTION: Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA. METHODS: Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis. RESULTS: Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO. DISCUSSION: The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA. CONCLUSION: The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA. TRIAL REGISTRATION: NCT02708797.

Atrial fibrillation and migraine with aura in young adults with ischemic stroke.

BACKGROUND: Migraine is associated with an increased risk of ischemic stroke. The associations are stronger in migraine with aura than in migraine without aura, in women than in men, and in younger subjects. However, the mechanisms by which migraine might increase the risk of ischemic stroke are debated. METHODS: We analysed the associations between migraine without aura and migraine with aura and the causes of ischemic stroke in patients aged 18-54 years treated consecutively in a university hospital stroke center. RESULTS: A total of 339 patients (mean/SD age 43.8/8.8 years, 62.83% male) were included. Migraine with aura was diagnosed in 58 patients, and migraine without aura in 54 patients. Patients with migraine with aura were younger and had fewer traditional cardiovascular risk factors than patients with no migraine. Migraine with aura was strongly associated with atrial fibrillation (odds ratio, 5.08; 95% confidence interval, 1.24-21.92; p = 0.011) and negatively associated with atherosclerosis (odds ratio, 0.29; 95% confidence interval, 0.05-0.97; p = 0.033) and small vessel disease (odds ratio, 0.13; 95% confidence interval, 0.00-0.87; p = 0.022). No other cause of stroke was significantly associated with migraine. The most common cause of stroke was atherosclerosis in no-migraine patients, dissection in migraine without aura patients and patent foramen ovale in migraine with aura patients. Atrial fibrillation was, together with dissection, the second leading cause of stroke in migraine with aura patients, accounting for 10.34% of cases in this subgroup. CONCLUSION: We showed that atrial fibrillation was a common cause of ischemic stroke in young adults with migraine with aura.

Functional connectivity of hypothalamus in chronic migraine with medication overuse.

OBJECTIVE: To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. METHODS: Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. RESULTS: All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = -44, z = -62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. CONCLUSION: An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.

Late-onset neutropenia and neurological relapse, during long-term rituximab therapy in myelin oligodendrocyte glycoprotein-antibody spectrum disorder.

Late-onset neutropenia after rituximab therapy (LONART) is defined as a fall in the absolute neutrophil count below 500/mm3 at least 3 weeks after rituximab infusion, in the absence of any other explanation. LONART is rare during dysimmune conditions but can be life-threatening. We report on two patients with LONART and associated neurological relapse occurring in myelin oligodendrocyte glycoprotein (MOG)-antibody spectrum disorders. Rituximab was reintroduced in one patient, while the second patient was switched to tocilizumab. LONART can occur during anti-MOG spectrum disorders. Neurologists should be aware of this rare and treatable complication. Regular monitoring of blood cell counts is needed, and patients should be informed of the need to consult their physician if symptoms of infection appear.

Cryptogenic Ischemic Stroke in Migraine: Role of Patent Foramen Ovale.

Introduction: Migraine with aura (MWA) has been associated with cryptogenic ischemic stroke (CIS) after adjustment for the presence of a patent foramen ovale (PFO) assessed by a transcranial Doppler. This study aimed at evaluating the association of MWA with causal PFO assessed by Transesophageal echocardiography (TEE) in CIS. Methods: Patients aged 18-54 years consecutively treated for first acute ischemic stroke in a university hospital stroke unit, between January 2017 and December 2019, were included in this cross-sectional study. Associations between migraine subtypes and PFO were tested for all PFO, possibly causal PFO (PFO with large shunt and/or atrial septal aneurysm [ASA]), and the probably causal PFO subset (large shunt and/or ASA, plus risk of paradoxical embolism [RoPE] score ≥ 7). We adjusted the association between migraine subtypes and possibly causal PFO, which included the probably causal subset for age, sex, large artery atherosclerosis, and small vessel disease. Results: A total of two hundred and two patients with CIS were included, of whom 42/202 (20%) had MWA, 32/202 (15%) had migraine without aura, and 128/202 (63%) had no migraine. MWA was associated with possibly causal PFO (OR = 4.0, 95%CI [1.78-9.3], P < 0.001) and with probably causal PFO (OR = 5.4, 95%CI [2.37-13], P < 0.001). In a multinomial logistic regression analysis, MWA remained associated with possibly causal PFO (OR = 3.24, 95% CI [1.45-7.2], P = 0.004). Conclusion: In a young adult population with CIS, MWA was strongly associated with possibly causal PFO, i.e., with a large shunt or combined with an interatrial septal aneurysm.

Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression.

BACKGROUND: It is currently unknown whether early B cell reconstitution (EBR) in MS patients under rituximab is associated with a risk of relapse or progression. OBJECTIVES: Analyzing EBR in rituximab-treated patients and its putative association with clinical findings. METHODS: Prospective lymphocytes immunophenotyping was performed in a monocentric cohort of MS patients treated by rituximab for 2 years. EBR was defined when B cells concentration was > 5 cells/mm3. B cell subsets were retrospectively associated with clinical data. Clinical and radiological monitoring included relapses, EDSS (Expanded Disability Status Scale), SDMT (Symbol Digit Modalities Test), and MRI. RESULTS: 182 patients were analyzed (61 remitting-relapsing and 121 progressive-active). 38.5% experienced EBR at least once, but very few (7/182) showed systematic reconstitution. Most patients remained stable upon treatment, regardless of the occurrence of EBR. Dynamics of B cell reconstitution featured increased naïve/transitional B cells, and decreased memory subsets. Homeostasis of the B cell compartment differed at baseline between patients experiencing or not EBR upon treatment. In patients with EBR, reciprocal dynamics of transitional and pro-inflammatory double-negative B cell subsets was associated with better response to rituximab treatment. CONCLUSION: EBR is common in rituximab-treated MS patients and is not associated with clinical disease activity. EBR in the peripheral blood may reflect regulatory immunological phenomena in subgroup of patients.

Venetoclax with high-dose methotrexate and rituximab seem effective and well-tolerated in the treatment of central nervous system involvement of chronic lymphocytic leukemia: A case report.

Venetoclax with high-dose methotrexate and rituximab seem effective and safe to treat central nervous system involvement of chronic lymphocytic leukemia.

What is the Relevance of the Systematic Use of Gadolinium During the MRI Follow-Up of Multiple Sclerosis Patients Under Natalizumab?

BACKGROUND: Multiple sclerosis (MS) patients represent a population potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity. OBJECTIVE: This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment. METHODS: The MRI data results were retrospectively reviewed in a monocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed. RESULTS: A total of 129 patients were included in this study (65% female, mean age = 41 years, mean treatment duration 6.5 years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3 MRIs showed a new enhancing lesion, systematically encountered after treatment discontinuation. CONCLUSION: According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab.