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.

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.

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.

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.

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.

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.

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.

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.

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.

Frontal Intermittent Rhythmic Delta Activity (FIRDA) in the Neurological Intensive Care: Prevalence, Determinants, and Clinical Significance.

INTRODUCTION: Frontal intermittent rhythmic delta activity (FIRDA), a transient rhythmic slow wave pattern over the anterior EEG leads, has been reported in a wide variety of cerebral lesions and different metabolic disturbances. Few authors have analyzed the frequency and clinical significance of FIRDA in the critical care setting. We aimed to better understand these issues in our intensive care cohort and if possible, try to delineate its underlying mechanisms. METHODS: Video-EEG reports of consecutive adult patients in the neurological intensive care unit (NICU) since 2009 were retrospectively reviewed to identify cases with FIRDA. Demographic, clinical, and laboratory data were obtained from EEG reports and patient charts. Age- and sex-matched patients with acute stroke, hospitalized in NICU and no FIRDA on video-EEG monitoring served as the control group. RESULTS: Among 162 patients who underwent video-EEG monitoring, FIRDA was documented in 17%. Female prevalence was 50% and age ranged from 23 to 82 years. Twenty-three (82%) of patients with FIRDA had a diagnosis of stroke. Comparison of demographic characteristics, EEG findings, metabolic disturbances and prognoses revealed no differences between stroke cases with and without FIRDA, except for higher frequency of acute and chronic isolated posterior circulation infarcts in patients with FIRDA. CONCLUSION: FIRDA is more commonly encountered in the neurocritical care setting as compared with outpatient EEG clinics. Our findings in stroke patients indicate that involved vascular territories may be related to the generation of FIRDA.

The Success Rate of Neurology Residents in EEG Interpretation After Formal Training.

EEG is an important tool for neurologists in both diagnosis and classification of seizures. It is not uncommon in clinical practice to see patients who were erroneously diagnosed as epileptic. Most of the time incorrect interpretation of EEG contributes significantly to this problem. In this study, we aimed to investigate the success rate of neurology residents in EEG interpretation after formal training. Eleven neurology residents were included in the study. Duration of EEG training (3 vs 4 months) and time since completion of EEG education were determined. Residents were randomly presented 30 different slides of representative EEG screenshots. They received 1 point for each correct response. The effect of training duration and time since training were investigated statistically. Besides, we looked at the success rate of each question to see whether certain patterns were more readily recognized than others. EEG training duration ( P = .93) and time since completion of training ( P = .16) did not influence the results. The success rate of residents for correct responses was between 17% and 50%. On the other hand, the success rate for each question varied between 0% and 91%. Overall, benign variants and focal ictal onset patterns were the most difficult to recognize. On 13 occasions (6.5%) nonepileptiform patterns were thought to represent epileptiform abnormalities. After formal training, neurology residents could identify ≤50% of the EEG patterns correctly. The wide variation in success rate among residents and also between questions implies that both personal characteristics and inherent EEG features influence successful EEG interpretation.

Do Video-EEG Monitoring Findings in ICU Patients With Acute Stroke Predict Development of Seizures and Survival During Follow-up?

PURPOSE: Ischemic or hemorrhagic stroke are among the most common causes of seizures, especially in the elderly. EEG is the only technique that can detect epileptiform abnormalities (EA) and nonconvulsive status epilepticus (NCSE), which may negatively affect recovery of these patients. Herein we aimed to investigate the potential predictive value of long-term EEG findings in terms of poststroke seizures (PSS) and survival, in stroke patients followed up in the neurological intensive care unit (NICU). METHODS: Video-EEG reports of stroke patients (ischemic and hemorrhagic) hospitalized between 2009 and 2014 in our NICU were reviewed. Patients with <2 months of survival were excluded. Follow-up data were obtained via telephone calls or patient charts. The correlation between EEG findings and early (≤1 week) and late seizure (>1 week) occurrence, recurrent seizure development, outcome, and survival were analyzed statistically. RESULTS: Overall 50 patients (27 female, 23 male; age, 26-85 years) were included in the final analysis. Almost 60% developed PSS (~2/3 were early). There was no difference between ischemic versus hemorrhagic stroke patients ( P = .72). Recurrent seizures were more common in the late seizure group ( P < .001). EAs occurred in one-third of the study cohort. This finding did not predict seizure development ( P = .93) or survival ( P = .61). CONCLUSION: PSS are a frequent finding in stroke patients followed up in NICU. EAs are not uncommon, but do not predict seizure occurrence or survival.

A novel de novo mutation involving the MLL2 gene in a Kabuki syndrome patient presenting with seizures.

Kabuki syndrome is a rare multiple congenital anomaly disorder. Although mental retardation is one of the main features, various neurological symptoms such as hypotonia and seizures can occur. Here we report on a 18-year-old Turkish male patient who was diagnosed previously as Kabuki syndrome. Molecular genetic analysis showed a novel de novo heterozygous mutation (c.12964C > T [p.Gln4322*] ) in the MLL2 gene, that leads to the synthesis of a truncated protein. The aim of the present report is to increase the awareness of Kabuki Syndrome among adult neurologists and to present a previously unreported non-sense mutation in the MLL2 gene.

Brachial Diparesis due to Motor Neuronopathy as One of the Predominant Presenting Signs of Occult Small Cell Lung Carcinoma.

Sensory neuronopathy is a well-established presentation in paraneoplastic neurological syndromes that is mostly associated with small cell lung cancer and anti-Hu antibodies. Motor neuronopathy, on the other hand, is an extremely rare observation in this syndrome. A 56-year-old man presented with asymmetric brachial diparesis and sensory ataxia. Electrophysiological studies revealed sensory ganglionopathy and progressive anterior horn degeneration in cervical segments. Small cell lung carcinoma with associated anti-Hu antibodies was later diagnosed. The patient did not improve despite the administration of steroids and chemotherapy. Paraneoplastic syndromes may exceptionally present with a bilateral arm weakness. Cases accompanied by sensory ganglionopathy should therefore be promptly investigated for any underlying malignancy.

Refractory Lesional Parietal Lobe Epilepsy: Clinical, Electroencephalographic and Neurodiagnostic Findings.

INTRODUCTION: Specialized centers, in the management and surgical treatment of medically refractory epilepsy, emphasize the importance of differentiating the varieties of localization related epilepsies. There has been considerable recent interest in temporal and frontal lobe epileptic syndromes and less attention has been paid to parietal and occipital lobe epilepsies. METHODS: Here we report the clinical, electroencephalographic and neuroimaging characteristics of 46 patients with medically refractory lesional parietal lobe epilepsy who have been followed up for 1-10 years. RESULTS: In this study auras were reported in 78.3% of the patients and included sensory symptoms (72.2%), headache (36.1%), nausea and vomiting (36.1%), psychic symptoms (36.1%) and visual symptoms (16.6%). The most common ictal behavioral changes were paresthesia (69.6%) and focal clonic activity (39.1%). Tonic posture, various automatisms, head deviation, staring, sensation of pain and speech disturbances occurred to a lesser extent. Simple partial seizures were present in 69.6%. Complex partial seizures occurred in 43.5% and secondary generalized tonic clonic seizures were reported in 58.7% of the patients. Interictal routine EEG disclosed abnormal background activity in 1/3 of the patients. Nonlocalising epileptiform abnormalities were found in 34.8% of the patients. EEG findings were normal in 34.8% of the patients. The most common presumed etiologic factors were as follows: posttraumatic encephalomalacia, stroke, tumor, malformation of cortical development, atrophy, and arteriovenous malformation. CONCLUSION: Clinical, electrophysiological and neuroimaging features of the lesional symptomatic partial epilepsy patients may help us to localize the seizure focus in some patients with cryptogenic partial epilepsy. So that, the timing decision of the parietal lobe sampling with more invasive techniques like intracranial electrodes prior to epilepsy surgery would be easier.

Isolated central nervous system Whipple's disease: Two cases.

Although it is an orphan disease, isolated central nervous system Whipple's disease is one of the "must be known" conditions in neurology because it belongs to the list of "treatable disorders". Here, we present two cases which highlight the importance of early diagnosis. Additionally, we provide a discussion on up to date diagnostic approach to this life-threatening disorder.

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].

Lacrimation as an Ictal Autonomic Event in a Patient With Seizures Originating From the Right Hemisphere.

In dacrystic seizures lacrimation has previously been reported as an ictal autonomic event accompanying emotional and somatic signs. However, it has not been observed as an isolated event in autonomic seizures. We report a patient experiencing complex partial seizures characterized by lacrimation as the initial and most prominent ictal event, with no sign of crying. The patient's ictal electroencephalogram (EEG) suggested a focus in the right hemisphere, along with interictal single-photon emission computed tomographic (SPECT) and positron emission tomographic (PET) studies demonstrating hypoperfusion-hypometabolism in the right temporoparietal lobe. Magnetic resonance imaging (MRI) did not show any structural abnormalities. Involvement of the temporal lobe has been suggested for dacrystic seizures, and both dominant and nondominant hemispheric foci were detected in such cases. Therefore, partially in concordance with previous reports, our case may point to neurobiologic interaction, between the temporoparietal region and the hypothalamus, for mediating lacrimation.