GNB1 Encephalopathy: Clinical Case Report and Literature Review.

GNB1 encephalopathy is a rare genetic disease caused by pathogenic variants in the G Protein Subunit Beta 1 (GNB1) gene, with only around 68 cases documented worldwide. Although most cases had been caused by de novo germline mutations, in this case, the pathogenic variant was inherited from patient's mother, indicating an autosomal dominant inheritance pattern. The patient presented at 25 years of age with mild developmental delay and cognitive impairment, prominent generalized dystonia, and horizontal nystagmus which are all characterizing symptoms of GNB1 encephalopathy. Electroencephalography (EEG) showed no epileptiform patterns, and magnetic resonance imaging (MRI) revealed hypointensities in globus pallidus and dentate nucleus areas. The main theory for GNB1 encephalopathy pathogenesis is neuronal hyperexcitability caused by impaired ion channel regulation. Due to low specificity of symptoms, diagnosis relies on genetic testing. As there are no standardized GNB1 encephalopathy treatment guidelines, evaluation of different treatment options is based on anecdotal cases. Reviewing different treatment options, deep brain stimulation and intrathecal baclofen pump, as well as some other medications still in preclinical trials, seem to be the most promising.

Early Epileptic Seizures after Ischemic Stroke: Their Association with Stroke Risk Factors and Stroke Characteristics.

Background and Objectives: A growing number of stroke survivors face various stroke complications, including new-onset epileptic seizures (ESs). Post-stroke ESs are divided into early and late ESs based on the time of onset after stroke. Early ESs are associated with worse stroke outcomes, longer hospitalization and an increased risk of late ESs. A variety of risk factors for early ESs are being studied in order to prevent their occurrence. Therefore, we aim to determine the association of early ESs with ischemic stroke risk factors and characteristics. Materials and Methods: A total of 166 patients, treated for ischemic stroke in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics, were enrolled in a prospective cohort study. Initially, data about stroke risk factors, localization, severity and treatment were collected, followed by an observation period of 14 days for early ESs. Results: Early ESs occurred in 11 (6.6%) participants. The probability of early ESs after ischemic stroke among males and females (LogRank = 1.281; p > 0.05), younger (≤65 y) and older (>65 y) participants (LogRank = 0.129; p > 0.05) was the same. The presence of ischemic stroke risk factors, such as atrial fibrillation (LogRank = 0.004; p > 0.05), diabetes mellitus (LogRank = 1.168; p > 0.05) and dyslipidemia (LogRank = 0.092; p > 0.05), did not increase the probability of early ESs. However, participants without a prior history of arterial hypertension (LogRank = 4.453; p < 0.05) were more likely to develop early ESs. Stroke localization (anterior versus posterior) (LogRank = 0.011; p > 0.05), stroke severity (LogRank = 0.395; p > 0.05) and type of treatment (specific versus non-specific) (LogRank = 1.783; p > 0.05) did not affect the probability of early ESs.

GAD65 Antibody-Associated Epilepsy.

Autoimmune processes are an increasingly recognized cause of seizures. Antibodies against neuronal surface antigens are implicated in the development of acute symptomatic seizures secondary to autoimmune encephalitis, whereas antibodies against intracellular antigens (anti-glutamic acid decarboxylase (GAD) and onconeural antibodies) are found in cases of autoimmune-associated epilepsy (AAE). AAE is described as isolated drug-resistant epilepsy without any specific magnetic resonance imaging (MRI) or cerebrospinal fluid changes and with a very limited response to immunotherapy. We present a clinical case and a literature review on autoimmune-associated epilepsy to increase awareness of this disease and illustrate its complexity. This is a clinical case of a female with a history of refractory focal epilepsy. The patient had been given several trials of multiple antiepileptic drugs and their combinations without any clear effect. Multiple evaluations including brain MRI, PET, and interictal and ictal electroencephalograms were performed. An APE2 score was calculated with a result of 4 and, in the presence of anti-GAD65 antibodies in the serum, the diagnosis of AAE was confirmed. There was no effect after five sessions of plasma exchange; however, after a course of intravenous immunoglobulin, a positive but temporary clinical effect was noticed: anti-GAD65 levels initially decreased but rebounded to previous levels 6 months later.

Oxcarbazepine and Hyponatremia.

Background and Objectives: Hyponatremia is one of the most common adverse effects in patients treated with oxcarbazepine (OXC). Different risk factors for OXC-induced hyponatremia have been described as age, female gender, dosage, and combination with other drugs During our clinical practice, we noticed that a longer duration of treatment with OXC could be associated with a higher risk of hyponatremia, therefore, in this study, we aimed to evaluate factors that may increase the risk of OXC-induced hyponatremia. Materials and Methods: Data were retrospectively collected from our clinical database at the Department of Neurology of the Hospital of Lithuanian University of Health Sciences Kaunas Clinics. The sample was divided into three groups: OXC consumers (n = 31), other anti-seizure medications (ASMs) consumers (n = 43), and controls absent ASMs (n = 31). All groups were matched by age and gender. Hyponatremia was defined as <136 mmol/L. Results: The frequency of hyponatremia was significantly higher among OXC patients (61.3%) compared to other ASM patients (5.4%) and controls (3.2%). The mean serum sodium concentration in the OXC group was 133.1 ± 5.1 mmol/L. The frequency of severe hyponatremia among OXC-treated patients was 19.4%; this subgroup was older than patients with moderate hyponatremia and normonatremia and had a longer OXC treatment duration compared to a subgroup of normonatremia. The average duration of OXC therapy was 8.7 ± 5.5 years with a range from 1 to 21 years. Serum sodium concentration and duration of treatment with OXC demonstrated a significant negative correlation (r = −0,427, p = 0.017). Each year of therapy with OXC increased the risk of hyponatremia 1.3 times (OR = 1.326, 95% Cl 1.027−1.712, p = 0.031). Other factors (gender, age, polypharmacy, OXC dosage, and serum concentration) did not show a significant association with the development of hyponatremia. Conclusions: Longer duration of treatment with OXC is an important factor in the development and severity of hyponatremia.

Creutzfeldt-Jakob disease with neuroleptic malignant syndrome.

Creutzfeldt­Jakob disease (CJD) is a rare rapidly progressive fatal neurodegenerative disease. Neuroleptic malignant syndrome (NMS) is a complication of antipsychotic medications which may be used to treat neuropsychiatric symptoms of CJD. We present a case of a 51­year­ old woman with CJD who developed NMS after being prescribed quetiapine.

Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important.

BACKGROUND: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. OBJECTIVE: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. METHODS: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or >10. RESULTS: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. CONCLUSIONS: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.

Factors associated with adherence to disease modifying therapy in multiple sclerosis: An observational survey from a referral center in Lithuania.

AIM OF THE STUDY: To investigate adherence to disease modifying therapy (DMT) in Lithuanian population of multiple sclerosis patients and factors associated to it. METHODS: Patients receiving one of the following DMT's: Interferon ß 1a (Rebif) 44 micrograms three times a week subdermally (s/c) or Interferon ß 1a (Avonex) 30 micrograms weekly intramuscularly (i/m), or Interferon ß 1b (Betaferon, Extavia) 250 micrograms once in two days s/c, or Glatiramer acetate (Copaxone) 20mg daily s/c, were presented with a questionnaire inquiring their demographic and clinical characteristics and adherence to treatment profile, as well as HAD scale and SF-36 questionnaire. Those who missed at least one dose of DMT during last three months were considered non-adherent. RESULTS: In total, 207 patients were enrolled, 73 (35.3%) of them were non adherent during last three months. More patients with university education (p=0.004, χ2 =8.466 high school/vocational vs. university) as well as consuming >4 units/year of alcohol were non-adherent during last three months (p=0.005). Average score for anxiety (6.69±4.03 vs. 6.92±4.24) and depression (4.74±3.9 vs. 4.7±3.83) in HAD scale did not differ significantly between adherent and non-adherent groups. We did not find any significant difference in quality of life scores (SF-36 v.2) between the groups. No significant difference of adherence was found then comparing patients often suffering from drug side effects with those who experience rare or no side effects. In logistic regression model, patients consuming more than 4 alcohol units per year and patients with university education were more likely to miss at least one dose during last three months: 2.121 (95% CI: 1.143-3.937, p=0.017) and 2.409 (95% CI: 1.260-4.642, p=0.008) times accordingly. Patients with better quality of life scores were slightly less likely to be non adherent (OR 0.997 (95% CI: 0.994-0.999), p=0.0017). CONCLUSIONS: One third of patients were non-adherent during last three months. Worse adherence rates were associated with higher education and higher alcohol consumption. Education, alcohol consumption and quality of life scores were found to be significant factors for predicting non-adherence. We found no associations between adherence and anxiety, depression, or drugs side effects.

Crucial role of carotid ultrasound for the rapid diagnosis of hyperacute aortic dissection complicated by cerebral infarction: A case report and literature review.

Aortic dissection is a life-threatening rare condition that may virtually present by any organ system dysfunction, the nervous system included. Acute cerebral infarction among multiple other neurological and non-neurological presentations is part of this acute aortic syndrome. Rapid and correct diagnosis is of extreme importance keeping in mind the possibility of thrombolytic treatment if a patient with a suspected ischemic stroke arrives to the Emergency Department within a 4.5-h window after symptom onset. Systemic intravenous thrombolysis in the case of an acute brain infarction due to aortic dissection may lead to fatal outcomes. In this neurological emergency it is important to rule out underlying aortic dissection by choosing appropriately quick and accurate diagnostic tool. We aimed to present a prospective follow-up case, where carotid ultrasound examination was the primary key method that led to a correct diagnosis in hyperacute (<24h) Stanford type A aortic dissection presenting as an acute ischemic stroke, and thereafter with a repeated contrast-enhanced computed tomography and transthoracic echocardiography, helped to monitor topography of intravascular processes and hemodynamic properties during the clinical course of a disease, which influenced treatment decisions. Thus, we reviewed the literature mainly focusing on the various neurological aspects associated with aortic dissection.

EEG activation by neuropsychological tasks in idiopathic generalized epilepsy of adolescence.

THE AIM OF THE STUDY: To evaluate the effects of neuropsychological activation (NPA) tasks on epileptiform discharges in adolescents with idiopathic generalized epilepsy (IGE) and their possible relationship to clinical epilepsy-related factors, also to compare the effects of the NPA to the habitual methods of electroencephalographic (EEG) activation. METHODS/SUBJECTS: Fifty-nine patients with IGE aged 14-17 years underwent baseline video-EEG recording with habitual activation procedures followed by NPA tasks, and sleep EEG after sleep deprivation on the next day. RESULTS: At least one task of NPA showed provocative effect in 18.6% of cases. There was no difference between the provocative effects of action-programming and thinking NPA task groups as well as among individual NPA tasks. The provocative effects of NPA tasks were more prevalent in photosensitive cases, especially the tasks of action-programming type (p=0.04). The provocative NPA effects showed no relationship to gender, age, age at seizure onset, duration of epilepsy, treatment status, presence of myoclonias, recent generalized tonic-clonic seizures, family history of epilepsy. The provocative effects of NPA were comparable to those of hyperventilation (23.7%) and intermittent light stimulation (30.5%) (p>0.05). CONCLUSIONS: Although the provocative effects NPA tasks on epileptiform discharges on EEG did not outweigh the effects of the habitual activation procedures, NPA activation might be helpful as an additional diagnostic tool in adolescents with IGE in selected cases when routine EEG is not informative enough or when sleep EEG is readily unavailable, also in photosensitive cases. It may also help in providing advice for patients on safety issues.

Behavioral problems in children with benign childhood epilepsy with centrotemporal spikes treated and untreated with antiepileptic drugs.

The aim of this study was to investigate behavioral problems in two groups of children with benign childhood epilepsy with centrotemporal spikes (BECTS), i.e., those treated with antiepileptic drugs and those not treated in order to identify the factors associated with behavioral problems. MATERIAL AND METHODS. In total, 20 newly diagnosed untreated, 23 treated patients with BECTS, and 20 patients with acute/subacute peripheral nervous system disorders as a comparison group (aged 6-11 years) were examined. The evaluation was performed using the Lithuanian version of the Child Behavior Checklist (CBCL). Schooling parameters, clinical parameters, EEG parameters, and their relation to the results of the CBCL were also investigated. RESULTS. The treated patients with BECTS had significantly higher scores in the subscales of Social Problems, Anxious/Depressed, Aggressive Behavior, and Attention Problems compared with the scores of the patients with peripheral nervous system disorders. A significant relationship was established between the scores of native language grades and Attention Problems; grades in mathematics and treatment duration; and age when the first seizure occurred and Delinquent Behavior in the group of treated patients. The duration of epilepsy was positively correlated with the scores in the subscales of Withdrawn and Delinquent Behavior. The presence of additional extrarolandic focus and spread of focal specific discharges to the centrofrontotemporal and centroparietotemporal areas were related to higher scores in Social Problems, Attention Problems, and Delinquent Behavior in the group of the treated patients with BECTS. CONCLUSIONS. Children with BECTS, especially those treated and with a longer epilepsy course, were found to be at risk of behavioral problems. Lower grades were associated with a longer disease course and medications. The presence of extrarolandic discharges was related to higher CBCL scores in the group of the treated patients with BECTS.

Association of language dysfunction and age of onset of benign epilepsy with centrotemporal spikes in children.

BACKGROUND: Language dysfunction in children with benign epilepsy with centrotemporal spikes (BECTS) has been well recognized but data regarding its risk factors are heterogenous. AIMS: To assess language function in children with BECTS and its association with the age of epilepsy onset. METHODS: We assessed language function in 61 children with BECTS and 35 age and sex-matched controls. Children with BECTS performed significantly worse on all language tasks as compared to controls and overall better language function was positively correlated with older age of the child. Early age at seizure onset demonstrated significant negative correlation with language dysfunction, age below 6 years being related to the lowest performance scores. There was no relationship between the language function and the laterality of epileptic focus, seizure treatment status, or the duration of epilepsy. CONCLUSION: Children with BECTS have language difficulties that are more pronounced in younger age group. Despite better language functioning in older children with BECTS, their verbal abilities remain inferior to those of children without epilepsy. Early age at seizure onset is a significant factor predicting worse language functioning in children with BECTS.

Executive functions in adolescents with idiopathic generalized epilepsy.

UNLABELLED: Disorders of executive functioning have recently been reported in patients with juvenile myoclonic epilepsy (JME); however, data on other syndromes of generalized idiopathic epilepsy (IGE) other than JME, especially in adolescence, are scarce. The aim of this study was to explore specific executive functions in a group of adolescents with IGE of short duration and to evaluate the possible factors that might influence these functions. MATERIAL AND METHODS: Neuropsychological investigation of executive functions (the Verbal Fluency Test, the Five-Point Test, the Trail-Making Test, and the Stroop test) was performed in 59 patients aged 14-17 years and meeting the diagnostic criteria for IGE, and in the group of 59 age-matched controls without any history of epilepsy. RESULTS: The IGE group subjects scored worse than the controls in most of the executive function tests: phonemic (P=0.008) and semantic (P=0.001) word fluency, figural fluency (P=0.008), visual search and sequencing of numbers (P=0.001), and alternate number-letter sequencing (P=0.018). None of the test scores differed between the new-onset and the established IGE groups, or between the groups of cases with and without myoclonias. No relationship between executive functioning and gender, age, duration or activity of epilepsy, chronic use of treatment, or epileptiform discharges on electroencephalography was found. CONCLUSIONS: Executive dysfunction was present in adolescents with JME and other syndromes of IGE, manifesting with generalized tonic-clonic seizures without myoclonias, despite short duration and benign course of epilepsy.