**3. Methodology**

All patients underwent standard EEG evaluation with 21 canal EEG machine and distribution of electrodes according to system 10-20, duration of record was 20 minutes. Noticed abnormalities were rated as regional or generalised, with continual of intermitent occurence. Appearance of epileptiform ictal or interictal discharges was noted.

#### **3.1 Methods used to examine daytime sleepiness**

32 Novel Aspects on Epilepsy

Even 33% pacients with medically refractory epilepsy have sleep apnoe syndrome (Malow et al., 2000). Reason of higher appearance of sleep related breathing disorders in patients with epilepsy is not clear. It may be connected with higher weight of patients as effect of anticonvulsant therapy (Manni & Terzaghi, 2010), or changes of endocrine system (valproate). Sleep apnoe syndrome leads to fragmented macroarchitecture of sleep with repeated hypoxemia of brain in consequence of repeated apnoic episodes. This may cause higher frequency of epileptic seizures. It is important, that correct therapy of sleep apnoe syndrome (reduction of weight, indication of CPAP or BiPAP) may bring improvement of

Sleep disorders should be considered especially when patient with epilepsy indicates hypersomnia, but has low frequency of epileptic seizures, is treated with monotherapy of

Patient with epilepsy and EDS reguires accurate evaluation to detect reason of hypersomnia. Compensation of epilepsy should be examined. EEG during daytime and overnight-EEG should detect interictal or ictal discharges. This may cause microarousals and fragmentation of sleep with secondary hypersomnia. Adjusting of antiepileptic medication should reduce amount of epileptic seizures and improve sleep. It is recommended to avoid antiepileptic therapy with sedative effects (barbiturates, benzodiazepines) and useless combination of too

Correct sleep hygiene and life-style with regular and sufficient night-sleep and optimal

Hypersomnia in patients with epilepsy may be caused by sleep apnoe syndrome. This should be considered particulary in obese patients with morning headache and hypertension. Diagnosis is estimated by polysomnography. According to literature 1/3 patients with refractory epilepsy have obstructive sleep apnoe syndrome (Malow et al., 2000). Correct therapy of sleep related breathing disorders may improve quality of sleep. Antiepileptic therapy, which increase weight (valproate) should be avoided, as it may

Insomnia is another possible reason of daytime hypersomnia and fatigue of patients with epilepsy. It should be treated by behavioral and relaxation methods, improvement of sleep habits or by sedative drugs. If antiepileptic therapy is considered as reason of insomnia,



All patients underwent standard EEG evaluation with 21 canal EEG machine and distribution of electrodes according to system 10-20, duration of record was 20 minutes.

epilepsy (Foldvary, 2002).

many antiepileptic drugs.

**2. Objectives** 

Targets of this study were:

healthy controls

of epilepsy

**3. Methodology** 

antiepileptic drug and has low blood levels of medication.

surroundings is also important (Bazil, 2003, Happe, 2003).

worsten sleep apnoe syndrome (Bazil et al., 2002).

then it should be taken only in morning.

**1.4 Management of patient with epilepsy and sleep disorders** 

In both groups (patients with epilepsy and healthy controls) we used a questionnaire Epworth Scale of Sleepiness (ESS) (Johns, 1991). By answering eight questions about probability of falling asleep in standard situations we came to the result, i.e. score of daytime sleepiness ranging from 0 to 24. Rate 0-9 is considered as normal value, above 9 as elevated daytime sleepiness and value above 16 is considered as remarkably elevated daytime sleepiness (Watanabe et al., 2003).

All patients with epilepsy were evaluated by Multiple Sleep Latency Test (MSLT) (Carscadon & Dement, 1982) in order to objectivise the daytime sleepiness. The latency of sleep was measured in five 20 minute polysomnographic registrations in this test. Between the registrations the patient should be awake (Usui et al., 2008). Mean latency of sleep and appearance of REM sleep was noticed. Mean latency of sleep shorter than 6 minutes was considered as indicative of elevated sleepiness (American sleep disorders association, 1992).

#### **3.2 Methods used to register sleep architecture**

Nocturnal polysomnografy was used in both groups to evaluate quality of sleep. We used program Brain Quick System 98 for polysomnography. Scoring of sleep stages was done with Sleep View Rembrandt Sleep Analysis Program.

Registration and scoring of sleep stages was done according to criteria of Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects (Rechtschaffen & Kales, 1968). We used four electrodes (C3, C4, O1, O2, A1, A2) in EEG registration. When topographical localization of epileptiform discharges was needed, we used 19 EEG electrodes located according to international system 10-20. Standard localization of electrodes for electrooculogram and electromyogram m.mentalis was used.

The result of sleep analysis was hypnogram, amount of sleep stages (NREM S1, NREM S2, NREM S3+-S4, REM) in %, total sleep time in minutes and efficiency of sleep in %was marked. For purpose of registration of different abnormal movement manifestations (epilepsy, REM behavior diseases etc.), a video was recorded simultaneously with polysomnography.

#### **3.3 Characteristics of the group of patients with epilepsy**

We examined 100 patients with epilepsy who were admitted to the I. Neurology Clinic of Comenius University Hospital in Bratislava for diagnostic or therapeutic reasons in the period from January 2004 to January 2009. The group consisted of 49 men and 51 women, with the average age of 34.68 ± 13.55 years. Patients of the age 9 - 61 were included. Average duration of illness was 9.31 ± 9.93 years, ranging from 0.5 to 47 years. Medical history of duration and type of epilepsy was taken. International classification of epileptic seizures (1981, 1989) and International classification of epilepsy (1989) was used.

According to this classification 50 patients had focal symptomatic epilepsy, 26 patients had focal cryptogenic epilepsy. Generalised symptomatic epilepsy was diagnosed by 15 pacients and 9 patients had generalised cryptogenic or idiopathic epilepsy (see Fig.1).

Etiology of epilepsy was evaluated. Idiopathic or cryptogenic epilepsy have 35% patients and symptomatic epilepsy have 65% of patients. Detailed analysis of reasons of epilepsy in group of symptomatic patients showed these factors:

Daytime Sleepiness and Changes of Sleep in Patients with Epilepsy 35

patients used combination of lamotrigine/topiramate. Two patients used combination of carbamazepine/lamotrigine, carbamazepine/topiramate and combination valproate/ topiramate. One patient used combination carbamazepine/levetiracetam, carbamazepine/ gabapentin, carbamazepine/pregabalin, valproate/levetiracetam and topiramate/

**59.00% 29.00%**

**Monotherapy AED Two AEDs Three and more AEDs**

**Carbamazepine Valproate Lamotrigine Primidon Clonazepam Gabapentin**

**2%2%2%2%**

**52%**

**12.00%**

Fig. 2. Antiepileptic therapy in group of epileptic patients.

**23%**

**Phenytoin**

Fig. 3. Antiepileptic monotherapy in group of epileptic seuzures.

**17%**

zonisamid (see Table 1).


Fig. 1. Amount of patients according to type of epilepsy

Compensation of epilepsy was evaluated according to Diagnostic and therapeutic standard of epilepsy (Donáth, 1996). As insufficiently compensated epilepsy were rated patients with several epileptic seizures during last month. Partially compensated epilepsy had patients with minimally half of year seizure free period and fully compensated epilepsy had patients, who had not for last 3 years an epileptic seizure. According to these criteria 80 patients had insufficiently compensated epilepsy and 20 patients were rated as having partially or fully compensated epilepsy.

All patients were treated by antiepileptic medication. Monotherapy used 59 patients (59%), 29 pacients (29%) were treated by two antiepileptic drugs (AEDs) and 12 pacients (12%) have three and more AEDs (see Fig.2).

Most frequently used monotherapy was carbamazepine, which used 31 patients (it was 52,5% of patients treated by monotherapy). Valproate as monotherapy used 14 pacients (23,7% of patients on monotherapy), 10 patient (16,9%) used lamotrigin, one pacient (1,7%) used primidon, one patient (1,7%) was treated by clonazepam, one patient (1,7%) gabapentin and one patient phenytoin (1,7%) (see Fig.3).

Two AEDs were used by 29 patients. Most frequent combination of EADs was carbamazepine /valproate, which used 9 patients (31 % of all patients on combination of two AEDs). Next most commonly used combination of two AEDs was valproate/ lamotrigine used by 6 patients (20,7% of all patients on combination of two AEDs). Three

**15**

**9**



**50**

Fig. 1. Amount of patients according to type of epilepsy

gabapentin and one patient phenytoin (1,7%) (see Fig.3).

partially or fully compensated epilepsy.

have three and more AEDs (see Fig.2).

**Foc. symp. epi Foc. crypt. + idiop. epi Gen. sympt. epi Gen.crypt.+idiopat. epi**

Compensation of epilepsy was evaluated according to Diagnostic and therapeutic standard of epilepsy (Donáth, 1996). As insufficiently compensated epilepsy were rated patients with several epileptic seizures during last month. Partially compensated epilepsy had patients with minimally half of year seizure free period and fully compensated epilepsy had patients, who had not for last 3 years an epileptic seizure. According to these criteria 80 patients had insufficiently compensated epilepsy and 20 patients were rated as having

All patients were treated by antiepileptic medication. Monotherapy used 59 patients (59%), 29 pacients (29%) were treated by two antiepileptic drugs (AEDs) and 12 pacients (12%)

Most frequently used monotherapy was carbamazepine, which used 31 patients (it was 52,5% of patients treated by monotherapy). Valproate as monotherapy used 14 pacients (23,7% of patients on monotherapy), 10 patient (16,9%) used lamotrigin, one pacient (1,7%) used primidon, one patient (1,7%) was treated by clonazepam, one patient (1,7%)

Two AEDs were used by 29 patients. Most frequent combination of EADs was carbamazepine /valproate, which used 9 patients (31 % of all patients on combination of two AEDs). Next most commonly used combination of two AEDs was valproate/ lamotrigine used by 6 patients (20,7% of all patients on combination of two AEDs). Three





**26**

patients used combination of lamotrigine/topiramate. Two patients used combination of carbamazepine/lamotrigine, carbamazepine/topiramate and combination valproate/ topiramate. One patient used combination carbamazepine/levetiracetam, carbamazepine/ gabapentin, carbamazepine/pregabalin, valproate/levetiracetam and topiramate/ zonisamid (see Table 1).
