MRI Detection of the Cerebellar Syndrome in Creutzfeldt–Jakob Disease

Abstract

Creutzfeldt-Jakob Disease (CJD) is characterized by bilateral basal ganglia hyperintensities on T2W and diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) scans, consistent with its extrapyramidal neurological manifestations. MRI is diagnostically uninformative about the cerebellar symptoms, equally prominent in CJD. This study was undertaken to explain this apparent paradox. Eleven CJD patients with definite cerebellar or brain stem symptoms were selected from a large prospective study, as well as 11 healthy controls matched for age and gender. All subjects participated in a standardized MRI protocol, including SPGR, fluid-attenuated inversion recovery (FLAIR), DWI and diffusion tensor imaging (DTI). All subjects underwent detailed examination by a neurologist blinded to the radiological findings, who predicted the expected site of cerebral abnormalities. MRI showed good sensitivity for the abnormalities predicted in the cortex (80-90%) and basal ganglia (100%). None of the standard MRI sequences, including DWI, DTI, and FLAIR, revealed any tissue abnormalities in cerebellum or brain stem. Apparent diffusion coefficient (ADC) values, however, were substantially and significantly elevated in several cerebellar structures, where also the volumetric (VBM) analysis revealed elevated cerebrospinal fluid volume, suggesting focal cerebellar atrophy in these CJD patients. In patients with CJD, DWI appears sensitive to the reduced diffusivity in cortex and basal ganglia but insensitive to cerebellar involvement. We propose that the radiological hallmark of cerebellar pathology in CJD is atrophy, revealed quantitatively by both VBM and elevated diffusivity, which is identifiable on ADC maps but poorly visualized in nonquantitative DWI images.

Cerebral White Matter Disruption in Creutzfeldt-Jakob Disease

“…Previously, we reported significant cerebellar atrophy around the fourth ventricle in patients with CJD with definite cerebellar symptoms, and suggested that the atrophy may mask diffusion reductions. 3 Considering our current findings, it is also reasonable to consider cerebellar symptoms as a result of disrupted efferent fibers emanating from the cerebellum to other structures.…”

“…There is also emerging consensus regarding imaging findings at early stages of the disease, which consist of reduced diffusion of striatum and thalamus. DWI is not sensitive to cerebellar degeneration, 3 and cortical diffusion reductions are easily detectable only in individual patients; it is not yet established why these are elusive in group analyses. 5 All these brain areas are richly interconnected by known white matter pathways, and constitute known functional circuits concerned primarily with movement control.…”

“…Neuropathologic studies demonstrate deposition of the abnormal prion protein (PrP Sc ), astrogliosis, spongiform change, and neuronal loss in the striatum, thalamus, cerebellum, and cortex, 2 but these observations are typically made at terminal disease stages. Recent neuroimaging work with DWI has confirmed the involvement of these structures at early stages of the disease, [3][4][5][6] but these studies were all focused on reduced diffusion in cerebral gray matter, thought to reflect the PrP Sc deposition and/or vacuolation. 7,8 It is likely that PrP Sc propagates along white matter pathways, 9,10 and such propagation studies may reveal the spread of the pathogen in the human brain.…”

Multiparameter MR Imaging in the6-OPRIVariant of Inherited Prion Disease

“…This approach allowed us to have a more homogeneous cohort and minimize the Clinical Dementia Rating Scale SD across the patient group. Nine individuals with the 6-OPRI mutation were studied (6-OPRI group: mean age, 38.1 Ϯ 3.6 years; median MiniMental State Examination, 19 [range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]; all codon 129MM). Sixteen healthy volunteers with no history of neurologic disorder were included (Controls group: mean age, 37.1 Ϯ 10.7 years; all Mini-Mental State Examination, 30); Table 1.…”

“…These tools have not been applied in IPD, except for patients with the E200K mutation. [16][17][18] We performed VBM, MTR-VBA, and MD-VBA in a cohort of patients with IPD who have the 6-OPRI mutation, some of whom were previously studied with alternative methods. 12,13 We hypothesized that this multiparametric approach would localize brain abnormalities corresponding to known clinical symptoms and neuropsychological deficits and, further, that MTR and MD would quantify microstructural changes even in areas without significant volume loss on VBM.…”