Download c) people with a family history of CJD

CREUTZFELD- JACOB DISEASE
INTRODUCTION :
“Prion diseases, more commonly referred to as Creutzfeld-Jakob
Disease (CJD), are a group of progressive, neurodegenerative
conditions that infect both animals and humans”
Kathryn Prout, Feb. 2000
“….. the agents have also been called unconventional slow infectious
agents. Smaller than viruses, these agents have been described as
proteinaceous and infectious, leading Prusiner and colleagues to
label them prions”
Victoria McGreevy Steelman, 1994
“The source of CJD remains unknown ; however, the agent has
been isolated from or transmitted experimentally to many different
animals. The range of these hosts is extensive, including monkeys
and other primates, sheep, goats, deer, calves, mink, ferrets, cats,
raccoons, skunks, mice and other rodents, and rabbits. It has
therefore been postulated that these animals may actually be the
reservoir for CJD transmission.”
Victoria McGreevy Steelman, 1994
CJD is one of a family of diseases called Transmissible Spongiform
Encephalopities (TSE’s), caused by an infectious agent which
invades the brain and causes mental and physical collapse. The
causative agent may reside in the body for long periods of time
undetected, but once patient is symptomatic progression is rapid
and fatal.
Different forms of the disease exist in humans and animals but they
all result in spongiform encephalopathy, named so as under
microscopic examination there are areas of brain cell with similar
appearance to sponge.
Specific examples of mammalian TSE’s include:
Scrapie
TME (Transmissible mink encephalopathy)
CWD (Chronic wasting disease): muledeer, elk
BSE (bovine spongiform encephalopathy) : cows
Humans are susceptible to several prion diseases :
* CJD : Creutzfeld-Jakob Disease
GSS : Gerstmann-Straussler-Schenker syndrome
FFI : Fatal familial Insomnia
Kuru
Alpers syndrome
CJD can be further subdivided into four main types ;
Familial
Iatrogenic
Variant
Sporadic/ Classical
PRIONS, WHAT ARE THEY AND HOW DO THEY INFECT
As mentioned earlier the cause of prion disease are prions. This
idea was initially suggested in 1982 by Stanley Prusiner. Normal
proteins when formed into a living cell fold up and are thus very
flexible and can adapt several shapes, this particular feature being
suspected to be the root of this problem.
Prion protein, PrP, exist both normally and abnormally, PrPc and
PrPsc, the normal form exists naturally in the brain but it’s function
is unknown.
The abnormal form has unusual properties. Firstly unlike its normal
form it is not broken down by enzymes. Secondly it forms
clusters/clumps called Scrapie-Associated fibrils (SAF’s), these
clumps form amyloids. In some cases of CJD, Amyloid deposits,
known as plaques are found in the brain post mortem, these are not
dissimilar to other diseases such as Alzheimers and also the normal
ageing brain.
What causes Prion disease?
The diseases are related to the presence of the earlier mentioned
PrPsc. In the normal proteins they are broken down by enzymes
once they do their job, however abnormal PrP are not broken down.
The rogue protein results from a change in the shape of the normal
one. Once formed in the body they can recruit and convert more
normal ones into abnormal form, setting off a chain reaction leading
to an accumulative build up of rogue proteins. This process causes
brain damage which interferes with normal brain function. The
function of the normal proteins is still unclear, but it has been
hypothesised that they are involved in the transport of messages
between specific brain cells.
In sporadic prion disease, this change in protein structure occurs
spontaneously and apparently at random, as a chance event
without any known cause.
In familial CJD, it is known that there are mutations in the PrP gene
which are inherited from one parent. These may produce forms of
the PrP molecule which are more likely to be converted into
abnormal form. Finally, in CJD acquired by transmission (variant
and iatrogenic), PrPsc molecules enter the body via an outside
source and corrupt the PrPc of the host.
The PrP gene can exist in two forms. We each inherit two PrP
gene’s, one from each parent. In just over half the population one
of each form is inherited and these people are called heterozygotes.
In all other cases, two identical copies are inherited; such people
are termed homozygotes. Most people with CJD are homozygotes;
it may be that they produce a PrP more vulnerable to conversion,
however it is as yet unknown.
C JD
Sporadic
U.K.
Familial
Iatrogenic
Transmission :
- largest portion of cases in
Classical
Not infectious in conventional terms, i.e.
Droplet
Blood or sexual contact
Touch
Only transmissible when tissue from an infected person/
animal is passed into the body of another person/ animal
Iatrogenic
surgical instruments
Corneal transplants
Human growth hormone
Variant
linked with contact with BSE contaminated beef
Sporadic
no link between BSE and CJD
Incubation
Unsure how long – possibly 20 years or more
Diagnosis
Definite diagnosis on post mortem
For variant – brain and tonsil biopsy
Management
Supportive, rapid referral to multidisciplinary team.
Total care required until death usually resulting from
pneumonia
Variant
The following is a brief overview/ factfile of the various types of
TSE’s affecting humans, excluding CJD :
* GSS occurs at 2% of rate of CJD. It is distinct from CJD, it
occurs every 4th-5th decade. It is characterised by cerebellar ataxia
and concomitant motor problems, dementia less common and
disease course lasts several years to death.
* FFI presents with an untreatable insomnia and dysautonomia.
Pathology is characterised by severe selective atrophy of the
thalamus.
* Alpers Syndrome is the name given to prion diseases in infants.
* Kuru refers to a canabilistic tribe in Papau New Guinea.
Progressive neurodegenerative disease, thought to have been
transmitted via the ritualistic eating of their dead relatives as a sign
of respect during mourning.
We shall briefly describe Iatrogenic and Inherited CJD firstly and
then focus on the two more prevalent types, i.e. vCJD an Classic/
Sporadic CJD.
Iatrogenic CJD
This is an acquired form of the disease where the rogue proteins are
introduced to the individual through surgery or medical treatment.
There is no evidence of normal social contact presenting a risk,
however once a person is infected the brain and certain other
tissues become infectious.
Transmission occurs only in a few specific ways ;
the majority of suffers of iatrogenic CJD contracted it via
contaminated human pituitary growth hormone
some cases have come from fertility treatment using human
pituitary derived gonadotrophin
direct inoculation from cerebral tissue, e.g. corneal grafts and
dura mater
surgical equipment from neurosurgical use on patient with
sporadic CJD
Signs & Symptoms
mood swings and behavioural change
problems with balance and gait. Tremor and rigidity of limbs
difficulties with carrying out skilled movements
headache, dizziness and double vision
dysarthria
dementia later in illness
Familial CJD
In familial CJD there is a mutation of the Prp gene, which seems to
make conversion to PrPsc more likely. There are two other
previously mentioned brain diseases which closely resemble familial
CJD, i.e. GSS and FFI, both are associated with PrP mutations. The
mechanics of the prion protein are discussed later on.
Signs & symptoms
initially depression, memory lapses, maybe unusual fatigue.
However rapid progression to dementia distinguishes it from
depression.
Within weeks, unsteadiness and lack of co-ordination.
Sudden jerky movements, rigid limbs, maybe blindness and
incontinence
This type often strikes at an earlier age than sporadic, the course of
illness is longer and patient may survive several years after onset of
symptoms.
The mentioned mutations can be detected via blood test. Therefore
at risk family members can now be screened for the presence of the
genes responsible. It may also be possible to tell from the form of
the gene whether the person will develop the illness early on or
later.
The symptoms for GSS starts with clumsiness, unsteadiness and
shakiness together with rigidity of limbs. Dementia sets in later and
the patients may survive for many years.
In FFI the main symptom is a progressive untreatable form of
insomnia. FFI differs
from other prion diseases as it only affects the Thalamus.
RISK FROM BLOOD TRANSFUSION
There is differing opinion whether there is a transmission risk with
blood transfusions.
“There is evidence from research that blood of experimentally
infected animals contains an infective agent….. Animal studies have
demonstrated that the agent causing scrapie replicates first in the
spleen and other lymphoid tissues but reaches highest titer in the
brain, where it results in the clinical appearance of the disease.
Hence peripheral tissue in contact with blood also harbors PrP
infectivity.”
Ricketts et al 1997
They also speculate that if CJD is transmissible in blood, cases
should occur in young persons, particularly if the incubation period
is short, and even if it is long we should have seen evidence by
now. Literature from the CJD Support Network also state that
CJD sufferers are no more likely to have received blood than nonsufferers so there is no convincing evidence that this is a cause.
INVESTIGATIONS CARRIED OUT FOR DIAGNOSIS
Blood tests; to rule out any other cause of symptoms. They
will also test for the prion disease susceptible genotype
EEG; this is primarily useful for diagnosis of sporadic as there
is a characteristic period sharp wave complexes
MRI; in some cases of classic/ sporadic CJD the protein
plaques are visible
CSF; there are sometime detectable PrPsc proteins visible
Brain biopsy; not very reliable as an unaffected area of brain
may be biopsied
Tonsil biopsy; the PrPsc for vCJD is present in most cases and
is one of very few ways of definite diagnosis
Autopsy; this is the only definitive exam as the spongiform
vacuoles in the brain tissue are evident under microscopic
examination.
DIAGNOSTIC CRITERIA FOR VARIANT CJD
I
a) Progressive neuropsychiatric disorder
b) Duration of illness >6 months
c) Routine investigations do not suggest an alternative diagnosis
d) No history of potential iatrogenic exposure
II
a) Early psychiatric symptoms,
i.e. Depression, anxiety,
apathy, withdrawal, delusions
b) Persistent painful sensory
symptoms, this includes both
frank pain and/or unpleasant
dysaesthesia
c) Ataxia
d) Myoclonus or chorea or
dystonia
e) Dementia
III
a) EEG does not show the
typical appearance of sporadic
CJD, i.e. generalised triphasic
periodic complexes at
approximately one per second
(or no EEG performed)
b) Bilateral Pulvinar high signal
on MRI scan
IV
a) Positive tonsil biopsy
DEFINITE : IA( progressive
neuropsychiatric disorder) and
neuropathological confirmation of
vCJD, i.e. spongiform change and
extensive PrP deposition with
florid plaques, throughout the
cerebrum and cerebellum
PROBABLE : I and 4/5 of II and
III a) and III b)
Or I and IV a)
Department of Health, July 2000, Monthly Creutzfeld-Jacob Disease statistics,
Department of Health
http://www.doh.gov.uk/cjd/stats/july00.htm
SPORADIC CJD
CJDcauses progressive loss of mental abilities and has neurological
symptoms including unsteadiness and clumsiness
It affects 1 person per million per year
50 or so new cases per year in the U.K.
85% of these cases are sporadic – having no known cause –
changes in protein structure is spontaneous, the remainder
comprising familial, iatrogenic and variant CJD
Sporadic CJD affects age group 40 – 75
Peak age of onset 60 – 65 years
Worldwide distribution
SYMPTOMS
Non-specific initial signs ; Dizziness
Headaches
Depression/ mood swings
Insomnia
Memory lapses
There is often a rapid progression to dementia and the onset of
obvious neurological symptoms
Cognition – memory lapses lengthen
Loss of concentration
Loss of problem solving skills
Disorientation
Inability to perform A.D.L.’s
Mobility unsteadiness and ataxia can be first symptoms
Involuntary jerking and abnormal movement
Tremor
Rigidity
Apraxia – inability to perform complex and
sequential tasks
Communication – slurring and quiet speech
Dysphasia
Loss of language content
Reduced comprehension
Nutrition swallowing difficulties – choking, excessive
saliva
Malnutrition
Vision blurring of vision
Poor identification of common items
Visual hallucinations
Cortical blindness
Seizures focal then tonic-clonic in the final stages of
disease
70% of patients die within 6 months of onset of symptoms
It is possible these patients have no insight into their condition
beyond the early part of their disease
Eventually these patients are unable to speak, see or move and
require total nursing care
VARIANT CJD
First identified in 1996. Quite distinct from sporadic CJD as it
affects a younger age group, course of illness is longer in variant –
typically around a year, symptoms at outset are more psychiatric
than neurological. On post-mortem there are changes aside from
the characteristic spongiform change were found- florid plaques :
deposits scattered throughout the brain and surrounded by
spongiform change
Duration of the disease ranges from 8 – 58 months
SYMPTOMS
Initially anxiety, depression, withdrawal, personality changes
– patients are often referred to psychiatrists which leads to
diagnosis delay
Sensory – persistent sensory changes, pain and odd
sensations in face or limbs pins and needles
Onset of more noticeable neurological symptoms
Motor – movement disorder is a clear sign. Ataxia –
progressive unsteadiness and clumsiness. Rigidity
Cognitive – memory loss, poor concentration
Communication – disorientation, loss of language skills.
Inability to read or write, slurring & quite speech. Dysphasia
Nutrition – locking of jaw, lack of swallow abilities
Vision – double or blurred vision. Hallucinations, gaze palsy
cortical blindness.
Ethical decisions regarding artificial means of providing nutrition
need to be addressed as soon as possible to avoid difficult decisions
later
Management
Good total nursing care of patient. Provision of support to family/
carers
Quick referral to physio, o.t., social services, speechj and language
team, nutritionalists, psychiatric community and district nurse
teams.
INFECTION CONTROL
There is no evidence of an
increased incidence of CJD in
any specific in any specific
occupational group that might
be exposed.
The degree of infectivity during
the long asymptomatic period is
unknown, but patients are
infective throughout the
duration of the symptomatic
illness.
Measures to minimise risk of
reprocessing surgical instruments
after any surgical procedure ;
1. Effective and
thorough cleaning of
surgical instruments to
remove as much
organic debris as
possible before
sterilisation
2. Instruments
designated for a single
episode of use should
be discarded after use
and never reprocessed.
3. Single use kits should
always be used for all
lumbar punctures
4. Where practical
options for single use
instruments are
available, which do not
compromise clinical
outcome, considerations
should be given to
using them
5. Flexible endoscopes
should have a unique
identifier recorded in
the patient, theatre or
endoscopy notes after
every use to facilitate
traceability.
RISK GROUPS
DEFINITION
(1) Known
Patients diagnosed
as having CJD or
related disorders
such as GSS, Kuru
or other prion
diseases
(2) Suspected Clinical symptoms
suggestive of CJD
or related
disorders but
diagnosis not
confirmed
(3) At risk
Asymptomatic
patients potentially
at risk of
developing CJD or
related disorder,
i.e.
a) recipients of
hormone derived
from human
pituitary glands
b) recipients of
dura mater grafts
c) people with a
family history of
CJD
Blood is very unlikely to present a
risk of transmission. Therefore,
blood, urine, faeces and swabs
can be collected and handled in
the normal way ( universal
precautions) without special
precautions.
OXFORDSHIRE HEALTH SERVICE, INFECTION
CONTROL SERVICE –
Management of patients with Creutzfeld-Jakob Disease (CJD)
Or Gerstmann-Straussler-Scheinker Syndrome (GSS)
(Transmissible Spongiform Encephalopathies)
Infection Control Manual 3.9.1 – 3.9.6.
INFECTION CONTROL
“Prion disease is not infectious in the conventional sense; normal
contact between people has not been shown to represent a risk
…….. There is no evidence of risk to carers through contact that
would occur in the normal caring situation”
“ The abnormal proteins associated with prion disease are resistant
to normal sterilisation procedures”
“The degree of infectivity of tissues will vary depending on the type
of prion disease ; pathogenesis of vCJD seems to be quite distinct
from that of sporadic or inherited prion disease…”
Kathryn Prout ,(2000) NT Learning Curve – Help at hand for people
dealing with prion disease, Nursing Times Feb. 2000
ACTION ON MEDICAL EQUIPMENT
PATIE
NT
GROUP
INVOLVIN
G
BRAIN/SPINE/EY
E
NOT
INVOLVING
BRAIN/SPINE/EY
E
At Risk
incinerate
disinfect
Suspect
quarantine
quarantin
e
Known
incinerate
incinerate
Douglas Clarkson,(2000) Cross infection of Creutzfeld-Jakob
Disease, Nursing Times Feb 2000, Vol.96, No. 6
“Incineration destroys prions and is consistently recommended as
the method of choice whenever possible”
Victoria M. Steelman, 1997
N.B. STILL NO DEFINITIVE
STERILISATION TECHNIQUES
DUE TO PRION PROTEIN
RESISTANCE TO HEAT AND
CHEMICAL INACTIVATION
RESEARCH ONGOING
Neurologist &
Neurology nurses
Social services
Physio &
Occupational therapy
Speech &
language
therapist
District
Nurses
nurse
PATIENT &
FAMILY/ CARERS
Incontinence
specialist
Macmillan
team/
Marie Curie
Respite care
centre
Community
Psychiatric team
Dietician
Prion unit, St. Mary’s
Human BSE Foundation
National CJD Support
network
National CJD surveillance
unit
Compiled by Natalie Walton & Niall Bennett