Joseph Kaleyias

Sleep and epilepsy in children and adolescents

Epilepsy and sleep disorders are considered by many to be common bedfellows. Several sleep phenomena may occur during nighttime taking a wide variety of forms and which can mimic seizures. Although most seizure sub-types have the potential to occur during sleep or wakefulness, sleep has a well-documented and strong association with specific epilepsy syndromes. Seizures in sleep also tend to occur during lighter stages of non-REM (NREM) sleep. The neurophysiologic process involved in the deepening of NREM sleep may also facilitate both seizures and IEDs. Epilepsy per se and/or seizures themselves promote sleep disruption and significantly affect the quality, quantity, and architecture of sleep. There are many causes of sleep disruption in patients with epilepsy, including inadequate sleep hygiene, coexisting sleep disorders, and circadian rhythm disturbances. Seizures themselves can disrupt sleep, even when they occur during wakefulness. Anti-epileptic drugs (AEDs) can also alter sleep in positive and negative ways, and these effects are independent of anticonvulsant actions. The end result of sleep disruption is excessive daytime sleepiness, worsening seizures, and poor quality of life. Screening for sleep disorders in the epilepsy population and appropriate intervention strategies will lead to overall improved quality of life and seizure control.

Severity of obstructive sleep apnea in children with sickle cell disease.

Objective To characterize polysomnographic (PSG) findings of children with sickle cell disease (SCD) suspected of having sleep disordered breathing (SDB). Methods Families of 100 consecutively referred children with SCD completed the Childrens Sleep Habit Questionnaire during a routine visit to identify concerns regarding sleep habits and sleep behavior. Of these, 48 children were identified as displaying behaviors suspicious of SDB. Nineteen agreed to an overnight PSG. The results from the PSGs of the SCD with obstructive sleep apnea syndrome (OSAS) group (SCD-OSAS; group 1) were compared with the results of 10 age, sex, and ethnicity-matched patients identified as OSAS with no medical comorbidities (uncomplicated OSAS; group 2). Results SDB was identified in 79% of the SCD group. As compared with the uncomplicated OSAS group, the SCD with OSAS group displayed nocturnal desaturation with lower nadir values, of longer duration, with a 4-fold increased risk for oxygen desaturation below 85%, higher percentage of total sleep time with end-tidal carbon dioxide (ET CO2) values >50 mm Hg, with a 3.7-fold increased risk for spending more than 25% of total sleep time with ET CO2 more than 50 mm Hg and higher peak ET CO2 with a 7-fold increase for peak ET CO2 above 53 mm Hg. Conclusions Children with SCD suspicious of SDB may have not only a higher incidence of OSAS, but also more severe nocturnal desaturation and hypercapnia as compared with children with uncomplicated OSAS.

Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety.

Background: Zonisamide (ZNS), a sulphonamide derivative, is a new-generation anticonvulsant with multiple potential mechanisms that contribute to its antiepileptic efficacy and may also explain its as yet incompletely assessed utility for non-seizure disorders such as headaches, neuropathic pain, and weight loss. Objective: A review of the pharmacokinetics, pharmacodynamics, evidence for efficacy in different seizure types and non-seizure conditions, adverse effects, and tolerability of ZNS is presented. Methods: A review of all manuscripts published in the English literature on ZNS was performed in preparing this manuscript. Results/conclusions: ZNS has a broad label for use in Japan, while the regulatory bodies in the USA and Europe have approved it for use only as an adjunctive therapy for partial seizures in adults. It has favorable pharmacokinetic characteristics, proven efficacy in seizure disorders, and is well tolerated in long-term use.

The Clinical and Laboratory Assessment of the Sleepy Child

Excessive sleepiness is defined as sleepiness that occurs in a situation when an individual would usually be expected to be awake and alert. Hypersomnia is characterized by recurrent episodes of excessive daytime sleepiness (EDS) or prolonged nighttime sleep, which affects the everyday life of the patient. Clinical surveys have reported that EDS is a complaint observed in up to 68% of normal high school children, with a negative impact in academic achievement and extracurricular activity. Clues toward recognizing childhood daytime sleepiness may be sleeping longer hours than expected for age, daytime naps beyond normal for age, being sleepy when other children of the same age are active and alert, and sleeping more than previously. Causes of EDS are arbitrarily divided into 3 categories: insufficient nighttime sleep, fragmented nighttime sleep, and increased drive of sleep. A list of various causes of EDS in children has been discussed. A detailed history along with examination of the upper airway is crucial in evaluating patients with EDS. Appropriate screening tools such as sleep logs, sleepiness scales, and sleep questionnaires further help in identifying and quantifying the degree of sleepiness. Confirmatory tests such as polysomnography, multiple sleep latency test, and actigraphy along with referral to a sleep physician may be necessary in appropriate cases. Details of other ancillary testing such use of cerebrospinal fluid orexin levels, HLA subtyping, and so on have also been provided.

Sleep Disorders in Children With Cancer

Approximately three-fourths of all pediatric cancer patients will be long-term survivors; however, there can be a steep cost for cancer survivorship. Cancer treatment involves exposure to chemotherapy, surgical intervention, and radiation, which can cause lasting long-term toxicities. Children with brain tumors have the highest prevalence of long-term morbidities. These effects can be attributed to direct neurologic damage to the developing brain caused by tumor, hydrocephalus, surgical removal of the tumor, and the effects of irradiation. The late effects experienced by childhood cancer survivors involve multiple domains, one of which is sleep disorders. Sleep dysfunction has an increased prevalence in the pediatric cancer survivor population. These issues are disruptive to patients and cause a decrease in quality of life. This review focuses on sleep disorders that occur in pediatric cancer survivors and discusses the possible causes, the assessments used to determine specific sleep disorders, and treatment modalities used to ameliorate this dysfunction with the hope of improving patients quality of life.

Sleep-wake patterns of seizures in children with lesional epilepsy.

This study examined diurnal patterns of seizures and their occurrence during wakefulness and sleep in children with lesional focal epilepsy. We reviewed 332 consecutive children with lesional focal epilepsy and video-electroencephalogram monitoring during a 3-year period. Data were analyzed in relationship to clock time, wakefulness/sleep, and seizure localization. The distribution of lesions in 66 children (259 seizures) included mesial temporal, 29%; neocortical temporal, 18%; frontal, 29%; parietal, 13.5%; and occipital, 12%. Seizures in patients with frontal lesions occurred mostly during sleep (72%). Seizures in mesial temporal (64%), neocortical temporal (71%), and occipital (66%) lesional epilepsy occurred mostly during wakefulness. Temporal lobe seizures occurred more frequently during wakefulness (66%), compared with extratemporal seizures (32%) (odds ratio, 2.67; 95% confidence interval, 1.61-4.42). Temporal lobe seizures peaked between 9:00 am and noon and 3:00-6:00 pm, whereas extratemporal seizures peaked between 6:00-9:00 am. Sleep, not clock time, provides a more robust stimulus for seizure onset, especially for frontal lobe seizures. Temporal lobe seizures are more frequent during wakefulness than are extratemporal seizures. Circadian patterns of seizures may provide additional diagnostic and treatment options, such as differential medication dosing and sleep-schedule adjustments.

Electroencephalogram monitoring during intracranial surgery for moyamoya disease.

We describe our experience with intraoperative electroencephalography in moyamoya surgery, a method to monitor for ischemic changes during the procedure and to minimize the risk of intraoperative and perioperative stroke. Case records and intraoperative electroencephalography recordings of all patients (n=220) treated with surgical revascularization for moyamoya (pial synangiosis) performed for 14 years (1994-2008) were reviewed. Electroencephalographic slowing occurred in 100 cases (45.5%), and was persistent in nine cases (9%). Slowing coincided with specific operative manipulations, most commonly while suturing the donor vessel to the pia, and during closure of the craniotomy. Slowing generally occurred bilaterally, independently of the side of intervention. The presence, length, and severity of slowing were not predictive of perioperative ischemic events. We present additional data on intraoperative electroencephalography with a modified montage to accommodate the craniotomy. Although not predictive of perioperative ischemic events in this series, electroencephalographic changes were correlated with specific operative interventions, and revealed global responses to unilateral manipulation. These findings suggest that prospective analyses of this technique may elucidate additional methods of predicting (and possibly preventing) perioperative ischemic events.

Nocturnal Paroxysmal Dystonia

Nocturnal paroxysmal dystonia (NPD) along with paroxysmal arousals (PAs) and episodic nocturnal wanderings (ENW) are considered the three characteristic manifestations of nocturnal frontal lobe epilepsy (NFLE). Episodes of NPD begin as paroxysmal arousals, but are subsequently associated with more complex movements including bipedal automatisms, rhythmic twisting movements of the trunk and pelvis, vocalization, and tonic or dystonic posturing lasting less than a few minutes. The epileptic versus nonepileptic origin of NPD has been extensively debated. A network including frontal and possible extrafrontal limbic structures is involved in the genesis of the complex epileptic manifestations of NFLE. Recently, we have started recognizing the co-occurrence of NFLE with parasomnias. The observation that similar motor features can accompany both arousal disorder parasomnias and seizures, including those of NFLE has led to the hypothesis that both phenomena may indicate a release of normal neocortical inhibition of central pattern generators in mesencephalon, pons, and/or spinal cord. The predominant source of confusion is episodes characterized by sudden arousal from sleep with motor activity and often dramatic or bizarre behaviors. As such, the disorders to be considered are the NREM arousal parasomnias, rapid eye movement (REM) sleep behavior disorder, and nocturnal panic attacks as they may present in the similar fashion. A small dose of carbamazepine treatment is effective in 70 % of the patients, whereas a third of the patients, commonly with a high seizure frequency, are drug resistant. In patients with NFLE, use of individually tailored antiepileptic drug (AED) dosing, that is, higher doses of AEDs in the evening, may be helpful.