Deep brain stimulation of anterior nucleus and centromedian nucleus of thalamus in treatment for drug-resistant epilepsy.

INTRODUCTION: Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for resective surgery. For these patients, deep brain stimulation (DBS) may constitute the last resort in the treatment of DRE. STATE OF THE ART: We undertook a systematic review of the current literature on DBS efficacy and the safety of two thalamic nuclei-anterior nucleus of the thalamus (ANT) and the centromedian nucleus of the thalamus in the management of patients with DRE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL) was conducted. CLINICAL IMPLICATIONS: We found 30 articles related to ANT DBS and 13 articles related to CMN DBS which were further analysed. Based on the clinical research articles, we found a mean seizure frequency reduction for both thalamic nuclei. For ANT DBS, the mean seizure frequency reduction ranged from 48% to 75%, and for CMN DBS from 46.7% to 91%. The responder rate (defined as at least 50% reduction in seizure frequency) was reported to be 53.2-75% for patients after ANT DBS and 50-90% for patients after CMN DBS. FUTURE DIRECTIONS: ANT and CMN DBS appear to be safe and efficacious treatments, particularly in patients with refractory partial seizures and primary generalised seizures. ANT DBS reduces most effectively seizures originating in the temporal and frontal lobes. CMN DBS reduces mostly primary generalised tonic-clonic and atypical absences and atonic seizures. Seizures related to Lennox-Gastaut syndrome respond very favourably to CMN DBS.

Deep brain stimulation of the subiculum in the treatment for refractory temporal lobe epilepsy due to unilateral mesial temporal lobe sclerosis.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. The main pathological changes primarily involve hippocampal sclerosis (HS). Early resective surgery of the sclerotic hippocampus is typically associated with favorable clinical outcomes. However, not all patients are suitable candidates for resective surgery of mesial temporal lobe structures. Therefore, alternative treatment modalities should be considered. We present the case of a 50-year-old right-handed woman with left HS who underwent unilateral subiculum stimulation for drug-resistant epilepsy (DRE). Since the age of 10, the patient had been experiencing focal to bilateral tonic-clonic seizures (FBTCS). Despite multiple antiseizure medications, she experienced 12 to 17 FBTCS per month in the last two years. Due to concerns about potential memory decline and personal preferences, she refused resective surgery. As an alternative, the patient underwent left unilateral subiculum stimulation. The stimulation resulted in a nearly 67 % reduction in seizure frequency at the last follow-up (20 months after surgery). This case highlights that drug-resistant epilepsy may be effectively treated with subicular stimulation in patients with HS.

Multifocal drug-resistant epilepsy in a patient with a newly discovered mutation in tuberous sclerosis complex 1 gene treated by deep brain stimulation in the anterior thalamic nucleus.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the tumor suppressor genes TSC1 or TSC2. TSC is characterized by the formation of multiple tumors in various organs. The most common neurological manifestation of the disorder is epilepsy present in 79-90% of cases. At least one-third of TSC patients develop drug-resistant epilepsy (DRE) which remains a great challenge for clinicians. Neuromodulation is an option in cases of multifocal epilepsy, epilepsy originating in eloquent areas, or the inability to identify the ictal onset zone. Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) may be used in the treatment of multifocal DRE. Here, we present a case of a patient with multifocal DRE caused by TSC, who was treated with ANT-DBS. A follow-up period of eight months showed that the patient's multifocal DRE was successfully treated by ANT-DBS.

Deep brain stimulation in a patient with progressive myoclonic epilepsy and ataxia due to potassium channel mutation (MEAK). A case report and review of the literature.

Progressive myoclonic epilepsy (PME) is characterized by prominent myoclonus, generalized tonic-clonic seizures, and less often focal, tonic, or absence seizures. The KCNC1 mutation is responsible for specific clinical phenotype of PME which has been defined as myoclonic epilepsy and ataxia due to potassium channel mutation (MEAK). We present a case of a 44 years-old male patient with genetically proven MEAK who underwent subthalamic nucleus/substantia nigra (STN/SNr) deep brain stimulation (DBS) for his pharmacological-refractory myoclonus and drug-resistant epilepsy (DRE). Since the age of 4-5 years, the patient had been suffering from intention tremor, and later the myoclonic jerks, ataxia involving the upper limbs and walking difficulties worsened. The first bilateral tonic-clonic seizure (BTCS) occurred at the age of 22. The patient agreed to staged bilateral implantation of DBS electrodes placed in the STN/SNr region. The follow-up lasts more than 24 months. The myoclonic jerks assessed by Unified Myoclonus Rating Scale (UMRS) were reduced by nearly 70 % and BTCS was completely abolished. The patient's ataxia and dysarthria did not improve. Early diagnosis with genetic testing may significantly help in counseling patients with PME and enables to undertake the surgical approach targeting the STN/SNr.

Clinical efficacy and safety of anterior thalamic deep brain stimulation for intractable drug resistant epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) is a neuromodulation therapy for patients with refractory focal seizures evolving into bilateral tonic-clonic seizures when pharmacotherapy as well other neuromodulation techniques including vagus nerve stimulation or responsive neurostimulation have failed. OBJECTIVE: We performed a prospective single-center study investigating the clinical efficacy and exact ANT DBS lead location in patients with DRE. METHODS: The primary outcome measure was the proportion of patients with more than 50 % reduction in diary-recorded seizures when compared to three preoperative months (baseline seizure frequency). The close postoperative follow-up was performed every 3 months. The seizure frequency, stimulation settings and adverse events were closely monitored during follow-up visits. We also analyzed the seizure outcome with location of ANT DBS active contacts. RESULTS: Between May 2020 and October 2022, 10 adult patients with a mean age of 38.5 years (range, 30-48 years) underwent bilateral ANT DBS surgery (mean duration of DRE 28.6 years, range 16-41 years). The median seizure count in three months period preceding surgery (baseline seizure count) was 43.2 (range, 4-150). Nine patients achieved more than 50 % seizure reduction at the last follow-up (mean range 3-33 13.6 months, months). ANT DBS caused seizure reduction 3 months after procedure as well as at last follow-up by 60.4 % and 73.3 %, respectively. Due to relatively small number of studying individuals we cannot precisely locate the area within ANT associated with good clinical outcome. Patients with temporal lobe epilepsy had a remarkable reduction of seizure frequency. No patient suffered transient or permanent neurological deficits. CONCLUSIONS: Clinical efficacy of ANT DBS may support more widespread utilization of this neuromodulation technique especially for seizures originating from temporal lobes.

Attitudes towards the switching of anti-epileptic medications in pharmacies: the patients' perspective.

Purpose: A survey of epilepsy patients' experiences of and attitudes towards the pharmacy switching of anti-epileptic medications. Methods: A structured questionnaire was administered to a group of epilepsy patients treated at the Institute of Psychiatry and Neurology and the Medical University of Silesia, Poland. Two hundred and eleven patients (mean [± SD] age: 41.0 ± 15.6 years) were recruited; 60.6% were women. 68.2% had been treated for over 10 years. Results: Most individuals (63%) claimed that they had never bought a generic substitute medication. Among the patients who declared that a switch had been proposed to them at a pharmacy (~40%), only 68.7% received any explanation at all from a pharmacist. Some reported positive emotions mostly related to a lower price of the new drug but also to the explanations received. Most respondents who accepted the pharmacy switch (67.4%) did not notice any significant changes in the efficacy or tolerability of treatment, while the remaining subjects reported an increase in seizure frequency (23.2%) and deterioration in treatment tolerance (9%). Conclusions: Around 40% of Polish epilepsy patients have been confronted with a proposal to switch their anti-epileptic medications at a pharmacy. More of them report negative attitudes towards the pharmacist's proposal than do not. It is possible that one of the major reasons for this is the insufficient information provided by pharmacists. It remains to be established whether the reported decrease in seizure control could be accounted for by a low concentration of the anti-epileptic drug in the blood after the switch.

The impact of bipolar spectrum disorders on professional functioning: A systematic review.

Aims: The impact of bipolar spectrum (BS) disorders on professional functioning has not been systematically reviewed yet. Since even subsyndromal symptoms may disturb functioning, the determination of the prognostic value of the spectrum of bipolarity for employment seems extremely relevant. The aim of this study was to assess the impact of BS disorders on professional functioning. Materials and methods: A systematic review of the literature (namely, cohort and cross-sectional studies) investigating a link between BS disorders and employment was performed in accordance with PRISMA guidelines. BS was defined based on the concept of two-dimensional BS by Angst. Occupational outcomes and factors affecting employment were evaluated as well. Results: Seventy-four studies were included. All disorders comprising BS had a negative impact on occupational status, work performance, work costs, and salary, with the greatest unfavorable effect reported by bipolar disorder (BD), followed by borderline personality disorder (BPD), major depressive disorder (MDD), and dysthymia. Employment rates ranged from 40 to 75% (BD), 33 to 67% (BPD), 61 to 88% (MDD), and 86% (dysthymia). The factors affecting employment most included: cognitive impairments, number/severity of symptoms, namely, subsyndromal symptoms (mainly depressive), older age, education, and comorbidity (substance abuse, personality disorders, anxiety, depression, ADHD, PTSD). Conclusion: Bipolar spectrum symptoms exert a negative impact on professional functioning. Further evaluation of affecting factors is crucial for preventing occupational disability.

ECT in an Adolescent With Schizophrenia and Seizures: Case Report.

Electroconvulsive therapy (ECT) has been recognized as an effective treatment option in catatonia, and for prolonged or severe affective episodes and schizophrenia. Response rates vary from 40 to 80% in adolescents. The procedure is safe if the required precautions are undertaken. Nonetheless, ECT remains a serious clinical challenge in patients with comorbid seizures. We present a case study of a 17-year-old female student suffering from schizophrenia who was scheduled for ECT due to prior treatment inefficacy. Seizures had occurred a few days before the first ECT session. Nevertheless, the patient received the ECT course, combined with clozapine at 125 mg/day, after neurological diagnosis and treatment modification because the illness became life-threatening. The patient's clinical outcome was satisfactory without any seriously adverse events and further improvements were observed in the mental state following long-term psychosocial treatment at our inpatient unit. A few months later, epilepsy was however diagnosed with probably coexistence of partial seizures and seizure-like events without EEG correlate. Administering ECT in patients with seizure comorbidity was also investigated based on previous research. Data on this is, however, extremely scarce and to the best of our knowledge, the safety and efficacy of using ECT in adolescents with schizophrenia and seizures has yet not to any great extent been discussed in the literature.

Real-life anti-smoking practices among Polish neurologists.

Purpose: The aim of the present study was to assess attitudes of Polish neurologists towards cigarette smoking and their real-life anti-smoking practices. Methods: A study questionnaire was constructed, and distributed among Polish neurologists (n = 101; 73% females). More than two thirds (70%) of the study group worked in in-patient neurological wards with separate stroke units. Results: Seventy five percent of the study group documented the smoking status of their patients in medical files. Two thirds of the study group collected data on patient's cigarette smoking during each visit. Only 54% and 22% of study participants routinely assessed the severity of tobacco dependence and diagnosed tobacco dependence according to the ICD-10 criteria, respectively. Two thirds of physicians declared routinely using any anti-smoking intervention, but only 12% used the recommended 5'A (Ask, Advice, Assess, Assist, Arrange) model of behavioral intervention and only 11% introduced Evidence Based Medicine (EBM)-supported pharmacotherapy. The vast majority of study participants (80%) did not try to increase their professional skills in anti-smoking interventions. Conclusions: Real-life anti-smoking practices among Polish neurologists are generally unsatisfactory and do not follow EBM-based guidelines. The low percentage of neurologists who diagnose and treat nicotine dependence may negatively impact the efficacy of secondary stroke prevention in Poland.

The prevalence of depressive and anxiety symptoms in Polish epilepsy patients - The context of pharmaco-resistance.

PURPOSE: Patients with epilepsy (PWE) are at a higher risk of experiencing depressive and anxiety symptoms than the general population; these symptoms are more prevalent in patients with drug-resistant epilepsy (DRE) compared to those with non-drug-resistant epilepsy (NDRE). The aim of the present study was to compare the level of reported depressive and anxiety symptoms in patients with DRE and patients with NDRE and to examine the relationships between demographic and epilepsy-related variables and severity of depression and anxiety symptoms. MATERIAL AND METHODS: A total of 193 adult PWE, divided into a DRE group (n = 87), and an NDRE group (n = 106), completed the Beck Depression Inventory (BDI) and the Stat-Trait Anxiety Inventory (STAI-Sand STAI-T). Data analysis included sociodemographic and disease-related variables such as the type of epilepsy syndrome, age at onset of disease, and duration of the disease. RESULTS: The DRE group presented a higher score of BDI than the NDRE group (p = 0.04). Age correlated with the score of STAI-S in the NDRE group (r = 0.22). Sex was the only significant predictor of the score of STAI-T in the NDRE group. Men from the DRE group presented higher scores in BDI, STAI-S, and STA-T compared with the NDRE group. CONCLUSIONS: Patients with DRE reported more severe depressive symptoms than patients with NDRE. In NDRE patients, the level of anxiety, considered as a state, was correlated with age. Sex was a significant predictor of the level of anxiety in DRE patients. Pharmaco-resistance was significantly associated with severity of depression and anxiety in male patients.

Comparison of plasma, saliva, and hair lamotrigine concentrations.

BACKGROUND: In some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy. METHODS: Plasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography-tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland. RESULTS: Plasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05). CONCLUSIONS: The lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).

Enzymatic replacement therapy in patients with late-onset Pompe disease - 6-Year follow up.

INTRODUCTION: Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy, affecting skeletal muscles, which, if untreated, leads to disability and/or respiratory failure. The enzyme replacement therapy (ERT) improves muscle strength and respiratory function and prevents disease progression. We present a 6-year follow-up of 5 patients with LOPD treated with ERT. METHODS: Five patients with LOPD received ERT: two started treatment in 2008, other two in 2010 and one in 2011. All patients received recombinant human alpha-glucosidase in dose 20mg/kg intravenously every two weeks. Physical performance was assessed in 6-minute walk test (6MWT) and spirometry was performed to examine FVC and FEV1. Liver enzymes, CK levels were also assessed. RESULTS: The walking distance in 6MWT increased by average 16.9±2.26% in the first three years of treatment. Similar changes were detected in spirometry: the most significant FVC increase was observed in two patients with the highest FVC values before treatment, which increased to normal values adjusted for age and sex in three years of treatment, that is by 28% and 34%. In two other patients FVC reached 88% and 76% of predicted values. ERT also improved the liver and muscle enzymes levels. CONCLUSION: The improvements of exercise tolerance and FVC were observed in all patients in the first three years of treatment and were the most pronounced in the longest-treated patients and with the least severe neurological and respiratory symptoms. Our research suggests that early start of the ERT results in higher improvement of respiratory and ambulation functions.

Mechanical thrombectomy in acute stroke - Five years of experience in Poland.

OBJECTIVES: Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. METHODS AND RESULTS: We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. RESULTS: Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% - emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b-TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization - in 30.7%, mRS of 0-2 - in 31.4% and mRS of 6 in 22% of cases. CONCLUSION: Our results can help harmonize standards for MT in Poland according to international guidelines.

Autoimmune meningitis and encephalitis in adult-onset still disease - Case report.

INTRODUCTION: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown cause. Its symptoms usually include persistent fever, fugitive salmon-colored rash, arthritis, sore throat (not specific), but it may also lead to internal organs' involvement, which presents with enlargement of the liver and spleen, swollen lymph nodes, carditis or pleuritis - potentially life-threatening complications. In rare cases, AOSD can cause aseptic meningitis or/and encephalitis. CASE PRESENTATION: We report a case of 31-year-old male patient, who was referred to neurological department for extending diagnostics of frontal lobes lesions with involvement of adjacent meninges. Abnormalities have been revealed in brain MRI, which was performed due to persistent headaches, visual disturbances, fever, fatigue and cognitive decline. Wide differential diagnosis was performed including laboratory findings, contrast enhanced MRI, MR spectroscopy, flow cytometry and finally brain biopsy to exclude neoplastic or infectious origin. Final diagnosis of autoimmune meningoencephalitis in adult-onset Still disease has been made. CONCLUSION: Adult-onset Still disease is a rare cause of inflammatory changes in central nervous system, which if diagnosed, may be treated successfully with steroids (commonly available agent), intravenous immunoglobulins or more specific immunomodulating regiments.