Idiopathic progressive chorea: misnomer or still reality? A case with neuropathological disconfirmation

Abstract

Dear Sir,Most of the rarer causes of chorea have been clarified in thelast decades [1], so that the classic term of ‘‘idiopathicchorea’’ has been critically put into question.A 50-year-old Caucasian woman was referred formarked and progressive generalized chorea. The onset wasabout 1 year before and a depressive syndrome was alsopresent. Past medical and family histories were unre-markable. Slight dysarthria and adiadochokinesia werenoted. Ocular movements were normal. Deep tendonreflexes were diffusely enhanced and plantar response wasin extension bilaterally. Routine serology, ceruloplasmin,tumour markers, HIV serology, onconeural- and auto-antibodies were negative. The anti-streptolysin-O titre wasborderline and careful examination of blood smears failedto demonstrate acanthocytes. A magnetic resonance and a99mTc-ECD SPECT brain scans were not significant. Theneuropsychological assessment evidenced only minorimpairment in selective attention and slight dysexecutivenotes. Genetic testing for Huntigton’s disease (HD, 17/25triplets), DRPLA (150/150), SCA17 (36/37), SCA1 (21/30), SCA2 (23/23), SCA3 (20/22), SCA6 (11/12), SCA7(9/11), and FXTAS (23/23) were negative. Progranulin andPRNP mutations or C9orf72 expansions were absent. Anti-basal ganglia antibodies (ABGA) testing (courtesy ofDr. Giovannoni and Martino, UCL, UK) resulted in a weakpositive binding to pyruvate kinase M1 (60 kDa), while nobinding was shown for both gamma-neuron specific eno-lase, and aldolase C.Since neuroleptics were ineffective, a trial with high-dose IV steroids was attempted, with no immediateimprovement (HD Functional Capacities score: 2/13, stageIV; Folstein Chorea Scale score: 37/57). Three monthslater, only minor changes were noted (HDFCS: 3/13, stageIV; FCS: 27/57). The patient further deteriorated present-ing diffuse spasticity and dystonia. Due to worseningdysphagia the patient was referred for PEG positioning, butshe anyhow died of aspiration pneumonia about 4 yearssince the onset of chorea.The neuropathological study was carried out on forma-lin-fixed sections stained with hematoxylin-eosin, cresylviolet for Nissl substance, Heidenhain-Woelcke for myelin,thioflavine S for amyloid, and silver salts for neurofibrillarychanges (Bodian’s method). Immunohistochemistry wasperformed with antibodies to beta-amyloid (4G8), alpha-synuclein (4D6), ubiquitin (polyclonal), phosphorylated tau(AT8), prion protein (3F4), GFAP (polyclonal), CD3/43,leucocytes common antigen CD45, and MBP (polyclonal).Histopathological examination revealed mild neuronal lossin the cerebral cortex and basal ganglia. Reactive astrogl-iosis and microglia activation were marked in the thalamus,caudate, putamen and substantia nigra (SN) and morepronounced in the brainstem and cerebellum. Slight peri-vascular lymphocytic infiltration was present in the hemi-spheric and cerebellar white matter as well as in thestriatum, thalamus and brainstem. Extracellular deposits orintracellular inclusions were absent but esinophilic, ubiq-uitin-positive inclusions suggestive of Marinesco bodieswere found only in the SN. No clear retrospective corre-lation with imaging data was possible.