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1.
Brain ; 143(1): 191-209, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31834353

ABSTRACT

Temporal lobe epilepsy represents a major cause of drug-resistant epilepsy. Cognitive impairment is a frequent comorbidity, but the mechanisms are not fully elucidated. We hypothesized that the cognitive impairment in drug-resistant temporal lobe epilepsy could be due to perturbations of amyloid and tau signalling pathways related to activation of stress kinases, similar to those observed in Alzheimer's disease. We examined these pathways, as well as amyloid-ß and tau pathologies in the hippocampus and temporal lobe cortex of drug-resistant temporal lobe epilepsy patients who underwent temporal lobe resection (n = 19), in comparison with age- and region-matched samples from neurologically normal autopsy cases (n = 22). Post-mortem temporal cortex samples from Alzheimer's disease patients (n = 9) were used as positive controls to validate many of the neurodegeneration-related antibodies. Western blot and immunohistochemical analysis of tissue from temporal lobe epilepsy cases revealed increased phosphorylation of full-length amyloid precursor protein and its associated neurotoxic cleavage product amyloid-ß*56. Pathological phosphorylation of two distinct tau species was also increased in both regions, but increases in amyloid-ß1-42 peptide, the main component of amyloid plaques, were restricted to the hippocampus. Furthermore, several major stress kinases involved in the development of Alzheimer's disease pathology were significantly activated in temporal lobe epilepsy brain samples, including the c-Jun N-terminal kinase and the protein kinase R-like endoplasmic reticulum kinase. In temporal lobe epilepsy cases, hippocampal levels of phosphorylated amyloid precursor protein, its pro-amyloidogenic processing enzyme beta-site amyloid precursor protein cleaving enzyme 1, and both total and hyperphosphorylated tau expression, correlated with impaired preoperative executive function. Our study suggests that neurodegenerative and stress-related processes common to those observed in Alzheimer's disease may contribute to cognitive impairment in drug-resistant temporal lobe epilepsy. In particular, we identified several stress pathways that may represent potential novel therapeutic targets.


Subject(s)
Amyloid beta-Peptides/metabolism , Cognitive Dysfunction/pathology , Epilepsy, Temporal Lobe/pathology , Hippocampus/pathology , Peptide Fragments/metabolism , Plaque, Amyloid/pathology , Temporal Lobe/pathology , tau Proteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/metabolism , Autopsy , Case-Control Studies , Child , Child, Preschool , Cognitive Dysfunction/complications , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology , Drug Resistant Epilepsy/complications , Drug Resistant Epilepsy/metabolism , Drug Resistant Epilepsy/pathology , Drug Resistant Epilepsy/surgery , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/metabolism , Epilepsy, Temporal Lobe/surgery , Female , Hippocampus/metabolism , Hippocampus/surgery , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Male , Middle Aged , Neurosurgical Procedures , Plaque, Amyloid/metabolism , Temporal Lobe/metabolism , Temporal Lobe/surgery , Young Adult , eIF-2 Kinase/metabolism
2.
Neurol Clin Pract ; 7(2): 109-117, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28409062

ABSTRACT

BACKGROUND: This study investigated the quality of care delivered by nurse practitioner (NP)-physician teams employed to expand clinic appointment availability for patients with epilepsy. METHODS: We performed a retrospective observational cohort study of patients with epilepsy presenting to the Penn Epilepsy Center for a new patient appointment in 2014. During this time, patients were seen either by an NP-physician team care model or a more traditional physician-only care model. These care models were compared with regard to adherence to the 2014 American Academy of Neurology epilepsy quality measures at the initial visit. Clinical outcomes of seizure frequency, presentations to the Emergency Department, injury, and death were assessed over the subsequent year. RESULTS: A total of 169 patients were identified by our inclusion and exclusion criteria: 65 patients in the NP-physician team care model cohort and 104 patients in the physician-only care model cohort. The NP-physician team care model saw, on average, 3 more patients per clinic session. There were no meaningful differences between these cohorts in baseline characteristics. The NP-physician team care model showed equivalent adherence to the physician-only care model for the epilepsy quality measures, with superior adherence to the counseling measures of querying for side effects, provision of personalized epilepsy safety education, and screening for behavioral health disorders. The 2 care models performed similarly in all clinical outcomes. CONCLUSIONS: An NP-physician team care model employed to increase availability of care could also improve quality of care delivered.

3.
J Drugs Dermatol ; 15(7): 891-2, 2016 Jul 01.
Article in English | MEDLINE | ID: mdl-27391641

ABSTRACT

Xanthelasma palpebrae are common lesions on both medical and dermatology patients. They are significant from both medical and dermatologic perspectives. They serve as a sentinel for elevated cholesterol as well as a cosmetic dermatologic issue. Treatment of these lesions requires consideration of diagnosing and treating any underlying cholesterol problem as well as removal of existing lesions. We report a simple yet effective method for treatment of these lesions.

J Drugs Dermatol. 2016;15(7):891-892.


Subject(s)
Electrosurgery/methods , Eyelid Diseases/diagnosis , Eyelid Diseases/surgery , Xanthomatosis/diagnosis , Xanthomatosis/surgery , Female , Humans , Middle Aged , Treatment Outcome
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