Recent advancement in studies on pathogenesis led to development of disease–modifying therapies such as nucleic acid therapies for neuromuscular disorders. Such therapies target disease causing genes and proteins, but therapeutic benefits in clinic is limited at a symptomatic stage of disease. To overcome this, strategies for prevention have been actively developed for neurodegenerative disease. Before manifestation of core motor/cognitive symptoms, preclinical and then prodromal stages exist during the progression of neurodegeneration. At preclinical stage, molecular changes occurs but symptoms are hardly detectable. At prodromal stage, heralding symptoms appear prior to manifestation of core symptoms. In cohort studies on at–risk subjects, mild motor/cognitive symptoms emerge ∼20 years prior to the onset of subjective symptoms in various diseases. For instance, non–motor symptoms including REM sleep behavior disorder occurs approximately 15 years before clinical diagnosis of Parkinson disease, which is made on the basis of subjective motor symptoms. The effects of disease–modifying therapy for preventing neurodegeneration is clearly shown in a clinical trial of nusinersen, a nucleic acid therapy of spinal muscular atrophy, for pre–symptomatic subjects, in which initiation of disease–modifying therapy before manifestation achieved potent therapeutic effects particularly in mild patients. Currently, cohort studies, biomarker research, and novel therapies are being developed to further prevent various neurodegenerative diseases.

We proved an overview of prevention medicine in neuroimmunological disease, especially focusing on multiple sclerosis (MS). Due to lack of large–scale primary–prevention studies, there are no concrete data on primary prevention for MS. Therefore, in this review article, we discussed risk factors for developing and worsening MS, including genetic factors (HLA), environmental factors (viral infection and sunlight exposure), and non–environmental factors (cigarette smoking). We also commented on secondary prevention therapies for MS currently available in Japan, including natalizumab, ofatumumab, fingolimod, siponimod, dimethyl–fumarate, glatiramer acetate, and interferon beta I a/b.

The number of patients with dementia is rapidly increasing, and it has become an important issue not only in medical care but also in society. As a countermeasure against dementia, prevention of dementia has been emphasized. Until recently, efforts have been made to improve lifestyle habits for the prevention of dementia. In Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), multidomain intervention of diet, exercise, cognitive training and vascular risk monitoring prevent cognitive decline in at–risk elderly people. In Lancet commission, modifying 12 risk factors was stated for the prevention of dementia. In World Health Organization guidelines, the 12 interventions for the risk reduction of cognitive decline and dementia were assessed. Recently, the disease–modifying therapies which affect the pathophysiological mechanisms in Alzheimer disease have been developed. The monoclonal antibodies, aducanumab, lecanemab and donanemab that selectively bind for amyloid β protein were effective for the prevention against the progression in early Alzheimer disease in phase 2 or 3 trials. Aducanumab and lecanemab have been approved by the US Food and Drug Administration. These new disease–modifying therapies might be promising preventive method in future.

Interventions before the onset of cerebrovascular disease in terms of preventive medicine, it is classified into 2 stages. As for zero–level prevention, it is a lifestyle intervention for the entire population. So–called primary prevention is an approach to a group of patients who already have vascular risk factors.

Zero–level prevention : To reduce the occurrence of risk factors for cerebrovascular disease, the goal is to educate the public widely on the impact of risk factors on the development of stroke and cardiovascular disease, and to manage lifestyle habits appropriately. These include salt reduction, smoking cessation, alcohol conservation, and improved nutrition and diet, including increased physical activity, and are tailored to each stage of life in all generations.

Primary prevention : Appropriate management of major risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and atrial fibrillation, to prevent their development. The goal of blood pressure control is set at <130/80 mmHg and a combination of calcium channel blockers, diuretics, angiotensin–converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), are recommended. In diabetic patients, not only proper management of blood glucose, but also strict control of cardiovascular risk factors such as blood pressure and dyslipidemia is important for stroke prevention. In patients with dyslipidemia, LDL–cholesterol should be controlled to <120 mg/dL. On top of diet, HMG–CoA enzyme inhibitors (statins), ezetimibe, proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are used. For patients with non–valvular atrial fibrillaiton, primary prevention of cardiogenic cerebral embolism is achieved with anticoagulants starting at a CHADS2 score of 1. Prefer DOAC over warfarin. Left atrial appendage closure devices are now also considered in atrial fibrillation patients at high risk of bleeding.

Migraine is one of the most disabling diseases with a significant socioeconomic impact. In Japan, five types of triptans have been approved since 2000. Furthermore, the development of lomerizine and the approval of valproic acid and propranolol for migraine prophylaxis have greatly improved the treatment of the patients with migraine. Clinical Practice Guideline for Chronic Headache 2013 was published by the Japanese Headache Society, which had prompted evidence–based migraine treatment. However, we cannot get the enough effects. Calcitonin gene–related peptide (CGRP) is a neuropeptide that has an important role in migraine pathophysiology and is a target for migraine preventive therapies. Monoclonal antibodies targeting CGRP (galcanezumab, fremanezumab and eptinezumab) and its receptor (erenumab) showed consistent efficacy for migraine prophylaxis with excellent safety profiles. The effects on refractory cases have also been reported, and it is expected to bring the good news to many patients who have not been effective with existing migraine prophylaxis, and a paradigm shift in migraine treatment is expected.

The discovery and approval of novel treatments and vaccines are altering the trajectory of neuroinfectious illnesses.

As for bacterial meningitis, the pneumococcal vaccine and Haemophilus influenzae type b vaccine have reduced the incidence of bacterial meningitis in children. The pneumococcal vaccine is now routinely administered to adults as well to prevent pneumonia, but problems of serotype substitution have arisen, including for children. Additionally, recently approved medications for the treatment of systemic myasthenia gravis and neuromyelitis optica spectrum diseases, such as eculizumab and labulizumab, increase the risk of meningococcal infection in adults and may result in meningitis. As a result, it is critical to immunize patients against meningococcal meningitis before administration and to describe the risks to the patient and family.

For tetanus, additional immunization with absorbed tetanus toxoid or concomitant use of human tetanus immune globulin should be taken into account, depending on the condition of the wound. According to an evaluation of contamination, wound depth, and consequences from neuropathy or ischemia, aggressive debridement should be taken into consideration for non–open wounds.

Vaccines for shingles have been approved for patients over 50 years of age, both live attenuated vaccines and genetically engineered vaccines. Given that both are successful in avoiding the disease's start, it is important to recognize the benefits and drawbacks of each and employ them appropriately.

The Japanese encephalitis virus, a flavivirus, is subject to routine vaccination in childhood, but it is known that the antibody retention rate declines in adults, and additional vaccination should be considered for those who work in rural areas in endemic areas. Although Japan has not licensed a vaccine for the tick–borne encephalitis virus, the administration should be taken into account if the individual will be living in an area where it is common or will be visiting a forest.

There is also disagreement over the effectiveness of long–term SARS–CoV–2 vaccines, and further understanding of the etiology is preferred.

Objective : This prospective, observational study aimed to investigate the infusion time and patient satisfaction with intravenous immunoglobulin (IVIg) maintenance therapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

Methods : A total of 23 patients aged 20 years or older who received regular maintenance therapy with 5% IVIg (n＝10) or 10% IVIg (n＝13) were included. The infusion preparation and administration times were measured for both groups. Quality of life (QOL), treatment satisfaction, and work productivity impairment were also investigated.

Results : The total infusion time was approximately half for the 10% IVIg group compared to the 5% IVIg group (204 min vs. 437 min, p＝0.0026). The 10% IVIg group had a higher mean index value on EuroQol 5 Dimensions 5–level (EQ–5D–5L) than the 5% IVIg group (0.74 vs. 0.57) with better scores in all 5 dimensions. The treatment satisfaction scores and work productivity impairment were similar in both the groups.

Conclusion : Although the therapeutic effect of 10% IVIg was comparable to that of 5% IVIg, the shorter infusion time of 10% IVIg was considered to improve the QOL.

We report a case of hemichorea–hemiballismus suspected to be caused by repeated nocturnal hypoglycemia. A 76 years old man with type 2 diabetes mellitus, using insulin glargine, was admitted to our hospital for treatment of hemichorea–hemiballismus. Although his blood glucose level and HbA1c were within normal range at the time of admission, the repeated nocturnal hypoglycemia might cause the involuntary movements. Involuntary movements due to hyperglycemia are well known, but similar symptoms with hypoglycemia or rapid correction of blood glucose levels have been reported. When a patient receiving medication to cause severe hypoglycemia such as insulin, presents with involuntary movements, we have to consider the possibility that the involuntary movement may be induced by hypoglycemia, even if a single blood glucose level or HbA1c is normal.

I report a 50–year–old man with generalized anti–muscle–specific tyrosine kinase (MuSK) antibody–positive myasthenia gravis (MG). He first experienced diplopia and heaviness in his neck muscles 2 years prior. He was diagnosed with generalized MuSK–MG, with high anti–MuSK antibody levels (80.5nmol/L) and negative anti–acetylcholine receptor antibodies. Repetitive median nerve stimulation significantly decreased the compound thumb muscle action potentials. His myasthenic symptoms consisted of moderate myasthenia in all extremities, with bilateral ptosis and diplopia but no bulbar symptoms. His moderate myasthenic symptoms were resistant to oral corticosteroids with repetitive simultaneous intravenous immunoglobulin (IVIG), and methylprednisolone pulses following cyclophosphamide injection for almost 2 years. He underwent an extended endoscopic thymectomy owing to a suspected hyperplastic thymus in the right anterior mediastinumfrom contrast–enhanced chest computed tomography (CT). Complete histopathological examination revealed almost fatty tissue, including an involuted, but not hyperplastic, thymus. His myasthenic symptoms deteriorated after thymectomy. Simultaneous IVIG and steroid pulse therapy caused a transient decrease in anti–MuSK antibody titers but did not improve his myasthenic symptoms. Subsequent repetitive PE at 1– to 3–month intervals caused a steady decline in the anti–MuSK antibody titers from the preoperative titer of 32.6 to 0.7–1.8nmol/L. His myasthenic symptoms gradually improved, and bilateral ptosis and diplopia disappeared.

Although a hyperplastic thymus was suspected on contrast–enhanced CT, an almost fatty tissue containing an involuted thymus was excised. Thymectomy did not improve his myasthenic symptoms, as recently reported. In refractory MuSK–MG, repetitive plasmapheresis is more effective than simultaneous IVIG and steroid pulse therapy in decreasing anti–MuSK antibodies and ameliorating myasthenic symptoms. I report this as a suggestive case for treating refractory MuSK–MG patients.

Here we present the case of a 34–year–old female patient who developed difficulty in managing her finances since the age of 32 years, and later had memory impairment at age 33 years. At age of 34 years, she experienced dizziness on walking, and visited the emergency department after stumbling and falling while walking. Brain MRI revealed symmetric extensive abnormal signal areas in the deep white matter of the cerebrum, and she was therefore referred to our department. Her Mini–Mental State Examination score was 29 and Frontal Assessment Battery score was 14, and deep tendon reflexes in the upper and lower limbs were hyperactive. Blood laboratory data and spinal fluid tests were all normal. T2–weighted images revealed a linear, relatively low signal intensity area within the white matter lesion, suggestive of a tigroid pattern. Nerve conduction studies revealed peripheral neuropathy suggestive of demyelination. Based on the results of previous examinations, we suspected adult–onset leukodystrophy. Subsequently, the patient was diagnosed with metachromatic leukodystrophy (MLD) after measuring arylsulfatase A in white blood cells and performing a genetic test. The tigroid pattern on MRI is useful in differentiating diseases presenting with white matter lesions.

She was a 39–year–old female who was 13 weeks pregnant. Her chief complaints were a left oculomotor nerve palsy and nausea. Brain MRI revealed an abnormal intensity extending from the corpus callosum, right medial temporal lobe, and left mesencephalic pontine tegmentum. Her serum aquaporin 4 antibody was positive. Based on the clinical, MRI and laboratory findings, a diagnosis of aquaporin4 IgG–positive neuromyelitis optica spectrum disorder (NMOSD) was made. Intravenous methylprednisolone : (IVMP) was initiated ; however her condition did not improve significantly. We, therefore, performed immunoadsorption plasmapheresis (IAPP) repeatedly, and she recovered fully from her symptoms. She was prescribed prednisolone 10mg/day to prevent relapse. During these treatments, her condition remained stable and no adverse effects on her pregnancy and delivery were indicated. There have been no reports on evidence based treatment of NMOSD during pregnancy. Our case suggest that IVMP, IAPP and prednisone in NMOSD can be effective and safe in early second trimester.