Headache; rare presentation of miller fisher syndrome

Introduction: Miller Fisher is a known variant of Guillain Barre Syndrome with the triad of ophthalmoplegia, areflexia and ataxia. This case will discuss a rare presentation with a severe headache. Case Presentation: A 51 year old male initially presented with blurry vision and a severe occipital headache with no papilledema. Patient endorsed having an upper respiratory-like illness 1-2 weeks prior to symptoms onset. Initial head CT was negative. The lumbar puncture was performed, and noted to have an opening pressure of 320 mmHg. Other values were normal. Serum studies were positive for GQ1B antibody. This gave the diagnosis of Miller Fisher Syndrome. IVIG treatment was initiated and symptoms largely improved, including the headache. Severe headache is usually not a symptom of Miller Fisher Syndrome. In a case series including 27 patients with Miller Fisher Syndrome, only two reported a headache. One study proposed that an increase in CSF protein could lead to outflow obstruction, increasing ICP and leading to headaches. However our patient’s CSF protein was 45 mg/dl. Another potential explanation could be injury to the ventral and dorsal roots of cranial nerves by antibodies to GD3 and GD1b. A different study discovered that along with antibodies to GQ1b, in rare cases patients also develop antibodies to GD3 and GD1b. With such a small percentage of patients being positive for the antibodies to GD3 and GD1b, it was theorized that this could be the reason for the headache. Unfortunately, in our case, both GD1b and GD3 antibodies were negative. Discussion: Headaches are a rare symptom of Miller Fisher with unknown pathophysiology. More research is needed, especially in antibody related nerve damage. Nonetheless, physicians need to identify this symptom and know headaches are usually self-limiting

Brain and spinal cord MRI lesions in primary progressive vs. relapsing-remitting multiple sclerosis

Background: Primary progressive (PP) multiple sclerosis (MS) is considered a clinically distinct entity from the spectrum of relapsing-remitting (RR) forms of the disease. Objective: To compare the presence of brain and spinal cord lesions between PP and RR subjects. Methods: We studied people with PPMS [n = 40, 17 (42.5%) men, age 50.7 ± 7.7 years, disease duration 10.1 ± 7.4 years, Expanded Disability Status Scale (EDSS) score 4.6 ± 2.1] and RRMS [n = 40, 12 (30%) men, age 47.9 ± 4.2, disease duration 13.7 ± 5.9, EDSS 1.7 ± 1.3]. MRI of the brain and full spinal cord at 1.5T was analyzed to define patients having: 1. brain only, 2. spinal cord only, or 3. brain and spinal cord MS lesions. Results: Lesions in the brain only were less common in PP (n = 1, 2.5% of people) than RR (n = 10, 25%) (Fisher's exact p = 0.007). Lesions in the spinal cord only (PP: n = 6, 15%, RR: n = 3, 7.5%, p = 0.481) or brain plus spinal cord (PP: n = 33, 83%, RR: n = 27, 68%, p = 0.196) were similar between groups. PP had higher EDSS and timed 25-ft walk (Wilcoxon tests, both p < 0.001), higher age (t-test p = 0.049), lower disease duration (t-test, p = 0.02), and a similar sex ratio (Fisher's exact p = 0.352) vs. RR. Conclusions: We report a topographic difference in MRI lesion involvement between PPMS and RRMS. Lesions restricted to the brain are more common in RRMS. These findings provide support to the notion that PP may have features distinctive from the RR spectrum of the disease. Longitudinal comparisons and quantitative MRI analysis would be necessary to confirm and extend these results. Keywords: Multiple sclerosis, MRI, Brain, Spinal cord, Primary progressive, Lesion

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.)