Multiple sclerosis (MS) is a demyelinating disease of the central nervous system of unknown etiology. Based on a hypothesis that MS is caused by certain viral infections, the efficacy of interferon β was examined in patients and it became the first disease-modifying drug (DMD) approximately 30 years ago. Through the series of research utilizing experimental autoimmune encephalomyelitis, many other DMDs were later developed. With emerging insights on limitation of the animal model, newer treatment strategies are being developed based on pathological findings from MS patients. In the current article, the history of MS treatment and its future prospects will be reviewed and discussed.

To estimate the medical costs related to Parkinson’s disease (PD) by Hoehn and Yahr (HY) scale, we conducted a descriptive study by using a large-scale hospital based administrative claims database in Japan. Approximately 20,000 PD patients who had a diagnosis of PD with HY severity between April 2008 and December 2018 were included in the analysis. Estimated PD related outpatient costs, frequency of hospitalization, length of stay, and inpatient costs were increased with HY severity. Our estimates of the PD related medical costs are based on the large-scale claims database, despite limitations such as the reliability of HY severity in the claims data, could be used in future cost-effectiveness studies for treatment of PD.

This study aimed to clarify associations between neuropsychological scales and regional cerebral blood flow (rCBF) of on ‍¹²³I-IMP-SPECT in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI). Forty-two participants (mean age, 65.5 ± 8.9 years; mean disease duration, 11.1 ±5.7 years) were evaluated using the Wechsler Adult Intelligence Scale, third edition (WAIS-III), Wechsler Memory Scale, revised (WMS-R), Stroop test, Category word fluency, Auditory verbal learning test, Raven colored progressive matrices, Trail Making Test-B, and Clock drawing test. Participants were classified into PD-MCI and PD non-demented (PD-ND) using ten of these scales or its subtests. The rCBF of the posterior cingulate gyrus, precuneus, and parietal lobes was evaluated by ‍¹²³I-IMP-SPECT using the easy Z-‍score imaging system (eZIS analysis). Extent was the extent index of voxels showing z-score > 2, and Severity was mean z-score in those regions on eZIS analysis. Cingulate island sign score (CIScore) was the ratio of integrated z-scores of the posterior cingulate gyrus to those of the posterior cortex.Twenty-three participants were diagnosed with PD-MCI (55%). The rCBF indices were significantly increased in the PD-MCI group compared to the PD-ND group (Extent: P = 0.047; CIScore: P = 0.006). These indices were significantly correlated with WAIS-III Processing Speed (Extent: P = 0.041, R = −0.317; Severity: P = 0.047, R = −0.309), Stroop effect (Extent: P = 0.003, R = 0.443; Severity: P = 0.004, R = 0.437), WMS-R Visual memory (Extent: P = 0.019, R = −0.361; Severity: P = 0.014, R = −0.375), and Delayed memory score (Extent: P = 0.005, R = −0.423; Severity: P = 0.044, R = −0.312). The rCBF indices showed no correlations with the number of impaired cognitive domains. Collectively, decreased posterior parietal area rCBF and lower scores on selective neuropsychological scales might be helpful to detect a transition period from PD-MCI to PD-D.

Here, we report a case of an 85-year-old man who presented sudden onset of diplopia, dysarthria, and gait disturbance. On admission, he exhibited bilateral adduction palsy, convergence palsy, and binocular exotropia in the forward gaze showing wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. He had a history of chronic nonvalvular atrial fibrillation. DWI-MRI revealed acute ischemic lesions in the paramedian pontine tegmentum, lower midbrain, both cerebellar hemispheres, and left frontal cortex. He was thus diagnosed with an acute phase of cardioembolic stroke. Subsequently, the right eye adduction palsy in the forward gaze was slightly improved, but other eye movement disorders persisted during discharge from the hospital. The pathology was suspected to involve bilateral damages to both medial longitudinal fasciculus and the paramedian pontine reticular formation. WEBINO syndrome was not only ascribed to lacunar infarction and large artery atherosclerosis but also cardioembolic stroke. The presence of other non-eye symptoms and multiple ischemic lesions could be the characteristics of WEBINO syndrome following cardioembolic stroke.

A 36-year-old man with ulcerative colitis presented with bloody stools at the beginning of October 2020. His condition had been stable without treatment since diagnosis 4 years prior. He was administered 4,000 mg of salazosulfapyridine orally and the bloody stools resolved. Fifteen days after treatment, he was admitted to our hospital with swelling and pain in his right lower leg. Laboratory results revealed an elevated erythrocyte sedimentation rate (43 mm/hr) and mildly elevated C-reactive protein levels (4.08 mg/dl). His D-dimer level was also elevated at 7.6 μg/ml. MRI using fat saturated T₂-weighted imaging demonstrated marked hyperintensity in the fascia of the lower leg flexor and blood vessels of interstitial. In gadolinium-enhanced T₁-weighted images, the deep veins were found to be dilated and the vein walls and their surrounding areas strongly contrasted, suggestive of localized fasciitis. No abnormalities were found on biopsy of his right gastrocnemius muscle on the 5th day after admission. Two days after the muscle biopsy, the patient began experiencing swelling and pain in his left lower leg. The high intensity lesions in his right leg were reduced on MRI performed the same day, but that of the fascia between the left gastrocnemius and soleus muscles was noted. We administered 60 mg (1.0 mg/kg/day) of prednisolone orally on day 9 and the pain and swelling in both legs promptly resolved. The prednisolone was tapered to 5 mg/day and as of the time of writing, resolution of pain and swelling has been maintained. Gastrocnemius myalgia syndrome, which causes pain and localized fasciitis, is often reported as a complication of Crohn’s disease but is rare in conjunction with ulcerative colitis. It is important that clinicians are aware of this syndrome so it can be recognized early and successfully treated.

Case 1: A 64-year-old woman with acute ptosis and diplopia was admitted to our hospital. She had right oculomotor nerve palsy with preserved pupillary reaction without any other neurological deficits. MRI showed abnormal enhancement in the right oculomotor nerve. An ovarian tumor was detected on CT examination, and was pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Cerebrospinal fluid cytology disclosed malignant lymphoma cells. Based on the above findings, we concluded that she had neurolymphomatosis (NL) of the right oculomotor nerve. Case 2: A 63-year-old woman was admitted to our hospital due to weakness of the bilateral lower extremities and gait disturbance. Lumbar MRI showed enhanced lesions in the cauda equina, and we diagnosed her as having DLBCL based on bone marrow aspiration study. She later developed right oculomotor nerve palsy with preserved pupillary reaction together with the right abducens and hypoglossal nerve palsies, which were caused by NL. Our cases suggest that oculomotor nerve palsy with preserved pupillary reaction can be a clinical feature of NL. Although NL mainly affects the subperinerium, as parasympathetic fibers are located in the periphery of the oculomotor nerve and supplied by pia matar blood vessels, patients with NL may shows this clinical feature.

A 43-year-old-woman developed paresthesia, weakness of limbs, dysphagia and deep sensory impairment 12 days after vaccination of Pfizer COVID-19 vaccine. Her deep tendon reflexes were absent and cerebrospinal fluid showed normal cell counts and protein level. Anti-ganglioside antibodies were negative, and F wave frequency was decreased in nerve conduction studies. We diagnosed her as immune mediated polyneuropathy caused by COVID-19 vaccine, and plasma exchange improved her symptoms. Compared with Guillain–Barré syndrome and polyneuropathy following COVID-19 infection and COVID-19 vaccination, deep sensory impairment was the most characteristic of this case. We supposed that non-antigen specific mechanism played an important role in the pathogenesis of this case.

In February 2020, a 51-year-old woman experienced leg myalgia and noticed calf muscle movements that resembled a rippling wave while crouching down. In June 2020, she complained of bilateral arm myalgia. In August 2020, she developed left ptosis, had difficulty raising her bilateral arms, and developed diplopia and was admitted to our hospital. Anti-acetylcholine receptor antibodies turned out to be positive. We made a diagnosis of myasthenia gravis and acquired rippling muscle disease (RMD). Her myasthenia gravis symptoms and myalgia decreased with oral prednisolone. Contrast-enhanced computed tomography revealed thymoma. She underwent extended thymectomy and was discharged from the hospital. Her myalgia worsened, but it was responsive to methylprednisolone pulse therapy. CAV3 gene mutations are recognized as causes of congenial RMD whereas acquired RMD is associated with myasthenia gravis. Acquired RMD is rarely reported in Japan, but should be kept in mind as a condition treatable with immunotherapy.

A 23-year-old woman, who had been suffering from migraine since primary school age, presented with left arm paralysis three days after one such migraine attack. On admission, brain MRI diffusion-weighted imaging (DWI) demonstrated high-signal-intensity lesions in the white matter of the right fronto-parietal lobe, and no abnormal lesions were evident in the limbic system. Although the patient had a fever of 38.7°C, the CSF cell count was not elevated. On the 4‍^th day, the left arm paralysis worsened, with an increase in body temperature to 39.8°C. Brain MRI revealed that the white matter lesions had spread to the right postcentral gyrus and the bilateral insular cortex. Also, MR angiography demonstrated no spasms or dissection of the major vessels. On the 6‍^th day, the CSF cell count was elevated to 54/μl and herpes simplex virus DNA was detected. Acyclovir and steroid pulse therapy ameliorated the symptoms. Cervical artery dissection and reversible cerebral vasoconstriction are well known complications of migraine attack. However, herpes simplex encephalitis should also be considered as a differential diagnosis in patients with a high fever of unknown origin.