Stiff-Person Syndrome, SPS
スティッフパーソン症候群（Stiff-Person Syndrome, SPS）は、極めて稀な自己免疫性の神経疾患で、筋肉の硬直や有痛性の痙攣を特徴とします。 主に体幹や四肢の筋肉が徐々にこわばり、音や接触などの刺激で症状が悪化するのが特徴です。
概要
疾患分類: 自己免疫性神経疾患
有病率: 約100万人に1人程度とされる非常に稀な病気
発症年齢: 多くは30〜50歳頃に発症し、女性に多い
原因: 抑制性神経伝達物質（GABAやグリシン）の働きが低下することで筋肉が過剰に収縮。抗GAD抗体や抗アンフィフィシン抗体などの自己抗体が関与。
⚠️ 主な症状
筋肉の硬直: 胸・腹部・背中など体幹部から始まり、徐々に全身へ広がる
有痛性筋痙攣: 強い痛みを伴う筋肉の収縮。音、接触、情動変化などで誘発される
ミオクローヌス: 筋肉のピクつき（不随意な収縮）
歩行困難: 腰や下肢の硬直により転倒しやすくなる
その他: 嚥下障害、呼吸困難、自律神経症状、意識障害などが出る場合もある。
診断
血液検査: 抗GAD抗体などの自己抗体の検出
筋電図: 筋肉の持続的収縮を確認
臨床症状: 特徴的な筋硬直と痙攣の経過から診断される。
治療
薬物療法:
ジアゼパム（鎮静薬）
バクロフェン（筋弛緩薬）
コルチコステロイド（免疫抑制）
免疫療法: リツキシマブ、血漿交換、免疫グロブリン療法など
目的: 根治は難しく、症状緩和と生活の質改善が中心。
まとめ
スティッフパーソン症候群は 自己免疫異常による抑制性神経伝達の低下が原因で、筋肉の硬直や痙攣を引き起こす稀少疾患 です。診断には抗体検査や筋電図が用いられ、治療は薬物や免疫療法による症状緩和が中心となります。
Abstract
Stiff Person syndrome (SPS) is a rare autoimmune disorder of the central nervous system characterized by stiffness and spasms in the lumbar and proximal lower limb muscles. Nonmotor symptoms include phobias, anxiety, and depression. SPS exists on a spectrum ranging from a focal disease known as the stiff limb syndrome to progressive encephalomyelitis with rigidity and myoclonus. Collectively, these conditions may be referred to as stiff person spectrum disorders, as they share similar core clinical features and autoantibodies against several neuronal proteins, which are involved in modulating central hyperexcitability. Antibodies against the glutamic acid decarboxylase enzyme are most frequently associated with SPS but their role in disease pathogenesis remains uncertain. Other antibodies associated with SPS now include those against the glycine receptor, amphiphysin, dipeptidyl-peptidase-like protein 6, gephyrin, γ-aminobutyric acid receptor A (GABAAR), and the GABAAR-associated protein. First-line treatments for SPS include diazepam and baclofen. Patients who do not respond adequately may benefit from immunotherapy. Intravenous immunoglobulin has the most supporting evidence, and while several other immunotherapies are used, further trials are required to determine their efficacy. Further studies to establish the precise role of autoantibodies in the pathogenesis of SPS are also needed to better understand and manage this disabling condition.
Abstract
Central nervous system hyperexcitability disorders, known as stiff-man/person syndrome (SPS), are thought to be related to the regulatory disturbance of inhibitory synaptic transmission of motor neurons in the brainstem and spinal cord. SPS is characterized by stiffness and spasms of the axis and limbs and is divided into two clinical subgroups: classic SPS, which affects the lumbar, trunk, and proximal limb muscles, and SPS-plus syndrome. The latter comprises (1) the stiff-limb subtype, in which symptom is limited to the lower limbs; (2) jerking stiff-man syndrome, characterized by chronically progressive stiffness and myoclonus; and (3) acute-onset and progressive encephalomyelitis with rigidity and myoclonus. Almost 80% of patients with classic SPS harbor autoantibodies against glutamic acid decarboxylase 65 (GAD65). In approximately 30-40% of patients, SPS accompanies type I diabetes, and anti-GAD65 antibodies are detected frequently in type I diabetes. However, the antibody-recognizing epitopes might be different between SPS and diabetes. Other autoantibodies against glycine receptor α1 (12% of patients with SPS) and GABA(A)-receptor associated protein (70% of patients with SPS) have been reported. In paraneoplastic SPS, anti-amphiphysin antibodies have been shown in patients with breast cancer or small cell lung cancer. One case of mediastinal tumor with anti-gephyrin antibodies has also been reported. However, the roles of these autoantibodies in the pathomechanisms of SPS have not yet been elucidated.
Abstract
Stiff person syndrome (SPS) is an autoimmune CNS disorder characterized by muscle rigidity, spasms and anxiety. The majority of patients have high-titer autoantibodies (ab) against glutamate decarboxylase (GAD65). A pathogenic role of SPS-associated IgG with ab against GAD65 has been shown for anxiety-like behavior but not for the core motor signs. We repetitively injected the purified IgG fraction of an SPS patient with severe motor impairment but without anxious comorbidity containing high titers of anti-GAD65 ab (SPS-IgG) into the lateral ventricle (i.c.v.) or intrathecally (i.th.) at the spinal level in experimental rats. We analyzed the effects on motor and anxiety-like behavior. Non-SPS human IgG fractions served as controls. Animals injected i.c.v. with SPS-IgG showed stiffness-like behavior with impaired walking ability and reduced grip strength of the upper limbs as well as postural and sensorimotor dysfunction. Testing for anxiety-like behavior revealed no significant differences between SPS and control IgG-treated rats. IgG deposits were found only in rats treated with SPS-IgG and were localized predominantly in CNS structures involved in motor control including globus pallidus, internal capsule, striatum and anterior thalamus. Double immunofluorescence staining revealed that predominantly GABAergic interneurons were positive for i.c.v. injected SPS-IgG. Rats injected i.th. with SPS-IgG did not present obvious motor symptoms and had a normal synaptic transmission at the spinal level. We conclude that SPS-like motor dysfunction can be induced in rats by passive transfer of IgG from an SPS-patient with high titer of anti-GAD65 ab. GABAergic dysfunction in supraspinal motor pathways rather than in the spinal cord may lead to motor deficits observed in the rats contrasting observations made in SPS with amphiphysin antibodies.
