Periodic Hyper Somnolence as Initial Presenting Manifestation of Nocturnal Frontal Lobe Epilepsy
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.288982
Source of Support: None, Conflict of Interest: None
NFLE seizures often have bizarre or dramatic clinical manifestations including vocalization, posturing, hyper motor automatisms, and sometimes ambulation. As a result of their unusual and varied manifestations, they may be difficult to distinguish from non-epileptic behaviors during sleep, particularly NREM arousal parasomnias (such as sleep terror, somnambulism, confusional arousals). The latter are common, quasi-physiological phenomena characterized by autonomic and motor features, including ambulation, apparent distress and directed behaviors, arising during slow wave sleep. They typically develop in childhood, but may persist into adulthood. NFLE usually requires treatment with anti-epileptic drugs (AEDs). In contrast, NREM arousal parasomnias are only occasionally associated with significant morbidity. As a result, reassurance is often sufficient, and medical treatment is necessary only in selected cases. Often the greatest challenge, however, is in establishing a definitive diagnosis. Without this, appropriate treatment may be denied to some individuals, and unnecessary (and potentially harmful) treatments administered to others.
Periodic hyper somnolence is common in general population. Etiologies include sleep apneas, circadian rhythm disorders and parasomnias. Herein, we report a patient who presented with complaints of intermittent need for an excessive amount of sleep (hyper somnolence) associated with stereotype episodes during sleep, which lead to the diagnosis of NFLE.
A 23-year-old graduate student was brought by his roommate with a complaint of periodic hypersomnolence, with an elevated Epworth sleepiness score of 15 (abnormal more than or equal to 11). He was concerned that his periodic hypersomnolence would affect his examination. On further enquiry, he was found to have a history of sleeping for 18-20 hours, which would happen continuously 6-7 days, seven to eight times a year for the past six years. Apparently, he had no warning symptoms and couldn't predict when he would have such episodes. This was associated with movements during sleep, in which his peer observed him sitting in bed looking around and returning to sleep within one minute. He also had up to seven episodes of bicycling movements with tonic posturing of left arm and left leg every night, of which he has no memory.
He did not any previous medical history or used any medications. His social history was negative for tobacco or alcohol abuse. He had one paternal uncle with epilepsy for which he was receiving treatment.
Neurological examination, routine laboratory testing and MRI of brain with or without gadolinium were reported to be normal.
A sleep diary obtained two weeks prior to polysomnography study (PSG) excluded insufficient sleep time (550 ± 62 minutes). Of note, the study was done during the days that were reported to be the patient's normal days and not during one of his periodic abnormality, as the frequency of these was unpredictable.
Attended overnight PSG showed normal REM sleep latency (65 minutes) and multiple spontaneous arousals (8.0 per hour) during non REM sleep. No other primary sleep disorders were detected. Multiple sleep latency testing was consistent with objective hypersomnia, with a mean sleep latency of 4.5 minutes (abnormal less than 8 minutes), without sleep onset REM periods.
A full set of EEG channels was recorded during PSG. Stereotyped clinical seizures were captured consisting of repetitive blinking, head turning and left arm elevation, and corresponded with frontally predominant epileptiform activity on EEG.
Treatment was started with topiramate, which was titrated to 200 mg at night with improvement of hypersomnia and elimination of nocturnal paroxysmal arousals and tonic posturing events.
Nocturnal frontal lobe epilepsy (NFLE), seizures have a variety of clinical manifestations, including dystonic posturing, vocalization including screaming and roaring, hyper motor automatisms (including pelvic thrusting, thrashing, 'cycling' or kicking) and sometimes walking or running. Clinical features of NFLE were analyze into three main types: paroxysmal arousals, brief often stereotyped, arousals from sleep, often considered to be fragments of larger attacks); paroxysmal nocturnal dystonia seizures, more dramatic attacks with dystonic posturing or hyper motor automatisms, usually lasting less than a minute, and episodic nocturnal wonderings, in which individuals may walk or run, often in an agitated fashion. Many clinicians now simply refer to 'minor attacks' (corresponding to paroxysmal arousals) and major attacks (other seizures type). Of note, seizures in NFLE are usually short, often under 30 seconds of duration and rarely lasting than 2 minutes. Some (but by no means all) individuals with NFLE are woken by, and retain awareness during, their seizures, and have recollection of events afterwards. Often, these individuals will report a clear aura (often sense of choking or breathlessness) and may remember uncontrollable stiffening or other movements of the limb.
In addition to the seizures semiology, NFLE has other distinctive clinical features, which are of relevance in making the diagnosis:
First, seizures occur predominantly from stage 2 NREM sleep. This means they can occur at any time of the night but are common soon after falling asleep or just before waking (when stage 2 sleep is copious): some people with NFLE may have seizures during a brief nap.
Second, seizures in NFLE frequently occur many times per night. Proviniet al. documented a range of 1-0 reported seizures per night, but with often far greater numbers been recorded on overnight video EEG- PSG.
Third, onset may be at any time of life (in childhood, adolescence or later in life) and onset at any age from 1 to 64 years has been reported.
In order to initiate the most appropriate treatment, accurate diagnosis is of paramount importance. The most important aspect of the diagnostic process is taking an adequate history. This may be challenging. The nocturnal nature of events means that witness accounts may be absent, particularly if the patient sleeps alone; even in those individuals whose attacks are witnessed, descriptions may be limited as the witness maybe asleep at the onset of attack, which often takes place in darkness. It is, however, vital that efforts are made to obtain any potential witness description, as accounts from the patient are often very limited and even a little additional information may be valuable.
A useful adjunct in this setting is FLEP scale, a validated questionnaire for the diagnosis of nocturnal events. This is simple, brief, validated clinical scale, which can help the clinician distinguish between NFLE and Parasomnias on the basis of key features from the history. FLEP scale was initially reported with a positive predictive value (PPV) of 0.91 and a negative predictive value (NPV) of 1, suggesting it to be an effective diagnostic instrument. In an independent validation study comparable results were obtained (PPV of 1 and NPV of 0.91). In this study, a high proportion of non-diagnostic 'indeterminate' scores were noted (30.9%), predominantly in individuals with REM behavior disorder, and authors also raised concerns that patients with extensive wandering during NFLE seizures ran the risk of being misclassified as parasomnias/pseudoseizures on the basis of scale. Despite this, the statistical analyses indicate that the scale represents a useful screening tool for NFLE, particularly for patients in whom further investigation may be difficult.
In some cases, however, the diagnosis remains in doubt after the history is obtained, and further investigation is necessary. Interictal EEG often contributes little, as this is normal in parasomnias and also in more than 50% of the individuals with NFLE. When possible, the most useful investigation is the recording of attacks on video EEG monitoring (or video EEG polysomnography). It is important that the PSG is ordered with a full set of EEG channels. Even when attacks are captured, however, ictal EEG maybe unhelpful and careful semiological analysis of events is required to make a definite diagnosis. Semiological features, which may be used to distinguish parasomnias from NFLE on video, have been identified; bicycling movements and dystonic postures strongly favor NFLE, whereas a prolonged duration, waxing and waning pattern, and indistinct offset, yawning, nose rubbing, rolling over, sobbing, physical/verbal interaction and a failure to fully awaken after an event clearly favour parasomnias. Interestingly, certain features (such as screaming and ambulation) do not discriminate at all between NFLE and parasomnias, and brief arousals of epileptic and non-epileptic origin may be indistinguishable. Characteristics which may distinguish between NFLE and parasomnias [Table 1].
Somnambulism may range from semi purposeful walking to more complex task such as driving; distress cries and aggressive behavior may also occur. In REM sleep behavior disorder (RBD), muscle tone is pathologically retained during REM sleep, allowing dreams to be 'acted out'. These manifestations can resemble NFLE; however, RBD usually occurs in the early morning and can be associated with vivid dream recall. Hypersomnolence has diverse etiologies including primary sleep disorders, metabolic disturbances, medications, psychiatric and neurological disorders (sleep apnea), circadian rhythm sleep disorder, parasomnias., Excessive day time sleepiness as the presenting symptom of NFLE was originally reported in 1986. Subsequent series demonstrated EDS in up to 75% of patients.
Management of NFLE requires treatment with anti-epileptic drugs (AEDs) to control seizure activity. While topiramate has demonstrated efficacy in NFLE, alternative AED choices would also have been valid. Deciding which AED to start is based upon several factors, including patient co morbidities, AED side effect profiles, cost, and reproductive considerations in human. In addition, controlled of seizures may require more than one AED. Given the complexity of AED regimens and the potential for seizures to evolved or change over time, long time management of NFLE should be referred to an epilepsy specialist.
In the context of a patient presenting with episodic hypersomnolence and stereotyped nocturnal events, clinical suspicion should be high for Nocturnal frontal lobe epilepsy. Referral to an epileptologist and/or sleep medicine is recommended, and comprehensive evaluation should be undertaken, including a detailed clinical history, and either polysomnography study to exclude primary sleep disorders, video EEG monitoring to capture the stereotyped episode, or both. A useful adjunct in this setting is FLEP scale, a validated questionnaire for the diagnosis of nocturnal events.
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