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Distinguishing Sleep Disorders from Seizures Diagnosing Bumps in the Night

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Distinguishing Sleep Disorders from Seizures Diagnosing Bumps in the Night ORIGINAL CONTRIBUTION Distinguishing Sleep Disorders From Seizures Diagnosing Bumps in the Night Christopher Paul Derry, MRCP; Margot Davey, FRACP; Murray Johns, FRACP; Katie Kron, BSc; Deborah Glencross, BSc; Carla Marini, PhD; Ingrid E. Scheffer, PhD; Samuel F. Berkovic, MD Background: Abnormal paroxysmal events in sleep may Intervention: Two independent interviews were con- be parasomnias or epileptic seizures. In nocturnal fron- ducted in each case, with the patient and a witness, by tal lobe epilepsy (NFLE), the unusual seizure features of- researchers blinded to the diagnosis. ten lead to diagnostic confusion with nonepileptic para- somnias; video-electroencephalography monitoring is Main Outcome Measure: The diagnosis obtained from usually required to make the diagnosis. scores on the FLEP scale was compared with the con- firmed diagnosis in each patient. Objective: To examine the reliability of the clinical his- tory in diagnosing NFLE, using the Frontal Lobe Epi- Results: Nocturnal frontal lobe epilepsy was correctly lepsy and Parasomnias (FLEP) scale. diagnosed from the FLEP score in 31 of 31 patients, with a sensitivity of 1.0 (95% confidence interval [CI], Design: The FLEP scale, comprising specific questions 0.85-1.00), specificity of 0.90 (95% CI, 0.73-0.97), reflecting the diagnostic features of NFLE and parasom- positive predictive value of 0.91 (95% CI, 0.75-0.97), nias, was developed by an expert panel following re- view of the literature. It was then validated in a sample and negative predictive value of 1.00 (95% CI, 0.85- of individuals with firmly diagnosed nocturnal events. 1.00). Setting: Patients were recruited after appropriate diag- Conclusions: A diagnosis of NFLE can be made reli- nostic workup in tertiary sleep and epilepsy referral cen- ably using the clinical features identified in the FLEP scale. ters in Melbourne, Australia. This may reduce the requirement for tertiary referral and extensive inpatient monitoring. Participants: Sixty-two patients (45 men) with parox- ysmal nocturnal events. Arch Neurol. 2006;63:705-709 HE DIAGNOSIS OF ABNOR- frontal lobe epilepsy (NFLE) occurs spo- mal paroxysmal motor radically or as an inherited form with an events in sleep presents a established genetic basis (autosomal domi- particular challenge for the nant NFLE [ADNFLE]).3 Mutations in 2 clinician. On the one hand, genes that encode the ␣4 and ␤2 subunits Tsuch events may be parasomnias, such as of the neuronal nicotinic acetylcholine re- sleepwalking or sleep terrors; these are be- ceptor (CHRNA4 and CHRNB2) have been nign nonepileptic sleep disorders defined associated with ADNFLE,4-6 although such as “unpleasant or undesirable behavioral mutations are only identified in a minor- 7 Author Affiliations: Epilepsy or experiential phenomena that occur pre- ity of families with this condition. Sei- Research Centre, Department of dominantly or exclusively during the sleep zures in NFLE may have bizarre clinical Medicine (Neurology), period.”1 On the other hand, they may be features, with vocalization, complex au- University of Melbourne, epileptic seizures, requiring investiga- tomatisms, and ambulation; investiga- Austin Health (Drs Derry and tion and treatment. In many cases, distin- tion with electroencephalography (EEG) Marini, Mss Kron and guishing seizures and parasomnias by and magnetic resonance imaging often Glencross, and Profs Scheffer means of the clinical history is relatively shows no abnormality.8 These character- and Berkovic), Paediatric Sleep straightforward.2 However, a particular istics result in frequent misdiagnosis, with Department, Monash Medical Centre (Dr Davey), and Sleep form of epilepsy that is increasingly rec- the events often being labeled as pseudo- Unit, Epworth Hospital ognized poses a diagnostic challenge. Sei- seizures or parasomnias and some cases (Dr Johns), Victoria, and Royal zures arising from the frontal lobes often previously being designated as “paroxys- Children’s Hospital, Melbourne occur during sleep and, in many patients, mal nocturnal dystonia.”9 Conversely, (Prof Scheffer), Australia. are entirely restricted to sleep. Nocturnal some parasomnias may be violent and con- (REPRINTED) ARCH NEUROL / VOL 63, MAY 2006 WWW.ARCHNEUROL.COM 705 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 fused with NFLE. Such misdiagnoses are clearly to the VALIDATION STUDY detriment of the patient, who may be denied appropri- ate treatment or treated inappropriately. Aims While typical parasomnias are often not a significant clinical problem, individuals with severe or frequent events The aim of the study was to compare the diagnosis made using often seek medical attention. A number of historical fea- the FLEP scale with the standard diagnostic test (ie, expert in- tures have been described that may distinguish NFLE from terview and, when necessary, recording of events using video- parasomnias,8,10 but the value of these features has not EEG monitoring). It was hypothesized that the total score, cal- been systematically assessed. As such, most authorities culated by summing the individual scores on completion of the recommend video EEG or video EEG–polysomnogra- scale, would accurately predict diagnosis; an overall positive phy10 (PSG) for the diagnosis of paroxysmal nocturnal score should predict epilepsy, with a zero or negative score pre- dicting parasomnias. events. These investigations are the “gold standard” in this situation; they involve monitoring patients in sleep through neurophysiological, cardiorespiratory, and video Inclusion and Exclusion Criteria modalities and recording their nocturnal events. They are expensive and inconvenient investigations requiring ad- The study population comprised patients who had been re- ferred to a sleep physician or neurologist with a history of noc- mission to the hospital and are only practical if the noc- turnal events of uncertain cause. Individuals with NFLE were turnal events are happening on a frequent, preferably eligible for the study if they had a history consistent with NFLE nightly, basis. In those patients with less frequent events, and at least 1 of the following: video-EEG monitoring with clini- it will often not be possible to capture an event during a cal or electrographic evidence of nocturnal frontal lobe sei- monitoring period, in which case the investigation will zures or a genetic mutation consistent with ADNFLE. In fami- not usually clarify the diagnosis. In addition, access to lies with ADNFLE, no more than 2 family members from the video-EEG and PSG monitoring services varies widely in same kindred were recruited. different regions, and for many patients, these investi- Patients with parasomnias were recruited in 2 subgroups. The gations are not available. In many cases, therefore, the first group consisted of subjects who were referred to a sleep clinic effective standard for diagnosis is the expert clinical in- for diagnosis of their nocturnal events but in whom a definite diagnosis of “typical” parasomnia was made by the specialist with- terview; in this situation, the history is vital and holds out recourse to video-EEG monitoring. In this group, the diag- the key to arriving at the correct diagnosis. nosis was made on the basis of the history independently by 3 There is, therefore, a need to establish the reliability clinicians (a consultant adult epileptologist, a consultant pedi- of historical features in distinguishing nocturnal frontal atric epileptologist, and a consultant sleep pediatrician), none lobe seizures from parasomnias in those situations in of whom were involved in the validation of the FLEP scale. The which video EEG and PSG are impractical or unhelpful. second group comprised cases in which there was diagnostic un- We have developed the Frontal Lobe Epilepsy and Para- certainty on the basis of the history alone and in which the di- somnias (FLEP) scale to achieve this. Through valida- agnosis was established by video-EEG or PSG monitoring. These tion of this scale in patients with established diagnoses, cases were designated “atypical” parasomnias. we have confirmed the value of the clinical history in the diagnosis of nocturnal events. Recruitment Patients with nocturnal events were recruited from 4 centers in METHODS Melbourne, Australia (Austin Health, Royal Children’s Hospi- tal, Monash Medical Centre, and Epworth Hospital). Subjects with NFLE and atypical parasomnias (confirmed by video-EEG SCALE DEVELOPMENT AND STRUCTURE or PSG monitoring) were recruited retrospectively from a re- view of existing medical databases and records covering a 10- year period. All patients with confirmed diagnoses who could The FLEP scale (Table) was developed by an expert panel fol- still be contacted were approached regarding participation as well lowing review of the literature. The scale consists of a series of as all new cases identified during admission for investigation dur- specific questions based on the clinical features of NFLE and ing a 2-year period. Subjects with typical parasomnias were re- parasomnias. Particular consideration was given to the non- cruited as a consecutive case series seen at a pediatric sleep clinic rapid eye movement (NREM) arousal parasomnias, such as sleep during a 2-year period. All subjects gave their written informed walking and night terrors, because these conditions are most consent to the study protocol, which was approved by the medi- commonly confused with NFLE,8,10 but the scale was designed
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