Burkojus, Dovydas

Background and Objectives: People with epilepsy frequently complain of poor sleep quality, excessive daytime sleepiness (EDS), and insomnia. Therefore, this study aimed to evaluate differences in anxiety and depression symptoms, as well as clinical characteristics, across groups defined by sleep quality in patients with epilepsy. Materials and Methods: Seventy-eight adults with epilepsy were assessed using standardized questionnaires for sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Epworth Sleepiness Scale, ESS), insomnia severity (Insomnia Severity Index, ISI), and psychiatric symptoms (PHQ-9, GAD-7, and HADS). Demographic data (age and sex), seizure frequency and characteristics, use of antiepileptic drugs (AEDs), and EEG findings were collected. Patients were divided into groups based on sleep quality scores, and comparisons were made regarding anxiety, depression, and selected clinical variables. Associations were analyzed using t-tests, chi-squared tests, and Spearman correlation coefficients. Results: Poor sleep quality (PSQI > 5) was present in 70.9% of patients and was significantly associated with insomnia, daytime sleepiness, depression, and anxiety symptoms (p < 0.001 for all comparisons). Patients who had experienced generalized tonic–clonic seizures (GTCS) in the past year had significantly worse sleep quality compared to those without GTCS (p = 0.025). Clinical insomnia (ISI ≥ 15) was observed in 23.1% of cases and was significantly associated with the presence of seizures (p = 0.015). EDS was present in 19% of cases and was associated with depressive symptoms (p = 0.019). A higher concentration of levetiracetam was associated with better sleep quality, whereas a higher concentration of lamotrigine was associated with worse sleep quality (p = 0.024 for both). EEG abnormalities, seizure frequency, and duration of epilepsy were not associated with sleep quality. Conclusions: Poor sleep quality was reported in 70% of the study patients and was associated with increased insomnia severity, EDS, and psychiatric comorbidities. People with EDS were more likely to have higher levels of depression and anxiety. Patients who experienced GTCS within the past year were significantly more likely to report poor sleep quality. Insomnia was associated with older age and female sex. Seizure-free patients had less insomnia. Nevertheless, no associations were found between sleep evaluation scores and other demographic or clinical epilepsy characteristics.

Objectives Sleep and epilepsy share a reciprocal relationship, with a myriad of factors contributing to both sleep disruption and poor seizure control. Idiopathic generalized epilepsies (IGE) are a group of homogeneous epilepsy syndromes that are especially prone to an increased risk of seizures upon sleep deprivation. Currently, very few studies have explored the relationship between sleep fragmentation and epilepsy-related factors, such as interictal activity, and even fewer have done so in the context of IGE. In this study, we investigated whether sleep fragmentation is related to clinical and electroencephalography (EEG) characteristics in a small sample of patients with IGE. Materials and Methods We conducted a prospective, cross-sectional study of people with IGE. We collected data regarding patient age, epilepsy syndrome, and seizures. Participants were asked to complete the Pittsburgh Sleep Quality Index (PSQI) questionnaire. We then performed overnight polysomnography (PSG) and 24-hour EEG with additional oculography and chin muscle electrodes to distinguish sleep stages. The spike index (SI) during sleep was calculated as the sum of the durations of all epileptic discharges divided by the total sleep time. The duration of an epileptic discharge was measured from the start of the spike/polyspike to the end of the final wave. The arousal index (AI) was extracted from the PSG data according to the American Academy of Sleep Medicine guidelines. Data were analyzed using SPSS version 30. Spearman's rank correlation coefficient was used to evaluate the correlation between SI and AI, as well as between AI and PSQI. The Mann-Whitney U test was used to compare median values between independent groups. Results We enrolled a total of 16 patients (11 female) with a mean age of 14.7 years (±1.9). The IGE syndromes included juvenile myoclonic epilepsy (JME, n=7), juvenile absence epilepsy (JAE, n=5), and epilepsy with generalized tonic-clonic seizures alone (GTCA, n=4). The median PSQI score was 5 (IQR 2.25-9.50), with 8 of 16 patients (50%) reporting scores ≥5, indicating poor subjective sleep quality. The median SI was 0.0001 (IQR 0-0.009) and the median AI was 11.1 (IQR 9.25-20.3). A moderate positive correlation was found between the SI and AI (ρ=0.527, p=0.036). No significant correlation was observed between the AI and PSQI scores (p=0.834). Five of the 16 patients experienced daily seizures (absences, myoclonic seizures, or both); this subgroup had a median SI of 0.01 (IQR 0.006-0.02) and a median AI of 15.6 (IQR 10.1-22.4). The difference in AI between patients with and without daily seizures was not statistically significant (p=0.364). Conclusions In this study of a small sample of IGE patients, we found that interictal epileptic discharges may contribute to sleep fragmentation, as indicated by the moderate positive correlation between the spike and arousal indices. This relationship appeared to be independent of daily seizure occurrence or subjective sleep quality, highlighting that subclinical interictal activity itself may be a driver of poor sleep architecture in this population. The finding that half of our patients reported poor subjective sleep quality emphasizes the importance of screening for sleep problems in individuals with IGE. Further studies with larger sample sizes are needed to draw more reliable conclusions.

Su febrilia infekcija susijęs epilepsijos sindromas (FIRES) yra retas neaiškios etiologijos epilepsijos sindromas, kurio metu po karščiavimo epizodo pasireiškia dažni epilepsijos priepuoliai. Aprašomas 6 metų paciento, sergančio FIRES, klinikinis atvejis. Pacientui skirtas kompleksinis gydymas imunoterapija, vaistais nuo epilepsijos ir pradėta taikyti ketogeninė dieta. Dėl FIRES retumo trūksta geros kokybės tyrimų, kuriais vadovaujantis būtų galima užtikrinti tinkamą šių pacientų priežiūrą. Pristatydami šį klinikinį atvejį ir literatūros apžvalgą, aptariame savo patirtį, gydant FIRES sergantį pacientą. Gydymas ketogenine dieta, tocilizumabu ir anestetiku propofoliu buvo sietinas su dislipidemija ir pankreatitu. Nors dabartinėse FIRES gydymo gairėse kol kas trūksta duomenų apie kanabidiolio naudą, mūsų paciento atveju gydant kanabidioliu stebėtas reikšmingas epilepsijos priepuolių sumažėjimas. Dėl FIRES retumo ir sudėtingumo, tikslinga didinti budrumą dėl vaistų šalutinio poveikio bei aprašyti veiksmingus gydymo būdus.

The importance of sleep has been reported for decades. Epilepsy is a heterogeneous disorder comprising multiple elements that might influence sleep and wakefulness. Notably, animal studies show disruptions of the circadian molecular system in different models of epilepsy, along with altered rest–activity and other circadian rhythms. So far, studies of molecular circadian systems in people with epilepsy are lacking, prompting further research. Seizures—the primary and most debilitating symptom of epilepsy—and interictal activity disrupt regular sleep and sleep–wake rhythms. Alterations in one’s sleep structure are seen in both drug-naïve and drug-resistant patients with epilepsy. In particular, low sleep efficiency, a reduction in total sleep time, and changes in sleep stages were found in both homogenous and mixed samples of epilepsy patients. Both ictal and interictal activity were also shown to be associated with changes in peripheral circadian phase biomarkers such as melatonin and cortisol. Moreover, epilepsy comorbidities, antiseizure medications, and a variety of syndromes can be a cause of sleep problems or even sleep disorders. Sleep disorders vary depending on various comorbidities and syndromes, and encompass all major groups of sleep disorders defined in the International Classification of Sleep Disorders. Controversial findings on the effects of various antiseizure medications were found in the literature. However, medications such as benzodiazepines, gabapentinoids, and barbiturates are particularly associated with excessive daytime sleepiness. Overall, a sleep evaluation must be included in the management of every patient with epilepsy.

Neramus vaiko miegas yra gana dažna priežastis, dėl kurios į šeimos gydytojus kreipiasi tėvai. Tačiau ne visos su vaiko miegu susijusios problemos yra miego sutrikimai ir, atvirkščiai, dalis vaikų miego sutrikimų gali likti nepastebėti ar netinkamai įvertinti. Remiantis Amerikos miego medicinos akademijos rekomendacijomis, vaikų normali miego trukmė gali varijuoti atsižvelgiant į amžių - kūdikiai gali išmiegoti iki 16 valandų, o paaugliams gali pakakti ir 8 valandų miego per parą (1 lentelė) [1]. Siekiant tinkamai įvertinti, ar vaiko miegas normalus, vertėtų atsiminti vaikų miego fiziologiją, kuri skiriasi įvairiose amžiaus grupėse. Kūdikių miegas yra fragmentuotas, miego ciklai trumpesni nei vyresnių vaikų ar suaugusiųjų, kūdikiams būdingi dažnesni prabudimai - daugiafazis miegas. Ilgainiui miegas gilėja ir tampa vienfazis, t. y. 3-5 metų vaikas dažniau išmiega visą naktį, nebelieka dienos miego poreikio, tačiau verta atminti, jog šis procesas kiekvienam vaikui vyksta individualiai [2, 3]. Šiame straipsnyje trumpai apžvelgiamos dažniausios vaikų miego problemos.

Objectives Pathogenic variants in the PRRT2 (proline-rich transmembrane protein 2) gene have been identified as the main cause of an expanding spectrum of disorders, including paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy, which places this gene at the border between epilepsy and movement disorders. The clinical spectrum has largely expanded to include episodic ataxia, hemiplegic migraine, and complex neurodevelopmental disorders in cases with biallelic mutations. In this case series report we would like to explore clinical symptoms for patients with PRRT2 gene variant. Materials and Methods We report 8 patients (1 male and 7 females) from 4 different families. Each family had one member diagnosed with early onset epilepsy undergo whole exome sequencing with epilepsy gene virtual panel. Other family members were tested by targeted Sanger sequencing. The most common PRRT2 gene pathogenic variant NM_145239.3:c.649del was confirmed for all patients. Results 6/8 patients had early onset epileptic seizures (median age 5 months) which responded well to standard treatment. 4 patients are on medication at the analysis time and 3 patients were prescribed valproic acid and one patient uses phenytoin. 6/8 of these patients had appropriate development for age. 2/8 patients have autistic traits and intellectual disability with psychiatric disease possibly caused by other reasons. Seizures resolved without treatment in one case. 2 adult patients have symptoms of hemiplegic migraine that started in the teenage years. One patient had seizures as a baby and now involuntary movements were noticed in adulthood. Conclusions We confirm that PRRT2 gene variants cause wide range of symptoms: familial benign epilepsy, hemiplegic migraine and movement disorder. Treatment with valproic acid was effective for our patients. It is very important to properly recognize families with possible PRRT2 gene variants to hasten and optimize genetic testing.

Objectives We aim to describe the reciprocal relationship and its various aspects between sleep and epilepsy. Materials and Methods A thorough overview of the available literature about sleep and epilepsy was conducted. The various aspects of the relationship between sleep and epilepsy are illustrated by clinical case examples. Results The recently published consensus review of standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid disorders by the European Academy of Neurology, the European Sleep Research Society, and the International League Against Epilepsy has highlighted sleep-related epilepsies based on how sleep affects epilepsy in regards to clinical symptoms and electroencephalographic findings. On the contrary, epilepsy, along with antiseizure medications, in turn, has various effects on sleep structure, cognitive functioning, and the sleep-wake cycle. It is also more prevalent in people with epilepsy to have comorbid sleep disorders such as parasomnias, sleep-disordered breathing, or insomnia. Poor control of seizures has a negative impact on sleep, while poor sleep, in turn, has negative effects on seizure control, albeit these effects differ in different types of epilepsies. However, current studies often involve mixed samples of patients and are scarce. Based on current data, it is difficult to provide high-quality recommendations regarding the evaluation of patients with sleep-related epilepsy. Conclusions Epilepsy has varying and complex effects on sleep, and vice versa, although the true impact in multiple different aspects is yet to be determined.

Objectives Mitochondrial diseases are a diverse set of disorders that arise from abnormalities in the function of mitochondria. These conditions present a wide spectrum of clinical manifestations, which can make diagnosis challenging. Moreover, genetic diagnosis of mitochondrial disease can be complex because genetic variants can be found in mitochondrial DNA or nucleus DNA. In this review, we will explore three clinical cases to illustrate the complexities of mitochondrial diseases. Materials and Methods . Results Case 1. A 15-year-old girl has been experiencing various impairments since childhood, including growth retardation, hypothyroidism, cataracts, optic nerve atrophy, neurosensory deafness, mitral valve insufficiency, cardiomyopathy, chronic kidney disease, delayed sexual maturation, and a lipoma in the brain. Despite treatment, her symptoms have been progressively worsening, with episodes of metabolic acidosis occurring more frequently. Additionally, she has experienced deteriorating gait, tremors, and fatigue. Her mother and grandmother died at a young age. Both of them had kidney failure and hearing impairments. The whole exome sequence (WES) was performed and after additional bioinformatics analysis, a likely pathogenic variant in the MT-ND1 gene m.3761C>A was found in our patient which causes mitochondrial complex I deficiency. This diagnosis explains her symptoms and possibly the premature deaths of her female family members. Case 2. A 19-month-old boy was first admitted to the hospital due to status epilepticus. His condition worsened over time as he developed encephalopathy, tetraparesis, polyneuropathy, and epilepsia partialis continua. From the onset of the disease, he had mildly elevated transaminases, which later progressed to liver failure. WES confirmed compound heterozygous pathogenic in POLG gene: heterozygous pathogenic NM_002693.3(POLG):c.2243G>C (p.Trp748Ser) variant and heterozygous likely pathogenic variant NM_002693.3(POLG):c.2666C>T (p.Ala889Val). The Alpers-Huttenlocher syndrome diagnosis was confirmed. Case 3. A 13-year-old boy presents with progressive tetraparesis, cognitive decline, and seizures every few years. Brain MRI findings at 9 years old indicate non-specific changes suggestive of mitochondrial leukoencephalopathies and bilateral optic nerve atrophy. Holter monitoring revealed supraventricular extrasystoles, and he developed hypothyrosis. Genetic testing revealed MT-ND5 gene heteroplasmic pathogenic variant NC_012920.1:m.8344A>G. Conclusions Mitochondrial diseases can manifest in a variety of ways, making early diagnosis challenging. Nevertheless, the common thread among these disorders is the impairment of organs sensitive to energy requirements. A holistic approach to patient care and interdisciplinary collaboration is essential to facilitate accurate diagnosis. With the advancement of genetic testing capabilities, it is now possible to diagnose mitochondrial diseases more accurately and provide timely and high-quality patient care.

Objectives We present a case of a 6-year-old patient with febrile infection-related epilepsy syndrome (FIRES) treated with various antiseizure medications, including cannabidiol (CBD), as well as a ketogenic diet (KD) and immunotherapy. Materials and Methods A case study was conducted by summarizing the data of the patient based on medical records from the Hospital of Lithuanian University of Health Sciences Kauno klinikos database. Results A 6-year-old patient was admitted to the pediatric intensive care unit (PICU) due to intractable focal and generalized tonic-clonic seizures. Autoimmune, metabolic, genetic, infectious, structural, and other etiologies were unremarkable and remain to be determined. Immunotherapy, including intravenous steroids and immunoglobulin, tocilizumab, and anakinra, were ineffective. Various antiseizure medications were trialed; however, the introduction of CBD and reaching its dose of 15 mg/kg/day at day 72 of the disease reduced seizures significantly; therefore, no further treatment in the PICU was required. The ketogenic diet was introduced within two weeks; however, it had to be discontinued due to hypertriglyceridemia as a side effect of coadministration of propofol or tocilizumab. It was reintroduced after 4 months of treatment and is successfully continued in conjunction with antiseizure medication and remains effective. The patient currently has up to 6 tonic seizures per day, severe encephalopathy, and brain atrophy evident in MRI scans. Conclusions Current evidence does not support the early introduction of CBD in cases of FIRES, although it might be useful in conjunction with other antiseizure medications in the acute or chronic phases of FIRES. It is vital to anticipate the side effects of different therapies in order not to deviate from currently proposed treatment strategies.

Objective: Medicines are the leading cause of poisoning in children. Fentanyl is a synthetic opioid with a strong analgesic effect and has dangerous adverse effects: respiratory depression, hypotension, and somnolence. Accidental exposure to fentanyl patches in children has a case-fatality rate of 48% [1]. We present a case of accidental child exposure to a fentanyl patch. Case report: A 9-year-old male presented to the emergency department (ED) unconscious and with respiratory insufficiency. His parents reported that the day before he had fallen and abraded his left knee, and his mother has placed a skin plaster on his knee. After placement of the plaster, the boy started to feel nauseous and vomited several times. Later, he fell asleep and was found unresponsive in the morning. Upon admission to ED the Glasgow Coma Score was 7–8, he had pinpoint pupils and shallow breathing, oxygen saturation was 95% (on 6 L/min of oxygen by nasal canulae), and arterial blood pressure was 93/ 60 mmHg with tachycardia 120/min. The patient’s knee was covered by a 100 mg/h fentanyl patch which was removed immediately. Biochemistry results showed amylase 2121 U/L, alkaline phosphatase (ALP) 262 U/L, alanine aminotransferase (ALT) 32.6 u/ L, and aspartate aminotransferase (AST) 166.6 U/L. A brain computerised tomography (CT) scan showed no specific pathological findings. An magnetic resonance imaging (MRI) scan revealed bilateral, symmetric lesions consistent with hypoxic and toxic encephalopathy. Patient treatment included intravenous naloxone 0.1 mg, mechanical ventilation, and continuous infusion of dopamine 10 mcg/kg/min. The patient was discharged from the Children’s Intensive Care unit 4 days after admission in a hemodynamically stable condition. The boy was fully conscious but had profound anxiety. The patient became blind and had tetraparesis with only minimal movements of proximal limbs. At the time of writing this case report, he is continuing his treatment in a rehabilitation center. Conclusion: in this case, accidental intoxication happened to a child because his mother mistook the fentanyl patch for a sticker plaster, which she had kept after the death of her relative who had been using the patches. Even though in Lithuania there are laws regulating the utilization of drugs, this case proves that regulation is not effective and information for patients is scarce.