The perceived health of children with epilepsy, sense of control, and support for their families.

AIM: The aim of this study was to evaluate the perceived health of children with epilepsy as experienced by the respondents to a questionnaire, to assess the sense of control over their child's epilepsy, and how much support they feel they received in various environments. METHODS: In this observational study, the data were collected using a questionnaire that was sent to families of children with epilepsy, who were treated at University Children's Hospital in Ljubljana, Slovenia from January to September 2016. The questionnaire consisted of 29 questions related to their epilepsy. RESULTS: There were 1198 patients who met the entry criteria for the study and were sent the questionnaire, of which 181 (15.1%) responded. The diagnosis of epilepsy was established in 91.2% of patients (8.8% were patients after a first unprovoked seizure), of which drug-resistant epilepsy was reported in 33.3%. Patients had epilepsy diagnosed for a mean of 4.9 ±â€¯4.4 years. Of all patients, 82.4% of patients were taking antiepileptic drugs (AEDs) at the time of inquiry. The longer the patient had epilepsy diagnosed, the lower was the perceived health (p = 0.004). Patients with pharmacoresistant epilepsy, those who had seizures, and those who were receiving AEDs had significantly lower scores of perceived health compared with those who did not (p < 0.001; p < 0.001; and p = 0.016, respectively). Of all responders, 79.8% responded that they feel that they have their child's condition under control. The child's condition was considered under control more often if the child had no reported seizures (p < 0.001) and if the family had enough support in the health system (p = 0.002) or psychological support (p = 0.005). Patients with pharmacoresistant epilepsy more often replied that they do not have enough support in the health system (p = 0.006). CONCLUSIONS: Our study suggests that the presence of seizures, pharmacoresistant epilepsy, years of epilepsy diagnosis, and prescription of AEDs have a significant negative effect on the perceived health of children with epilepsy. Enhancement of the support families received in different environments can offer an opportunity to improve the sense of caregivers' control over child's epilepsy.

The use of quetiapine in treatment of acute psychotic symptoms in an adolescent patient with primary brain calcification: a case report.

BACKGROUND: Primary brain calcification (PBC), a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas, typically presents with various neurological and psychiatric symptoms in the fourth or fifth decade of life or later. We present the case of a patient with psychiatric manifestations much earlier than usual, in the second decade of life. CASE PRESENTATION: The case of an adolescent female with acute psychotic symptoms, emotional instability, disorganized and suicidal behavior, stereotypical movements, below average intelligence and a three-year history of headaches is reported. Among others, the presentation included tactile hallucinations with secondary hypochondriacal delusions, which are rarely described in this diagnosis. Massive calcinations in the area of the basal ganglia and thalamus were determined by computerized tomography. Other causes of brain calcification were excluded. No causative mutations were found in selected genes. All the symptoms apart from lower intellectual abilities improved with quetiapine and sertraline. The patient showed no side effects. CONCLUSIONS: This case report highlights the successful use of quetiapine for symptomatic treatment of acute psychosis due to PBC in an adolescent without exacerbating extrapyramidal symptoms.

Cannabidiol for treatment of refractory childhood epilepsies: Experience from a single tertiary epilepsy center in Slovenia.

PURPOSE: Refractory epilepsies in children present a major burden for patients and their families. Cannabidiol (CBD) has been suggested as a potential treatment for refractory epilepsies. The aim of this study was to evaluate the effectiveness of add-on therapy with CBD for the treatment of refractory childhood epilepsies. METHOD: Patients with childhood-onset refractory epilepsy, treated at the tertiary epilepsy center of the University Children's Hospital Ljubljana, Slovenia, were included in the study. Add-on therapy with CBD was initiated once the child's epilepsy was categorized as pharmacoresistant to other antiepileptic drugs/therapies. The dosage of CBD was gradually increased to at least 8mg/kg/day. The effect of CBD treatment was evaluated by the reduction in seizure burden and presence of side effects (positive and negative). Serial electroencephalography was performed in some children. RESULTS: Sixty-six patients were included in the analysis. Thirty-two (48.5%) patients had a more than 50% improvement regarding seizure burden, 14 of whom (21.2%) became seizure-free. None of the patients reported worsening of seizure frequency, but CBD had no effect in 15 (22.7%) patients. Some patients reported less vigorous seizures, shorter duration of seizures, shorter time to recovery, and other positive side effects of CBD treatment. Adverse effects were reported in 5/66 children. CONCLUSIONS: In our cohort of patients, CBD was found to have potential benefits as add-on therapy for refractory childhood epilepsies, mainly by reducing seizure burden.

Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder.

BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is a rare autosomal dominant pain disorder linked to a mutation in the SCN9A gene, which encodes voltage-gated sodium channel Nav1.7. Abnormal pain sensitivity occurs because of changes in the properties of voltage-gated sodium channels. Different mutations in SCN9A and a spectrum of clinical expressions have been described. CASE-DIAGNOSIS/TREATMENT: Here we describe a 3-year-old child with a rare clinical picture of PEPD. Extremely painful voiding had been present since the child's birth. The diagnosis was confirmed by the detection of a heterozygous pathogenic mutation in the SCN9A gene, c.554G>A (p.Arg185His) inherited paternally. The same mutation was also found in the girl's father, who has occasionally had some pain in his jaw while yawning since childhood. Significant reduction of the pain was achieved with carbamazepine. CONCLUSIONS: The case is interesting because the same mutation as that found in the girl and her father has been found in patients with small fiber sensory neuropathy. These data do not correlate with the clinical picture of our case and her father, but intra- and interfamily phenotypic diversity in symptoms associated with a gain-of-function variant of Na(V)1.7 are also described and may explain our case.

Multiple sclerosis in a 4-year-old boy: a case report and literature review.

Pediatric onset multiple sclerosis (POMS) in the very young is a very rare entity and presents a difficult diagnostic challenge due to overlapping signs and symptoms with other diseases. We present a 4-year-old boy who initially presented with right-sided hemiparesis and demyelinating lesions on MRI. Follow-up MRI examinations 3 and 6 months later revealed new demyelinating lesions. Ten months after initial presentation, he presented with right-sided hemiparesis, central facial nerve palsy on the right side and new demyelinating lesions on MRI. Two clinical events and new MRI lesions on follow-up MRIs confirmed the diagnosis of POMS. He was treated with rituximab and experienced no further relapses or radiological progression during the follow-up period.

Melatonin vs. dexmedetomidine for sleep induction in children before electroencephalography.

Background and objectives: In children requiring electroencephalography (EEG), sleep recording can provide crucial information. As EEG recordings during spontaneous sleep are not always possible, pharmacological sleep-inducing agents are sometimes required. The aim of the study was to evaluate safety and efficacy of melatonin (Mel) and dexmedetomidine (Dex; intranasal and sublingual application) for sleep induction prior to EEG. Methods: In this prospective randomized study, 156 consecutive patients aged 1-19 years were enrolled and randomized by draw into melatonin group (Mel; n = 54; dose: 0.1 mg/kg), dexmedetomidine (Dex) sublingual group (DexL; n = 51; dose: 3 mcg/kg) or dexmedetomidine intranasal group (DexN; n = 51; dose: 3 mcg/kg). We compared the groups in several parameters regarding efficacy and safety and also carried out a separate analysis for a subgroup of patients with complex behavioral problems. Results: Sleep was achieved in 93.6% of participants after the first application of the drug and in 99.4% after the application of another if needed. Mel was effective as the first drug in 83.3% and Dex in 99.0% (p < 0.001); in the subgroup of patients with complex developmental problems Mel was effective in 73.4% and Dex in 100% (p < 0.001). The patients fell asleep faster after intranasal application of Dex than after sublingual application (p = 0.006). None of the patients had respiratory depression, bradycardia, desaturation, or hypotension. Conclusions: Mel and Dex are both safe for sleep induction prior to EEG recording in children. Dex is more effective compared to Mel in inducing sleep, also in the subgroup of children with complex behavioral problems. Clinical Trial Registration: Dexmedetomidine and Melatonin for Sleep Induction for EEG in Children, NCT04665453.

A right-to-left shunt and prothrombotic disorders in pediatric patients presenting with transient ischemic attack.

Arterial ischemic stroke is an important cause of morbidity and mortality in pediatric population. A right-to-left shunt (RLS) across the patent foramen ovale was recently demonstrated as a possible risk factor for pediatric stroke. Prothrombotic disorders are frequently identified in pediatric patients with stroke. Data regarding RLS and prothrombotic disorders in pediatric patients presenting with transient ischemic attack (TIA) are lacking. The aims of the present study were (1) to compare the prevalence and grade of RLS in pediatric patients presenting with TIA vs. controls using contrast transcranial Doppler with Valsalva maneuver and (2) to identify prothrombotic disorders in pediatric patients presenting with TIA. Twenty-three consecutive pediatric patients presenting with TIA were included in the study. Logistic regression analysis showed that RLS was significantly associated with TIA (OR 4.75, 95 % CI 1.39-16.2, p = 0.013). The prevalence of RLS was significantly higher in patients in comparison to controls (p = 0.019). Significantly more microembolic signals (MES) were detected in patients than in controls (p = 0.003). Prothrombotic disorders were identified in 14 of the 23 patients. Both the prevalence of RLS and number of detected MES were significantly higher in pediatric patients presenting with TIA in comparison to controls. Prothrombotic disorders were identified in a high proportion of patients. These findings suggest that paradoxical embolism may be important in pediatric patients presenting with TIA.

Difficult to treat absence seizures in children: A single-center retrospective study.

Objectives: The aim of this study was to analyse the characteristics of typical absence seizures (AS), myoclonic AS and AS with eyelid myoclonia in children and to find associations between these characteristics and difficult to treat absence seizures (DTAS). Methods: This was a single-center retrospective study. Electronic health records of pediatric patients with a clinical diagnosis of AS treated at a single tertiary epilepsy center between January 2013 and June 2020 were reviewed. Clinical characteristics, seizure information, ASM, and therapeutic response of patients were recorded. All patients were followed up for at least 1 year. DTAS were defined as failure to achieve remission after treatment with at least 2 anti-seizure medications (ASM), regardless of whether remission was achieved eventually in the study period. Results: Data from 131 patients were available for analysis. Remission was achieved after the first ASM treatment in 81 (61.8%) patients, and eventually in 120 (91.6%) during the study period. Epilepsy was classified as DTAS in 18 (13.7%) patients. AS were more often difficult to treat in patients with myoclonic AS and AS with eyelid myoclonia (40.0%), compared with patients with typical AS (11.4%; p = 0.012, 95% CI 1.480-25.732). A positive family history of epilepsy (p = 0.046; 95% CI 1.021-8.572), a higher seizure frequency (p = 0.023, 95% CI 1.009-1.126) prior to ASM treatment, and longer time between seizure onset and treatment onset (p = 0.026; 95% CI 1.006-1.099) were also associated with DTAS. Significance: Our study suggests that several clinical characteristics of AS are associated with DTAS. One of these was the time between onset of AS and initiation of ASM treatment, which can be shortened with better care, suggesting that early diagnosis and treatment may improve prognosis in pediatric patients with AS. These findings remain to be confirmed in larger prospective studies.

Children with cavernous malformations of the central nervous system.

BACKGROUND: Cavernous malformations (CM) of the central nervous system (CNS) are a rare pathology in the pediatric population that may present with an acute onset of severe neurological symptoms. OBJECTIVE: The aim of our study was to evaluate the clinical presentation, family history, genetic background, radiological features, treatment and outcome of children with CM. METHODS: This observational cohort study included all children with CM of the CNS diagnosed in the period 2000-2020 at University Children's Hospital in Ljubljana, Slovenia. Whole exome sequencing was utilized. RESULTS: We identified a cohort of 20 children with CM (mean age 9.3 years, range: 10 days-18.4 years). In our cohort, 16 patients were symptomatic and 4 were asymptomatic; 7 patients had a solitary lesion, and 13 had multiple lesions. Children with multiple lesions become symptomatic at an earlier age compared with children with solitary lesions. We identified five families with familiar cavernous malformation (FCM) syndrome affecting two or more generations; FCM represented 65% of all pediatric cases identified in our study. We confirmed a mutation in FCM associated genes in all but one patient with multiple lesions, with the KRIT1 mutation being the most common. CONCLUSION: Multiple CM lesions and symptomatic brainstem lesions are associated with worse neurological deficits in pediatric patients. Not all cases of multiple lesions can be linked to mutations in KRIT1, CCM2, or PDCD10, which may indicate that there are other as yet unidentified genes associated with FCM.

Clinical and Radiological Characteristics of Non-Benign Pineal Cyst Lesions in Children.

Background: With the increasing availability and advances in brain imaging, pineal cyst lesions (PCL) are becoming a common finding in the pediatric population. In the absence of evidence-based guidelines, optimal diagnostic and therapeutic approaches have not been established, and there is a risk of under- or overtreatment of these patients. Objectives: The aim of our study was to evaluate the clinical presentation and radiological features of PCL in a cohort of pediatric patients and to identify clinical parameters more commonly associated with neoplasms in the pineal region. In addition, the prevalence of PCL in the pediatric population of Slovenia was estimated. Methods: In this observational, cohort study, children treated at University Children's Hospital, Ljubljana, Slovenia in the period 1997-2016 were included if PCL was found on brain imaging. We analyzed indications for referral to a neurologist, clinical signs and symptoms, radiological features, treatment and outcome. Results: The cohort consisted of 143 children with PCL. Pineocytoma was suspected in 31 children (21.7%). Six children underwent surgery - pineocytoma was confirmed in two cases and germinoma in one (2/3 of these children had signs of increased intracranial pressure (ICP), while PCL was benign in the remaining 4 cases. Only 2 PCL enlarged during the study period, both <2mm, none of these children developed neoplasm. Two children had PCL >20mm in diameter; both showed signs of increased ICP, one patient was found to have a germinoma of the pineal region, while the other had no neoplasm. Conclusions: Most PCL do not change their features during radiological follow-up and even atypical PCL are very rarely associated with a malignant neoplasm of the pineal region. A PCL larger than 20 mm and signs of increased ICP were identified as potential markers for selecting patients at risk.

Epidemiological and clinical characteristics of multiple sclerosis in paediatric population in Slovenia: A descriptive nation-wide study.

BACKGROUND: Although multiple sclerosis usually affects young adults, paediatric-onset multiple sclerosis (pMS) is increasingly recognized in the past ten years. The aim of the present study was to evaluate the incidence of pMS in Slovenia and to characterize the clinical, laboratory and neuroradiological characteristics of pMS at the disease onset. METHODS: We performed a national retrospective descriptive study including all patients diagnosed with pMS between January 1992 and June 2017. We reviewed data of all patients younger than 18 years at the first demyelinating event. RESULTS: The estimated incidence of pMS was 0.66/100,000 children per year. We included 61 patients (77% were female) with a median age at diagnosis of 16.3 years. In 4 patients, onset of pMS was before the age of 12 years old (childhood-onset pMS). Relapsing-remitting multiple sclerosis was most prevalent, with only 2 patients presenting a primary progressive pMS. Polysymptomatic pMS was found at onset in 59% of patients and monosymptomatic in 41%. In the cerebrospinal fluid study, 88% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (100% of patients). CONCLUSION: The clinical pattern of pMS in our cohort of patients was characterized by polysymptomatic presentation and predominantly sensory symptoms at onset, developing a relapsing-remitting pMS pattern. It is important to gather more information about the incidence of pMS and its initial presentation and clinical course to improve early recognition and appropriate initiation of immunomodulatory treatment.