This patient, a 65-year-old male, presented with 6 months of difficulty walking and 4 months of forgetfulness and hallucinations. Examination found he was semiconscious with rigidity and myoclonic jerks. Imaging and tests were consistent with a prion disease like Creutzfeldt-Jakob disease (CJD). A lumbar puncture found elevated proteins. He was diagnosed with a rapidly progressive neurodegenerative condition likely CJD.

1. CASE PRESENTATION
NEUROLOGY
By- Dr. Armaan Singh

2. HISTORY OF PRESENT ILLNESS
• According to family members this 65 y/o male patient developed difficulty in walking for the
past 6 months.
• Patient was apparently normal 6 months back when he started developing gradual difficulty
in walking, in form of in coordination so that he used to walk holding on to walls or other
support available .

3. HISTORY OF PRESENT ILLNESS
• They were also complaining forgetfulness, hallucinations for past 4 months.
• Gradually family Members noticed that patient was becoming forgetful over time, and he used
to forget familiar faces, names, topic he discussed half an hour back

4. HISTORY OF PRESENT ILLNESS
• They gave h/o altered sensorium with mycoclonic jerks for 2 months.
• He also used to develop sudden , brief loss of contact with the environment.

5. HISTORY OF PRESENT ILLNESS
• His sensorium became gradually impaired .
• He was admitted at a hospital in nepal 2 months back, diagnosed as a case of Neurosyphilis,
was given benzathine penicillin but did not improved.

6. HISTORY OF PRESENT ILLNESS
• He became irritable in the hospital, for which he was given serenace (Haloperidol)and
thereafter he became unconscious, rigid.
• Despite withdrawing Serenace , his sensorium did not improved and since then he gradually
slipped to unconscious state. He was referred to BLK with these complaints.

7. PAST HISTORY
• He was diagnosed with hypertension 3 years back.
• No h/o DM

8. ON EXAMINATION
• He is semiconscious
• Vitals at the time of admission
BP:138/100 mm hg
PR: 98/minute
RR: 30/minute
Temp: 101* f
CVS :S1 S2 + No abnormal sounds
Chest: Bilateral air entry positive , No crepitations
Abdomen: Soft , No Swellings.

9. NEUROLOGICAL EXAMINATION
• Patient was opening his eyes spontaneously
• Not following commands
• Moving his limbs(flexion) in response to painful stimuli.
• Pupils: Normal in size , reacting to light
• No apparent cranial nerve abnormality

10. NEUROLOGICAL EXAMINATION
• Motor exam: Rigidity felt in all 4 limbs which is more in upperlimbs
• Flexion of both his upperlimbs in response to deep painful stimuli
• DTR-
• Plantar response: flexor response in both feet
• Myloclonic jerks – present in all 4 limbs.

11. INVESTIGATIONS
• CSF FLUID EXAMINATION FOR CELL COUNT
Clear ,colourless
Microscopic examination:
Total leucocyte count 5 cells/cu mm
(Adults- 0-5 cells/cu mm Neonate-0-30 cells/cu mm)
Differential leucocyte count
neutrophils 6/10 cells counted
lymphocytes 4/10 cells counted

12. INVESTIGATIONS
• TORCH PANEL- negative
• TB PCR
M.Tuberculosis complex : not detected
nontuberculosis mycobacteria: not detected
• CMV PCR- Negative.
• TPHA CSF- Negative
• Cryptococcal antigen CSF-Negative.
• CSF Indian ink staining -Encapsulated yeast cells resembling
Cryptococcus species not seen.

13. INVESTIGATIONS
• CSF Cerebrospinal fluid
Gram stain :
No cells seen.
No organisms seen.
Culture &sensitivity:
The culture is sterile after 5 days of aerobic incubation at 35
degree centigrade.

14. INVESTIGATIONS
CT SCAN OF THE HEAD – PLAIN
• The cerebral parenchyma shows normal attenuation values.
• The ventricles, cisterns and sulci are generally prominent.
• Bilateral basal ganglia calcification is seen.
• There is no midline shift.
• The cerebellar hemispheres and brain stem are normal.
• The 4th ventricle is normal in size and midline in position.
CONCLUSION:
The findings are consistent with diffuse cerebral atrophy consistent with the age of the
patient.

15. INVESTIGATIONS
• MRI findings are suggestive of marked diffuse cerebral atrophy with symmetric
diffuse signal alteration and restricted diffusion involving bilateral basal ganglia.
The thalami (pulvinar) or neocortex do not reveal any restricted diffusion. In view of short history,
possibility of rapidly progressive neurodegeneration - ? Creutzfeldt Jakob disease (sCJD) may be
considered. However, differentials of infective etiology with basal ganglia ischemia cannot be
entirely excluded. Clinical correlation & further work up with CSF analysis and EEG is suggested.
• Also noted are chronic white matter ischemic changes & mild cerebellar atrophy. No brainstem
atrophy is seen.

16. DWI

17. DWI

18. DWI

19. DWI

20. DWI

21. DWI

22. T2 FLAIR

23. T2 FLAIR

24. T2 FLAIR

25. EEG

26. SLOW VIRUS INFECTIONS
• Slow virus infections are also known as prion diseases, after the presumed infectious agent,
as well as transmissible spongiform encephalopathies (TSEs), after the histopathologic
changes associated with these infections.

27. SLOW VIRUS INFECTIONS
• Prions are proteinaceous infectious particles (PrPs).
• The brain pathology of prion diseases consists of a vacuolar (spongiform) degeneration of the
neuropil, cortical neurons, and subcortical gray matter with neuronal loss and gliosis.

28. SLOW VIRUS INFECTIONS
• Early diagnosis is difficult, in part because prions do not have nucleic acids, making
conventional nucleic acid–based viral detection systems ineffective.
• PrPs also elude detection by not producing a humoral immune response.

29. TYPES OF SLOW VIRUS INFECTIONS
• Slow virus infection Host
• Creutzfeldt-Jakob disease (CJD) Humans
• Gerstmann-Straussler-Scheinker disease Humans
• Fatal familial insomnia Humans
• Kuru Humans
• Scrapie Sheep, goats
• Bovine spongiform encephalopathy Cattle, humans
• Chronic wasting disease Mule deer, elk
• Transmissible mink encephalopathy Mink
• Feline spongiform encephalopathy Cats

30. TYPES OF SLOW VIRUS INFECTIONS
• Prion diseases are categorized into three groups: sporadic, (85%), hereditary &acquired(15%)
• 15% consist of hereditary forms (hereditary Creutzfeldt-Jakob disease [CJD], Gerstmann-
Straussler-Scheinker disease, fatal familial insomnia) and acquired forms.
• Acquired forms may be transmitted iatrogenically (through human growth hormone therapy, dura
mater grafts, or other neurosurgical procedures) or through cannibalism (kuru) , variant CJD
(vCJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) in cattle.

31. WORLD HEALTH ORGANIZATION DIAGNOSTIC CRITERIA FOR
CREUTZFELDT-JAKOB DISEASE
• 1. Creutzfeldt-Jakob Disease (CJD) clinical diagnosis:
Criteria for probable sporadic CJD:
• The clinical diagnosis of CJD is currently based on the combination of
progressive dementia, myoclonus, and multifocal neurological
dysfunction, associated with a characteristic periodic
electroencephalogram (EEG).
• However, new variant CJD, most growth hormone-related iatrogenic
cases, and up to 40% of sporadic cases are not noted to have the
characteristic EEG appearance. This
hampers clinical diagnosis, and hence surveillance, and illustrates
the need for additional diagnostic tests.

32. WORLD HEALTH ORGANIZATION DIAGNOSTIC
CRITERIA FOR
CREUTZFELDT-JAKOB DISEASE
• Proposed criteria for probable sporadic CJD:
a. Progressive dementia.
and
b. At least two out of the following four clinical features:
i. Myoclonus.
ii. Visual or cerebellar disturbance.
iii. Pyramidal/extrapyramidal dysfunction.
iv. Akinetic mutism.
and
2. A typical EEG during an illness of any duration.
and/or
3. A positive 14-3-3 cerebral spinal fluid assay and a clinical duration to death less than 2 years.
4. Routine investigations should not suggest an alternative diagnosis.

33. NEW-VARIANT CREUTZFELDT-JAKOB DISEASE:
SUSPECT CASE DEFINITION
• New-variant Creutzfeldt-Jakob disease (nvCJD) cannot be diagnosed with certainty on clinical
criteria alone at present.
• However, based on the 23 neuropathologically confirmed cases, the diagnosis of nvCJD
should be considered as a possibility in a patient with a progressive neuropsychiatric
disorder, with at least five out of the following six List 1 clinical features. The suspicion of
nvCJD is strengthened by the following criteria in List 2.

34. NEW-VARIANT CREUTZFELDT-JAKOB DISEASE:
SUSPECT CASE DEFINITION
• A patient with a progressive neuropsychiatric disorder and five out of the six clinical features in List 1 and all of the
criteria in List 2 should be considered as a suspect case of nvCJD for surveillance purposes.
• List 1
1. Early psychiatric symptoms.
2. Early persistent parasthesias/dysesthesias.
3. Ataxia.
4. Chorea/dystonia or myoclonus.
5. Dementia.
6. Akinetic mutism.
• List 2
1. The absence of a history of potential iatrogenic exposure.
2. Clinical duration more than 6 months.
3. Age at onset less than 50 years.
4. The absence of a PrP gene mutation.
5. The EEG does not show the typical periodic appearance.

35. DEFINITION OF CREUTZFELDT-JAKOB DISEASE
SUBTYPES
• Sporadic CJD
1. Definite Diagnosed by standard neuropathological techniques and/or immunocytochemically
and/or Western blot-confirmed protease-resistant PrP and/or presence of scrapie associated
fibrils.
2. Probable
a. Progressive dementia and at least two out of the following four clinical features:
• Myoclonus.
• Visual or cerebellar disturbance.
• Pyramidal/extrapyramidal dysfunction.
• Akinetic mutism.
and
b. A typical EEG during an illness of any duration
and/or
c. A positive 14-3-3 CSF assay and a clinical duration to death less than 2 years.
d. Routine investigations should not suggest an alternative diagnosis.
3. Possible Same clinical criteria as definite but no, or atypical, EEG and duration less than 2 years
• Iatrogenic CJD Progressive cerebellar syndrome in a recipient of human cadaveric-derived pituitary hormone;
Or sporadic CJD with a recognized exposure risk, e.g., antecedent neurosurgery with dura
mater graft
• Familial CJD Definite or probable CJD plus definite or probable CJD in a first-degree relative

36. NEUROPATHOLOGICAL CRITERIA FOR CREUTZFELDT-JAKOB
DISEASE AND OTHER HUMAN TRANSMISSIBLE
SPONGIFORM ENCEPHALOPATHIES
• 1. Creutzfeldt-Jakob disease (CJD)—sporadic, iatrogenic (recognized risk) or familial (same disease in first
degree relative or disease-associated PrP gene mutation): Spongiform encephalopathy in cerebral and/or
cerebellar cortex and/or subcortical gray matter; and/or encephalopathy with prion protein (PrP) immunoreactivity
(plaque and/or diffuse synaptic and/or patchy/perivacuolar types).
• 2. New-variant CJD—Spongiform encephalopathy with abundant PrP deposition; in particular, multiple fibrillary
PrP plaques surrounded by a halo of spongiform vacuoles (“florid” plaques, “daisy-like” plaques) and other PrP
plaques, and amorphous pericellular and perivascular PrP deposits; especially prominent in the cerebellar
molecular layer.
• 3. Gerstmann-Sträussler-Scheinker disease (in family with dominantly inherited progressive ataxia and/or
dementia and one of a variety of PrP gene mutations): Encephalo(myelo)pathy with multicentric PrP plaques.
• 4. Familial fatal insomnia (in member of a family with a PrP gene mutation at codon 178 in frame with methionine
at codon 129): Thalamic degeneration, variable spongiform change in cerebrum.
• 5. Kuru: Spongiform encephalopathy in the Fore population of Papua New Guinea.

37. CONDITIONS THAT MAY CAUSE A CREUTZFELDT-
JAKOB DISEASE-LIKE ELECTROENCEPHALOGRAM
• Alzheimer’s disease
• Hyperammonemia
• Lewy body disease
• Binswanger’s disease
• AIDS dementia
• Hyperparathyroidism
• Hypo- and hypernatremia
• Hypoglycemia
• Multiple cerebral abscesses
• MELAS syndrome
• Hepatic encephalopathy
• Baclofen, mianserin, metrizamide, and lithium toxicity
• Postanoxic encephalopathy
• MELAS ( mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)

38. CONDITIONS OTHER THAN CREUTZFELDT-JAKOB
DISEASE THAT CAN HAVE A POSITIVE 14-3-3 RESULT
• Herpes simplex and other encephalitides
• Stroke (especially recent)
• Subarachnoid haemorrhage
• Hypoxic/Ischemic encephalopathy
• Barbiturate intoxication
• Glioblastoma
• Carcinomatous meningitis (especially small-cell lung carcinoma)
• Paraneoplastic encephalopathy
• Corticobasal degeneration