Tau-predominant-associated pathology in a sporadic late-onset Hallervorden-Spatz syndrome

• Published in: Movement disorders 2006-01, Vol.21 (1), p.107-111
• Main Authors: Zarranz, Juan J., Gómez-Esteban, Juan C., Atarés, Begoña, Lezcano, Elena, Forcadas, Maribel
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - analysis; Axons - pathology; Basal Ganglia - pathology; Biological and medical sciences; Brain - pathology; Brain Stem - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diagnosis, Differential; Hallervorden-Spatz; Humans; Inclusion Bodies - pathology; Iron - analysis; Lewy Bodies - pathology; Male; Malformations of the nervous system; Medical sciences; Middle Aged; Myelin Sheath - pathology; Neurodegenerative Diseases - pathology; Neurofibrillary Tangles - pathology; Neurology; Pantothenate Kinase-Associated Neurodegeneration - genetics; Pantothenate Kinase-Associated Neurodegeneration - pathology; Protein Folding; Spheroids, Cellular - pathology; tau Proteins - analysis; Tauopathies - genetics; Tauopathies - pathology; TAV; Thalamic Nuclei - pathology; α-synuclein
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.20661

Hallervorden–Spatz syndrome (HSS) is a heterogeneous clinicopathological disorder currently included within the broader title of neurodegeneration with brain iron accumulation (NBIA). The classic histological hallmarks of HSS are axonal spheroids and excessive iron‐containing granules accompanied by neuronal loss and gliosis in the globus pallidus and substantia nigra reticulata. In the modern literature, attention has been drawn to the co‐occurrence of two other histological markers: Lewy bodies mainly composed of abnormal α‐synuclein, and neurofibrillary tangles due to hyperphosphorilated tau aggregation. Discrepancies exist regarding the importance of these molecular changes and its relevance for the nosology of HSS. Most authors have emphasized the importance of the Lewy body–like pathology, favoring the inclusion of HSS within the α‐synucleinopathies. We report on a case of late‐onset HSS, with the typical histological findings restricted to the basal ganglia and cerebellum in which tau pathology was exceedingly more abundant than α‐synuclein pathology. This case contributes to the increasing evidence about the heterogeneity of HSS. We favor the view that the molecular changes and the protein misfolding underlying the Lewy body and tangle formation in HSS/NBIA are secondary to the main pathological process and should not be taken as the basis for its nosological classification. © 2005 Movement Disorder Society