Creutzfeldt-Jakob Disease (CJD) Creutzfeldt-Jakob Disease (CJD)

1. Musa Abu Sabha Section 7 Lab 73
Creutzfeldt-Jakob Disease (CJD)

2. Creutzfeldt-Jakob Disease (CJD)

3. 1. Case presentation ( findings and investigations )
2. Definition and Etiology
3. Mode of Transmission
4. Epidemiology
5. Pathogenesis
6. Clinical Findings and Diagnosis
7. Treatment and Prevention
8. Infection Control
Outline

4. • A 42-year-old woman from India without any known comorbidities developed gait and stance
unsteadiness around 1 month prior to presenting to ER. It was rapidly followed by development
of tremulousness in both hands. she was diagnosed by an orthopedic surgeon that she was
having a fracture of her right tibia and received plaster casting of her right leg. However, her
neurological illness continued to go downhill as she developed intermittent abnormal twisted
posturing of her right hand, suggestive of focal dystonia. Subsequently, she developed
progressive deterioration of her cognitive function for around 2 weeks before coming. Reduced
attention span, impairment of short-term memory, behavioral abnormality, and language
problems in the form of comprehension difficulty as well as irrelevant talking were the major
features at the onset of her cognitive disturbance. Over the course of 3–4 days prior to
admission, her higher mental function deteriorated severely enough amounting to akinetic mute
state. There was no family history of similar illness.
Case presentation

5.  Clinical findings:
1-Akinetic mute state.
2-Paratonia in both upper limbs and left lower limb.
3- Intermittent focal myoclonic jerks.
4- Bilateral extensor plantar response.
 Investigations :
Blood count and metabolic parameters normal
Syphilis, human immunodeficiency virus (HIV), herpes simplex
virus, human herpes virus-6
negative
C-reactive protein, folate, vitamin B12, erythrocyte
sedimentation rate, and homocysteine levels
normal

6. MRI revealed bilateral caudate nucleus and putaminal hyperintensity

7. EEG showed diffuse slowing of background activity with periodic sharp
wave complexes along with intermittent triphasic waves

8. Definition and Etiology
• Prion protein is encoded by PRNP gene , and is composed of 253
amino acids . Prion , as other proteins , is folded , but most of these
folds are alpha helices . This protein can be found in the cell
membrane of neurons yet its function is unknown . Some studies
suggest that it engages in synapses between neurons and in copper
uptake
• Prion diseases are a group of neurodegenerative diseases caused by
the conversion of the normal form of prion protein (PrPC,) with an
alpha-helical structure into an abnormal form of the prion protein
(PrPSc) which has a beta-pleated sheet structure.

9. Definition and Etiology
• CJD belongs to a family of prion diseases or transmissible spongiform
encephalopathies which can cause several fatal neurodegenerative
disorders in humans and animals .The peak age of onset is between
55 and 75 years and the mean survival is 6 months only. The
infectious agent is “prion” (a protein) that can be transmitted either
by direct contact with contaminated tissue or via inheriting a
mutation in the prion protein gene. However, most cases of CJD are
sporadic.

10. Mode of Transmission :
• CJD transmission depends on its type ; there are 4 different
types of CJD :
1- Familial : autosomal dominant mutations in the PRNP gene encoding the
prion protein , the most common mutation being the one at the 200th codon .”
It could be transmitted to offspring via genetics “.

11. Mode of Transmission :
• CJD transmission depends on its type ; there are 4 different
types of CJD :
2- Acquired : Iatrogenic or oral transmission from human or animal. Through
some surgical procedures, transmission occurs when exposed to the infected
brain or nervous tissue.

12. Mode of Transmission :
• CJD transmission depends on its type ; there are 4 different
types of CJD :
3- Variant : by consuming infected beef resulting in a bovine disease similar to
human CJD called bovine spongiform encephalopathy (BSE) or “mad cow”
disease .

13. Mode of Transmission :
• CJD transmission depends on its type ; there are 4 different
types of CJD :
4- Sporadic (sCJD) : Occurs spontaneously, without a known cause .

14. Epidemiology
1-Creutzfeldt-Jakob disease (CJD) affects about 1 individual per million per year
worldwide.
2-Sex , Age and Seasonal Occurrence : sCJD occurs equally in both sexes with a
peak age of onset between 60 and 69 years . sCJD occurs all year round, with no
seasonal specificity .
3-Duration / Survival Rate :
• A study conducted by Chen C. and his team revealed that in China , 78.5 % of
patients die within one year of onset .
• A study conducted by the European CJD Surveillance Network (EuroCJD)
involving 2,451 sCJD patients, who died between 31 December 1992 and 31
December 2002, revealed that 85.8 % of patients died within one year of onset
.

15. Epidemiology
3-Duration / Survival Rate :
• On the contrary, a survey by the Japanese CJD surveillance program showed
significantly longer disease durations in Japanese patients with prion diseases
(most of them with the sCJD subtype), in which the mean disease duration of
855 patients was 17.4 months and only 46.0 % died within one year of onset.
• Unfortunately , there is no accessible data for sCJD cases in South Asia or
Africa.
“These studies indicate that the duration of this disease is short .”

16. Epidemiology
4- Mortality Rate :
• An international study on the epidemiologic characteristics of sCJD involving
3,720 sCJD cases from nine European countries, as well as from Australia and
Canada, revealed that the overall annual mortality rate from sCJD is 1.39 per
million . The countries with the highest mean mortality rates per million from
sCJD are France and Switzerland (1.51 and 1.72, respectively).

17. Epidemiology
The mean mortality rates per million from sCJD according to the data of the CJD International
Surveillance Network from 1993 to 2013. a Data from the member states of the CJD
International Surveillance Network. The mortality rate of one per million is marked with a
dotted line. b The mean mortality rates per million of all member states. Solid line represents
the fitting trend

18. Pathogenesis :
 CJD is caused by “infectious” prions (PrPSc) that are usually
produced endogenously but may also be acquired .
 PrPSc → conformational change of physiological PrPc ( from an alpha
helices-rich protein into a beta plated sheets-rich protein )→ formation of
condensation centers + PrPSc accumulation ( unknown mechanism ) →
plaque formation → neuronal cell death ( Apoptosis induced by 14-3-3
protein )→ progression to spongiform encephalopathy (seen as
intracytoplasmic vacuoles within the neurons of cerebral and cerebellar
cortex on H&E) .
 It is believed that the host is immunotolerant against prions because there
is no difference in the primary structure of normal and abnormal PrP, and
prions do not induce a marked immune response .

19. Pathogenesis :

20. Pathogenesis :

21. Clinical Findings and Diagnosis
General Symptoms:
Creutzfeldt-Jakob disease is marked by rapid mental deterioration, usually within a few
months. Initial signs and symptoms typically include:
• Personality changes will usually develop first in variant CJD
• Anxiety
• Depression
• Memory loss
• Impaired thinking
• Blurred vision or blindness
• Insomnia
• Difficulty speaking
• Difficulty swallowing
• Sudden, jerky movements mainly in sporadic CJD
As the disease progresses, mental symptoms worsen. Most people eventually lapse into a
coma. Heart failure, respiratory failure, pneumonia or other infections are generally the
cause of death. Death usually occurs within a year.

22. Clinical Findings and Diagnosis
Diagnosis : Since it affects many areas in the brain , CJD mimics several diseases ,
making its diagnosis really hard but we can use:
1- Imaging ,such as MRI, of the brain may be performed during medical
evaluation, both to rule out other causes and to obtain supportive evidence for
diagnosis.
2- Electroencephalogram (EEG): electrodes placed on the patient’s scalp detect
and record the patterns of electrical activity generated by the brain. Can help in
diagnosing CJD.
3-CSF markers : The most useful CSF markers of CJD are >protein 14-3-3 and
total tau.
4- Brain biopsy or an examination of brain tissue after death : The only way to
confirm the presence of Creutzfeldt-Jakob disease

23. Treatment and Prevention
Treatment :
• Treatment of prion diseases remains supportive; no specific therapy has been
shown to stop the progression of these diseases.
Prevention :
• There is no drug or vaccine available for prevention.

24. Infection Control
The following recommendations are supposed by WHO to maintain the safest
method for ensuring that there is no risk of residual infectivity on contaminated
instruments and other materials :
1- Incineration :
• Use for all disposable instruments, materials, and wastes.
• Preferred method for all instruments exposed to high infectivity tissues.
2-Autoclave/chemical NaOH methods for heat-resistant instruments.
3-NaOH or undiluted sodium hypochlorite for surfaces and heat sensitive
instruments.
4-Autoclave/chemical methods for dry goods

25. References :
• Lahiri, D., Pattnaik, S., Bhat, A., Dubey, S., Biswas, A. and Roy, B., 2019. Young-onset
sporadic Creutzfeldt–Jakob disease with atypical phenotypic features: a case report.
Journal of Medical Case Reports, 13(1).
 Sitammagari, K. and Masood, W., 2020. Creutzfeldt Jakob Disease. [online]
Ncbi.nlm.nih.gov. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK507860/?fbclid=IwAR0wUoF8NZ5UE_8RE4-
fgSxWwY0ap-BMvM1iboLmWknOvXDUz2SJnodr_nI#article-23799.s3 .
 Chen, C. and Dong, X., 2020. Epidemiological Characteristics Of Human Prion
Diseases. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890484/?fbclid=IwAR3JgWYuMt_z
wPUfrYRtYflftNg8H-OKM7SVTgk6mnA5kYDBQKs4kZYtFYE#CR24 .
• Emedicine.medscape.com. 2020. Prion-Related Diseases: Background,
Pathophysiology, Epidemiology. [online] Available at:
https://emedicine.medscape.com/article/1168941-overview
• WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies:
Report of a WHO Consultation, Geneva, Switzerland, 23-26 March 1999
• Centers for Disease Control and Prevention , National Center for Emerging and
Zoonotic Infectious Diseases (NCEZID) , Division of High-Consequence Pathogens and
Pathology (DHCPP)

26. Thank You !