悪性貧血に続いて広範囲に及ぶ多巣性脳病変と治療可能な認知症を呈し非傍腫瘍性自己免疫性全脳炎が考えられる1例—7年間の経過観察

A Case of Suspected Nonparaneoplastic Autoimmune Panencephalitis with Widespread Multifocal Brain Lesions and Treatable Dementia Following Pernicious Anemia: A Seven Year Follow-Up Study

症例は73歳の女性である。悪性貧血に続いて記憶障害，意識障害と四肢不全麻痺が亜急性に出現し，頭部MRIにおいて両側の大脳皮質と皮質下白質に多巣性病変を認めたが，ステロイドパルス療法が奏効した。悪性腫瘍の合併はなく，検索した範囲内では自己抗体は陰性で，脳脊髄液と脳組織所見において脳炎に合致する所見を認めたため，本症例は治療可能な認知症の特徴を有し，原因となる自己抗体が明らかでない非傍腫瘍性自己免疫性脳炎と考えられる。脳炎症状発現時の病態基盤として悪性貧血と共通するような自己免疫性機序が関与し，非傍腫瘍性自己免疫性脳炎発症に至り全脳炎の病態を呈したと推定される。

Abstract

We present a case of a 73-year-old female who developed subacute memory disturbance, reduced consciousness and quadriparesis following pernicious anemia. Brain magnetic resonance imagings (MRI) in diffusion weighted, T2 weighted and fluid attenuated inversion recovery (FLAIR) images revealed hyperintensities in bilateral frontal, parietal, temporal and occipital cortices, left thalamus, bilateral splenium of corpus callosum, and bilateral subcortical white matters. Brain gadolinium enhanced T₁ weighted MRI revealed very slight post-contrast enhancement lesions in the right posterior temporal region and bilateral parietal regions. Serum was negative for anti- aquaporin (AQP) 4 antibody, anti-glutamic acid decarboxylase (GAD) antibody and anti-voltage-gated potassium channel (VGKC) antibody, and cerebrospinal fluid (CSF) was negative for anti- N-methyl-D-aspartate (NMDA) receptor antibody. CSF analysis showed slight protein elevation with normal cellular content. No evidence of neoplasm was observed using whole-body 18 F -fluorodeoxyglucose- positron emission tomography/computed tomography. Pathological findings of the left frontal lesion revealed perivascular and scattered parechymal T-lymphocytic infiltration, and astrogliosis without vascular hyalinization. Patient achieved partial recovery during two intraveneous pulse methylprednisolone treatments, and exacerbation afterwards. After the third intraveneous pulse methylprednisolone treatment, remission is sustained for six years. This case can be regarded as autoantibody-negative but probable autoimmune encephalitis with the features of nonparaneoplastic panencephalitis and treatable dementia. Nonparaneoplastic autoimmune panencephalitis with widespread multifocal brain lesions on brain MRI is extremely rare, with exception of anti- NMDA receptor antibody encephalitis.