Seizure control and complications in patients switching from clobazam to clonazepam due to drug shortage.

BACKGROUND: Antiseizure medication (ASM) shortages are a global problem that have a negative impact on outcomes such as seizure control in patients with epilepsy (PWE). In the case of clobazam (CLB) shortage, there is no study regarding the management strategy. This study aims to investigate the alteration in seizure frequency and the occurrence of side effects in PWE undergoing an abrupt switch from clobazam (CLB) to clonazepam (CLZ), during CLB shortage. MATERIAL AND METHODS: A retrospective study was conducted from electronic health records at our neurology outpatient clinic from January to July 2022. Change in seizure frequency and percentage of CLZ-associated side effects were determined as primary and secondary outcomes, respectively. Potential drug-drug interactions (Level C and above) were evaluated by using Lexicomp Drug Interaction Checker. RESULTS: The analysis included a total of 29 adult patients (15F, median age: 29). The switching ratio was 10 mg CLB for every 1 mg CLZ (10:1). Seizure frequency was higher during the CLZ period compared to the CLB period (p < 0.05), but no status epilepticus cases were observed. All patients exhibited potential drug-drug interactions, leading to reduced CLZ levels in 12 cases. A total of 36 CLZ-associated side effects were identified, with fatigue (19.4 %), drowsiness (16.6 %), and somnolence (13.8 %) being the most prevalent. A positive and strong correlation was found between CLZ dose and the number of side effects (r: 0.556; p: 0.002). CONCLUSION: The abrupt switch from CLB to CLZ was observed to increase seizure frequency without leading to status epilepticus in PWE. CLZ-associated side effects were found to be tolerable despite the abrupt switch. Future studies may explore the effect of alternative switching ratios.

Difficulties in the implementation of the ketogenic diet in adult patients with refractory epilepsy.

BACKGROUND: Ketogenic diet therapies (KDT) are appropriate therapeutic options for pediatric and adult patients with intractable epilepsy. The application of KDT among adult patients with refractory epilepsy is limited compared to children for several reasons, including poor compliance. We present the significant reasons for the lack of adherence to KDT in our adult patients with intractable epilepsy. METHODS: This study was conducted retrospectively in adult patients with drug-resistant epilepsy who wereofferedand accepted toimplementKDT between 2014 and 2021. Demographic and clinical data were collected via electronic health records. The eventual outcome of KDT results was obtained from the consultant dietitian. The prevalence and reasons for the failure to implement KDT were investigated. We also obtained detailed information about patients who successfully applied the KDT. RESULTS: A total of 33 patients (18F; median age 28) who wereoffered and accepted to implement KDT were included. Baseline seizure frequency was >4 per week in 49%, and more than half of the patients used >3 anti-seizure medications (ASM). Epilepsy types were temporal in 10 (30%), extratemporal in 10 (30%), generalized in 6 (18%), and unclassified in 7 (22%) patients.Only 3 patients (9%) were able to maintain KDT in the long term. One of them (33%) benefited from this therapy.In the remaining 30 patients, the reasons for failure were inability to contact the dietitian in 5, failure to apply KDT for a particular reason in 7, inappropriate blood test results or any medical/surgical comorbidities in 6, improvement in seizure burden due to change in ASM in 5, still insufficient knowledge of KDT in 3, unresponsiveness to diet due to incorrect implementation in 1 and unidentified reasons in 3 patients. CONCLUSIONS: A significant percentage of adult patients with refractory seizures failed to use KDTin our study(91%).Strategies to improve compliance and minimize the side effects might increase the number of drug-refractory epilepsy patients who could benefit from this therapy.

Adherence to epilepsy quality indicators in a tertiary referral center.

BACKGROUND: Quality indicators play an important role in healthcare quality and patient safety. The aim of this study is to identify specific clinical pharmacy interventions to improve adherence to quality indicators and minimize risks among patients with epilepsy. MATERIAL AND METHODS: A prospective, two-phase, observational study was conducted in a neurology outpatient clinic of a tertiary university hospital. In the first phase of the study, the rate of adherence to the quality indicators was evaluated with a checklist containing the quality indicators. In the second phase of the study, an expert panel meeting was convened to identify clinical pharmacist interventions to reduce the risks associated with non-adherence. The Fine-Kinney method was used to prioritize risks, and adherence rates with each quality improvement indicator (QI) were calculated. RESULTS: The study found that adherence rates were highest for QIs involving estimating the number and type of seizures, providing medical treatment or referring patients with evidence of mood disorders to mental healthcare, and co-managing prenatal care for women with epilepsy. The most non-adherence rates were found in QIs involving quality-of-life assessment, daily folate supplementation, and addressing the decreased effectiveness of oral contraception. The annual review of information about educational issues was also poorly provided. An expert panel decided to integrate a clinical pharmacist into the outpatient clinic to improve medication adherence, side-effect assessment, drug interaction assessment, patient education, lifestyle-modification education, depression/suicide-related behavior screening, quality-of-life assessment, and effectiveness evaluation of oral contraceptives for female patients using enzyme-inducing ASM. CONCLUSION: The study shows that medication adherence, assessment of side effects, drug interactions, and patient education are inadequately provided by neurologists in patients with epilepsy. Clinical pharmacists have a crucial role in reducing potential risks of non-adherence with quality indicators. By integrating clinical pharmacy services into routine epilepsy care processes, the quality of care can be improved. Future studies should focus on implementing these interventions and evaluating their impact on patient outcomes.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Periodic eye opening and upward eye deviation accompanied by burst-suppression, as an isolated clinical manifestation of acute post-hypoxic myoclonus.

Various movement disorders have been described following hypoxic-ischaemic brain injury. Here, we present a 72-year-old female patient who developed periodic opening and upward deviation of the eyes as an isolated clinical finding, within 24 hours after cardio-pulmonary arrest. These movements were accompanied by burst-suppression on EEG, and both clinical and electrophysiological findings were suppressed 18 hours after intravenous levetiracetam infusion. The strictly periodic nature of both EEG discharges and eye opening with vertical deviation suggest a cause due to either activation of a subcortical/brainstem pacemaker reciprocally stimulating the cortex, or, alternatively, post-anoxic burst activity of viable cortical neural networks, somehow stimulating the relevant oculomotor nuclei. Together with previous similar cases, our case expands the spectrum of post-resuscitation myoclonus syndromes with the addition of this rare isolated oculopalpebral subtype. [Published with video sequence].

Antiepileptic treatment for anti-NMDA receptor encephalitis: the need for video-EEG monitoring.

Anti-NMDA receptor encephalitis is a severe disorder characterised clinically by seizures, autonomic instability, and severe disturbances of memory, behaviour, and cognition. Due to the severity of symptoms, many patients are admitted to the intensive care unit. For some patients, the presence of various movement disorders and abnormal autonomic signs, as well as a history of seizures, lead to a false impression of status epilepticus, which is reported in 6% of the cases. Here, we present two young female patients, one of whom had ovarian teratoma. Both patients were referred to our neurological intensive care unit with a diagnosis of status epilepticus. However, prolonged video-EEG findings were compatible with encephalopathy. We avoided aggressive treatment with intravenous anaesthetics and both patients recovered after immunotherapy, one of whom received surgery. Physicians should be cautious in interpreting abnormal movements and autonomic signs in such patients and video-EEG monitoring is advised when status epilepticus is suspected. [Published with video sequences].

Diabetic uremic syndrome studied with cerebral MR spectroscopy and CT perfusion.

Diabetic uremic syndrome (DUS) is an increasingly reported acute neurometabolic cerebral disease with characteristic clinical and imaging features. Clinical spectrum includes a wide range of movement disorders such as acute parkinsonism. Imaging studies show reversible (with hemodialysis) bilateral lesions in the lenticular nuclei. DUS pathophysiology has not been entirely clarified yet. Our case study shows certainly that LN lesions are characterized with increased lactate peak with MR spectroscopy and decreased perfusion in computerized tomography perfusion along with increased diffusion with apparent diffusion coefficient (ADC) mapping in the subacute phase of the syndrome. Abnormalities were almost normalized quickly after metabolic control by hemodialysis. Together with reports indicating that a deficit of glucose use exacerbated with acute increase of uremic toxins in bilateral LN, observed changes (lactate peak and hypoperfusion) led us to state that a primary metabolic depression may cause this syndrome. Metabolic depression is probably due to uncompensated uremic toxin accumulation related mitochondrial supression and/or dysfunction. This definition fits well to the other elements of DUS such as ADC evolution and marked lesion regression. Our single case study is not supportive of other previously credited mechanisms such as microvascular dysfunction related focal ischemia or hypoperfusion, prolonged uremic toxin related histotoxic hypoxia, central pontine myelinolysis-like demyelination and posterior leukoencephalopathy spectrum disorder related vasogenic edema.

Spectrum of EEG Findings in Patients with Leptomeningeal Carcinomatosis and Seizures: Correlation with Neurodiagnostic Results and Outcome.

Purpose: Leptomeningeal carcinomatosis (LC) is a devastating condition in patients with systemic malignancies or primary brain tumors. Although much is known about neuro-radiologic investigations, there is very little information about EEG findings in these patients. Whether EEG is correlated with cranial magnetic resonance imaging (MRI) results and survival has not been investigated. Methods: Medical records of 2340 adult patients with the diagnosis of brain tumor, either metastatic (Group 1) or primary (Group 2), between 2000-2021 were reviewed for the presence of LC and seizures. Demographic and clinical features, laboratory results and Karnofsky performance scores of included patients were noted. Available routine EEG recordings were re-evaluated. Any possible correlation between EEG findings-MRI and EEG findings-survival were investigated statistically. Results: Sixty-six patients with LC and seizures were identified. The most common malignancies were lung cancer and glioblastoma multiforme. Twenty-six EEG recordings of 17 patients in Group 1, and 13 EEGs of 9 patients in Group 2 were available for final analysis. The most common EEG characteristic was background slowing (73%). The most frequent findings were rhythmic periodic patterns or spike wave activity (27%). Sporadic epileptiform discharges (8%) or ictal recordings (4%) were very rare. None of the EEG features correlated with MRI results or survival. Conclusion: There are various EEG patterns in patients with LC and seizures. The most common findings are related to background activity, with rhythmic periodic patterns or spike wave activity being observed less commonly. EEG characteristics do not predict MRI findings or survival.

Frequency and Types of Complications Encountered in Patients With Nonconvulsive Status Epilepticus in the Neurological ICU: Impact on Outcome.

Objectives. The frequency and types of complications in patients with nonconvulsive status epilepticus (NCSE) who are followed up in the intensive care unit (ICU), and the impact of these complications on outcome are not well-known. We investigated the complications and their effects on prognosis in NCSE patients. Methods. After reviewing the video-EEG monitoring (VEEGM) reports of all the consecutive patients who were followed up in our ICU between 2009 and 2019, we identified two groups of patients: 1-patients with NCSE (study group) and 2-patients who underwent VEEGM for possible NCSE but did not have ictal recordings (no-NCSE group). Electronic health records were reviewed to identify demographic and clinical data, duration of ICU care, medical and surgical complications, pharmacologic treatment, and outcome. These parameters were compared statistically between the groups. We also investigated the parameters affecting prognosis at discharge. Results. Thirty-two patients with NCSE comprised the study group. Infection developed in 84%. More than half were intubated, had tracheostomy or percutaneous endoscopic gastrostomy application. Refractory NCSE was associated with significantly more frequent complications and worse outcome. There was a higher tendency of infections in the study group (P = .059). Higher organ failure scores and prolonged stay in ICU predicted worse outcome (P < .05). Conclusion. The frequency of complications in patients with NCSE who are cared for in the ICU is considerable. Most of the complications are similar to the other patients in ICU, except for the higher frequency of infections. Increased physician awareness about modifiable parameters and timely interventions might help improve prognosis.

Lateralized Periodic Discharges in a Patient With Dural Arteriovenous Fistula: SPECT and DWI Studies Suggest They are Ictal.

Lateralized periodic discharges (LPDs) are unilateral electroencephalography (EEG) waveforms, recurring at regular intervals. There has been a long-lasting debate about whether they represent ictal or interictal phenomena. Very few patients in the literature have been investigated with multimodal functional imaging techniques. Here, we present a 58-year-old male patient with symptomatic epilepsy who had cerebral venous sinus thrombosis in the right temporo-parietal area and dural arteriovenous fistula (dAVF) over the left fronto-parietal region. He developed acute speech disturbances and altered mental status after a generalized tonic-clonic seizure. Video-EEG monitoring (VEEGM) demonstrated LPDs over the left fronto-central area, overlapping in part with the dAVF. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences revealed restricted diffusion compatible with cytotoxic edema, whereas single-photon emission computed tomography (SPECT) indicated hyperperfusion in the same region, leading to the conclusion that he was having possible nonconvulsive status epilepticus (NCSE). An increase in antiseizure medications led to gradual improvement in clinical status and the disappearance of LPDs.

Transcallosal endoscopic resection of hypothalamic hamartoma in a case with Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is a very rare syndrome characterized by hypothalamic hamartoma (HH), polydactyly, panhypopituitarism, imperforate anus and other visceral anomalies. Contrary to patients with isolated HH, neurological dysfunction and precocious puberty are uncommon and seizures are usually well controlled with anticonvulsant medication. Therefore, conservative management of HH is advised. To the best of our knowledge, seven cases of PHS with surgical resection of the HH have so far been reported. Five patients were either seizure-free or had >90% seizure reduction postoperatively. Here, we present a case of PHS of a patient who also underwent transcallosal endoscopic resection of the HH with a subsequent 70% reduction in seizure frequency.

Efficacy and Safety of Ketamine in Refractory/Super-refractory Nonconvulsive Status Epilepticus: Single-Center Experience.

Refractory/super-refractory nonconvulsive status epilepticus (r/srNCSE) is an acute life-threatening neurocritical entity with significant morbidity. Failure to control SE in its earlier stages leads to multiple molecular alterations in the brain such as downregulation of GABA-A and upregulation of NMDA receptors. Recently ketamine, an NMDA receptor antagonist, has gained increased attention as a therapeutic choice in controlling refractory/super-refractory SE. We aimed to analyze the efficacy and safety profile of ketamine in our center. We retrospectively identified all the patients with nonconvulsive SE who received ketamine during their follow-up in our neurological intensive care unit between 2009 and 2019. Information about demographic, clinical, and laboratory findings; concurrent antiseizure and anesthetic medications; time of initiation, dose and duration of ketamine infusion; any adverse effects and finally prognosis were collected. The effect of day of ketamine initiation and duration of infusion on ketamine efficacy were analyzed statistically. Seven patients (4 males, 3 females; age: 44-86 years) were included in the study. Encephalitis was the most common etiology. Concurrent antiseizure medications varied between 2 and 5. Six patients received midazolam before/during ketamine infusion. Ketamine was initiated 2 to 7 days after the onset of EEG monitoring and lasted 3 to 24 days with a maximum infusion dose ranging between 1 to 5 mg/kg/h. It was definitely effective in 4 patients, and possibly effective in an additional patient. Earlier initiation was correlated with higher efficacy (P = .047). There was a trend toward higher efficacy with longer duration of infusion (P = .285). Overall prognosis was poor with 29% mortality rate. Temporary hepatic failure occurred in 1 patient. Ketamine appears to be a promising drug in r/srNCSE. Earlier and prolonged infusion, as well as combination with benzodiazepines may increase its efficacy. Adverse events are rarely observed.

Generalized seizures aggravated by levetiracetam in an adult patient with phenylketonuria.

Phenylketonuria (PKU) is one of the most common inherited metabolic disorders, which is characterized by excessive accumulation of phenylalanine (Phe) in tissues. Generalized seizures occur in 25% of the patients. Little is known about seizures and their treatment in adult PKU patients, and information with newer antiepileptic drugs is lacking. Here we report an adult patient who developed generalized seizures later in life, despite strict dietary control, and whose seizures were aggravated by levetiracetam (LEV). Convulsions ceased after discontinuation of LEV and the patient has been seizure free on topiramate 125 mg/day.

An unusual complication of invasive video-EEG monitoring: subelectrode hematoma without subdural component: case report.

BACKGROUND: The potential complications of the subdural electrode implantation providing identification of the seizure focus and direct stimulation of the cerebral cortex for defining the eloquent cortical areas are epidural and subdural hematoma, cortical contusions, infection, brain edema, raised intracranial pressure, CSF leakage, and venous infarction have been previously reported in the literature. PURPOSE: To present the first case of subelectrode hematoma without subdural component that was detected during invasive EEG monitoring after subdural electrode implantation. CASE: A 19-year-old female with drug resistant seizures was decided to undergo invasive monitoring with subdural electrodes. While good quality recordings had been initially obtained from all electrodes placed on the right parietal convexity, no cerebral cortical activity could be obtained from one electrode 2 days after the first operation. Explorative surgery revealed a circumscribed subelectrode hematoma without a subdural component. CONCLUSION: Awareness of the potential complications of subdural electrode implantation and close follow-up of the clinical findings of the patient are of highest value for early detection and successful management.

Time to Detection of the First Seizure in Patients With Nonconvulsive Status Epilepticus in the Neurological Intensive Care Unit.

Video-EEG monitoring is often used to detect nonconvulsive status epilepticus (NCSE) in critical care patients. Short recording durations may fail to detect seizures. In this study, we investigated the time required to record the first ictal event, and whether it could be correlated with some clinical or EEG parameters. Video-EEG recordings of patients who were followed up in our neurological intensive care unit were evaluated retrospectively. The EEG recordings of patients with NCSE were reviewed to determine the timing of the first seizure occurrence. Demographic data and EEG findings were obtained from patient charts and EEG reports. Possible correlations between the presence of periodic discharges (PD), Glasgow Coma Scale (GCS) score and early seizure detection (defined as a seizure within the first hour of recording) were explored statistically. Out of 200 patients who underwent video-EEG monitoring, we identified 30 cases (15%; 18 male, 12 female; age 24-86 years; mean recording duration 99 hours) with NCSE. The first seizure was recorded within 0 to 1 hour in 22 patients (73%) and within 1 to 12 hours in 6 patients (22%). Interictal PDs were identified in 19 patients (63%). GCS score was ≤8 in 16 patients (53%). There was no correlation between early seizure detection and PDs (p=1.0) or GCS score (P = .22). In our study, >90% of the seizures were captured within 12 hours. This finding suggests that most of the NCSE cases can be identified even in centers with limited resources. The presence or absence of PDs or GCS score does not predict the timing of the first seizure.

Blockade of GABA synthesis only affects neural excitability under activated conditions in rat hippocampal slices.

The primary goal of this study was to establish whether inhibition of GABA synthesis was sufficient to induce network hyperexcitability in a rat hippocampal slice model comparable to that seen with GABA receptor blockade. We used field and intracellular recordings from the CA1 region of rat hippocampal slices to determine the physiological effects of blocking GABA synthesis with the convulsant, 3-mercaptoproprionic acid (MPA). We measured the rate of synthesis of GABA and glutamate in slices using 2-13C-glucose as a label source and liquid chromatography-tandem mass spectrometry. There was little effect of 3.5mM MPA on evoked events under control recording conditions. Tissue excitability was enhanced following a series of stimulus trains; this effect was enhanced when GABA transport was blocked. Evoked inhibitory potentials (IPSPs) failed following repetitive stimulation and MPA. Spontaneous epileptiform activity was seen reliably with elevated extracellular potassium (5mM). GABA synthesis decreased by 49% with MPA alone and 45% with the combination of MPA and excess potassium; GABA content was not substantially altered. Our data indicate: (1) GABAergic inhibition cannot be significantly compromised by MPA without network activation; (2) GABAergic synaptic inhibition is mediated by newly synthesized GABA; (3) there is a depletable pool of GABA that can sustain GABAergic inhibition when synthesis is impaired under basal, but not activated conditions; (4) overt hyperexcitability is only seen when newly synthesized GABA levels are low.

Multidrug resistance in patients undergoing resective epilepsy surgery is not associated with C3435T polymorphism in the ABCB1 (MDR1) gene.

PURPOSE: The C3435T polymorphism in the gene coding for P-glycoprotein (ABCB1) has been correlated with drug resistance in patients with epilepsy. However, replication studies have revealed conflicting results and the reason for this is not clear. We investigated the frequency of C3435T polymorphism in epileptic Turkish patients who underwent resective epilepsy surgery and compared our results with healthy controls. METHODS: DNA samples were obtained from 100 healthy controls and 89 consecutive adult patients who underwent resective brain surgery due to refractory seizures at our epilepsy center. Genotypes for the C3435T polymorphism were determined by PCR and restriction analysis. RESULTS: Comparison of drug-resistant patients and healthy controls revealed no significant difference in allele frequency (C vs. T; chi(2)=0.015, p=0.90) and genotype frequency (chi(2)=2.05, p=0.36). The findings in the pure hippocampal sclerosis (HS) group (n=73) were not significantly different from control subjects, either (allele frequency: chi(2)=0.29, p=0.59; genotype frequency: chi(2)=2.14, p=0.34). CONCLUSIONS: Our findings failed to prove an association between C3435T polymorphism and drug resistance in a sample of Turkish patients with refractory epilepsy who underwent resective brain surgery.

Predictive factors for postoperative outcome in temporal lobe epilepsy according to two different classifications.

PURPOSE: The determination of prognostic factors is important for predicting outcome after epilepsy surgery. We investigated the factors related to surgical outcome within a homogeneous group of patients suffering from pathologically proven mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), and compared Engel's outcome classification system with the latest one proposed by the ILAE. METHOD: We included 109 patients with MTLE-HS who were followed-up for at least 1 year after epilepsy surgery. A retrospective chart review was performed to extract patients' demographic details, and potential pre-postoperative risk factors. Outcome of surgery was defined by the Engel's and ILAE classifications. In addition, the course of prognosis was determined according to the changes in ILAE classifications on an annual basis. Univariate and multivariate logistic regression analyses were used for the latest available outcomes and two different courses of prognosis. RESULTS: The average duration of follow up was 4.78+/-2.55 years in the 109 patients with MTLE-HS. The univariate and multiple logistic regression analyses showed that the occurrence of seizures during the first month after surgery was a significant risk factor for a poor outcome. A history of trauma was also significant for patients with late recurrence of postsurgical seizures after at least 1-year seizure remission. CONCLUSION: The occurrence of seizures during the first month after surgery is a significant prognostic factor in patients with MTLE-HS. Ignoring early postoperative seizures in classification systems may result in difficulty in identifying the course of epilepsy after surgery.