Characterizing the driving dilemma among patients with psychogenic nonepileptic seizures: A single-center prospective cohort study.

OBJECTIVE: Driving is a critical topic to counsel among patients with epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES), with significant legal and public health implications. This prospective cohort study examined the frequency of ES and PNES in a single institution's Epilepsy Monitoring Unit (EMU) and assessed driving-related issues between each group. METHODS: Adult patients from the Mayo Clinic Arizona Epilepsy Monitoring Unit (EMU) were given comprehensive surveys addressing driving history. Descriptive analysis and statistics were used to summarize differences between patients with ES and PNES. Differences between patients with epilepsy and PNES were determined by Pearson chi-square. RESULTS: Nearly half (n = 75/163) of all patients admitted to the EMU were diagnosed with PNES. Although the PNES group had a statistically significant higher frequency of events (p = 0.01), 87.7% of these patients reported compliance with the driving law recommendations, suggesting a trend that patients who have been counseled regarding fitness-to-drive are likely to follow the recommendation. One-third of patients with PNES reported an event while operating a motor vehicle and 8% (n = 2/25) resulted in a motor vehicle collision severe enough to require hospitalization. In contrast to those with ES, 25% of patients reported a typical event while driving and 25% (n = 2/8) of those resulted in a collision requiring hospitalization. The incidence of habitual events while driving is higher in the population with PNES (n = 25) when compared to those with ES (n = 8); however, it appears that patients with PNES were less likely to become involved in an accident resulting in seriously bodily injury than in ES. CONCLUSIONS: Compared to patients with PNES, patients with ES have less frequent events but more severe collisions. This study reinforces the need for diligent driving counseling to help prevent driving-related injuries in patients with PNES and ES.

A Stroke Alert With Unexpected Outcome.

INTRODUCTION: Observational studies have suggested that intravenous (IV) thrombolysis may be unfavorable in patients with high-grade gliomas. However, current literature on thrombolysis outcomes in patients with primary brain tumors is largely limited to case reports and may be influenced by publication bias. CASE REPORT: A 69-year-old male presented with acute left hemiplegia, left hemisensory loss, neglect, dysarthria and right gaze preference (National Institutes of Health Stroke Scale 22). An emergent noncontrast head computerized tomography showed hypoattenuation in the right parietal lobe of unclear chronicity and IV thrombolysis with tissue plasminogen activator was administered within the 4.5 hour window. Following IV thrombolysis, a computerized tomography angiogram of the head and neck revealed no large vessel occlusion. However, a marginally enhancing, and centrally nonenhancing mass within the right parietal lobe associated with vasogenic edema was elucidated. Subsequently, the patient developed abnormal left hemibody tonic-clonic motor activity, left gaze preference and left-beating nystagmus concerning for focal motor status epilepticus. An emergent electroencephalogram, following administration of IV levetiracetam, showed right hemispheric electrographic seizures and right hemispheric periodic lateralized epileptiform discharges. Brain magnetic resonance imaging with gadolinium revealed 2.5 cm ring-enhancing mass in the right parietal lobe. The patient underwent right sided craniotomy with resection of the mass and pathology revealed Glioblastoma. CONCLUSION: We report a case of thrombolysis administered in a patient with high-grade glioma with no apparent complications.

Case Report: Opsoclonus-Myoclonus Syndrome Associated With Contactin-Associated Protein-Like 2 and Acetylcholine Receptor Autoantibodies in the Setting of Non-Small Cell Lung Carcinoma.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by "dancing" eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Refractory Left Focal Motor Status Epilepticus as Initial Clinical Presentation of Acute Basilar Artery Thrombosis.

Seizures are uncommon with posterior circulation strokes. They are more often associated with anterior circulation strokes, with only a limited number of cases of status epilepticus reported to be related to brain stem ischemia. The literature includes case reports of generalized tonic-clonic seizures and associated status epilepticus as an initial presentation of acute basilar artery thrombosis. However, there are only rare cases reporting focal motor seizure as status epilepticus in the setting of acute basilar artery thrombosis, an important clinical presentation that should prompt evaluation for acute brain stem ischemia.

Identifying and Addressing Barriers to Systemic Thrombolysis for Acute Ischemic Stroke in the Inpatient Setting: A Quality Improvement Initiative.

OBJECTIVES: To identify barriers to inpatient alteplase administration and implement an interdisciplinary program to reduce time to systemic thrombolysis. PATIENTS AND METHODS: Compared with patients presenting to the emergency department with an acute ischemic stroke (AIS), inpatients are delayed in receiving alteplase for systemic thrombolysis. Institutional AIS metrics were extracted from the electronic medical records of patients presenting as an inpatient stroke alert. All patients who received alteplase for AIS were included in the analysis. A gap analysis was used to assess institutional deficiencies. An interdisciplinary intervention was initiated to address these deficiencies. Efficacy was measured with pre- and postintervention surveys and institutional AIS metric analysis. Statistical significance was determined using the Student t test. We identified 5 patients (mean age, 73 years; 100% (5/5) male; 80% (4/5) white) who met inclusion criteria for the preintervention period (January 1, 2017, to December 31, 2017) and 10 patients (mean age, 71 years; 50% male; 80% white) for the postintervention period (October 31, 2018, to July 1, 2020). RESULTS: We found barriers to rapid delivery of thrombolytic treatment to include alteplase availability and comfort with bedside reconstitution. Interdisciplinary intervention strategies consisted of stocking alteplase on additional floors as well as structured education and hands-on alteplase reconstitution simulations for resident physicians. The mean time from stroke alert to thrombolysis was shorter postintervention than preintervention (57.4 minutes vs 77.8 minutes; P=.03). CONCLUSION: A coordinated interdisciplinary approach is effective in reducing time to systemic thrombolysis in patients experiencing AIS in the inpatient setting. A similar program could be implemented at other institutions to improve AIS treatment.

When Drugs Do Not Work: Alternatives to Antiseizure Medications.

PURPOSE OF REVIEW: Despite the increase in the number of novel antiseizure medications over the past 20 years, approximately one-third of patients will not have adequate seizure control on medications. For these patients, additional options need to be considered, including dietary, device, and surgical treatments. In addition, many complementary therapies can be considered as adjunctive treatment, with the intent of improving quality of life for persons with epilepsy and potentially allowing for improvement in seizure control. RECENT FINDINGS: This review outlines established and developing treatments for drug-resistant epilepsy. Surgical treatments, including resective surgery and vagus nerve stimulation, have been routine care for several decades. In the last several years, new neurostimulation options have been approved (responsive neurostimulation and deep brain stimulation) or are under development (continuous subthreshold cortical stimulation). For patients with lesion or well-defined seizure-onset zones, less invasive options including laser ablation and ultrasound therapy provide the potential for faster recovery times and less morbidity. Not all therapies are in the pharmacological or surgical arenas. This review also explores the evidence for complementary treatments, including relaxation and meditation techniques, and art and music therapy. Despite the range of antiseizure medications available, they still provide inadequate for a large number of patients with epilepsy, either due to ongoing seizures or intolerable side effects. Complementary therapies, including diet, meditation techniques, and music therapy, provide compelling treatment options to improve quality of life while potentially improving seizure control. In appropriate patients, stimulation devices or surgical resection can offer options for significant seizure reduction or even cure. The full range of therapeutics should be considered for each patient with epilepsy when they are struggling with inadequate seizure control or side effects with traditional pharmacological treatment.

The Dilemma of Resuming Antithrombotic Therapy After Intracranial Hemorrhage in Patients With Left Ventricular Assist Devices.

BACKGROUND/OBJECTIVE: Antithrombotic therapy is administered after left ventricular assist device (LVAD) implantation to prevent thromboembolic events. Intracranial hemorrhage (ICH) is a life-threatening adverse event requiring immediate discontinuation of antithrombotics. We investigated the timing of antithrombotic resumption after ICH in patients with LVADs and the association between timing and risk of recurrent hemorrhage and thrombotic events. METHODS: We performed a multicenter, retrospective analysis of patients with ICH occurrence during LVAD antithrombotic regimen with subsequent resumption of antithrombotics from January 1, 2010, to December 31, 2017. Covariates included age, international normalized ratio, antithrombotic dosing, timing of resumption, modified Rankin score, and subsequent hemorrhagic and thrombotic events within 1 year post-ICH. Patients who did not resume anticoagulation were excluded. RESULTS: Of 673 patients with LVADs, 85 (12.6%) developed ICH while being treated with antithrombotics. Forty-three were excluded due to death prior to resumption and one due to lack of resumption. The remaining 41 patients were on antithrombotics with a median (interquartile range [IQR]) international normalized ratio at ICH onset of 2.6 (1.8-3.6). Aspirin and warfarin were resumed at a median (IQR) of 5.5 (1.3-8.8) and 6.5 (4.0-15.5) days post-ICH, respectively. A continuous unfractionated heparin infusion was initiated in 16 (39.0%) patients at a median (IQR) of 2.5 (1.0-7.8) days post-ICH. During the 1-year follow-up after anticoagulation resumption, 11 (26.8%) patients suffered secondary hemorrhages and two (4.9%) suffered secondary thrombotic events. Using Kaplan-Meier method and log-rank test, we compared all patients who resumed anticoagulation by 6 days post-ICH to those who resumed after 6 days. There was no difference in freedom from secondary hemorrhagic event between the two groups (P = 0.75). CONCLUSION: Despite timing of resumption of antithrombotic therapy after ICH, recurrent hemorrhagic events can be expected in one-quarter of these patients over the subsequent year.

Nonconvulsive status epilepticus secondary to acute porphyria crisis.

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic-clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder.

Brain-Derived Neurotrophic Factor and Its Associations with Metabolism and Physical Activity in a Latino Sample.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with body weight and other health conditions but remains understudied in the Latino population. The aim of this study was to examine the associations of BDNF serum levels with body mass index (BMI), physical activity, and the rs6265 nonconservative polymorphism among 349 Latinos aged ≥18 years enrolled in the Arizona Insulin Resistance Registry. MATERIALS AND METHODS: Data on physical activity were acquired using a self-reported questionnaire. BDNF serum levels were measured utilizing a modified ELISA method, and the rs6265 polymorphism was genotyped by the Assay-by-Design service. Two sample t-tests or chi-squared tests were employed to compare demographics and outcomes between physically active and nonactive groups as well as between rs6265 CC and CT+TT groups. RESULTS: BDNF levels and rs6265 polymorphism did not differ significantly between the physically active (N = 195) and nonactive group (N = 154). Participants with the rs6265 polymorphism did not show any significant difference in BDNF levels or BMI when compared with those with the normal functional variant. Higher BDNF levels were significantly associated with higher age (r = 0.11, P = 0.04) and higher 2-hr glucose level (r = 0.11, P = 0.04). CONCLUSIONS: In this cross-sectional study, the rs6265 polymorphism was not associated with a higher risk of obesity, or lower circulating levels of BDNF. Thus, the rs6265 polymorphism may have a different impact in Latinos as compared with other previously studied populations.

Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists.

N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate a slow, Ca(2+)-permeable component of excitatory synaptic transmission in the central nervous system and play a pivotal role in synaptic plasticity, neuronal development, and several neurological diseases. We describe a fluorescence-based assay that measures NMDA receptor-mediated changes in intracellular calcium in a BHK-21 cell line stably expressing NMDA receptor NR2D with NR1 under the control of a tetracycline-inducible promoter (Tet-On). The assay selectively identifies allosteric modulators by using supramaximal concentrations of glutamate and glycine to minimize detection of competitive antagonists. The assay is validated by successfully identifying known noncompetitive, but not competitive NMDA receptor antagonists among 1800 screened compounds from two small focused libraries, including the commercially available library of pharmacologically active compounds. Hits from the primary screen are validated through a secondary screen that used two-electrode voltage-clamp recordings on recombinant NMDA receptors expressed in Xenopus laevis oocytes. This strategy identified several novel modulators of NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine H3 receptor ligand showed submicromolar potency at NR1/NR2B NMDA receptors, which raises the possibility that compounds can be developed that act with high potency on both glutamate and histamine receptor systems simultaneously. Furthermore, it is possible that some actions attributed to histamine H3 receptor inhibition in vivo may also involve NMDA receptor antagonism.