David B. Burkholder

Interictal Scalp Electroencephalography and Intraoperative Electrocorticography in Magnetic Resonance Imaging–Negative Temporal Lobe Epilepsy Surgery

IMPORTANCE Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging-negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. OBJECTIVES To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging-negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. DESIGN, SETTING, AND PARTICIPANTS Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging-negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. MAIN OUTCOMES AND MEASURES Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. RESULTS Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (P = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (P = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. CONCLUSIONS AND RELEVANCE Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging-negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy.

Associated Factors and Prognostic Implications of Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges.

IMPORTANCE The implications of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) sometimes found on prolonged electroencephalographic (EEG) recordings are uncertain. OBJECTIVE To evaluate the incidence of SIRPIDs and their clinical implications in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS A multicenter, international retrospective study was performed from October 1, 2012, through September 30, 2014, of consecutive adult patients hospitalized in intensive care units with alteration of consciousness who underwent EEG recordings at 3 separate centers. Demographic data, including admission diagnosis, age, sex, history of epilepsy, and EEG findings, were noted. Characteristics of SIRPIDs were documented. Data were evaluated for predictors of SIRPIDs and in-hospital mortality. Data analysis was performed from January 16, 2015, to June 15, 2015. MAIN OUTCOMES AND MEASURES Incidence of SIRPIDs, association of SIRPIDs with mortality and other EEG characteristics, and EEG and clinical predictors of mortality. RESULTS A total of 416 patients were studied. The median age of patients was 60 years (interquartile range, 46-71 years), and 252 (60.6%) were male. A total of 104 patients (25.0%) did not survive to hospital discharge. SIRPIDs were identified in 43 patients (10.3%). The proportion of patients with SIRPIDs was not significantly different across the 3 sites (P = .34). Anoxic brain injury (odds ratio [OR], 3.80; 95% CI, 1.73-8.33; P < .001), the use of antiepileptic medications (OR, 3.24; 95% CI, 1.31-8.00; P = .01), electrographic seizures (OR, 2.85; 95% CI, 1.13-7.19; P = .03), generalized periodic discharges with triphasic morphologic features (OR, 3.66; 95% CI, 1.67-8.02; P = .001), and sporadic sharp waves and periodic discharges (OR, 2.59; 95% CI, 1.13-5.92; P = .02) were independently associated with the presence of SIRPIDs. Older age (OR, 1.02; 95% CI, 1.01-1.04; P = .005), anoxic brain injury (OR, 3.49; 95% CI, 1.96-6.21; P ≤ .001), and absence of EEG reactivity (OR, 8.14; 95% CI, 4.20-15.79; P < .001) but not SIRPIDs (OR, 1.73; 95% CI, 0.79-3.78; P = .17) were independently associated with in-hospital mortality. CONCLUSIONS AND RELEVANCE In critically ill patients undergoing EEG recordings, SIRPIDs occurred in 43 (10.3%) and were associated with other electrographic abnormalities previously reported to indicate poor prognosis. However, SIRPIDs were not independently associated with in-hospital mortality.

Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM) proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca2+ ([Ca2+]i) responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca2+ regulatory proteins leading to increased store operated Ca2+ entry (SOCE) and cell proliferation. Using isolated human ASM (hASM) cells, incubated in the presence and absence cigarette smoke extract (CSE) we determined ([Ca2+]i) responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS) and cytokine generation. CSE enhanced [Ca2+]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca2+ regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.

Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy.

We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data.

Harry Lee Parker and paroxysmal dysarthria and ataxia

Objective: To review descriptions of paroxysmal dysarthria and ataxia in multiple sclerosis (MS), with special attention given to Parker and his 1946 case series. Methods: Evaluation of original publications describing paroxysmal dysarthria and ataxia, bibliographic information, writings, and unpublished letters from the Mayo Clinic Historical Unit. Results: In 1940, Störring described a patient with MS with paroxysmal symptoms that included dizziness and trouble speaking, but also unilateral extremity weakness. In 1946, Parker published a series of 11 patients with paroxysmal dysarthria and ataxia. Six of these patients had MS, and he recognized this phenomenon as a manifestation of the disease. The term “paroxysmal dysarthria and ataxia” was first used in 1959 by Andermann and colleagues. Since that time, paroxysmal dysarthria and ataxia has become a well-recognized phenomenon in MS. More recent reports have suggested that the responsible lesion is located in the midbrain, near or involving the red nucleus. Conclusions: Parker was the first to accurately describe paroxysmal dysarthria and ataxia in patients with MS.

Routine vs extended outpatient EEG for the detection of interictal epileptiform discharges

Objective: To compare the yield of epileptiform abnormalities on 30-minute recordings with those greater than 45 minutes. Methods: We performed a prospective observational cross-sectional study of all outpatient routine EEGs comparing the rate of interictal epileptiform discharges (IEDs) and clinical events during the initial 30 minutes (routine) with those occurring in the remaining 30–60 minutes (extended). A relative increase of 10% was considered clinically significant. Results: EEGs from 1,803 patients were included; overall EEG duration was 59.4 minutes (SD ±6.5). Of 426 patients with IEDs at any time during the EEG, 81 (19.1%, 95% confidence interval 15.6–23) occurred only after the initial 30 minutes. The rate of late IEDs was not associated with age, indication, IED type, or sleep deprivation. Longer recording times also increased event capture rate by approximately 30%. Conclusions: The yield of IED and event detection is increased in extended outpatient EEGs compared to 30-minute studies.

The origin of Woltman’s sign of myxoedema

Woltmans sign of myxoedema, named after Henry Woltman in 1956, is the delayed relaxation phase of the muscle stretch reflex in patients with myxoedema. Although a change in these reflexes was mentioned as being clinically evident possibly as early as the 1870s, no formal description was published until 1924 when William Calvert Chaney objectively quantified the change. Woltman was involved in training Chaney, and it has been proposed that he guided Chaneys study of these reflexes. Despite the attachment of Woltmans name to the eponym, little evidence exists that directly links him to the first objective study of the muscle stretch reflex in myxoedema performed by Chaney.

Blood-fluid level on computed tomography head: a sign of warfarin-associated intraparenchymal hemorrhage

“Blood/fluid level” represents interface between the plasma and sedimented blood and is defined radiologically as presence of area of low computed tomography (CT) attenuation above and high CT attenuation below a discrete line of separation in an area of intraparenchymal hemorrhage. It is a rare finding seen in association with large clot volume of intraparenchymal hemorrhage. We present a case of warfarin-related intraparenchymal hemorrhage presenting with a classic sign of “blood/fluid level” on CT head with small clot volume.

Structured handoff checklists improve clinical measures in patients discharged from the neurointensive care unit

SummaryWhile up to 80% of medical errors may result from poor communication at clinical transitions of care, there has been relatively little study of the effect of standardized communication tools on clinical quality measures. We prospectively examined the effect of a standardized handoff checklist on clinical outcomes for patients dismissed from the neurointensive care unit. We found that the checklist resulted in significant reductions in patients transferred with inaccurate medication reconciliation and unnecessary urinary catheters. Participating physicians were surveyed and generally viewed the handoff checklist favorably. Standardized communication tools such as checklists may play a useful role in reducing medical errors related to communication between patient care teams.

Charles E. Beevor's lasting contributions to neurology: More than just a sign

Charles Edward Beevor (1854–1908) was a prominent English neurologist who served in a variety of positions at the National Hospital for the Paralysed and Epileptic, Queen Square, from 1883 until his sudden death due to coronary artery disease in 1908. Staunchly committed to the meticulous study of neuroanatomy and physiology and education of his fellow physicians, Beevor was an accomplished clinician-scientist. He is most well known for describing the Beevor sign (commonly known as “Beevors sign”), which is the upward movement of the umbilicus with truncal flexion from a supine position, used to indicate a spinal cord lesion between the levels of T10 and T12. His sign has also been reported to be suggestive of facioscapulohumeral muscular dystrophy. While the initial description of the Beevor sign has traditionally been attributed to his 1903 Croonian Lectures, he actually first described his sign in his 1898 textbook Diseases of the Nervous System: A Handbook for Students and Practitioners. In addition to his eponymous sign, Beevor also made significant contributions to the understanding of the representation of motor movements in the cerebral cortex, and, of more importance, utilized a novel method to identify cerebral vascular territory maps that are still utilized by neurologists today.