前頭葉侵襲を伴うパーキンソン症候群と抗グリシン受容体抗体

Parkinsonian Syndrome with Frontal Lobe Involvement and Anti-Glycine Receptor Antibodies.

• Dominique Endres
• Harald Prüss
• Michel Rijntjes
• Tina Schweizer
• Rita Werden
• Kathrin Nickel
• Sophie Meixensberger
• Kimon Runge
• Horst Urbach
• Katharina Domschke
• Philipp T Meyer
• Ludger Tebartz van Elst

抄録

突出した前頭葉病変を伴う非定型パーキンソン症候群は、4Rタウパチー進行性上核麻痺（PSP）およびコルチコバサル変性（CBD）で起こり得る。運動障害の二次的な形態は、典型的にはStiff-Personスペクトラム症候群に関連する抗グリシン受容体（抗グリシン）抗体などの抗神経抗体を伴う自己免疫性脳炎、または硬直およびミオクローヌスを伴う進行性脳脊髄炎の文脈で起こりうる。最近、抗IgLON5疾患において、神経変性メカニズムと免疫学的メカニズムのオーバーラップが示唆されている。本研究では、前頭葉病変と抗GlyR抗体を有するパーキンソン症候群の患者を対象に、抗GlyR抗体を有する患者を紹介した。症状は60歳で不眠症に始まり、61歳以降、人格変化が増加し、妄想症状を伴ううつ病と診断された。重度の認知障害が出現し，左側に姿勢不安定を伴うパーキンソン症候群が強調された。人格の変化は前頭系が関与していた。磁気共鳴画像法（MRI）では低悪性度の中脳萎縮を認めた。また，[F]fluodeoxyglucose positron emission tomography (FDG PET)では中等度の前頭側と中脳の代謝低下を，[I]FPCIT single-photon emission computed tomography (SPECT)では両線条体のドーパミントランスポーターの利用可能性が著しく低下しており，顕著なnigrostriatal degenerationが認められた．さらに、抗GlyR抗体が患者の血清中に繰り返し検出された（最大力価1:640、参考：<1:20）。そのため、ステロイドとアザチオプリンによる抗炎症治療を行い、抗体価は1:80まで低下したが、臨床的な改善は認められなかった。脳脊髄液（CSF）診断、脳波検査では目立たない所見を示し、CSF抗GlyR抗体は陰性であった。 症例は前頭葉病変を伴う複合パーキンソン症候群であった。抗GlyR抗体価が高値であったため、自己免疫疾患の存在が議論された。しかし、自己免疫性抗GlyR抗体症候群の典型的な徴候（例えば、興奮亢進、CSF中の抗GlyR抗体、または他の炎症性CSF変化）が検出されなかったため、抗GlyR抗体が無関係な傍観者であった可能性を考慮すべきである。あるいは、抗GlyR抗体は、抗IgLON5脳症の場合のように、あからさまな臨床効果を発揮することなく、二次的に神経変性（最も可能性の高い4リピートタオパシー、PSPまたはCBD）を起こした可能性がある。この場合、そのような抗体は古典的な運動障害の臨床経過を修正する可能性もある。パーキンソン症候群における抗神経抗体の役割については、さらなる研究が必要である。

Atypical Parkinsonian syndromes with prominent frontal lobe involvement can occur in the 4R-taupathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Secondary forms of movement disorders may occur in the context of autoimmune encephalitis with antineuronal antibodies, such as anti-glycine receptor (anti-GlyR) antibodies, which are typically associated with Stiff-Person spectrum syndrome, or progressive encephalomyelitis with rigidity and myoclonus. Overlaps between neurodegenerative and immunological mechanisms have been recently suggested in anti-IgLON5 disease. In this case study, the authors describe a patient with a Parkinsonian syndrome with frontal lobe involvement and anti-GlyR antibodies. : The patient presented was a 63-year-old female. Her symptoms had begun with insomnia at the age of 60, after which, since the age of 61, increasing personality changes developed, leading to a diagnosis of depression with delusional symptoms. Severe cognitive deficits emerged, along with a left-side accentuated Parkinsonian syndrome with postural instability. The personality changes involved frontal systems. Magnetic resonance imaging (MRI) showed low-grade mesencephalon atrophy. [F]fluorodeoxyglucose positron emission tomography (FDG PET) depicted a moderate hypometabolism bilateral frontal and of the midbrain, while [I]FPCIT single-photon emission computed tomography (SPECT) revealed severely reduced dopamine transporter availability in both striata, indicating pronounced nigrostriatal degeneration. In addition, anti-GlyR antibodies were repeatedly found in the serum of the patient (max. titer of 1:640, reference: <1:20). Therefore, an anti-inflammatory treatment with steroids and azathioprine was administered; this resulted in a decrease of antibody titers (to 1:80) but no detectable clinical improvement. The cerebrospinal fluid (CSF) and electroencephalography diagnostics showed inconspicuous findings, and negative CSF anti-GlyR antibody results. : The patient presented here was suffering from a complex Parkinsonian syndrome with frontal lobe involvement. Because of the high anti-GlyR antibody titers, the presence of an autoimmune cause of the disorder was discussed. However, since no typical signs of autoimmune anti-GlyR antibody syndrome (e.g., hyperexcitability, anti-GlyR antibodies in CSF, or other inflammatory CSF changes) were detected, the possibility that the anti-GlyR antibodies might have been an unrelated bystander should be considered. Alternatively, the anti-GlyR antibodies might have developed secondarily to neurodegeneration (most likely a 4-repeat tauopathy, PSP or CBD) without exerting overt clinical effects, as in cases of anti-IgLON5 encephalopathy. In this case, such antibodies might also potentially modify the clinical course of classical movement disorders. Further research on the role of antineuronal antibodies in Parkinsonian syndromes is needed.