FTLD-UとPick球のないPick病―臨床と病理

FTLD-U and Pick Disease without Pick Bodies:a Clinical and Pathological Review

Ⅰ．歴史的経緯

　現在ではPick病はPick球を伴う症例のみを言うが，つい最近までこの概念は明確ではなくPick球を伴わず前頭側頭葉に高度の萎縮を示す症例もPick病とされていた（古典的Pick病）。古典的Pick病はArnold Pickが1892年以降，前頭側頭葉に限局した高度の萎縮を示し，この萎縮に関連した巣症状を示す一連の認知症の報告をしたことに始まる^1）。当時，Arnold Pickが重視したのは脳の病変局在とそれに対応する症状の関係であった。

　その後，Alois Alzheimerが嗜銀性を示す特有なPick球を発見したが，Pick球の存在をもってPick病の基本病理とするというコンセンサスは得られなかった。その理由はいくつか考えられるが，Pick病には前頭葉と側頭葉の特に前方部に強い限局性脳萎縮を示し，組織学的にまったく同じ変性像を示しながらPick球を欠く症例群が存在したことが最も大きな理由である。また，Pick球自体の意義についても，その分布が変性の最も強い領域ではなく，これよりも変性の軽い領域を中心に分布していることからPick球がPick病の本質であるとは考えられなかったことにもあると思われる。

Abstract

　Circumscribed cerebral lobar atrophy is observed in Pick disease with or without Pick bodies (conventional Pick disease) show circumscribed cerebral lobar atrophy.　Pick disease with Pick bodies was initially termed as 3-repeat tauopathy to distinguish this disease from the conventional Pick disease.　Case of Pick disease without Pick bodies formed a heterogeneous group.　In all cases of Pick disease without Pick bodies,except for rare cases without any type of inclusions 〔dementia lacking distinctive histology (DLDH)〕the presence of ubiquitinated inclusions was confirmed,which were broadly termed as frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).　In Japan,the number of cases of Pick disease with Pick bodies and those with FTLD-U appears to be almost the same.　The patterns of cerebral and subcortical nuclear degeneration are quite simillar in cases of Pick disease with Pick bodies and in cases of Pick disease with FLTD-U.　Investigation of the motor neuron system in FTLD-U cases revealed that approximately two-third patients had mild to severe degeneration in the upper motor neural system (pyramidal tract).　These cases of FTLD-U with motor neuron involvement formed an important group,namely,FTLD with motor neuron disease (FTLD-MND).　Amyotrophic lateral sclerosis with dementia (ALS-D) in which degeneration of the lower motor neurons was generally prominent in comparison to the mild pyramidal tract degeneration in the case of FTLD-MND,is also a type of FTLD-MND.　Thus,conventional Pick disease was further classified into Pick disease,FTLD-MND,FTLD-U (in a narrow sense),and DLDH.