CJD – A downward spiral of depression into dementia and death

Post prepared by Dr Mariam Kemal, PGY-3 (Internal medicine), Monmouth Medical Center

Case History:

This 66 year old female had been living alone independently.  However, her neighbors became concerned when she had seemed more withdrawn than usual for about a month, and then stopped going out of the house and paying her utility bills.  Ultimately, one of them  noticed a dead cat in the house, and immediately called patient’s son who lived out-of- state, and he requested that she be admitted hospital.  At the time of her initial evaluation, she was depressed and had a urinary tract infection.  She was treated for the infection, and when she expressed suicidal ideation she was transferred to the psychiatric unit. While she was on the psychiatric unit she developed slurred speech, right arm clumsiness and and unsteady gait.   She was transferred back to the medical service and underwent a diagnostic evaluation.   Her brain MRI showed diffusion restriction in left putamen and caudate nucleus. Her EEG was also abnormal.  Her spinal fluid was ultimately positive for presence of Protein 14-3-3, indicating Creutzfeldt –Jacob disease.  She has progressed to a very debilitated state in just two week – Her speech was limited to a few intermittent slurred words, she was not able to walk and had diffuse myoclonic jerks. She was transferred to hospice.  Her brain was sent for autopsy to The National Prion Disease Pathology Surveillance Center which confirmed the presence of abnormal protease resistant prion protein (PrPSc), commonly identified as PrP 27-30, confirming the diagnosis of sporadic Creutzfeldt-Jacob disease.
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What is Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease (“CJD”) is a rare brain disorder that causes rapidly progressive dementia with muscle twitching, leading to death within several months.

CJD usually affects older adults.


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It is caused by abnormal proteins called “prions” that infect the brain.

“Classic” CJD has been transmitted by infected organs during transplant surgery.

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“Variant” CJD (“mad cow disease”) has been transmitted by infected beef.

In addition to dementia and myoclonus, many CJD patients also exhibit behavioral change (including depression), balance problems, and sleep disturbance.

It is the presence of these unusual clinical features, and the rapid rate of clinical deterioration, that distinguish CJD from other dementias like Alzheimer’s disease.

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How is Creutzfeldt-Jakob disease diagnosed?

MRI imaging of the brain can show characteristic findings:

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The electroencephalogram (EEG) can show periodic complexes:

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The spinal fluid can show the 14-3-3 protein.

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However, a brain biopsy demonstrating spongiform change is still necessary to confirm the diagnosis in many cases:

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How is Creutzfeldt-Jakob disease treated?

Sadly, there are no treatments that can stop or cure the disease, and all affected patients die within several months.

Memory misplaced

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Post written by Dr. Farida A. Malik , PGY3 Medical Resident, Monmouth Medical Center

Case Summary

This 69 year old lady had a remote history of breast cancer, hypertension and hypothyroidism.  She was brought to the Emergency Room by her husband because of abrupt onset confusion after waking up that morning. She was disoriented and was noted to ask the same questions over and over again. She had no difficulty walking, talking or dressing herself. She denied having headache or visual problems. There was no history of head trauma, seizures or any prior similar episodes.

When she was seen in the in the ER she knew her name and recognized her husband.  She was able to follow simple commands.  She had no recollection of events since morning or the day before. She repeatedly asked how she got to the hospital, despite being told several times that her husband brought her. Neurological examination otherwise was unremarkable.

CT scan of head, MRI of the brain and EEG were all normal.

She was diagnosed with TRANSIENT GLOBAL AMNESIA.

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The family was reassured about the benign nature of the condition and she was discharged home the next day still with memory lag.

Discussion

Transient global amnesia (TGA) is a clinical syndrome of reversible anterograde amnesia accompanied by repetitive questioning that occurs in middle-aged and elderly individuals.

The incidence of TGA is 5.2 to 10 per 100,000 per year overall, but 23.5 to 32 per 100,000 per year in adults aged 50 and over.

During a TGA episode recall of recent events simply vanishes. One may also draw a blank when asked to remember things that happened a day, a month or even a year ago.  Unlike “soap opera amnesia” (Jason Bourne) affected patients do remember who they are and recognize the people they know well.  But that doesn’t make their memory loss less any less disturbing.

Fortunately, episodes are usually short-lived, recover spontaneously, and are unlikely to recur.

The precise cause of TGA is unknown.  Atherosclerotic risk factors (eg. hypertension, diabetes, hypercholesterolemia) are not associated with TGA.
However there may be a link between TGA and history of migraines.

The primary site of neurologic functional disturbance is the medial temporal lobe and hippocampus.
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The pathogenesis of this transient disruption is unknown. Current theories include arterial ischemia, venous congestion, and migraine, but no theory explains all of the clinical features.

The diagnosis is made by the following signs and symptoms:

  • Sudden onset of memory loss, verified by a witness
  • Retention of personal identity despite memory loss
  • Normal cognition, such as the ability to recognize and name familiar objects and follow simple directions
  • Absence of signs indicating damage to a particular area of the brain, such as limb paralysis, involuntary movement or impaired word recognition
  • Duration of no more than 24 hours
  • Gradual return of memory
  • No evidence of seizures during the period of amnesia
  • No history of active epilepsy or recent head injury

Some common triggers identified are:

  • Sudden immersion in cold or hot water
  • Strenuous physical activity
  • Sexual intercourse
  • Medical procedures, such as angiography or endoscopy
  • Mild head trauma
  • Acute emotional distress, as might be provoked by bad news, conflict or overwork

There are no confirmatory diagnostic tests. The initial evaluation and management of patients with TGA focuses on excluding other diagnoses and should include the following:

  • If the patient is symptomatic on presentation, the patient should be observed in the hospital until the amnesia resolves.
  • Diagnostic testing includes oxygenation status, serum electrolytes, glucose, and a toxicology screen.

The need for further testing varies depending on the circumstances, such as how typical the event is for TGA, the presence of vascular risk factors, and whether the ictus was observed. Patients with recurrent or brief episodes, or activity suggesting motor automatism should be evaluated with EEG for possible epilepsy. A neuroimaging study may be performed in all patients, preferably a brain MRI with DWI, to exclude acute ischemia, head trauma, and other causes.

Treatment is not required for TGA. The condition usually does not recur, and the patient does not need to be restricted from driving unless events are recurrent.

There is no increased risk of mortality, epilepsy, or stroke following TGA as compared with age-matched controls.

New Brain Imaging for Alzheimer’s Disease

Amyloid proteins in normal brains (left) and abnormal ones (right) visualized with GE Healthcare’s PET tracer flutemetamol.

Alzheimer’s disease is the commonest cause of dementia, and as the population is aging, it’s prevalence is increasing.

Alzheimer’s disease presently affects 5 million Americans aged 65 or older.  Without a major medical breakthrough, by 2025 this number is expected to have risen to 7 million, and by 2050 it could reach 14 million

The costs of caring for Alzheimer’s patients is also increasing, estimated at $203 billion in 2013, and $1.2 trillion by 2050,  including a 500% increase in combined Medicare and Medicaid spending.

Clearly, finding that major therapeutic breakthrough is crucial, and had been identified as a priority by the Obama Administration.

The first barrier to starting any clinical trial is accurate case ascertainment – we have to be able to correctly identify early Alzheimer’s patients for new experimental treatments.

So far, the only definitive test for Alzheimer’s disease is examination of brain tissue (usually obtained at autopsy) for identification of the characteristic pathologic changes of Amyloid paque and Neurofibrillary tangles:

Alzheimer’s disease is usually diagnosed based on  clinical criteria, but many patients diagnosed this way are later found to have other causes of dementia when their brains are examined at autopsy, in other words they were misdiagnosed as Alzheimer’s.

With more research trials and potential new effective therapies on the horizon, it is going to become more important to establish a diagnosis of Alzheimer’s more accurately and earlier, perhaps even pre-symptomatically (i.e. mild cognitive impairment or MCI), so that treatment to reverse the build up of plaque and tangles is more likely to be effective.

New positron emission tomography (PET) technology can actually quantify the amount of amyloid in affected patients’ brains.  A recently published small study showed a very high correlation between amyloid identified on PET scans and amyloid plaque demonstrated in brain biopsy specimens taken from demented patients.

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These tests are going to be very important for research studies.

However, don’t rush to your private doctor’s office asking to have one done just yet!

Although approved by the FDA, these test are not yet covered by Medicare or other insurance covering, and cost between $1500 and $3000.

Furthermore, these are new tests, and their role in clinical neurology practice in still unclear.

Some of these issues were recently clarified in a report by the Amyloid Imaging Taskforce convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging:

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This taskforce concluded that a Amyloid PET scan is indicated for:

Progressive memory impairment or dementia with atypical features, where a positive PET would indicate definite Alzheimer’s, and a negative scan would rule it out and lead to further testing for other possible causes.

Younger patients (aged 50-65) with suspected Alzheimer’s, in whom making a definitive diagnosis is crucial for log term planning and future medical decision making.

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The taskforce concluded that a Amyloid PET scan is unnecessary and/or unhelpful for:

Patients with typical Alzheimer’s disease,

Determining the severity of dementia,

Asymptomatic patients with a family history of dementia or positive apolipoprotein E4 status,

Patients who complain of memory loss but have no objective findings,

Testing purely for medico-legal, disability, insurance or employment related issues.

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Find out more:

Click here to find out more about Memory loss, Mild Cognitive Impairment and Alzheimer’s.

Click here to find out more about diagnosing Alzheimer’s.

Links to the Alzheimer’s Association, Alzheimer’s Foundation of America and CDC Healthy Brain Initiative

Amnesia, it’s not just for soap operas

When people of think of amnesia, they usually first think of the mysterious stranger in a soap opera, who shows up in town after an accident or traumatic experience, having forgotten their own identity, and the efforts that ensue to uncover the missing information.

Actually, in medical practice this type of “soap opera” amnesia is psychogenic, a so-called psychogenic fugue state, very different from the amnesia seen with organic neurologic disorders like head trauma or stroke.

The character Dory in the 2003 Pixar Movie Finding Nemo is a better representation of organic neurologic amnesia – she has anteriorgrade amnesia and cannot retain new information, but remembers her name and other details of her own identity.

Another good example of organic anteriograde amnesia is the media is Leonard in the 2000 movie Memento,

It is thought that new memories are formed by a structure of the brain known as the Papez ciruit or limbic system, which includes the hippocampus, (subiculum), fornix, mammillary bodies, anterior thalamic nucleus, cingulum, and entorhinal cortex.

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Any lesion or process which interrupts this circuit will prevent the formation of new memories, leading to anteriograde amnesia.

Temporary Anteriograde amnesia can be caused by:

zzzzmedications, benzodiazepine anesthesia or “conscious sedation“,

zzzzhead trauma – post-traumatic amnesia or PTA,

zzzzand from Transient Global Amnesia (TGA).

TGA is a sudden onset of temporary anteriograde amnesia usually lasting lasting 4-12 hours.  It is often triggered by an emotional event or sexual intercourse.   During the episode, the affected patient is alert and lucid, cognizant of their own identity, but appears perplexed and may ask the same questions repeatedly.  The exact cause is unknown.  The recurrence rate is low.

More permanent anteriograde amnesia can be caused by:

zzzzinfarction of the hippocampi, as can be seen in the cardioembolic stroke syndrome “top of the basilar syndrome”,

zzzzbrain damage resulting from herpes encephalitis,

zzzzor from hemorrhage into the mamillary bodies – “Korsakoff’s psychosis”.

Korsakoff

Korsakoff’s psychosis is caused by thiamine deficiency, usually related to chronic alcoholism.  Affected patients have permanent anteriograde amnesia, and so they live in the past, and confabulate (make up details) to fill in the gaps in their memory.