Multiple system atrophy (MSA) is one of the representative neurodegenerative diseases and is an intractable disease. MSA has a wide variety of phenotypes, characterized by a combination of various degrees of parkinsonism, cerebellar ataxia, and autonomic disturbance. Many cases are difficult to diagnose, and especially early diagnosis is extremely difficult. So far, MSA has been diagnosed based on the second consensus statement in 2008, but there were some problems, such as low sensitivity in early diagnosis. So, the Movement Disorder Society created new diagnostic criteria in 2022, and MSA is currently diagnosed based on these diagnostic criteria. Based on these diagnostic criteria, the diagnosis of MSA improved sensitivity and specificity compared to the second consensus statement. However, further improvement is needed, especially in terms of sensitivity, and further revisions are required in the future. Therefore, we are developing new imaging biomarkers that will contribute to early diagnosis and elucidation of pathophysiology. Individual Voxel–based Morphometry Adjusting Covariates (iVAC) is a new brain volumetry that distinguish between Parkinson disease (PD) and MSA with a sensitivity of 98.1%, specificity of 96.2%, positive predictive value of 96.3%, and negative predictive value of 98.1%. We noticed that 123I–FP–CIT Single Photon Emission Computed Tomography (SPECT) bound to the serotonin transporter (SERT), and developed serotonin transporter SPECT. We found that in MSA–P, there was consistently increased accumulation in the pons from the early stages and that this accumulation decreased as the disease progressed. We assessed the longitudinal MRI of MSA and pontine volume decreased ranging from 3.6% to 16.8% per year (mean 9.1%), exhibiting a nonlinear decline. The predictive model suggested that pontine atrophy may begin before the onset of MSA–C symptoms, potentially contributing to earlier diagnosis.

Therapies for cerebrovascular disease evolved rapidly in 2024–2025 across intravenous thrombolysis (IVT), endovascular therapy (EVT), adjunctive pharmacology, and minimally invasive surgery for intracerebral hemorrhage (ICH).

Advance in acute reperfusion therapy : Within 4.5 hours of acute ischemic stroke onset, several trials and an updated meta–analysis support tenecteplase 0.25 mg/kg as noninferior to (and in aggregate marginally favorable over) alteplase 0.9 mg/kg for functional outcomes, with comparable symptomatic intracranial hemorrhage and mortality. Beyond 4.5 hours in large–vessel occlusion (LVO), imaging–selected tenecteplase IVT did not improve 90–day disability, and adding IVT to EVT failed to show benefit ; however, in settings without EVT access, IVT improved functional independence, suggesting context–dependent utility. TEMPO–2 showed no benefit for IVT in minor stroke (NIHSS ≤ 5) with proven occlusion, discouraging routine use in this subgroup. EVT indications continued to broaden. Pooled randomized data in large–core infarction and basilar artery occlusion demonstrated better functional outcomes and lower mortality versus medical therapy. Post–reperfusion management is pivotal. Across four RCTs, more intensive blood–pressure targets after successful EVT did not improve outcomes and were associated with lower odds of achieving mRS 0–2, while symptomatic hemorrhage and mortality were similar.

Advance in antithrombotic therapy : Adjunctive argatroban or eptifibatide with IVT (MOST) was neutral for disability and associated with higher mortality ; dual antiplatelet therapy reduced early neurologic deterioration in moderate noncardioembolic stroke (ATAMIS) without 90–day benefit ; conversely, argatroban improved outcomes in patients with early neurologic worsening (EASE). For secondary prevention in non–valvular atrial fibrillation, early direct oral anticoagulant initiation (≤4 days) was noninferior to delayed initiation, and effects were not modified by infarct size, supporting routine early start ; apixaban was not superior to aspirin for cryptogenic stroke with atrial cardiopathy.

Advance in ICH : A contemporary randomized trial (ENRICH) showed that early minimally invasive endoscopic evacuation improved 6–month disability and reduced 30–day mortality in selected cortical hematomas, marking a rare positive advance in hemorrhagic stroke care.

In 2024, following lecanemab in 2023, donanemab was approved and we have two types of anti–amyloid antibody drugs available for patients with Alzheimer disease in clinical settings in Japan. A number of agents are in development that target the causative proteins of neurodegenerative diseases such as tau, α–synuclein in addition to amyloid–β. In this article, we describe the results or plans of clinical studies relevant to amyloid–β, tau and α–synuclein that have been newly reported in 2024.

Since the reclassification of coronavirus disease 2019 (COVID–19) as a Category 5 infectious disease in Japan in May 2023, two years have passed, and society has gradually returned to a pre–pandemic state. However, new challenges have emerged in the field of neuroinfectious diseases. In recent years, the use of biological and immunosuppressive agents in the treatment of neuroimmunological disorders has markedly increased. Consequently, there is growing concern about the potential resurgence of invasive meningococcal disease (IMD), which had declined during the pandemic due to public health measures.

Progressive multifocal leukoencephalopathy (PML), a rare but often fatal demyelinating disease of the central nervous system, is associated with immunosuppressive therapies and is caused by reactivation of the JC virus (JCV), a member of the Polyomaviridae family. In addition, the varicella–zoster virus (VZV), for which routine immunization with an inactivated vaccine was introduced in Japan in 2025, is known to cause a broad spectrum of neurological complications―including postherpetic neuralgia, paralysis, meningitis, and encephalitis―that can significantly impair quality of life.

This review provides an overview of the current epidemiological trends, pathophysiological mechanisms, diagnostic considerations, and preventive strategies for three major neuroinfectious diseases―IMD, PML, and VZV–associated neurological disorders―in the context of post–pandemic neurological practice.

Recent advances and new knowledge in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) were reviewed.

In NMOSD, the real–world treatment patterns and relapse in satralizumab–treated Japanese patients reported a majority of patients were relapse–free after initiating satralizumab treatment and the number of glucocorticoid–free patients without relapse increased over time under continuous satralizumab prescription. The real–world safety and effectiveness of satralizumab in Japanese patients based on post–marketing surveillance of clinical use reported satralizumab was found to be safe, well tolerated, and effective, and the results are consistent with those of clinical trials. In inebilizumab, end–of–study analysis of the N–MOmentum trial, including the randomised controlled period and open–label extension period, showed continued and sustained clinical benefits of long–term inebilizumab treatment. In eculizumab, evaluation of effectiveness and safety in routine clinical care in Europe showed an increased risk of attacks after the first vaccination and fatal systemic infections during eculizumab.

In MOGAD, the study about an optimal oral corticosteroid regimen at the onset to delay time to first relapse was reported. As results, in patients dosed ≥12.5 mg/day for at least 3 months, hazard of relapse was reduced corresponding to an 88% reduction in relapse risk compared with those never treated in this range. Authors concluded the optimal dose to delay first relapse is 12.5 mg of prednisone daily in adults for a minimum of 3 months. The study investigating the association of time to treat the first attack with relapse risk and MOG–IgG serostatus reported both the time to treatment of the first attack and immunosuppressant maintenance treatment were independently associated with the risk of relapse, and the former was also associated with MOG–IgG seronegative conversion, suggesting the association between timing of acute treatment for the first attack and the long–term prognosis. The study about the long–term outcomes of adult patients with MOGAD and factors affecting relapse risk and neurologic outcomes reported the highest risk of a relapse in MOGAD occurred early, and in multivariate analysis, initiation of maintenance treatment after the first attack was associated with a lower relapse risk.

The current treatment of autoimmune encephalitis primarily involves immunotherapy and, in paraneoplastic cases, tumor–directed therapy. Immunotherapy typically involves intravenous steroid pulse therapy, intravenous immunoglobulin, and plasma exchange during the acute phase. In severe cases, additional treatments such as rituximab or cyclophosphamide are often administered. For recurrent cases, oral corticosteroids and immunosuppressive agents such as azathioprine are commonly used as maintenance therapy. Before initiating immunotherapy, it is essential to screen for latent infections and hematologic abnormalities such as cytopenia. After starting treatment, regular monitoring of liver function, renal function, and blood cell counts is necessary to ensure safety and detect adverse effects early. These approaches are largely based on expert opinion rather than robust clinical evidence, and many are not covered by national health insurance systems. To address this gap, several randomized, double–blind, placebo–controlled trials are currently underway, investigating the efficacy and safety of agents such as inebilizumab, satralizumab, rozanolixizumab, and bortezomib in patients with autoimmune encephalitis. Conventional therapies often rely on broad immunosuppression or non–selective antibody removal, which may result in suboptimal efficacy and frequent adverse effects. Consequently, there is growing interest in the development of more targeted and less toxic therapeutic strategies. One such promising approach is chimeric antigen receptor (CAR) T–cell therapy, which offers the potential for highly specific immune modulation with reduced systemic side effects.

Here, we review papers published in 2024 on clinical trials, focusing primarily on pharmacotherapy for PD. Two phase 2 trials of GLP–1 receptor agonists for PD were reported ; lixisenatide suppressed progression of motor symptoms, whereas NLY01, a pegylated exendin–4 analogue, did not reach its primary endpoint. Of note, in subjects under 60 years of age, NLY01 also showed improvement in motor symptoms. A fourth year analysis of an open–label extension study of prasinezumab, a monoclonal antibody binding to aggregated α–synuclein, reported results suggesting inhibition of motor symptom progression in PD with the PPMI cohort as an external control. Another anti–aggregated α–synuclein antibody, Lu AF82422, demonstrated target engagement in human subjects. As an active immunotherapy, UB–312 was safe and induced immunity to α–synuclein. Fecal microbiota transplantation reported to be effective in 2023, but not in 2024. As a symptomatic therapy, levodopa–carbidopa (ND0612) continuous subcutaneous injection was reported to be effective in reducing off–time and has a good safety profile. P2B001, a fixed–dose combination of pramipexole extended–release and rasagiline, were useful as first–line treatment. The combination of buspirone and zolmitriptan, as well as the Chinese herbs Tianqi Pingchan granules and amantadine extended–release were useful in suppressing dyskinesia in PD. Clenbuterol may improve cognitive tasks in PD. Bumetanide and cannabinoids were ineffective against PD, while oxycodone and high–dose levodopa–benserazide were ineffective for central pain in PD. A pilot study demonstrated the usefulness of personalized adaptive deep brain stimulation. Two papers reported transcutaneous vagus nerve stimulation is effective for gait disturbance in PD. A report on language rehabilitation found that Lee Silverman voice treatment was effective and NHS speech and language therapy had no clinical efficacy. Acupuncture shown in a randomized controlled trial to be effective for sleep disturbances in PD. Palliative care contributes to improved QOL for patients with PD and related disorders.

Multiple system atrophy (MSA) and the hereditary spinocerebellar ataxias (SCAs) remain progressive, disabling disorders for which disease–modifying therapies (DMTs) have long been elusive. Over the past five years, however, development has diversified across complementary biological axes while outcome measures and natural–history resources have matured, together strengthening trial readiness.

For MSA, DMT programs cluster around five themes : (1) α–synuclein–directed approaches (passive/active immunization, antisense oligonucleotides, and oligomer modulators) with phase 2 signals but mixed primary outcomes ; a phase 3 program for the antibody amlenetug is underway. (2) Oligodendroglial support via S1P5 receptor agonism is in randomized evaluation. (3) Mitochondrial/CoQ10 pathway modulation has yielded a positive phase 2 signal for high–dose ubiquinol on UMSARS Part II. (4) Metal homeostasis targeting―exemplified by the iron–chaperone ATH434―has produced encouraging early clinical and imaging readouts. (5) Cell therapy with intrathecal mesenchymal stromal cells shows feasibility in small controlled studies. Importantly, negative trials (e.g., sirolimus ; myeloperoxidase inhibition) refine priorities and trial design.

For SCA, the pipeline is anchored by (a) gene– and sequence–directed strategies, (b) glutamate modulation (troriluzole), (c) proteostasis/autophagy modulators with mixed results, (d) metabolic interventions where primary CoQ10 deficiency is clinically actionable, and (e) exploratory cell–based approaches.

Translational enablers include earlier diagnosis and biologically grounded stratification, robust natural–history platforms, refined scales, fluid and imaging biomarkers, and digital gait/speech measures suited to decentralized trials.

In summary, DMT development for MSA and SCA is entering a multi–pathway phase. Success will likely depend on earlier–stage enrollment, genetics– and biology–based subtyping, and rigorous, patient–centered endpoints while interpreting external–control evidence with appropriate caution.

Motor neuron diseases (MND) are devastating neurodegenerative disorders that primarily affect motor neurons, including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal bulbar muscular atrophy (SBMA). In 2024, based on the results of the JETALS trial, ultrahigh–dose methylcobalamin therapy was approved in Japan for ALS. This review provides a comprehensive overview of the clinical advancements in MND research and summarizes key literature on therapeutic approaches from 2024.

This review outlines new promising therapies and clinical research in peripheral neuropathies. In 2024, Japanese version of clinical practice guideline for Guillain–Barré syndrome (GBS) was published. The results of a Japanese physician–initiated phase III trial of a complement C5 inhibitor (eculizumab) for the treatment of GBS were also published. Unlike the promising results of the phase II trial, the phase III trial failed to achieve its primary endpoint. Partial results from clinical trials using another complement inhibitor (C1q inhibitor) have shown efficacy. Japanese clinical practice guideline of chronic inflammatory demyelinating peripheral polyneuropathy (CIDP) was also published in 2024. Clinical trials are ongoing for drugs targeting complement for CIDP. The clinical trial for efgartigimod showed very promising results (about 70%–response rate), which is now available for the treatment of CIDP in Japan. For hereditary ATTR amyloidosis (ATTRv), various new therapeutic agents of oligonucleotide therapeutics are emerging, and many clinical trials are underway.

The revised version of the guidelines, including both myasthenia gravis (MG) and Lambert Eaton myasthenic syndrome (Japanese MG/LEMS guidelines 2022), were published. The new guidelines include the concept that treatment for MG is often lifelong and should aim to maintain a sufficient quality of life and mental health. The goal of MG treatment is minimal manifestations (MM) or a better status with an oral prednisolone dose of 5 mg/day or less (MM–5 mg). It was reported that approx. 10% to 20% of individuals with MG remain refractory to immunosuppressive therapy, and this high rate plus the side effects of treatment with corticosteroids and other immunosuppressive agents may require new MG treatments. Eculizumab, a humanized monoclonal antibody against the terminal C5 complement molecule, prevents the formation of the membrane attack complex and reduces damage caused by complement mediated acetylcholine receptor (AChR) antibodies. Both the international consensus guidance and the Japanese MG/LEMS guidelines state that eculizumab should be considered for the treatment of severe, refractory, AChR–positive generalized MG. Efgartigimod is an anti–neonatal fragment crystallizable (Fc) receptor immunoglobulin G (IgG)1 Fc fragment. The randomized, double–blind, placebo–controlled, phase III ADAPT trial showed that efgartigimod was well tolerated and efficacious in patients with generalized MG. Efgartigimod is expected to have benefits in not only AChR–positive but also muscle–specific tyrosine kinase–positive and seronegative refractory MG patients in Japan.

This review outlines recent advances reported in 2024 concerning therapeutic approaches specifically targeting autonomic symptoms in diseases characterized by autonomic dysfunction. Comprehensive treatment strategies for each autonomic nervous system disorder, including those addressing motor manifestations, are beyond the scope of this article and are discussed elsewhere.

This review summarizes notable developments in the treatment of epilepsy and headache in 2024. In epilepsy care, significant progress has been made in neuromodulation therapies, especially deep brain stimulation (DBS) and responsive neurostimulation (RNS), for drug–resistant epilepsy. DBS targeting the anterior nucleus of the thalamus (ANT) is now covered by insurance in Japan. Recent studies have explored other thalamic targets such as the centromedian (CM) and pulvinar nuclei, with promising results.

However, individual responses to DBS vary, and recent research has focused on predictors of efficacy. For instance, early seizure propagation to the thalamus and high epileptogenicity indices have been associated with poor outcomes. Conversely, stimulation at frequencies resembling seizure termination rhythms may enhance DBS effectiveness.

RNS, though not yet approved in Japan, offers a less invasive treatment for epilepsy, especially when the epileptic focus is bilateral or near the eloquent cortex. RNS is often used for mesial temporal lobe epilepsy or cases involving speech or primary sensory–motor areas. Emerging evidence supports RNS targeting of the CM nucleus in generalized epilepsy. Additionally, studies suggest that stimulation sites with strong connectivity to epileptic networks―often in areas with cortical thinning―may yield better outcomes, indicating a shift toward network–level therapeutic strategies.

Laser interstitial thermal therapy (LITT), a minimally invasive surgical technique, is increasingly utilized in North America. While seizure control rates are lower than resective surgery, LITT is associated with shorter hospital stays and fewer complications, especially when epileptic foci are near the eloquent brain regions. Recent prospective studies report favorable seizure control and quality–of–life improvements with LITT. To note, recurrence rates remain high in cases with a history of focal to bilateral tonic–clonic seizures.

In pharmacotherapy, newer antiseizure medications like brivaracetam and cenobamate have shown promising efficacy and tolerability. Attention has been drawn to cardiovascular risks associated with enzyme–inducing drugs in elderly patients.

In headache research, anti–CGRP monoclonal antibodies (e.g., galcanezumab, fremanezumab, eptinezumab) are now widely used for migraine. Recent studies also highlight the role of glial activation and neuroinflammation in migraine pathophysiology, supported by PET/MRI and experimental models.

【目的】小児神経疾患の人生会議（advance care planning：ACP）におけるadvance life planning（ALP）の重要性を明らかにする．

【方法】当院において小児神経疾患のACPに参加した代理意思決定者である家族33名に質問紙調査を行なった．比較対象として，院内のメディカルスタッフ23名および小児神経科医14名にも同調査を行った．全体および属性に対して量的検討を，また自由記載の回答に対して質的帰納的分析を行なった．

【結果】回答を70名（100%）から得た．「ALPの認知」は70名中23名（33%）であった．家族7名・メディカルスタッフ13名および小児神経科医3名で，メディカルスタッフは家族より認知の割合が高かった（p<0.05）．一方，「ACPには，ALPが必要」と70名（100%）および「ACPはALPである」と66名（97%）が回答し，属性の回答比率で有意差は認めなかった．質的検討からも，ACPにはALPが必要を得た．同時に，ACPの大切な要素・医療者に求められること・ACPの課題が得られた．

【結論】小児神経疾患のACPにはALPが重要である．しかし，本研究参加者のALPに対する認知は低かった．適切なACPを行うために，ALPの認知を高める必要がある．

【目的】補体標的薬を導入した当院の重症筋無力症（myasthenia gravis：MG）患者の治療経過を検討する．

【方法】2024年4月までにeculizumabまたはravulizumabを導入したMG連続8例を対象に，患者背景と治療経過を後方視的に検討した．

【結果】8例のサブタイプは早期発症MG 5例，胸腺腫関連MG 2例，後期発症MG 1例であった．Eculizumabで開始した5例中，1例は継続，1例は改善し中止，3例はravulizumabへ移行した．Ravulizumabで開始した3例は継続した．Quantitative MG（QMG）スコアは，6例は1～23点改善したが，うち2例はeculizumabからravulizumabへの移行で臨床的に増悪した．残る2例は2点悪化したが自覚症状は改善した．Prednisolone内服量は5例で不変，10 mg/day以上内服の3例で1～5mg減量した．

【結論】補体標的薬により全例でQMGスコアまたは自覚症状が改善したが，eculizumabからravulizumabへの移行で増悪する例に留意する．Prednisoloneは10 mg/day以下内服症例での減量や中止の可否は，MG病態に基づいて慎重に検討する．補体標的薬で症状改善した後には，補体標的薬の中止を考慮する余地がある．

目的：眼科診療科を院内に持たない急性期病院における神経免疫疾患の治療における課題を特定するため，近隣眼科との診療連携状況の調査を行った．

対象と方法：2019年1月から2023年11月の間に，眼科から紹介された合計1,174例の症例が後ろ向きに調査され，そのうち1,089例を解析した．調査項目には，紹介元の医療機関，患者の主訴，臨床診断，発症から眼科受診までの日数，および眼科から病院受診までの日数などが含まれた．

結果：紹介患者の主訴で最も多かったのは複視（314例，28.8%）で，続いて視野障害（215例，19.7%），視力低下（169例，15.5%）であった．複視の原因とされた主な臨床診断は，脳神経麻痺（100例，31.8%，うち単麻痺97例，複数麻痺3例），重症筋無力症（myasthenia gravis：MG）が17例（5.4%），脳血管障害が14例（4.5%）であった．視野障害の原因とされた主な臨床診断は脳血管障害が44例（20.5%）で，特発性視神経炎は3例（1.4%）であった．視力低下の原因とされた主な臨床診断は脳血管障害が34例（20.1%）であり，多発性硬化症（multiple sclerosis：MS）・視神経脊髄炎スペクトラム障害（neuromyelitis optica spectrum disorder：NMOSD）・特発性視神経炎は8例（4.7%）であった．視力低下の症例は，視野障害の症例と比較して，発症から当院受診までの日数が有意に長かった（中央値で視力低下が7.0日に対し，視野障害は4.0日）．発症14日以内の視力低下症例について，紹介元の眼科を年間紹介数で2群（3例以上/3例未満）に分けて検討したところ，紹介数が多い眼科群の方が，少ない眼科群に比べ，「当院への紹介日数の中央値が7日以内」である施設の割合が有意に高いことが示された（92.3% vs. 50.0%, p=0.035）．

考察：神経免疫疾患の治療には眼科との緊密な連携が不可欠であり，特に視力低下を呈する症例に対しては，より重点的な対策が必要であると考えられた．

症例は，38歳女性．抗アクアポリン4（aquaporin–4：AQP4）抗体陽性視神経脊髄炎関連疾患の患者で，出産を契機に脊髄炎が再発した．Satralizumabを導入したが，育児のため5–6週間ごとの投与間隔になった．Satralizumab使用中に再発し，抗サトラリズマブ抗体が陽性であった．Inebilizumabへ切り替え後，再発はない．

Satralizumabの投与間隔延長が，血中濃度低値につながり抗薬物抗体産生リスクとなった．Satralizumab使用中の再発には，抗薬物抗体の測定が病態の評価に有用な可能性がある．

頚部への放射線治療後に遅発性の首下がり症（dropped head syndrome：DHS）を呈した2症例を経験した．症例1は69歳女性．61歳時に上咽頭癌，右副神経リンパ節転移に対する化学放射線療法を施行した．66歳頃から首下がりが出現した．頚部筋などの筋力低下や萎縮を認めた．針筋電図検査では筋原性変化と神経原性変化が混在していた．症例2は77歳男性．67歳時に甲状腺原発悪性リンパ腫に対して放射線治療を行った．77歳頃から首下がりが出現した．頚部造影MRIでは頚部筋に造影効果を認めた．2症例はいずれも症状が放射線照射野に限局していたことから，放射線治療後の神経筋障害と診断した．癌の治療成績が向上し，長期生存が可能となった患者が増加していることから，今後遅発性放射線障害によるDHSの症例は増加する可能性があり，神経内科医が知っておくべき疾患と考えられる．

急性の偶発性微小脳梗塞（acute incidental cerebral microinfarct：aiCMI）が最近注目され，認知症外来で偶然認められることも少なくない．aiCMIは他の脳梗塞と同様，多くが動脈硬化に由来し，血管性認知症の成因に関わることが知られている．本邦でその頻度を調べた報告は少ないが，認知症外来を中心とする当院MRI検査室では1.0%にみられた．Alzheimer病（Alzheimer disease：AD）に血管性認知症が合併することは少なくないことから，認知症外来では，aiCMIや血管性認知症にも注目し，患者の生活の質（quality of life：QOL）の向上のために，適切な診断とケアを行うと良いと思われる．