Cerebral and cerebellar white matter tract alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

BACKGROUND: To examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms. METHODS: In a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients. RESULTS: Whole brain tractography presented significantly reduced QA values in patients (0.282 ± 0.056, as compared to controls (0.325 ± 0.046, p < 0.001). 9 fiber clusters of tracts correlated negatively to the dystonia score of patients: the middle cerebellar peduncle and the tracts of both cerebellar hemispheres as well as corpus callosum, forceps minor, the superior cortico-striate tracts and the superior thalamic radiations of both cerebral hemispheres (False Discovery Rate FDR = 0.041). CONCLUSION: The finding of a reduced global structural connectivity within the white matter and of negative correlation of motor system-related tracts, mainly those between the basal ganglia, cortical areas and the cerebellum, fits well to the concept of a general functional disturbance of the motor system in PKAN.

Cerebral blood flow in dystonia due to pantothenate kinase-associated neurodegeneration.

BACKGROUND AND PURPOSE: The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron. MATERIAL AND METHODS: Under resting conditions, cerebral blood flow was measured by the magnetic resonance imaging technique of arterial spin labelling in cortical areas and basal ganglia in eight pantothenate kinase-associated neurodegeneration patients and 14 healthy age-matched control subjects and correlated to T2* time of these areas and - in patients - to clinical parameters. RESULTS: Despite highly significant differences of T2* time of the globus pallidus (20 vs 39 ms, p < 0.001), perfusion values of this nucleus were nearly identical in both groups (32 ± 3.3 vs 31 ± 4.0 ml/min/100 g) as well as in total brain gray matter (both 62 ± 6.7 resp. ±10.3 ml/min/100 g), putamen (41 ± 5.4 vs 40 ± 6.1 ml/min/100 g), in selected cortical regions, and the cerebellum. Correlations between perfusion and T2* time to clinical data did not reach significance (p > 0.05). CONCLUSION: The absence of any obvious deviations of perfusion in the group of patients during a resting condition does not support the view that (non-functional) vascular pathology is a major pathogenic factor in pantothenate kinase-associated neurodegeneration in the younger age group. The findings underline the value of the arterial spin technique to measure cerebral blood flow in areas of disturbed susceptibility.

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.

Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.