Diagnostic utility of prolonged ambulatory video-electroencephalography monitoring.

OBJECTIVES: Ambulatory video-electroencephalography (video-EEG) represents a low-cost, convenient and accessible alternative to inpatient video-EEG monitoring, however few studies have examined their diagnostic yield. In this large-scale retrospective study conducted in Australia, we evaluated the efficacy of prolonged ambulatory video-EEG recordings in capturing diagnostic events and resolving the referring question. METHODS: Sequential adult and paediatric ambulatory video-EEG reports from April 2020 to June 2021 were reviewed retrospectively. Data collection included patient demographics, clinical information, and details of events and EEG abnormalities. Clinical utility was assessed by examining i) time to first diagnostic event, and ii) ability to resolve the referring questions - seizure localisation, quantification, classification, and differentiation (differentiating seizures from non-epileptic events). RESULTS: Of the 600 reports analysed, 49 % captured at least one event, and 45 % captured interictal abnormalities (epileptiform or non-epileptiform). Seizures, probable psychogenic events (mostly non-convulsive), and other non-epileptic events occurred in 13 %, 23 % and 21 % of recordings respectively, with overlap. Unreported events were captured in 53 (9 %) recordings, and unreported seizures represented more than half of all seizures captured (51 %, 392/773). Nine percent of events were missing clinical, video or electrographic data. A diagnostic event occurred in 244 (41 %) recordings, of which 14 % were captured between the fifth and eighth day of recording. Reported event frequency ≥ 1/week was the only significant predictor of diagnostic event capture. In recordings with both seizures and psychogenic events, unrecognized seizures were frequent, and seizures may be missed if recording is terminated early. The referring question was resolved in 85 % of reports with at least one event, and 53 % of all reports. Specifically, this represented 46 % of reports (235/512) for differentiation of events, and 75 % of reports (27/36) for classification of seizures. CONCLUSION: Ambulatory video-EEG recordings are of high diagnostic value in capturing clinically relevant events and resolving the referring clinical questions.

Central neurogenic hyperventilation secondary to suspected metastatic renal cell carcinoma.

Central neurogenic hyperventilation (CNH) is a neurogenic disorder rarely described within Emergency Medicine literature. CNH is a primary cause of hyperventilation, most commonly due to primary central nervous system neoplasms. Patient presentation varies based on the underlying cause, and may present with a sole chief complaint of dyspnea. We present a case of an adult male with a history of deep vein thrombosis, anticoagulated on apixaban, and extensively metastatic renal cell carcinoma who presented with a two-week history of dyspnea. Evaluation in the emergency department showed a primary respiratory alkalosis with a compensatory metabolic acidosis. Diagnostic work-up failed to reveal a cardiac, pulmonary, metabolic, or toxic cause. During the emergency department course, the patient became dysarthric and altered, at which point, computed tomography scan of the head revealed a pontine hemorrhage. The hemorrhage was stabilized with prothrombin complex concentrate, but the patient's dyspnea and mental status deteriorated throughout the course of his hospitalization. While the cause of the patient's hemorrhage was not elucidated, given the patient's widely metastatic disease, it was presumed to be secondary to metastasis. Our case highlights both a unique cause of a rare disorder of hyperventilation, and a diagnostic challenge to the emergency medicine provider. It is important to consider central causes of hyperventilation in patients with dyspnea and neurologic symptoms.

Acquired cardiac channelopathies in epilepsy: Evidence, mechanisms, and clinical significance.

There is growing evidence that cardiac dysfunction in patients with chronic epilepsy could play a pathogenic role in sudden unexpected death in epilepsy (SUDEP). Recent animal studies have revealed that epilepsy secondarily alters the expression of cardiac ion channels alongside abnormal cardiac electrophysiology and remodeling. These molecular findings represent novel evidence for an acquired cardiac channelopathy in epilepsy, distinct from inherited ion channels mutations associated with cardiocerebral phenotypes. Specifically, seizure activity has been shown to alter the messenger RNA (mRNA) and protein expression of voltage-gated sodium channels (Nav 1.1, Nav 1.5), voltage-gated potassium channels (Kv 4.2, Kv 4.3), sodium-calcium exchangers (NCX1), and nonspecific cation-conducting channels (HCN2, HCN4). The pathophysiology may involve autonomic dysfunction and structural cardiac disease, as both are independently associated with epilepsy and ion channel dysregulation. Indeed, in vivo and in vitro studies of cardiac pathology reveal a complex network of signaling pathways and transcription factors regulating ion channel expression in the setting of sympathetic overactivity, cardiac failure, and hypertrophy. Other mechanisms such as circulating inflammatory mediators or exogenous effects of antiepileptic medications lack evidence. Moreover, an acquired cardiac channelopathy may underlie the electrophysiologic cardiac abnormalities seen in chronic epilepsy, potentially contributing to the increased risk of malignant arrhythmias and sudden death. Therefore, further investigation is necessary to establish whether cardiac ion channel dysregulation similarly occurs in patients with epilepsy, and to characterize any pathogenic relationship with SUDEP.

Deep brain stimulation for drug-resistant epilepsy.

OBJECTIVES: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug-resistant epilepsy, its safety, and the factors influencing individual outcomes. METHODS: A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug-resistant epilepsy. Reference lists of these articles were used to source further articles. RESULTS: Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%-90% seizure reduction with ANT-DBS, and a 48%-95% seizure reduction with HC-DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three-fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders-experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox-Gastaut syndrome. SIGNIFICANCE: We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large-scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response.

A midline pelvic mass: Ovarian fibroma appearing vaginal in nature.

Introduction: Ovarian fibroma is an uncommon, benign, stromal neoplasm that is a mixture of collagen-producing mesenchymal cells. There are varying sonographic and computed tomography features described in literature of smaller scale studies. Case Report: We describe a case of an ovarian fibroma presenting as a midline pelvic mass mimicking a vaginal cuff tumour in a 67-year-old patient with surgical history of a hysterectomy. Computed tomography and ultrasound were utilised to evaluate the mass and guide management of the patient. The mass was initially suspected on CT-guided biopsy as a vaginal spindle cell epithelioma amongst other potential differential considerations. With robot-assisted laparoscopic surgery and histologic analysis, the true diagnosis of an ovarian fibroma was reached. Discussion: An ovarian fibroma is an uncommon, benign, stromal ovarian tumour, representing just 1-4% of all ovarian tumours. Its widely varying imaging features present a challenge when radiologically evaluating ovarian fibromas or pelvic tumours, as the differential diagnoses are extensive and ovarian fibromas are often misdiagnosed until surgical resection. We highlight the features of ovarian fibromas and the potential value of pelvic/transvaginal ultrasonography in management of ovarian fibroma and other pelvic masses. Conclusion: The use of computed tomography and ultrasound aided in the diagnostic and treatment pathway of this patient with a pelvic mass. There is high utility of sonography in evaluating such tumours to elucidate salient features, expedite diagnosis, and guide further management.

Management of Severe Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a devastating and disfiguring disease of the skin involving the terminal follicular epithelium within the apocrine-gland-bearing skin. We present an interesting case of a 58-year-old female who presented with a 10-year history of refractory HS of the gluteal, perineal, perianal, and groin region. She had been chronically treated with multiple antibiotics in the past with no improvement. The patient subsequently underwent surgical local excision with complex closure. Medical management alone may not be optimal, especially in refractory disease. Early and aggressive surgical intervention and interdisciplinary approach are needed for patients with chronic and advanced stage of HS.

Revisiting the MotionWatch8©: Calibrating Cut-Points for Measuring Physical Activity and Sedentary Behavior Among Adults With Stroke.

Reduced moderate-to-vigorous physical activity (MVPA) and increased sedentary behavior (SB) are common following stroke, which can limit stroke recovery and contribute to greater cognitive decline. Hence, the MVPA and SB of adults with stroke should be measured concurrently using objective methods. One currently available method for objectively measuring MVPA and SB is the MotionWatch8© (MW8). However, adults with stroke can have significant mobility restrictions (depending on stroke severity) and thus it is important to determine separate MVPA and SB cut-points for adults with stroke, as well as validate separate cut-points: (1) when the MW8 is worn on the stroke affected side compared to the non-affected side; and (2) for adults with mild stroke versus adults with moderate-to-severe stroke. In the current study, we concurrently measured MW8 actigraphy (worn on both the stroke affected side and the non-affected side) and indirect calorimetry during 10 different activities of daily living for 43 adults with stroke (aged 55-87 years). Using intra-class correlations (ICC), we first investigated the agreement of the MW8 when placed on the affected side as compared to the non-affected side for: (1) all participants irrespective of stroke severity; (2) participants with mild stroke, classified as a Fugl Meyer motor score of ≥79/100; and (3) participants with moderate-to-severe stroke (i.e., Fugl Meyer < 79/100). We then determined cut-points for all participants-as well as separate cut-points based on stroke severity-on both the stroke affected side and non-affected side for SB and MVPA using receiver operating characteristic curves. The results of our analyses indicate that the agreement in MW8 output between the stroke affected and non-affected sides was moderate across all participants (ICC = 0.67), as well as for each sub-group (mild stroke: ICC = 0.64; moderate-to-severe stroke: ICC = 0.77). Additionally, the results of our cut-point analyses support using different cut-points for different levels of stroke severity and also for the stroke affected side. We determined the following cut-points: (1) for the affected side, adults with mild stroke have cut-points of SB ≤134 counts per minute (CPM) and MVPA ≥704 CPM, while adults with moderate-to-severe stroke have cut-points of SB ≤281 CPM and MVPA ≥468 CPM; and (2) the non-affected side, adults with mild stroke have cut-points of SB ≤162 CPM and MVPA ≥661 CPM, while adults with moderate-to-severe stroke have cut-points of SB ≤281 CPM and MVPA ≥738 CPM. Hence, these data provide a new measure for concurrently examining the dynamic relationships between MVPA and SB among adults with stroke.

Cluster-Buster: Finding dense clusters of motifs in DNA sequences.

The signals that determine activation and repression of specific genes in response to appropriate stimuli are one of the most important, but least understood, types of information encoded in genomic DNA. The nucleotide sequence patterns, or motifs, preferentially bound by various transcription factors have been collected in databases. However, these motifs appear to be individually too short and degenerate to enable detection of functional enhancer and silencer elements within a large genome. Several groups have proposed that dense clusters of motifs may diagnose regulatory regions more accurately. Cluster-Buster is the third incarnation of our software for finding clusters of pre-specified motifs in DNA sequences. We offer a Cluster-Buster web server at http://zlab.bu.edu/cluster-buster/.