Creutzfeldt Jakob Disease MRI

A 40 yo female brought to casualty, unconscious since 1 day, history of rapidly progressive dementia, abnormal cognition, was under psychiatric treatment. 

HIV non reactive.

                     

MRI Brain Axial FLAIR and Diffusion shows: 

Diffuse cerebral cortical atrophy.
T2 hyper intensity with restricted diffusion involving caudate nuclei, putamen , dorso medial thalami. Involvement is bilateral and relatively symmetrical.
Cerebral cortical T2 hyper intensity with restricted diffusion in bilateral fronto temporo parietal regions and cingulate gyri.

MRI findings with rapidly progressive dementia clinically goes in favor of Creutzfeldt Jakob Disease.


Creutzfeldt Jakob Disease

Syn: A transmissible Spongiform Encephalopathy.
A fatal and potentially transmissible disorder caused by prion (a proteinaceous infectious particle devoid of DNA or RNA).
Clinically characterized by Rapidly progressive dementia.

Types of CJD
Sporadic (sCJD)
New variant (nvCJD)

nvCJD common in younger age group where as sCJD common in older age group, 7th decade.
nvCJD limited to Europe where as sCJD occurs throughout world, in all races.
CJD, a prion disease can be inherited, sporadic or acquired (infectious), 10-15% of human prion disease cases associated with dominant mutations in autosomal prion protein (PrPc) gene (PRNP) on chromosome 20.

Clinical presentation
Most common is rapidly progressive dementia associated with myoclonic jerks and akinetic mutism
Variable pyramidal, extrapyramidal and cerebellar signs.

Staging, Grading or Classification Criteria for CJD
• Definite CJD
Characteristic neuropathology
Protease-resistant PrP by Western blot
• Probable C]D
Progressive dementia; typical findings on EEG
More than 2 of following: Myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism
• Possible CJD
Progressive dementia; atypical findings on EEG
More than 2 of following: Myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism.
Duration less than 2 years.

Imaging wise best diagnostic clue is T2 hyper intensity involving bilateral basal ganglia, thalami and cerebral cortex with an associated atrophy, both the findings are progressive on follow up imaging.
Among basal ganglia, caudate and putamenal involvement is more common than Globus pallidi.
In cerebral cortex frontal and temporal lobes are commonly involved.
Prominently involves cortical gray matter. White matter is spared.

Neuroimaging
CT is often normal. May show only cerebral cortical atrophy with dilatation of lateral ventricles. Atrophy will be progressive on follow up imaging.
MRI is investigation of choice. Hyper intensity with restricted diffusion involving deep grey nuclei and cerebral cortical gray matter. Diffusion hyper intensity may subside later in disease. An associated atrophy. Contrast enhanced MRI going to non contributory.

T1 Hyperintensity in the region of globus pallidi is rare but reported in cases of sporadic CJD.

Two signs described in nv CJD:
1. Pulvinar sign: Due to involvement of pulvinar nuclei (posterior portion) of thalami, bilateral symmetrical T2 hyper intensity.
2. Hockey stick sign: bilateral symmetrical T2 hyper intensity involving Pulvinar and dorso medial thalamic nuclei.

Imagingwise DDs
Hypoxia / Anoxia.
Other causes of dementia with an associated atrophy like Alzheimer dementia, Frontotemporal dementia.
Wilson disease.
HIV Encephalopathy and AIDS dementia complex.
Leigh disease but primarily a childhood disease.

Definitive diagnosis of prion disease requires brain biopsy.

CJD has long incubation period, but rapidly progressive once clinical symptoms begin.
Rapidly progressing dementia with death usually ensuing within months of onset. Mean duration of sCJD is 8 months. nvC]D has longer course mean duration of 16 months.

No effective treatment.

Reference : Diagnostic imaging Osborn.

Wilson disease MRI

A 29 yo female under psychiatric treatment for hyper activity and easy irritability, ataxic gait, dysarthria and tremors. 

KF ring in eyes on clinical examination. 

Usg abdomen normal.

MRI Brain

Axial FLAIR images shows bilateral symmetric T2 hyper intensity involving caudate nuclei, putamen, thalami, peri aqueductal grey matter and tegmentum of mid brain supportive to clinical diagnosis of Wilson’s disease. Mild focal parenchymal swelling with faint foci of high signals on diffusion attributed to prolonged T2 effect.

Wilson Disease

Syn: Hepatolenticular degeneration.

An inborn error of copper metabolism characterized by Liver cirrhosis, Kayser - Fleischer ring of cornea, softening and degeneration of Basal ganglia.

Imaging wise best diagnostic clue is bilateral symmetric T2 hyper intensity in basal ganglia and thalami. Focal parenchymal swelling noted in initial stages of disease followed by atrophy. 

Location wise most commonly involves putamina (with predilection for outer rim), Pons (dorsal and central region) > followed by Caudate, Globus pallidi, Thalami (ventro lateral nuclei) > Mid brain, Cerebellum (vermis and dentate nuclei) > Dentato rubro thalamic, Ponto cerebellar and cortico spinal tracts > Cortical and sub cortical white matter. 

Neuroimaging

CT is often normal. May find atrophy in later stage of disease. Copper deposition in basal ganglia does not increase density on CT. Even contrast enhanced CT going to be non contributory. 

MRI the investigation of choice.

On T1w images, signals usually reduced. Occasionally increase in signal noted in affected basal ganglia due to para magnetic effect of deposited copper. Increased signal in Globus pallidi if there is an associated porto systemic encephalopathy, a hepatic component of WD. 

On T2 and FLAIR images, hyper, hypo as well as mixed signals are known. Hyper intensity is more common than hypo intensity. Hypo intensity is possible due to increase in Iron content in affected deep grey nuclei. 

A characteristic ‘ Face of Giant panda’ sign , is described on axial Flair and T2w sections at the level of mid brain, occur due to hyper intensity in the region of tegmentum with low signal in red nuclei, normal signals of pars reticulata of substantia nigra.

Dw images provide data on histo pathological stages of WD in a given case. In acute stages of disease immediately after onset of neurological symptoms a high signal may be noted on diffusion in the affected areas. The signal intensity reduces on subsequent imaging. However an increase in signal can be noted again in later stages of disease if there is an associated necrosis, spongiform degeneration and demyelination in the affected nuclei. 

Post contrast MRI is non contributory, not needed for diagnosis. 

MR Spectroscopy may show reduced NAA / Creatinine ratio, reduced Choline / Creatinine ratio, Reduced Myoinositol in cases of porto systemic shunting. 

Imaging wise DDs

Leigh disease.

CO poisoning.

Creutzfeldt Jakob disease. 

Japaneses Encephalitis.

Clinical presentation

Most common signs and symptoms

- Neurologic : Asymmetric tremor, ataxia, dyskinesia, dysarthria, dystonia mainly face, incoordination, parkinsonian like symptoms.

- Psychiatric : Hyperkinetic behavior, irritability, emotional liability, difficulty in concentration, depression, psychosis, mania, personality change.

- Acute hepatitis, Kayser Fleischer ring in cornea. 

- Subtle pyraminal signs in up to 20% of cases. 

40- 50% present with liver disease. 35-50% with neurological and psychiatric symptoms. 

KF Rings always present in neurologic WD.

Age and Gender

Often recognized in 2nd to 3rd decade. 

M = F; but for fulminant WD with liver failure, encephalopathy and coagulopathy is more common in females with ratio of 1:4. 

Onset of liver disease usually at the age of 8-16 yrs. 

Hepatic form of WD is most common presentation in children where as Neuro psychiatric symptoms are common in older individuals. Neurological symptoms are rare before 12 yrs.

Once symptomatic WD is fatal if untreated. 

Fulminant WD has mortality of 70%. 

Treatment

Penicilline, Trientine, Zinc, NH4 tetr thiomolybdate.

Liver transplant for severe hepatic decompensation. 

Reference: Diagnostic imaging Osborn.