Early-stage volume losses in the corpus callosum and thalamus predict the progression of brain atrophy in patients with multiple sclerosis.

BACKGROUND: A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. METHODS: To develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS-with either relapsing-remitting MS (86%) or secondary progressive MS (14%)-and 41 healthy controls were included in this longitudinal retrospective analysis over an observational period of approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters. RESULTS: At baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of the corpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition. CONCLUSION: Decreased volumes of the corpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL.

Successful treatment of intractable menstrual migraine with the traditional herbal medicine tokishakuyakusan.

In this report, we present the successful treatment of five consecutive cases of premenopausal women suffering from severe menstrual migraine with tokishakuyakusan (TSS). Two patients were complicated by tension-type headache (TTH), and another patient was by medication overuse headache (MOH). The effects of triptans were limited in all of them. After starting TSS, they showed dramatic improvement in the severity and frequency of their attacks. The patients with TTH and MOH also showed dramatic improvement in their symptoms. TSS could be a promising alternative choice for patients with intractable menstruation-related headaches that are refractory to conventional treatments, including triptans.

MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy.

OBJECTIVE: To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody. METHODS: In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody-positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008-2014). We then analyzed the findings in MOG antibody-positive cases. RESULTS: Three more patients, as well as the index case, were MOG antibody-positive, and all were adult men (median age 37 years, range 23-39 years). The main symptom was generalized epileptic seizure with or without abnormal behavior or consciousness disturbance. Two patients also developed unilateral benign optic neuritis (before or after seizure). In all patients, brain MRI demonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense lesions, which were swollen and corresponded to hyperperfusion on SPECT. CSF studies showed moderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated total protein levels, but myelin basic protein was not elevated. A screening of encephalitis-associated autoantibodies, including aquaporin-4, glutamate receptor, and voltage-gated potassium channel antibodies, was negative. All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone, and the unilateral cortical MRI lesions subsequently disappeared. No patient experienced relapse. CONCLUSIONS: These MOG antibody-positive cases represent unique benign unilateral cortical encephalitis with epileptic seizure. The pathology may be autoimmune, although the findings differ from MOG antibody-associated demyelination and Rasmussen and other known immune-mediated encephalitides.

Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody.

INTRODUCTION: Neuromyelitis optica (NMO), an autoimmune astrocytopathic disease associated with anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions preferentially involving the optic nerves and spinal cord. However, previous in-vivo experimental models injecting human anti-AQP4 antibodies only resulted in mild spinal cord lesions compared to NMO autopsied cases. Here, we investigated whether the formation of severe NMO-like lesions occurs in Lewis rats in the context of experimental autoimmune encephalomyelitis (EAE), intraperitoneally injecting incremental doses of purified human immunoglobulin-G from a NMO patient (hIgGNMO) or a high affinity anti-AQP4 monoclonal antibody (E5415A), recognizing extracellular domain of AQP4 made by baculovirus display method. RESULTS: NMO-like lesions were observed in the spinal cord, brainstem, and optic chiasm of EAE-rats with injection of pathogenic IgG (hIgGNMO and E5415A), but not in control EAE. Only in higher dose E5415A rats, there were acute and significantly severer clinical exacerbations (tetraparesis or moribund) compared with controls, within half day after the injection of pathogenic IgG. Loss of AQP4 was observed both in EAE rats receiving hIgGNMO and E5415A in a dose dependent manner, but the ratio of AQP4 loss in spinal sections became significantly larger in those receiving high dose E5415A up to about 50 % than those receiving low-dose E5415A or hIgGNMO less than 3 %. These lesions were also characterized by extensive loss of glial fibrillary acidic protein but relatively preserved myelin sheaths with perivascular deposition of IgG and C5b-9, which is compatible with post mortem NMO pathology. In high dose E5415A rats, massive neutrophil infiltration was observed especially at the lesion edge, and such lesions were highly vacuolated with partial demyelination and axonal damage. In contrast, such changes were absent in EAE rats receiving low-dose E5415A and hIgGNMO. CONCLUSIONS: In the present study, we established a severe experimental NMO rat model with highly clinical exacerbation and extensive tissue destructive lesions typically observed in NMO patients, which has not adequately been realized in in-vivo rodent models. Our data suggest that the pathogenic antibodies could induce immune mediated astrocytopathy with mobilized neutrophils, resulted in early lesion expansion of NMO lesion with vacuolation and other tissue damages. (350/350).

Recurrent hypogeusia in a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Hypogeusia, a condition with diminished sense of taste, is caused by several conditions, including zinc deficiency and as a side-effect of drugs, but is not common in neurological disorders. A 55-year-old Japanese man with a 30-year history of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presented with hypogeusia during hospitalization for a recurrence of CIDP. The hypogeusia improved after treatment with high-dose intravenous methylprednisolone (HIMP). Two years later, hypogeusia developed again. A complete taste deficit was revealed by a filter paper test. Brain MRI showed enhancement of the bilateral facial nerve ganglia. Hypogeusia was partially ameliorated after extensive immunosuppressive therapy with repeated HIMP and plasma exchange. Improvement was more prominent in the area innervated by the chorda tympani nerve than that innervated by the glossopharyngeal nerve. To our knowledge, this is the first report of recurrent hypogeusia, which might be caused by cranial nerve injury associated with CIDP.