Does glucose influence multidien cycles of interictal and/or ictal activities?

PURPOSE: There are multidien patterns of seizure occurrence. Predicting seizure risk may be easier with biomarker correlates to multidien patterns. We hypothesize multiday hyper or hypoglycemia contributes to seizure risk. METHODS: In a type I diabetic (T1D) with focal onset epilepsy with continuous glucose monitoring (CGM) and responsive neurostimulation (RNS) devices, we studied multiday interictal activities (IEA), seizures, and glucose. Hourly CGM data was matched to hourly RNS captures of interictal and ictal activities over 33 months. RNS detection settings were unchanged. Multidien cycles were analyzed, active blocks of IEA and ictal episodes defined, and tissue glucose averages studied. RESULTS: Average glucose was 161 mg/dl. A 40-day cycle of interictal and ictal activities occurred, though no similar glucose cycle was evident. Glucose elevations relative to patient average were associated with increases in IEA but not seizure. Frequent seizures were not associated with obvious elevations or decreases of glucose from baseline, most seizures occurred at +/- 10 mg/dl of average daily glucose (i.e. 150-170 mg/dl). CONCLUSION: Tissue glucose may influence IEA but may not influence multiday seizure activity or very frequent seizures. In an ambulatory T1D patient multiday hypo or hyperglycemic extremes do not appear to provoke seizure activities.

Pregnancy outcomes in women with epilepsy and MTHFR mutations supplemented with methylated folate and methylcobalamin (methylated B12).

Antiseizure medications (ASM) may contribute to adverse fetal outcomes in pregnant women with epilepsy (WWE). Folate processing (Methylenetetrahydrofolate reductase, MTHFR) gene abnormalities are common in women with epilepsy and depression. L-methylfolate supplements may bypass MTHFR deficiencies, yet their use in WWE during gestation or on fetal development is not well studied. We examine pregnancy histories of three WWE who supplemented with either folate or L-methylfolate and methylcobalamin (methylated B12) during pregnancies. Their pregnancy outcomes improved with L-methylfolate and methylcobalamin supplementation. L-methylfolate and methylcobalamin supplementation merits further study in WWE who have MTHFR mutations, fertility, recurrent miscarriage and or depression histories.

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.

OBJECTIVE: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System. METHODS: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. RESULTS: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. SIGNIFICANCE: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.

Are there mortality risks for patients with epilepsy who use cannabis treatments as monotherapy?

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

Continuous monitoring devices and seizure patterns by glucose, time and lateralized seizure onset.

OBJECTIVES: To investigate if glucose levels influence seizure patterns. MATERIALS AND METHODS: In a patient with RNS/NeuroPace implanted bi-temporally and type 1 diabetes mellitus, seizure event times and onset locations were matched to continuous tissue glucose. RESULTS: Left focal seizure (LFS, n = 22) glucoses averaged 169 mg/dL, while right focal seizure (RFS, n = 23) glucoses averaged 131 mg/dL (p = 0.03). LFS occurred at mean time 17:02 while RFS occurred at 04:23. LFS spread to the contralateral side (n = 19) more than RFS (n = 2). CONCLUSION: Seizure onset laterality and spread vary with glucose and time of seizure.

Pilot data on responsive epilepsy neurostimulation, measures of sleep apnea and continuous glucose measurements.

OBJECTIVES: To match responsive neurostimulator (RNS) and polysomnographic data to determine if RNS detections and stimulations correlate with measurements of sleep disordered breathing and continuous glucose measurements (CGM). MATERIALS AND METHODS: In a patient with an RNS with detection/stimulation leads implanted bi-temporally detection-stimulation counts were matched by time with coinciding polysomnogram and CGM data. RESULTS: Temporal dispersion of RNS DSC were independent of measures of sleep apnea, hypopnea or glucose. CONCLUSION: Hippocampal nighttime responsive neurostimulation therapies did not appear to worsen measures of normal or abnormal sleep.

Individualizing therapies with responsive epilepsy neurostimulation - A mirtazapine case study of hippocampal excitability.

OBJECTIVES: This study aimed to investigate mirtazapine-induced changes in responsive neurostimulator (RNS) recordings in a patient with epilepsy. MATERIALS AND METHODS: Cortical detection/stimulation counts from an RNS implanted in a patient with bitemporal epilepsy were matched to mirtazapine use to see if that drug altered hippocampal excitability. RESULTS: Mirtazapine decreased hippocampal stability; when mirtazapine was held after a washout period, DSC counts declined, but when it was retrialed, DSC counts increased. Responsive epilepsy neurostimulator system data helped design an optimal and individualized medication regimen for our patient with drug-resistant focal epilepsy. CONCLUSIONS: Responsive neurostimulator systems in epilepsy may assess a medication's effect on hippocampal excitability. Mirtazapine worsened hippocampal excitability in a patient with bitemporal epilepsy.

Mitigating bit flips or single event upsets in epilepsy neurostimulators.

OBJECTIVES: The objective of this study was to review software errors known as single event upsets (SEUs) or bit flips due to cosmic rays in epilepsy neurostimulators. MATERIALS AND METHODS: A case report of a single event upset or bit flip is discussed; device manufacturers and publicly available data were queried for both incidence and types of error as well as strategies of software error mitigation. RESULTS: Neurostimulators, like other implanted devices such as pacemakers, are prone to single event upsets. Strategies for SEU mitigation are reviewed. CONCLUSIONS: Cosmic radiation can threaten RAM and settings of neurostimulators; neuromodulation teams and device designers need to take this threat into account when designing multifunctional neuromodulation systems.

Expression of CK7, Cam 5.2 and Ber-Ep4 in cutaneous squamous cell carcinoma.

BACKGROUND: Cytokeratin 7 (CK7) and Cam 5.2 are often used to differentiate extramammary Paget's disease (EPD) from squamous cell carcinoma (SCC) in situ because they are generally considered to be expressed in the former but not in the latter. However, we have encountered CK7+ and Cam 5.2+ SCCs. METHODS: We evaluated CK7, Cam 5.2 and Ber-Ep4 expression in SCC and EPD. RESULTS: We found significant CK7 and Cam 5.2 positivity in SCCs, particularly in those with a pagetoid pattern. Only one case expressed Ber-Ep4. CONCLUSIONS: We conclude that CK7 and Cam 5.2 expression may occur in SCC. A panel including Ber-Ep4 is advisable for immunohistochemical differentiation of EPD from SCC.

Infectious complications of dermatologic procedures.

Although the infection rate of dermatologic procedures is extremely low, it is important to understand the serious complications that may result from one of these rare events. With the ever increasing number of dermatologic procedures performed, research continues to build regarding cutaneous infections. In order to properly treat a surgical site infection, the etiology and course of the infection must be known. The common microbes, types of infections, prophylaxis, and treatments involved in dermatologic surgery are reviewed.