| Nightmare (adult) | Night terror | Nocturnal epilepsy | |
|---|---|---|---|
| Incidence | 5 to 10% | 1 to 3% | Unknown |
| Sleep stage | During REM Anytime during the night the night | Stage 4 In first few hours of sleep | Often stage 2 Anytime during |
| Age of onset | Variable | Early childhood | Late childhood or adolescence Occasionally in adulthood |
| Change with age | Often diminishes with age May remit and recur | Diminishes with age Gone by young adulthood | Heterogeneous course May be less severe later in life |
| Symptoms | Frightening dreams Detailed story line No motor activity No injury | Inconsolable terror Not associated with dream Low-level motor activity Autonomic activation Injury rare | With or without fear and autonomic activation Hallucinations or illusions possible Stereotypical, paroxysmal motor activity Injury possible |
| Sleep resumption | Often delayed | Usually rapid | Usually rapid |
| Precipitating factors | PTSD Unusual stressors | PTSD Sleep deprivation | Sleep deprivation Physical and emotional stressors |
| Frequency | Irregular | 1 to 2 times per month or less | Extremely variable Can occur in clusters |
| Recollection | Variable | Often none | Variable |
| PTSD: Posttraumatic stress disorder | |||
These seizures are clinically polymorphous but stereotypical in each patient. Seizure type varies depending on which frontal lobe region is affected.
Nocturnal seizures universally have an explosive onset, with motor symptoms such as jerking, rocking, pelvic thrusting, tonic posturing, kicking, scrambling about, and touching the bed with one’s hand. Other possible occurrences include:
- sensory phenomena such as illusions and hallucinations, sensations of buzzing, vibration, and olfactory or gustatory sensations
- aphasia or other vocal events, such as laughing, screaming, or making odd noises
- fear and autonomic discharge simulating a night terror or panic attack.7
Confusion also is possible, although consciousness many times is preserved through the episode.
As with other seizures, sleep disruption exacerbates NFLE. Most patients have a normal interictal EEG.
Because NFLE is often misdiagnosed as a parasomnia, the psychiatrist needs to consider this disorder in the differential diagnosis. Any patient with a suspected parasomnia should be evaluated by a neurologist for NFLE if:
- the nocturnal events have not ceased by young adulthood
- events consist of prominent stereotypical motor symptoms that occur in clusters and/or have caused physical injury.
Extended history: Family stories
Ms. J’s neurologist asked whether any relatives have experienced similar nocturnal events.
Upon talking with family members, she learned that her aunt (her father’s sister) experienced nocturnal hallucinations and panic episodes well into her 50s. Her first cousin (her aunt’s daughter) also has nocturnal hallucinations and panic episodes and runs in her sleep. Two of her father’s cousins—twin brothers—were also affected. One of the brothers experienced explosive episodes, sometimes assaulting the other brother while asleep; he once had to be restrained from jumping out a window.
Other family members or surviving spouses described similar events that are clinically consistent with frontal lobe seizures. Interestingly, tic disorders run in the same branches of the family as the seizures.
Ms. J was diagnosed with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) based on her diagnosis of NFLE and family history of similar events.
The authors’ observations
ADNFLE is an inherited disorder that displays 70% penetrance.8 Families in Australia, Canada, Spain, Japan, Korea, Germany, Great Britain, Italy, and Norway have been described with the disorder. No accurate prevalence data exist.9
Ms. J’s family traces its roots to Lithuania and White Russia (now Belarus) and is Ashkenazi Jewish. No literature describes the disorder in this population or these locations.
ADNFLE was the first genetic epilepsy to be associated with a defect in a single gene. It was recognized as a disorder in 1994, having previously been described with different names by multiple authors.
The disorderis a “channelopathy,” signifying a defective ion channel resulting in abnormal neuronal cell membrane conduction. The affected gene is the acetylcholine receptor, which is widely distributed in the brain. Missense mutations of the receptor gene lead to a change in an amino acid found in the center of the receptor pore. Ordinarily, the centers of ion channel pores are lined with hydrophobic amino acids to facilitate entrance of ions. The mutations in affected individuals result in a hydrophobic amino acid substitution. Different families display different mutations of the gene.10
In ADNFLE, there is mutation in the second transmembrane region of the alpha-4 subunit of the neuronal acetylcholine receptor. Defective receptors result in reduced channel permeability to calcium, causing fast desensitization and receptor hypoactivity. This has been postulated to cause an imbalance in excitatory/inhibitory synaptic transmission.11 Further study will elucidate the acetylcholine receptor’s relationship to brain functioning.
Treatment: Medication trial
Lamotrigine was started at 25 mg/d and titrated upward by 25 to 50 mg per week. When the dosage reached 500 mg/d, seizure frequency was reduced to once weekly.
Because Ms. J’s seizures were associated with stress and fatigue, she reduced her work hours and modified her job duties. Alcohol increased the frequency of the seizures, so she abstained from alcohol consumption. She also adhered to a consistent bedtime and slept at least 8 hours every night. After making these lifestyle modifications, Ms. J’s seizers decreased to once per month.