SUDEP classification: Discordances between forensic investigators and epileptologists

We compared sudden unexpected death in epilepsy (SUDEP) diagnosis rates between North American SUDEP Registry (NASR) epileptologists and original death investigators, to determine degree and causes of discordance. In 220 SUDEP cases with post-mortem examination, we recorded the epileptologist adjudications and medical examiner- and coroner- (ME/C) listed causes of death (CODs). COD diagnosis concordance decreased with NASR’s uncertainty in the SUDEP diagnosis: highest for Definite SUDEP (84%, n = 158), lower in Definite Plus (50%, n = 36), and lowest in Possible (0%, n = 18). Rates of psychiatric comorbidity, substance abuse, and toxicology findings for drugs of abuse were all higher in discordant cases than concordant cases. Possible SUDEP cases, an understudied group, were significantly older, and had higher rates of cardiac, drug, or toxicology findings than more certain SUDEP cases. With a potentially contributing or competing COD, ME/Cs favored non–epilepsy-related diagnoses, suggesting a bias toward listing CODs with structural or toxicological findings; SUDEP has no pathognomonic features. A history of epilepsy should always be listed on death certificates and autopsy reports. Even without an alternate COD, ME/Cs infrequently classified COD as “SUDEP.” Improved collaboration and communication between epilepsy and ME/C communities improve diagnostic accuracy, as well as bereavement and research opportunities.     

Epilepsy and dental procedures. A review

This paper is a review of the dental management of patients with epilepsy. It includes discussion of the effects anti-epileptic drugs have on dental procedures and addresses complications and side effects of these drugs. A clinical case photo is presented to show gingival hyperplasia, along with four tables on which common antiepileptic medications are enumerated.     

Human papillomavirus testing 2007–2012: Co‐testing and triage utilization and impact on subsequent clinical management

In the United States, high‐risk human papillomavirus (HPV) testing is recommended for women with atypical squamous cells of unknown significance (ASC‐US) cytology, and co‐testing with cytology and HPV is a recommended option for screening women aged ≥30 years. No population‐based data are available to examine utilization of HPV testing in the United States. Using the New Mexico HPV Pap Registry data resource, we describe population trends (2007–2012) in utilization and positivity rates for HPV testing as a routine co‐testing screening procedure and for triage of ASC‐US and other cytologic outcomes. For women aged 30–65 years co‐testing increased from 5.2% in 2007 to 19.1% in 2012 (p < 0.001). Overall 82% of women with ASC‐US cytology who did not receive co‐testing also had an HPV test. HPV positivity was age and cytology result dependent but did not show time trends. For women with negative cytology, 64% received an additional screening test within 3 years if no co‐test was done or if it was positive, but this was reduced to 47% with a negative co‐test. Reflex HPV testing for ASC‐US cytology is well established and occurs in most women. Evidence for reflex testing is also observed following other abnormal cytology outcomes. Co‐testing in women aged 30–65 years has more than tripled from 2007 to 2012, but was still only used in 19.1% of women aged 30–65 years attending for screening in 2012. Women receiving co‐testing had longer repeat screening intervals, but rescreening within 3 years is still very common even with co‐testing.     

Disseminated coxsackievirus A6 affecting children with atopic dermatitis

Coxsackievirus A6 (CV‐A6) is an emerging pathogen that has in recent years been associated with atypical hand, foot and mouth disease. This manifests as a generalized papular or vesicular eruption, which may be associated with fever and systemic disturbance. We report a series of six children presenting to a single centre in the UK with disseminated CV‐A6 infection on a background of atopic dermatitis (AD). Our patients exhibited a widespread papular or vesicular eruption in association with exacerbation of AD. Several of our cases mimicked eczema herpeticum, but the extent was more generalized, and individual lesions were discrete rather than clustered and were less circumscribed in character. This series highlights that CV‐A6 infection may be encountered in the UK, and should be considered in the differential diagnosis of an acute exacerbation of AD, particularly in children.     

Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety

Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discriminant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes.     

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: Therapeutic implications

Purpose:   To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)–induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity.
Methods:   Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25–12.5 m m ) was delivered locally as a "pretreatment," followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 m m ) exposures were measured. In a last group of four rats, muscimol (0.8–2.5 m m ) was delivered epidurally during the ongoing, Ach-induced EEG seizure.
Results:   In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 m m . In the monkeys, subarachnoid muscimol pretreatments at 2.5 m m completely prevented the focal-seizure–inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 m m epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1–3 min.
Conclusions:   The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.