Sleep Complaints and Disorders in Epileptic Patients 순천향의대천안병원순천향의대천안병원신경과양광익

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1 Sleep Complaints and Disorders in Epileptic Patients 순천향의대천안병원순천향의대천안병원신경과양광익

2 Introduction The global physical, social and economic consequence of epilepsy are high. WHO 2000 study Improving QoL is increasingly being recognized as an important goal of epilepsy treatment. Sleep disturbance is known to be associated with impairment of QoL. Sleep disturbance in epilepsy patient may be underdiaganosed. Several studies have confirmed that sleep disturbances are common in epilepsy. Excessive daytime sleepiness Insomnia Fatigue or disrupted sleep Unusual movements and behaviors

3 Subjective sleep disturbance in patients with partial epilepsy: A Questionnaire-based study on prevalence an impact on QoL. Epilepsia 2004 Cross sectional Older than 18 years, 486 partial epilepsy vs. 492 control 1-2 AEDs Two-fold higher prevalence of sleep disturbance in partial epilepsy Disturbed sleep adversely affected QoL Two AEDs did not report more sleep complaints than those taking only one.

4 Patients with epilepsy had significantly more sleep disturbance even though their sleep quantity was comparable to controls.

5 Influence of sleep disturbance on QoL of patients with epilepsy. Seizure 2008 Older than 18 years old Epilepsy for at least 1 year, taking AED Exclusion: serious cognitive and medical disorders 124 enrolled EDS 16.9% (16.8% in woman, 20.6% in man) OSA 28.2% (24.3% in woman, 33.3% in man) Insomnia 24.6% (19.4% in woman, 30.9% in man)

6 Epileptic patients with sleep disturbance, mainly insomnia, have significant QoL impairment

7 Sleep hygiene in adult epilepsy patients: a questionnaire-based survey Acta Neurol Scand 2000 Cross sectional 270 epilepsy outpatients vs. 230 healthy Older than 18 years No major medical or psychiatric disorders Epileptic patient practice better sleep hygiene than healthy control Educational program indicating adequate sleep hygiene practice of epileptic patients No significant relationship between kind and/or severity of epilepsy and the degree of sleep hygiene

8 EDS and sleep complaints among children with epilepsy. Epilepsy & Behavior patient between 8 and 18 vs. control 14 idiopathic generalized, 12 LRE EDS is much more common AEDs type, epileptic type were not significantly associated with sleep complaints.

9 Sleep-wake habits and disorders in a series of 100 adult epilepsy patients -A prospective study. Seizure 2006 Over a period of 16 weeks, prospectively assessed Older than 18 years Exclusion: neurological, psychiatric or severe medical dz. Subjects with spontaneous reports of sleep complaints and use of hypnotics over 4 weeks Healthy subjects: hospital staff and relatives 100 epilepsy patients vs. 90 controls

10 Sleep-wake habits and the frequency of most sleep disorders are similar in non-selected epilepsy patients as compared to controls. sample size, selected for sleep disorders, control group-hospital staffs In epilepsy patients, EDS was predicted by a history of loud snoring and restless legs but by sleep apnea or epilepsy-related variables (including type of epilepsy, frequency of seizures, and number of AEDs)

11 Usefulness of Polysomnography in Epileptic Patients. Neurology adult (37 M, 26 F), 22 to 76 years Weekly to monthly seizure, 9-sz free for 1 year 40 partial, 12 generalized, 11 unknown Reason for PSG 12 Nocturnal spells 2 Excessvie daytime sleepiness 22 Suspected OSA 27 EDS + OSA Result 45(71%) OSA : 14 mild, 21 moderate, 10 severe 4 unrecognized nocturnal seizure 1 Narcolepsy 2 Insufficient sleep syndrome and possible idiopathic hypersomnolence 11 PLMI MLST : average mean sleep latency (6.8 minutes)

12 Hypersomnia in Epilepsy Patients Excessive daytime sleepiness is the most common complaint among patients with epilepsy. Self-reported sleep disorder symptoms in epilepsy. Epilepsia patients Patients with SPS, CPS had a higher incidence of sleep symptoms than those with generalized seizure. The most common complaint was frequent nocturnal awakenings. Poor seizure control was associated with significantly more sleep complaints. Partial seizure and more frequent seizures risk factor for EDS

13 Multiple sleep latency tests in epilepsy Clinical Electroencephalography patient (18 F, 12 M) with newly diagnosed or untreated complex partial seizures had MSLT after overnight sleep EEG during inpatient Epilepsy Unit. 20 to 49 years No previous evaluation for sleep disorders No significant medical, psychiatric diagnosis, sedative medications Excluded nocturnal seizure or sleep deprivation Mean sleep latency across 4 naps 8.4 ± 8 Clinically sleepy 20 Not sleepy 10 Mean latency 7.6 ± ± 9.5 Abnormal EEG 20 5 Rt-sided focus* 15 3 Lt-sided focus 5 2 SL > 8 minutes 10 9 SL 5-8 minutes 7 1 SL < 5 minutes 3 * Right temporal epileptiform activity correlated with sleepiness

14 Causes of EDS in Epilepsy-Multifactorial

15 Supplementary motor area seizure resembling sleep disorder Sleep year old woman had a two-year history of frequent sudden arousals from sleep followed by tachypnea and palpitation associated with event consisted of tremulous or clonic movements of both hands, followed by bilateral tonic posturing of the upper extremities seconds, 2-6 times per night

16 Supplementary motor area seizure resembling sleep disorder Sleep year old woman presentied with a complaint of frequent sudden arousals from sleep at night accompanied by lower limb elevation. 20 seconds, 2-5 attacks per night

17 Predictors of sleepiness in epilepsy patients Sleep years old 158 patients vs. 68 control (non-epileptic patient in neurological department) Exclusion: Patients referred primarily for a sleep disorder, significant medical, neurological, psychiatric disorders Control: minor neurological condition-headaches, neuropathy, vertigo, back pain, radiculopathy 45 (28%) epilepsy and 12 (18%) control had elevated ESS (>10) Variables as predictors of elevated ESS score (Multiple logistic regression) SA/SDQ RLS Number of AEDs Type of AEDs Diurnal variation of seizures History of epilepsy surgery Seizure-free for greater than 1 year Number of seizures in the last month Sedative medications Hours of sleep Significant predictors of an elevated ESS score SA/SDQ (OR=1.9, p<0.05) RLS (OR=3.4, p=0.002)

18 Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center. Epilepsy & Behavior 2006 Older than 16 years Tertiary care referral center ESS, BDI, SA/SDQ for OSA 136 patients ESS as dependent variable ESS score is higher than normal individual (mean ESS 4.6) 46 (35%) had ESS scores of % moderate depression 9.9% severe depression No abnormal cutoff values of SA score

19 Restless Legs Syndrome Zonisamide-induced RLS. Mov Disord 2007, Neurology 2003 Topiramate-induced RLS. J Neuorol 2007, 2009 Methosuximide, Phenytoin. Clin Neurol Neurosurg 1988 RLS resoved after methosuximide was replaced by VPA Symptoms improved when PHT was replaced by CBZ Seizure 2006 Sleep 2002

20 Parasomnia Parasomnia is frequently associated with epilepsy in children. Sleep disorders and their relationship to psychological disturbance in children with epilepsy. Child care health Dev 1998 Sleep terror, sleep walking Head banging Parasomnia coexist with epileptic seizure Recurrent nightmare and disorders of arousal in TLE. Brain Res. Bull confusional arousals 14 recurrent nightmares 4 night terrors 2 sleep walking

21 REM sleep behavior disorder in elderly subjects with epilepsy: Frequency and clinical aspects of comorbidity. Epilepsy Research 2007 Older than 60 years No antidepressant or any other drugs able to induce RBD No brain malignancy or degenerative brain disease 80 subjects (33 F, 47 M) Mean age 70.7 Video-PSG recording with 18 channel EEG ICSD-2 criteria for RBD Undiagnosed or misdiagnosed RBD can coexist with epilepsy in the elderly

22 Insomnia As compared to EDS, a few studies have systemically investigated insomnia in epileptic patient. Measuring insomnia with the insomnia severity index in epileptic patients. Sleep 2007 (abstract) 61 subjects Approximately 70% of epilepsy patients had insomnia using the ISI (insomnia Severity Index) There were no associations between ISI and seizure frequency, gender, age or number of AEDs. ISI and BDI (Beck Depression Inventory) correlated moderately

23 Causes of Insomnia in Epilepsy Nocturnal seizures and interictal epileptiform discharges causing repeated arousals AEDs (LTG, FBM) Withdrawal or tapering of AEDs during video-eeg monitoring Depression and anxiety Associated primary sleep disorder

24 Obstructive Sleep Apnea and Epilepsy OSA affect up to 24% of men and 9% of woman (ages 30 to 60 yrs) in general population, AHI >5 20% of woman and 28% of man (greater than 65 yrs) in general population OSA is common sleep disorders in epilepsy Exceed of the general population 71% - Malow et al., % - Marsilio et al., % - Ezpeleta et al., 1998 Mean AHI, 23 to 38

25 OSA is common in medically refractory epilepsy patients. Neurology 2000 Prospective study 39 candidates for epilepsy surgery without a history of OSA years Recurrent CPS with at least one seizure with the last month 13 (33%) RDI > 5 (5 RDI > 20) 50% of male, 19% of woman

26 OSA is associated with seizure occurrence in older adults with epilepsy. Neurology 2007 Cross sectional study 290, All types of epilepsy Exclusion : provoked seizure, neurological and unstable medical disorders, prior history of OSA Group 1: seizure onset at age 50 or older or seizure onset before 50 with increased frequency at or after age 50 Defined by a 20% or greater increase in seizure frequency over the preceding 3 months. Group 2: seizure onset before ate 50 with stable or improved frequency at or after ate 50 AHI > 5: 30% of woman, 73% of man

27

28

29 Improvement of epileptic seizure control with treatment of OSA Seizure patients, 21 to 79 years Seizure frequency and AEDs regimen were followed for at least one year following OSA treatment 1-4: seizure free. 5-7: improved after medication change. 8-10: minimal improved. 9: intolerated CPAP Improvement of the seizure frequency did not correlated with the RDI

30 Identification and treatment of OSA in adults and children with epilepsy : prospective pilot study. Sleep Medicine years older, 4 or more seizures a months, maintenance of AEDs, ability to complete survey Exclusion :(1) non-epileptic spell, (2) seizure secondary to drugs, alcohol, other medical illness, (3) poor compliance of AEDs (4) pregnancy (5) sleep disorder 8 week of base line vs. at least 8 week of data after treatment, no change of AED regimen Reduction 72% 47% 73% Unable to CPAP Unable to CPAP No change overall Reduction in night (71%) 60%

31 Treating OSA in adults with epilepsy. A randomized pilot trial. Neurology 2008 Randomized double-blind, multi-center Age 18 years or older Medically refractory partial or generalized epilepsy, defined by two or more seizures per month Exclusion Treated OSA Seizures secondary to drugs, alcohol, infection, neoplasia, demyelination, metabolic, or progressive degenerative disease Narcolepsy or another primary sleep disorder Poor compliance with AEDs VNS, pregnancy, significan medical or psychiatric disease Medical instability due to OSA Greater than 10 seizures a day University of Michigan Cleveland Clinic Foundation University of North Carolina Vanderbilt University

32 36 (80%) of 45 had OSA 50% or greater reduction in seizure 28% of the therapeutic 15% of the placebo (p=0.4) Small sample size Unable to isolate the effect of specific AEDs Excluded severe OSA

33 Possible Mechanism of OSA in Epileptic Patients AED influence OSA Barbiturates, benzodiazepines and possibly phenytoin may affect upper airway tone Weight gain treated VPA, GBP, CBZ, PGB, VGB Endocrine disorders including hypothyroidism and polycystic ovarian syndrome have also been associated with AED therapy -> risk of OSA Epilepsy patients are less physically in aeorbic endurance, muscle strength endurance and flexibility and greater BMI VNS may affect airway musculature or brain stem networks that regulate respiration Proposed mechanism OSA may exacerbate seizure Sleep fragmentation and deprivation Cerebral hypoxia Decreased cardiac out put, arrhythmia

34 Vagal nerve stimulation causes obstructive sleep apnea 대한수면연구학회. 양광익 /M Lt. MTLE The respiratory events were associated with the VNS firing

35 Summary (I) Sleep disturbances are common in epilepsy. Sleep disturbance in epilepsy patient may be under-diagnosed. Simple sleep questionnaires may be useful to screen for the presence of sleep disorders in patients with epilepsy. Excessive daytime sleepiness is the most common complaint among patients with epilepsy. Systemically studies on the epileptic patient with insomnia would be needed. OSA is common sleep disorders in epilepsy.

36 Summary (II) OSA can lead to sleep fragmentation and chronic sleep deprivation, which may facilitate seizures. Reducing factors which may promote seizures, such as sleep deprivation, could lead to more effective treatment strategies. Epilepsy patients should be questioned carefully for a sleep disturbance. Most of sleep disorders in epileptic patients could be controlled easily. It may be helpful to reduce seizure frequency and improve QoL.

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