Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and Lewy body pathology

Abstract

We describe an unusual case of Hallervorden-Spatz disease (HSD). After presenting with limb rigidospasticity at the age of 9 years, our patient developed progressive dementia, spastic tetraparesis and myoclonic movements, leading to akinetic mutism. He died of pneumonia at the age of 39 years. Autopsy revealed a severely atrophic brain, weighing 510 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids throughout the brain and spinal cord. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which were immunolabeled by anti-alpha-synuclein, were found in the brain stem, cerebral cortex and spinal gray matter. Sarkosyl-insoluble tau extracted from the temporal cortex resolved on immunoblots into three major bands of 60, 64 and 68 kDa and a minor band of 72 kDa, as reported for Alzheimer's disease. The present case, together with a few similar cases reported previously, may represent a particular subset of neuroaxonal dystrophy, i.e., HSD associated with extensive accumulation of both tau and alpha-synuclein.

Alpha-synuclein and Parkinson's disease

“…Neurofibrillary tangles and glial inclusions in progressive supranuclear palsy and in corticobasal degeneration, and Pick bodies in Pick's disease were labeled with an antibody against the C terminus, but not with an antibody against the N terminus of h-synuclein [106]. In addition, h-synuclein-positive LBs and LNs were detected in a case of Hallervorden-Spatz disease [107].…”

Altered Neuronal Mitochondrial Coenzyme A Synthesis in Neurodegeneration with Brain Iron Accumulation Caused by Abnormal Processing, Stability, and Catalytic Activity of Mutant Pantothenate Kinase 2

“…There is also deposition of proteinaceous material in axonal inclusions termed spheroids. These inclusions have been shown in various case reports to contain ␣-synuclein (␣-syn) and neurofilament proteins (Malandrini et al, 1995;Wakabayashi et al, 1999Wakabayashi et al, , 2000Galvin et al, 2000;Neumann et al, 2000;Saito et al, 2000). Many cases contain ␣-syn-positive Lewy bodies in addition to axonal spheroids, strengthening the link between NBIA and Parkinson's disease at the pathological level.…”

“…Many cases contain ␣-syn-positive Lewy bodies in addition to axonal spheroids, strengthening the link between NBIA and Parkinson's disease at the pathological level. Neurofibrillary tangles containing the microtubule-associated protein tau have also been observed in the cortex (Wakabayashi et al, 2000). Neuronal loss and gliosis accompany these pathological changes and can be widespread, involving cortical regions as well as basal ganglia and brainstem areas.…”

Neuropathological spectrum of synucleinopathies

“…71 However, the relationship between NAD and localized iron deposition in the brain to the defective PANK2 gene that is homologous to murine pantothenic kinase 1 67 is unknown. Depite the demonstration of AS-positive inclusions in NBIA I and extensive tau pathologic findings with neurofibrillary tangles in some cases, 72 often coexisting with LB in the same neuron, the pathogenesis of this diorder is unknown.…”