What Do Polysomnography and FDG-PET Show in Suspected FFI?

When doctors suspect fatal familial insomnia (FFI)—a rare inherited prion disease (a condition caused by abnormally folded proteins in the brain)—they must piece together a complex puzzle ^[1]. Diagnosis depends heavily on your clinical symptoms, family history, and genetic testing ^[2][3].

To gather more clues, your doctor may recommend two supportive tests: a video sleep study (called video-polysomnography) and a specialized brain scan called an FDG-PET scan ^[4][5]. These tests are optional or supportive investigations used in selected cases. Neither test can diagnose FFI on its own, nor do they measure exactly how your illness will progress ^[6][3]. Instead, they help rule out other conditions and identify patterns of sleep disruption and brain energy use that may suggest FFI ^[7][8].

How These Tests Fit Together

Confirming an FFI diagnosis involves multiple steps. Your doctor will evaluate your symptom history and neurologic exam, and they may use MRI, EEG, or spinal fluid tests to rule out other causes of severe insomnia, such as autoimmune conditions or other prion diseases like sporadic Creutzfeldt-Jakob disease ^[1][9].

Genetic testing is a central piece of this puzzle ^[3]. FFI is typically associated with a specific mutation in the PRNP gene called D178N, specifically when it occurs alongside a “methionine” (M) variation at codon 129 on the same gene ^[2]. Finding the D178N mutation with a different variation at codon 129 can cause a different disease entirely, and finding the mutation does not guarantee your current symptoms are FFI ^[2]. Because predictive genetic testing for a rapidly progressive illness has profound implications for you and your family, it should always involve pre- and post-test counseling with a genetic counselor ^[10][11].

The Video Sleep Study (Polysomnography)

A video-polysomnography evaluates abnormal sleep physiology. It is an overnight test conducted in a specialized sleep center ^[12].

What You Will Experience

During the setup, a technician will place small, painless sensors on your scalp, face, chest, and limbs ^[13]. These sensors record brain waves (EEG), eye movements, muscle activity, and heart rhythm ^[14][13]. You will wear elastic belts around your chest and abdomen to measure breathing effort, a finger clip to track oxygen, and a sensor near your nose to monitor airflow ^[13]. A video camera records your movements to help doctors correlate physical actions with brain wave activity ^[15][4]. The setup takes about an hour, and while wearing the wires can feel cumbersome, the procedure itself is non-invasive and safe ^[13].

What the Sleep Study May Show

In people with FFI, normal sleep architecture (the natural progression through sleep stages) becomes severely disrupted, though brief periods of abnormal sleep usually persist ^[7][15]. Findings that are characteristic or supportive of suspected FFI include:

• Loss of specific sleep stages: A marked reduction in sleep spindles (short bursts of brain activity normally seen in light sleep) and slow-wave sleep (the deepest, most restorative sleep stage) ^[15].
• Rapid shifts: The brain may rapidly cycle between periods of wakefulness and short bursts of non-restorative sleep ^[7].
• Reduced overall sleep: A marked decrease in total sleep time ^[7].

Other findings may occur but are nonspecific and can happen in many other conditions:

• Abnormal REM sleep: The dream phase (REM sleep) may be reduced ^[7]. Sometimes, the normal muscle paralysis of REM sleep is lost (REM sleep without atonia), leading to dream enactment or twitching ^[15][16].
• Breathing issues: The study may capture sleep apnea or abnormal breathing sounds (stridor), which can prompt separate respiratory evaluations but do not prove you have FFI ^[7][17].

Importantly, a sleep study can be inconclusive. Unfamiliar settings, medications, and the stage of your disease can all affect the results, meaning a normal or unclear study does not rule out FFI. Do not stop prescribed medications before the study unless directed by your sleep team.

The FDG-PET Brain Scan

An FDG-PET scan measures how different areas of your brain use glucose (sugar) for energy ^[8]. It does not directly show structural brain damage, but rather highlights areas that are underperforming chemically (hypometabolism) ^[8].

What You Will Experience

You will receive a small injection of a radiotracer, which carries a low but non-zero amount of radiation exposure ^[18]. You will rest quietly for 30 to 60 minutes while your brain absorbs the tracer, then lie still inside a scanner for about 30 minutes ^[18].

Because the tracer relies on sugar, you must follow your specific imaging center’s instructions regarding fasting duration, medication use, and managing diabetes or blood sugar control ^[18]. You must also inform them if you are pregnant, breastfeeding, or scheduled for a combined CT scan.

What the FDG-PET Scan May Show

In FFI, an FDG-PET scan may show:

• Thalamic hypometabolism: Reduced energy use in the thalamus, the brain’s main relay center that helps regulate sleep and wakefulness ^[8][19].
• Variable spread: Reduced energy use may sometimes be seen in other areas, such as the basal ganglia (deep brain structures involved in movement) and the outer layer of the brain (the cerebral cortex) ^[6][8]. This spread varies widely between patients.

Crucially, a “normal” FDG-PET scan does not rule out FFI. There have been genetically confirmed cases where the scan showed no significant abnormalities or lacked the typical thalamic pattern ^[1][20].

Seeking Specialized Care

Interpreting the subtle changes seen in these tests requires significant expertise ^[3]. It is important to have your tests coordinated by a tertiary care center (a major hospital with advanced specialists) or a doctor experienced in prion diseases, sleep medicine, or neurogenetics (the study of genetic brain disorders) ^[3][4].

Because FFI and similar conditions can progress quickly, contact your medical team urgently if you or a loved one experience sudden confusion, frequent falls, inability to eat or drink, swallowing or breathing problems, or unsafe nighttime behaviors. Ensuring your symptom relief and safety is a priority even while diagnostic tests are still being arranged.