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Adrian L Rabinowicz,1 Edward Faught,2 David F Cook,1 Enrique Carrazana1,3 1Clinical Development & Medical Affairs, Neurelis, Inc., San Diego, CA, USA; 2Emory Epilepsy Program, Emory University School of Medicine, Atlanta, GA, USA; 3John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USACorrespondence: Edward Faught, Department of Neurology, Emory University School of Medicine, 12 Executive Park Drive, NE, Atlanta, GA, 30329, USA, Tel +1 404 778-3444, Email rfaught@emory.eduPurpose: People with epilepsy may experience seizure clusters despite a stable regimen of antiseizure medications. Such clusters have the potential to last ≥ 24 hours, typically occur in the community setting, and may progress to medical emergencies, such as status epilepticus, if untreated. Thus, long-acting rescue therapy for seizure clusters is needed that can be administered by nonmedical individuals outside a hospital. Benzodiazepines are the foundation of rescue therapy for seizure clusters. The approved outpatient treatments (ie, diazepam, midazolam) have differing profiles that may affect multiple aspects of health-care utilization. The current labeling of these medications allows for a second dose if needed to control the cluster. Although no head-to-head studies directly comparing rescue treatments have been conducted, differences between studies with generally similar designs may provide context for the potential importance of second doses of rescue therapy on health-care utilization.Methods: For this analysis, large, long-term, open-label studies of approved seizure-cluster treatments designed for use by nonmedical caregivers were reviewed, and the percentage of seizure clusters for which a second dose was used or that were not controlled at 6, 12, and 24 hours was examined. Available data on hospitalizations were also collected.Results: The 3 identified studies meeting the inclusion criteria were for use of diazepam rectal gel, intranasal midazolam, and diazepam nasal spray. Across these studies, the use of a second dose ranged from < 40% at 6 hours to < 13% at 24 hours. Hospitalizations and serious treatment-emergent adverse events were reported variably across these studies.Conclusion: These results demonstrate the importance of second doses of rescue therapy for seizure clusters for optimizing health-care utilization. Need for second doses should be included as one component. In turn, when second doses are needed, they have the potential to curtail emergency department use and hospitalization and to prevent further seizure clusters.Keywords: diazepam, midazolam, nasal, rectal, acute repetitive seizures, twenty-four hours

Amyloid fibril formation is generally associated with many neurodegenerative disorders, including Alzheimer's disease (AD). Although fibril plaque formation is associated with biological membranes in vivo, the role of the cell surfaces in amyloid fibril formation and the molecular mechanism of amyloid toxicity are not well understood. Understanding the details of amyloid interaction with lipid membrane may shed light on the mechanism of amyloid toxicity. Using atomic force microscopy, we investigated aggregation of amyloid-β1-42 (Aβ1-42) on model phospholipid membranes as a function of time and membrane composition. Neutral, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic - 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DOPG), and cationic - 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were used to study the effect of lipid type on amyloid binding. We showed that both the charge on the lipid head group and lipid phase affect the interaction of amyloid oligomers with the membrane surface changing the rate of adsorption and causing changes in membrane structure and structure of amyloid deposits. We observed that amyloid aggregates progressively accumulate in a similar manner on the surface of neutral DPPC gel phase membrane and on the surface of fluid phase negatively charged DOPG membrane. In contrast to DPPC and DOPG, positively charged fluid DOTAP membrane and neutral fluid phase DOPC membrane contain amyloid deposits with reduced height, which suggests fusing of Aβ1-42 into the lipid membrane surface. [ABSTRACT FROM AUTHOR]

Examines the correlation between scalp electroencephalogram (EEG) and proton magnetic resonance spectroscopy (H-MRS) in temporal lobe epilepsy. Degree on the concordance of H-MRS with the lateralization side; H-MRS in patients with normal EEG spikes; Observation on the anterior predominance of the H-MRS abnormalities.

Seizures are extremely common in the elderly, with an annual incidence reaching 100 per 100 000 people aged over 60 years. Most are precipitated by acute symptomatic illnesses such as stroke or systemic disease. Chronic neurological diseases such as Alzheimer's disease may also cause seizures. The aetiology of seizures in many patients is unknown. Seizures may be situational and subside quickly, but the prevalence of chronic seizures - epilepsy - is as high as 1% in the elderly. The majority of seizures are of partial onset, especially complex partial. Complex partial seizures at this age may be very subtle and hard to diagnose. Generalised-onset seizures also occur, perhaps as a result of diffuse changes with aging or degenerative disease or to a combination of genetic and environmental factors. The prognosis for complete seizure control in this population is relatively favourable. Physiological and disease-related changes with aging result in complex pharmacokinetics. Most changes lead to a need for gentler drug treatment with cautious initiation of drugs at lower dosages. Consideration must be given to renal and hepatic function, protein binding and drug interactions. Determinations of free (unbound) drug concentrations are helpful for highly protein bound drugs. The dosages of newer drugs excreted renally must be adjusted based on creatinine clearance. The dosage of most drugs is determined empirically by careful observation of seizure control and adverse effects. Carbamazepine, valproic acid (sodium valproate), gabapentin and lamotrigine have certain theoretical advantages, but comparative trials of anticonvulsants in the elderly are needed. The ideal drug for older patients would be effective, without neurological toxicity, with low protein binding, a nonparticipant in drug interactions and amenable to once daily administration. [ABSTRACT FROM AUTHOR]