This patient, a 65-year-old male, presented with 6 months of gradually worsening gait difficulties and incoordination. Over the past 4 months, he developed forgetfulness, hallucinations, and sensorium changes. Exams found rigidity, myoclonic jerks, and a non-reactive semi-conscious state. Imaging and tests were suggestive of Creutzfeldt-Jakob disease (CJD), a prion disease characterized by spongiform changes in the brain. A definitive diagnosis requires brain biopsy or autopsy.

2.  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.  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.  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.  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.  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.  He was diagnosed with hypertension 3 years
back.
 No h/o DM

8.  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.  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.  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.  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.  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. 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. 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.  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.

26.  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.  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.  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.  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.  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.  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.  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 (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.  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.
6. Routine investigations that do not suggest an alternative diagnosis.
7. A magnetic resonance image showing abnormal bilateral high signal from the pulvinar on axial
T2-and/or proton-density-weighted images.

35.  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
and/or
Neuropsychiatric disorder plus disease-specific PrP gene mutation

36.  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.  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.  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