We describe a 60-year-old woman with combined central and peripheral demyelination who presented with obstinate constipation, weakness in the lower limbs, and a bilateral sensory disturbance below her chest followed by girdle sensation in the right region of the abdomen, which was responsive to steroid therapy and plasmapheresis. Serum anti-lactosylceramide antibody was positive without anti-neurofascin 155 antibody or anti-galactocerebroside antibody positivity. Two months later, the patient had a first relapse that was responsive to steroid treatment. A nerve conduction study confirmed reversible conduction failure (RCF) in both episodes. Our case is unique in that she had an RCF episode as well as some similarities to encephalomyeloradiculoneuropathy.

Multiple system atrophy (MSA) is a progressive and fatal α-synucleinopathy characterized by α-synuclein-positive (α-syn⁺) glial cytoplasmic inclusions in oligodendrocytes. The cerebellar variant (MSA-C) primarily affects olivopontocerebellar fibers, resulting in extensive demyelination and glial activation. To model this pathology, we developed a Tet-Off-based MSA-C mouse model with oligodendrocyte-specific overexpression of human A53T α-syn. Upon doxycycline withdrawal at 8 weeks of age, mice developed progressive cerebellar ataxia by 26 weeks and succumbed by 30 weeks. These mice exhibited severe demyelination and marked activation of microglia and astroglia in the brainstem and cerebellum, along with widespread propagation of α-syn oligomers and phosphorylated α-syn (p-α-syn) aggregates in oligodendrocytes, astrocytes, and neurons. Single-cell RNA sequencing of CD11b⁺ cells from the brain and spinal cord identified a distinct microglial cluster expressing Toll-like receptor 2 (Tlr2), transglutaminase 2 (Tgm2), arginase-1, macrophage scavenger receptor-1 (Msr1), inflammatory genes (such as Nfkbia, Nfkbiz, and Il1b), and chemokines (including Ccl3, Ccl4, and Ccl12). These microglia were located adjacent to p-α-syn aggregates and were distinct from previously described protective disease-associated microglia and border-associated macrophages. TLR2- and TGM2⁺Iba1⁺ microglia were particularly enriched in demyelinating lesions. Prophylactic administration of the CSF1R inhibitor BLZ945 exacerbated motor deficits and demyelination, significantly increasing this microglial population. Similarly, MSR1⁺ and CD68⁺ microglia/macrophages were observed in early pontocerebellar lesions of six human MSA-C autopsy cases. These findings suggest that this pro-inflammatory microglia subset plays a central role in disease progression and may represent a promising therapeutic target for modifying the course of MSA-C and related synucleinopathies.

症例は37歳男性．父に深部静脈血栓症の既往あり．数分間の全身痙攣があったが自然に軽快し，自宅で様子をみていた．翌日前頭部痛が出現後，強直間代性痙攣を繰り返し当院に搬送された．痙攣のコントロールが不良であり，全身麻酔を導入した．頭部CTで上矢状静脈洞血栓を認めたため，ヘパリン持続静注を開始後，ワルファリン内服を開始した．ワルファリン開始後Dダイマーが急激に上昇し，肺塞栓症を発症した．ヘパリン3000単位を急速静注し，ワルファリンを漸増したところ血栓は消退し，後遺症なく退院した．プロテインC活性が38%と低値であり，遺伝子検査ではエクソン7 c.631C>T, p.Arg211Trp変異を認めた．プロテインC欠乏症では，ワルファリン導入初期に血栓症が増悪することがある．脳静脈洞血栓症にワルファリンを導入する初期には，頻回なDダイマー測定が考慮される．