CJD classifications

  A characteristic feature of prions is their resistance to a number of normal

decontaminating procedures
 Prion diseases appear to result from accumulation of abnormal isoforms of the
PrP.
 CJD
 進展快速之失智症或智能衰退（mental decline），且常規檢查 已排除
可導致此情況的其他疾病。
 具有下列任一個神經學症狀： 1.肌躍症（myoclonus）。 2.視覺異常
（visual disturbance）或小腦功能失調（cerebellar dysfunction）。 3.錐
體路（pyramidal）或錐體外路（extrapyramidal）功能異常。 4.不動不
語症（akinetic mutism）。
 進行性神經精神異常（progressive neuropsychiatric disorder）。
 Genetic prion disease
 In this form, the disease is caused by an inherited abnormal gene (a
mutation in the human prion protein gene, PRNP).
 There are many identified different mutations and the different mutations
tend to be associated with different clinical pictures (such as age of
disease onset, rapidity of disease progression and particular symptoms).
 The mode of inheritance is termed ‘Autosomal Dominant
 Because of differences in their clinical features and the neuropathological
findings. They relate, in general, to different underlying genetic
abnormalities but they are all genetic diseases relating to mutations in
PRNP.
 GSS-- progressive cerebellar degeneration accompanied by differing
degrees of dementia.
 FII--Patients present in midlife with progressive insomnia and loss of the
normal circadian pattern. Mental status and behavioral changes also
develop but fall short of dementia until later in the disease. With disease
progression, motor disturbances such as myoclonus, ataxia, and spasticity
can occur, along with dysautonomia and endocrine disturbances.
 Kuru
 endemic in Papua New Guinea
 be transmitted from person to person by ritual cannibalism.
 tremors, ataxia, and postural instability, followed by loss of ambulation and
involuntary movements. 

CJD
 Sporadic CJD
 It was first described many years before the BSE epidemic, and is found in
countries throughout the world regardless of the presence of animal
diseases such as scrapie and BSE. There is therefore no evidence to
suggest that sporadic CJD is in any way the result of BSE. However, the
most favoured current theory suggests that the normal prion protein in
the brain undergoes a spontaneous change to the abnormal form
 Variant CJD
 variant CJD originated from transmission of infection from BSE in cattle to
humans via infectivity in food.
 Timing, geographic distribution, lab all suggest the source from BSE.
 Laboratory scientific work has shown that the protein agent involved in
variant CJD agent is very like that of BSE.
 Iatrogenic CJD
 most cases have arisen through the use of accidentally contaminated
Human Growth Hormone treatment in childhood or Human Dura Mater
Grafts used in surgery
 the history of a relevant medical or surgical treatment in the past
 症狀
 Neuropsychiatric symptoms
 Dementia
 behavioral abnormalities
 Deficits involving higher cortical function including aphasia,
apraxia, and frontal lobe syndromes
 Early signs--impaired concentration, memory, and judgment
 apathy and depression
 Sleep disturbances, particularly hypersomnia, but also
insomnia
 visual hallucinations 
 Myoclonus
 >90%
 Cerebellar manifestations
 nystagmus and ataxia
 2/3 病人有
 iCJD 較多
 Signs of corticospinal tract involvement
 hyperreflexia, extensor plantar responses (Babinski sign),
and spasticity
  40-80%
 Extrapyramidal signs 
 hypokinesia, bradykinesia, dystonia, and rigidity

sCJD
 Epidemiology
 Pathology
 In sporadic CJD (sCJD), the origins of the disease-causing form of the prion
protein are not known, but are not thought to be acquired.
 Cluster the results suggested that some sCJD cases may result from
exposure to a common external factor
 the role of BASE exposure as a source of sCJD is considered speculative
 Subtypes
 subtypes of sCJD are more usually classified based according to the
genotype of the prion protein (PRNP) gene codon 129 and the molecular
properties of the pathological prion protein
 The PRNP genotype may be homozygous or heterozygous for methionine
(M) or valine (V) at codon 129.
 MM1/MV1
 classic CJD" phenotype
 advanced age at onset
 a rapidly progressive dementia
 early and prominent myoclonus
 short duration of illness
 VV2
 10 percent
 ataxia at onset as an isolated feature
 late dementia
 a slightly longer duration of illness (mean seven to nine months)
 MV2
 10%
 ataxia, progressive dementia
 prominent psychiatric features
 longer duration
 PSWC 不常見
 MM2
  young age
 PSWC 不常見
  Thalamic MM2 Cortical MM2
 VV1
 1%
 progressive dementia
 younger age at onset
 longer duration 
vCJD
 Epidemiology
 It is believed that most cases of vCJD have been acquired by ingestion of
contaminated beef; genetic susceptibility may play a role in disease
manifestation.
 prominent tropism for lymphoid organs such as the tonsils and appendix
 症狀
 prominent sensory disturbances and psychiatric symptoms
 >90%
 Depression
 apathy, anxiety, irritability, social withdrawal, agitation, and
insomnia
 sensory=64%
 dysesthesias, paresthesias, and numbness; involve the face,
hands, feet, and/or legs; and are often lateralized