Makindo Medical Notes

Related Subjects: |Dementias |Gerstmann-Straussler-Scheinker Syndrome (GSS) |Fatal Familial Insomnia (FFI) |Creutzfeldt Jakob disease (CJD) |Variant Creutzfeldt Jakob disease (vCJD) |Kuru

Warped protein in wait
Midlife, sleepless nights stretch late
Dreaming while awake
Hell of night blurs into day
Reaching for sleep, far away
@DrCindyCooper

About

• A rare human prion disease that is fatal within 12-18 months
• First recorded case was in Venice in the 1700s

Aetiology

• Autosomal dominant inheritance (few sporadic)
• Missense mutation of the PRNP gene

Forms

• Fatal familial insomnia (FFI), which is autosomal dominant
• Sporadic fatal insomnia (sFI), which lacks the gene mutation

Clinical

• Median onset 56 yrs range 20-70s).
• Progressive insomnia, daytime hallucinations, memory loss
• Spasticity, autonomic dysfunction, weight loss.
• Tachycardia, hyperhidrosis, hypertension, dysarthria, dysphagia

Investigations

• FBC, U&E, ESR, LFT, Glucose, TFTs, Syphilis serology, HIV, B12, folate
• Polysomnography (PSG): reduction in total sleep time and a dysfunctional transition between sleep stages.
• Genetic testing can confirm the diagnosis of the familial form.
• EEG: Periodic sharp-wave complexes (PSWC) but non specific
• CSF: 14-3-3 protein is non-specific and may be seen found but not helpful
• CT/MRI: Exclude other causes. Reduced thalamic diffusion may be present on diffusion MRI due to gliosis. Atrophic changes.
• FDG-PET: hypometabolism in the thalamic and cingulate regions with a tendency to spare the occipital lobe.

Pathology

• Affects the thalamus, inferior olivary nucleus, cerebellum, spongiform changes in the cerebral cortex.
• Parietal, temporal, and frontal lobes have shown higher degrees of involvement compared to the occipital lobe.

Stages

• Stage 1: subacute onset of insomnia, worsens over a period of few months and causes psychiatric symptoms such as phobia, paranoia, and panic attacks. During this time, patients may report lucid dreaming.
• Stage 2: In the next 5-month period, psychiatric symptoms worsen along with worsening insomnia, and patients experience hallucinations. Autonomic dysfunction in the form of sympathetic hyperactivity is seen.
• Stage 3: This short stage of around three months is typically dominated by total insomnia and complete disruptions of the sleep-wake cycle.
• Stage 4: The final stage of the disease can last for six months or more and is defined by rapid cognitive decline and dementia. Patients experience an inability to voluntarily move or speak, which is followed by coma and eventual death.

Management

• Disease is usually incurable and management supportive
• Consider PEG for feeding. Involve palliative care.

References

• Fatal Familial Insomnia