1. Case Presentation

2. LW
85yr old lady
A year ago – past-times included…dancing, playing the drums, organising garden competitions, making straw hats
Over the last year she had had had to give some of this up to care for her husband
He has Alzheimer’s Dementia and his mobility and hearing had been deteriorating
She had been caring for her husband with no external help up until a few months ago

3. About 2-3 months ago there was a family dispute
-daughter worried not coping and wanted help at home
-father refused to have carers
-patient felt stuck in the middle
-had become increasingly anxious
2 months ago son moved more locally with some improvement in his mother’s symptoms
1 month ago sudden deterioration with increased anxiety and depression
Seen by Dr Bown and started in Mirtazepine 30mg OD but no improvement

4. Over a 2 week period become progressively worse
- more and more anxious
-“clutching herself”
-inconsolable
-withdrawn
-off food and drink.
GP had instituted 24 hour carers
Referred by GP to try and “break the cycle”

5. On Admission (12/9/08) Obs normal Clinically dry
AMTS not possible as not responding to questions- seemed to respond to son non-verbally
Exam normal except ?left facial droop- but no teeth in and son stated this appearance normal for her. Tone symmetrical, moving all 4 limbs, plantars downgoing
Bloods WCC Ur 27.8
Neut Cr 198
CRP <5
Rehydrated and CT head planned- no impression given!

6. When we first met her (13/9/08)
AMTS -age, dob, place, time of day, yr correct
Groaning and looked uncomfortable
Short answers to questions
Temp 37.7
Urine dip positive leucocytes and nitrites +++
WCC Neut CRP 9
Treated for UTI (iv amoxicillin + stat gentamycin) with some improvement
CT Brain- age consistent cerebral atrophy, some white matter small vessel ischaemic change

7. And then 2 days later on a Friday afternoon (15/9/08)
ATSP re: drop in GCS to 7/15
Had eaten breakfast that am and been talking with nurses. Some vomiting that am, gradual decline in responsiveness
Temp 37.9
No signs of meningism
Not moving any limbs, reflexes normal, plantars downgoing, PERLA
BM normal. Bloods no change. CXR normal. ABG normal.
Repeat CT head- nil change from previous
LP technically not possible

8. Impression
?worsened sepsis ?uti ?encephalitis
??contribution from mirtazepine (dose had been reduced)
???some psychiatric component
Management
-started on empirical aciclovir to cover possible encephalitis
-antibiotics for UTI
-mirtazepine stopped

9. Over that w/e…
Fluctuating GCS between 7 and 14- sometimes unresponsive, other times groaning, other times sitting up and more alert
Jerking movements of limbs noted-?partial seizures

10. Neurology Review O/E subtle myoclonus
Imp: likely rapid dementia with intercurrent UTI heralding admission
Advised the need to exclude reversible causes but ? CJD
Suggested Bloods, LP, MRI, EEG

11. Psychiatry Review
Not a depressive illness- may be a depressive component to illness which has an organic cause
But wouldn’t hurt to start citalopram!

12. All this while Fluctuations in GCS
Variable from day to day from groaning, barely responding to more alert, trying to answer questions, taking some food and water.
Increased tone noted in limbs

13. Results
Bloods- normal autoimmune screen, thyroid peroxidase antibody test, VDRL and plasma viscosity
MRI- movement artefact +++, peri-ventricular small vessel ischaemia and ischaemic damage within the brain stem
EEG- slow and fast activity, very non specific, consistent with organic encephalopathy
LP- WCC 1, RCC 1, protein 0.3, glucose not done, No growth on culture. Negative protein

14. Re- review Neurology -No clear neurological pathology
-No hard brainstem signs
-? Behavioural increase in tone
Psychiatry
-Organic illness

15. Rehabilitation
Although fluctuating general trend very very slow improvement
Plan is to try and rehabilitate
Variability continues even now…days where in bed, still looking uncomfortable, minimal conversation to days where sat out in the chair and even walked with zimmer frame
Started on lorazepam 0.5mg bd for tone
Was on citalopram but stopped due to low sodium- no change noted on stopping

16. Food for thought… Diagnosis is not always possible
Difference in opinion between specialities
Working with disabilities of illness to try and rehabilitate even when you don’t necessarily know what caused them
CJD as a cause of rapid cognitive decline…..

17. CJD

18. Transmissible Spongiform Encephalopathies
Under a microscope, the affected brain tissue looks like a
sponge

19. Prion protein
Cellular protein found in brain and spinal cord (lower levels in lymphoid tissue)
Function unknown
In CJD an altered form of the normal protein causes normal protein to change conformation and transform into an abnormal prion protein. The latter accumulates as it is resistant to proteases and leads to damage to brain cells
Where does this initial abnormal prion protein originate?
-Sporadic ?Somatic mutation
-Familial Inherited mutation
-Variant Consumption of meat contaminated with brain tissues of cows with BSE

20. Types of CJD Rare disease Sporadic (Most common- one per million)
Variant (Associated with BSE)
Familial (Mutations in PRNP gene)

21. Clinical Features Sporadic CJD Median age at death 68 yrs
Median duration of illness 4-5 months
Rapid dementia
Early neurologic symptoms e.g. myoclonus
Variant CJD
Younger 20-30’s
Duration months
Prominent psychiatric/ behavioural changes (anxiety, withdrawal, apathy, agitation, depression, personality change)
Painful dyesthesiasis
Delayed neurologic signs

22. Investigations EEG MRI CSF (Genetic testing)
Post mortem makes definitive diagnosis

23. EEG
Spike and wave pattern

24. EEG 60-80% will develop characteristic EEG pattern
BUT pattern develops throughout the course of the illness and, in some cases, may not appear until very late.
Therefore, finding a positive EEG may require repeat studies (possibly weekly) even very late into the illness course and these may not always be undertaken.

25. MRI

26. MRI Generally undertaken to exclude other illnesses
Cerebral atrophy may be seen
In a proportion, abnormalities of signal may be seen in the anterior basal ganglia and sometimes in the cortex.
These changes can be helpful in supporting a diagnosis of sporadic CJD.

27. MRI in Variant CJD
Characteristic abnormality seen in the posterior thalamic region (the so
called “pulvinar sign”) which is highly sensitive and specific for vCJD

28. CSF The routine examination of CSF is generally unremarkable
Total protein may be elevated but usually less than 1 gram per litre

29. CSF 14-3-3 Analysis Normal neuronal protein
Released into the CSF in response to a variety of neuronal insults
Therefore generally a non-specific finding and analysis cannot be used as a general screening test for sporadic CJD
Other illnesses, which can give a positive test, include:
Herpes simplex encephalitis
Recent cerebral infarction or haemorrhage
Subarachnoid haemorrhage
Hypoxic brain damage
Glioblastoma

30. CSF Analysis
However, usually a straightforward clinical matter to exclude the other possible illnesses which may give rise to an elevated level.
Therefore, in an appropriate clinical context, a positive test is strongly supportive of a diagnosis of sporadic CJD and a negative test is unusual.
In the United Kingdom, the National Laboratory for CSF test is in the National CJD Surveillance Unit.
If a case meets the diagnostic criteria for “possible sporadic CJD” and has a duration of less than 2 years then a positive test allows the case to be classified as “probable sporadic CJD”.

31. Management No cure Management is symptomatic MDT approach
As these diseases are rare, experience in local services is often limited. The National Prion Clinic has been established to provide a clinical service for people with or suspected to have any form of prion disease. Assessment, diagnosis, information, advice, support and counselling is available for patients, their families, health care professionals and members of the public.

32. Potential treatments under investigation
Pentosan polysulphate
Not licensed
Infused directly into the brain
MRC trial in 7 patients- may possibly prolong survival but did not halt deterioration in the brain
Quinacrine
Very limited evidence from laboratory tests for the potential use of quinacrine in human prion disease, and the evidence to date for any possible clinical benefit is very scarce
MRC trial ongoing

33. Monitoring
The National CJD Surveillance Unit, based in Edinburgh, was established in 1990 to monitor the incidence of all types of CJD and to investigate the occurrence of the disease.
It investigates each case of sporadic and variant disease in detail so that any change in the pattern of CJD following the occurrence of BSE can be detected, and provides up-to-date information on current trends and incidence of the disease.