Fatal familial insomnia is a rare neurodegenerative genetic disorder characterised by disturbances in sleep patterns. The insomnia, along with other neurological and autonomic symptoms, progressively worsens, resulting in coma and subsequent death. There is no cure for the disease, with treatments primarily involving symptom management and support for patients.

Understanding fatal familial insomnia 

Overview

Fatal familial insomnia (FFI) describes a genetic brain disorder causing an inability to sleep that will gradually worsen.

• It is caused by an autosomal dominant mutation in the prion-related protein gene (PRNP). Autosomal dominant mutations describe how only one copy of the mutated gene is needed to cause a certain condition. Therefore, if one parent carries the mutated gene, there is a 50% chance of their children also inheriting the condition
• It is a prion disease, which describes an accumulation of dysfunctional prion proteins within the brain, particularly within the thalamus. The thalamus is responsible for sleep regulation, motor function and other sensory signals. Prion build-up leads to neuronal death, leading to symptoms of the disorder
• Paired with the neurological symptoms, there are several nervous system disturbances, such as increased body temperature and increased heart rate
• Prognosis is poor, with all cases becoming fatal, with a disease course of 7-36 months¹
• FFI is extremely rare and has only been described in a few families. Prion diseases are described to affect 1 person per million

Symptoms 

There are four distinct stages of FFI symptoms described, although it should be noted that not all patients will experience all stages in order and timelines often differ. The general stages of FFI are described as:

Stage 1

3-6 months after onset

• Start of insomnia that worsens over the first few months
• Vivid lucid dreaming
• Psychological disturbances – paranoia, panic attacks, anxiety

Stage 2 

5-9 months after onset 

• Worsening of stage 1 symptoms
• Extreme insomnia – resulting in hallucinations
• Nervous system issues – high blood pressure, body temperature, trouble breathing, increased stress

Stage 3 

9-12 months after onset 

• Complete lack of sleep
• Rapid weight loss
• Trouble walking or with movement
• Myoclonus – involuntary twitching movements

Stage 4

Timeline: Last 6 months 

• Complete cognitive decline
• Dementia – confusion, unresponsive, lack of voluntary movement
• Hypnagogia – a constant state between wakefulness and sleep 
• Coma 

Eventually, after the 4 stages have occurred over approximately 18 months, death will occur.

Management strategies 

Although there is no cure, numerous strategies can help manage symptoms and temporarily relieve chronic insomnia for some comfort.

Pharmacological 

Clonazepam 

Clonazepam is a benzodiazepine that acts on GABA-A receptors to reduce the excitability of neurons within the brain.²

The drug interacts with the central nervous system and in particular, affects the muscles to reduce spasms and other involuntary movements. By taking these medications at night, it can reduce the movements during sleep, allowing better quality rest. Benzodiazepines are not recommended long-term, as they can be addictive and many build tolerance, leading to gradually higher doses being administered.

Zolpidem 

Zolpidem is a non-benzodiazepine drug that decreases the interactions between neurons in the central nervous system, helping patients sleep by promoting wakefulness. It has evidence of treating insomnia short-term in the early stages of the disease to alleviate discomfort.³

Vitamins

Certain vitamins have shown improvement in sleep length and quality such as vitamin B6, which has a role in brain development, and vitamin B12, which is involved in the production of the sleep hormone, melatonin.^4,5

These vitamins can be taken as supplements or supplied through a natural diet. Vitamin B6 can be found in a variety of foods, including meat, cereals and potatoes, whereas vitamin B12 is found in fish, meat, eggs and dairy.

Non-pharmacological

Cognitive behavioural therapy

Cognitive behavioural therapy (CBT) allows the body to resume its natural sleep and awakening patterns. It requires relearning and reconditioning of the brain to reduce levels of nighttime awakeness. CBT typically consists of a few components:

• Sleep control: Limit the amount of time in bed trying to sleep. Restricts sleep to build up tiredness
• Stimuli restriction: Avoid activities in bed or the bedroom such as working, reading and eating. Creates an association with your bed and sleep
• Cognitive restructuring: Changing the negative thoughts associated with trying to sleep to positive thoughts. For example, changing “If I can’t sleep tomorrow I will feel tired all day and get nothing done!” to “I will get to sleep although it may take time, and my body will sleep when it’s ready”
• Sleep hygiene: Guidelines that promote healthy sleep. It includes structured bedtime and waking-up routines, avoidance of caffeine, eating before bed and decreasing screen time
• Relaxation: Meditation and mindfulness practices can create a peaceful environment to promote sleep

Although CBT has evidence of treating insomnia in general, it hasn’t shown vast improvement in those with FFI, only in short-term symptom management. FFI is a neurodegenerative disease which will inevitably worsen over time.⁶

Exercise 

Exercise has been proven to help insomniacs. Increased physical output during the day helps increase serotonin, reduces anxiety and improves quality of life. All of this can have direct and indirect effects on sleep.⁷

Support

Physical care 

In the earlier stages of the disease, where cognitive and physical decline begins, it may be recommended to have assistance with daily activities. Whether this be a loved one, family member or an assigned healthcare provider, it can be beneficial to have around-the-clock care. This can be especially important when symptoms of dementia set in, as patients can forget to eat and drink and may need supervision with daily activities. 

Psychological support

From the point of diagnosis, the emotional strain can be overwhelming for both patients and those around them. It is important to be able to talk to an expert, or even to have the opportunity to talk to someone who is not close to you or your situation. A healthcare provider like a nurse or doctor can help find a counsellor and several private therapists are available too. Several helplines are available if urgent help, advice or company is needed, such as the Samaritans. 

Several online resources for various long-term and terminal illnesses exist:

• Healthtalk: Charity with different online informational topics and real-life accounts of both patients and carers 
• Marie Curie: Online chat and support lines, information on hospice and end-of-life care, terminal illness accounts 
• Support line: Website with links to various other supports, including terminal illness, end-of-life care and bereavement resources 

Palliative care

Palliative care describes the support and treatment of chronic and terminal illness to help alleviate symptoms and keep patients as comfortable as possible. This treatment will not cure any illness or disease but aims to give the patient the best quality of life possible. 

There are different options for palliative care, depending on the needs, preferences and complexity of the disease. It can be received at:

• Home
• A care home
• Hospice
• Hospital

Palliative and end-of-life services rely on the collaboration of different professionals, including doctors, psychiatrists, nurses, social care staff and physiotherapists. It involves the complete care of patients, with physical, social and spiritual input, if desired.

Family and caregiver support 

Genetic counseling

Since fatal familial insomnia is an autosomal dominant gene mutation, it can be passed down from parents to children. Once the disease presents itself within a family, it can be daunting to learn that the mutated allele could be present in other family members.

Genetic counselling involves meeting with a specialist geneticist and establishing the risk of disease for an individual or family. They can interpret genetic testing results to keep patients/families informed, allowing them to be prepared, explore their options and take control of their health.⁸

Summary 

Fatal familial insomnia is a rare inherited neurodegenerative prion disease with no known cure. With worsening insomnia and physical and mental decline, patients and their families must know what care and support are available to them. Although the disease cannot be treated, the symptoms can be managed to elevate the quality of care and make patients as comfortable as possible.