Spinal Cord Ischemia Related to Disc Herniation:Case Report and a Review of the Literature

Symptoms of spinal cord ischemia can mimic myelopathy due to spinal cord compression in the acute phase. Thoracic disc herniation with limited spinal cord compression but rapid progression of neurological symptoms causes a clinical dilemma as to whether emergency decompression should be performed. We report a case of acute progressive myelopathy due to spinal cord ischemia related to thoracic disc herniation initially managed by Th8 laminectomy with reduction of the herniated disc. Repeat imaging showed T2-weighted hyperintensity in the posterior cord. The clinical and radiological course supports posterior spinal artery ischemia. This case illustrates and a review of the literature shows that thoracic disc herniation may be complicated by ischemic myelopathy even in the absence of cord compression

Smoking at time of CIS increases the risk of clinically definite multiple sclerosis

Background: Cigarette smoking is a modifiable risk factor that influences the disease course of patients with multiple sclerosis (MS). However, in patients with a clinically isolated syndrome (CIS), there are conflicting results about the association between smoking and the risk of a subsequent MS diagnosis. The aim of this study was to determine the risk of clinically definite MS (CDMS) in smoking and non-smoking patients at time of a first demyelinating event. Methods: Two hundred and fifty patients, aged 18–50 years, were included in our prospective CIS cohort. At time of the first neurological symptoms, patients completed a questionnaire about smoking habits. Cox regression analyses were performed to calculate univariate and multivariate hazard ratios for CDMS diagnosis in smoking and non-smoking CIS patients. Results: One hundred and fourteen (46%) CIS patients were diagnosed with CDMS during a mean follow-up of 58 months. In total, 79 (32%) patients smoked at time of CIS. Sixty-seven % of the smoking CIS patients were diagnosed with CDMS during follow-up compared to 36% of the non-smoking CIS patients (p < 0.001). Smoking at time of CIS was an independent predictor for CDMS diagnosis (HR 2.3; p = 0.002). Non-smoking CIS patients who had a history of smoking did not have a higher risk for CDMS than those who had never smoked. Conclusions: Smoking at time of CIS was an independent risk factor for a future CDMS diagnosis. This is an additional argument to quit smoking at time of the first attack of suspected MS

HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population

OBJECTIVE: To investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases. METHODS: Blood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG-seropositive and 42 AQP4-IgG-seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors. RESULTS: No significant HLA association was found in MOG-IgG-seropositive patients. The AQP4-IgG-seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707-5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513-8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495-5.042, pc = 0.0199) compared with controls. CONCLUSIONS: The present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG-positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG-positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders

Decreased cerebral perfusion in Duchenne muscular dystrophy patients

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)