Clinical Symptoms of Human TSEs

	Sporadic CJD (sCJD) (85% of human TSEs)	Familial CJD (fCJD) (~10% of human TSEs)	Fatal Familial Insomnia (FFI)	GSS 6 disorders	Kuru	vCJD
Clinical symptoms at presentation	Demetia Ataxia Behavioral disturbance	Demetia Ataxia Behavioral disturbance	Insomnia	Dementia	headaches limb pains	sensory or phychiatric disturbances (depression/withdrawl) dysesthesia ataxia
Clinical symptoms during course of illness	Rapid clinical evolution Short total illness duration Dementia Myoclonus Pyramidal EEG changes Dysphasia Cerebellar EEG changes Akinetic mutism Primitive reflexes Cortical blindness Extrapyramidal EEG changes Lower motor neuron signs Seizures	Rapid clinical evolution Short total illness duration Dementia Myoclonus Pyramidal EEG changes Dysphasia Akinetic mutism Primitive reflexes Cortical blindness Extrapyramidal EEG changes Lower motor neuron signs Seizures	disruption of sleep/wake cycle myoclonus sympathetic hyperactivity dementia hallucinations stupor coma hyperhidrosin pyrexia tachycardia hypertension irregular breathing ataxia myoclonus dysarthria pyramidal signs	cereballar ataxia myoclonus - less common limb ataxia dysarthria nstagmus dementia parkinsonism deafness blindness gaze palsies seizures numbness Pyramidal EEG changes Extrapyramidal EEG changes	ataxia dysarthria limb rigidity or rigidity no myoclonus occasionally exaggerated startled response pathologic bursts of laughter dementia in late stages sometimes late stages placid mute unresponsive death often assoc. w/ decubitus ulcers hypostatic pneumonia	absence of triphasic EEG waves
Other notes	age at death 63-69yr mean duration of illness 5mo distinction from Alzheimer's is difficult except for the rapid clinical evolution and the presence of myoclonus in CJD	age at death 55-62yr duration of illness 3-51mo slightly earlier onset than sCJD	age at onset 35-61yr (avg. 40yr) duration of illness 7-36mo 7-18mo for M129 homozygotes 20-35mo for M129, V129 heterozygotes autosomal dominant inheritence	age at onset 40-60yr duration of illness 60-108mo incidence 2-5/100,000,000 dominant inheritence	duration of illness 12-18mo adults duration of illness 3-12mo juveniles incubation period - time from exposure to clinical symptoms ranges from 4.5 to >40yr	mean age at death 30yr; but really is determined by the age of exposure to BSE mean duration of illness 13mo incubation period - time from exposure to clinical symptoms probably 6-12yr (this is a bit longer than that for Kuru or iatrogenic indicating a species barrier) all homozygous for M129
Histological (note: the gross appearance of the brain may not change with TSE, and the degree of spongiform degeneration, astrocytic gliosis or presence of amyloid plaques vary widely)	spongiform degeneration always in cerebrum (cerebral cortex) but may be found in neocortex, hippocampus, putamen, caudate nucleus, thalamus and cerebellum (cerebellar cortex) nerve cell vacuolation, intense reactive astrocytosis and neural loss in some cases Kuru-type amyloid plaques in 5-10% of CJD cases in the granule cell layer of the cerebellar cortex	spongiform degeneration always in cerebrum (cerebral cortex) but may be found in neocortex, hippocampus, putamen, caudate nucleus, thalamus and cerebellum (cerebellar cortex) nerve cell vacuolation, intense reactive astrocytosis and neural loss in some cases	thalamus - has worse neuropathology cerebral cortex - mild spongiform degeneration cerebellum -some cell loss PrP^Res found in brain amyloid plaques absent PrP^Res found in brain	spinocerebellar or olivopontocerebellar degeneraton corticospinal tract eventually involved amyloid plaques widespread containing PrP^Sc cases within the granule cell layer of the cerebellar cortex	nerve cell vacuolation is characteristic cerebellar abnormalities amyloid plaques in all cases containing PrP^Sc cases within the granule cell layer of the cerebellar cortex	intense spongiform degeneration most intense in basal ganglia and thalamus (marked astrocytic gliosis also) PrP^Res present (large amounts in cerebellum found with spongiform degeneration, neuronal loss and astrogliosis) PrP^Sc in lymph tissue (not found in sCJD) in tonsils, lymph nodes, spleen and appendix (leading to concern of blood donor safety) assive amount of amyloid plaques in all cases many Kuru-like made up of PrP^Sc cases within the granule cell layer of the cerebellar cortex primarily the occipital lobe many within the center of vacuoles (florid plaques), also plaques in cerebellum (granule cell layer and cortex) more plaques than when present in sCJD or HGH iatrogenic CJD but do not resemble those in GSS amyloid plaques do not from in cattle with BSE, Prnp^0/0 / TgBoPrnp mice, felines or zoo ungulates.

Diagnosis is difficult during the early clinical manifestations of the various TSEs because they resemble other neurological problems such as Alzheimers. However, the rapid progression of other symptoms such as dementia is characteristic to human TSEs.

Genetic testing is used to determine if the patient is susceptible to any of the familial (inherited) forms of TSE; i.e. FFI, fCJD, GSS and thus potentially confirm the disease.

Due to many similarities among the human TSE, distinguishing between the different diseases often requires either genetic tests (or a family history of an inherited form of TSE) or neuropathologic verification (examining of the brain often after death).

Iatrogenic CJD is not listed in the table above. In essence, the clinical features of iCJD would resemble the features of the patient from which the PrP^Sc originated.

There are several different forms of CJD and GSSD, each with a range of clinical symptoms. The table above lists those that commonly occur.