Creutzfeldt-Jakob Disease: Pathogenesis and clinical findings
Author: Skye McIntosh Reviewers: Heather Yong Tony Gu Davis Maclean *Scott Jarvis *Gary Klein *Yan Yu * MD at time of publication
Familial (5-15%): Autosomal dominant inheritance of pathologic prion protein (PRNP) genes
Sporadic (85%)
Pathologic prion protein (PrPSc) form spontaneously from normal prion protein isoforms (PrPc)
Acquired (<1%) Variant: consuming bovine spongiform encephalopathy (BSE) infected beef (mad cow disease) Iatrogenic: related to medical intervention (e.g instruments contaminated with PrPSc) Note: The normal prion protein isoform (PrPc) is expressed predominantly in neurons. It is not intrinsically pathological. Presence of PrPSc kickstarts an “autocatalytic” process by which existing PrPSc converts more normal prion protein (PrPc) into pathological protein. Pathological prion proteins (PrPSc) enter host Astrogliosis: ↑ astrocyte cells infiltrate and occupy the space of lost neurons Vacuolation or spongiform changes: clusters of small vacuoles in synaptically dense cortical areas Pathologic prion proteins (PrPSc) are insoluble and aggregate within neurons Mechanism unknown Neuronal loss Creutzfeldt-Jakob Disease Fatal infectious brain disorder causing neuronal death Diffuse brain atrophy Exact mechanism unknown Frontal lobe atrophy The frontal lobes are responsible for executive function and personality Occipital lobe atrophy The occipital lobes are responsible for interpreting vision Basal ganglia atrophy The basal ganglia is responsible for sequencing voluntary movements Loss of inhibitory cortical neurons Hyper-excitable cortical neurons Myoclonus: quick involuntary muscle jerks Cerebellar atrophy The cerebellum is responsible for coordination and fine correction of movements Gait Slurred Extensive neuronal loss in the brainstem reticular activating system Coma Impaired control of respiratory muscles Pneumonia and respiratory failure ~ 75% mortality within 1 year Rapidly progressive dementia Anxiety, depression Visual hallucinations Double vision Bradykinesia: Tremor Rigidity: ↑ muscle tone ataxia speech Incoordination Personality changes Irritability slow movements Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 4, 2020 on www.thecalgaryguide.com