Sunil A. Mutgi

Emerging Subspecialties in Neurology: Telestroke and teleneurology

In 2013, Dall et al.1 projected that by 2025, the societal need for neurologists will exceed availability by 19%. This number failed to account for the disproportionate number of neurologists practicing in urban and academic centers, likely underestimating the gap in rural populations. In a recent effort to improve access to neurologic services in these areas, telestroke and teleneurology networks have being championed as the solution. With the emergence of these networks come unique challenges and opportunities in the distribution and breadth of neurologic care that fellows and residents will need to understand to optimally incorporate this tool into their future practices.

Hypomagnesemia in Intracerebral Hemorrhage

BACKGROUND Magnesium (Mg) is an essential element for the bodys normal physiological functioning. It has a major role in modulating vascular smooth muscle tone and peripheral arterial resistance. A low serum Mg level on admission (HMg0) has been associated with more severe presentation in patients with subarachnoid hemorrhage. However, data on HMg0 specifically in relation to intracerebral hemorrhage (ICH) are scarce. We sought to determine the incidence and clinical significance of HMg0 in patients with ICH. METHODS We reviewed the records of consecutive patients with ICH over a 2-year period. Data collected included initial Mg levels (Mg0), clinical and radiologic characteristics on presentation, and discharge outcomes. Regression analysis was performed to look for any association of low Mg0 with admission blood pressure (BP) and Glasgow Coma Scale (GCS) scores. We also examined the correlation of HMg0 with clinical/radiologic features, admission severity (based on the ICH score), and poor outcome on discharge. RESULTS In all, 33.6% presented with HMg0. Mg0 levels were negatively associated with systolic BP presentation (P < 0.0001) and positively associated with the initial GCS scores (P = 0.01). Multivariate logistic regression showed an association between HMg0 and severity at presentation (P = 0.03), but not with poor outcome on discharge (P = 0.26). CONCLUSIONS HMg0 occurs in one third of patients with ICH and is associated with more severe presentation and intraventricular hemorrhage. Mg levels on admission correlate inversely with systolic BP and directly with GCS scores at presentation. HMg0 does not influence outcomes at discharge.

Rivaroxaban for the treatment of cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is an uncommon condition in the general population, but occurs at a higher frequency among individuals aged ≤40 (1). To prevent thrombus growth and facilitate recanalization, warfarin anticoagulation is recommended (2). However, frequent international normalization ratio monitoring may burden young patients with active lifestyles. Rivaroxaban is a direct factor Xa inhibitor approved for venous thromboembolism and nonvalvular atrial fibrillation. It is a once-daily medication that requires no blood monitoring. Here, we report the outcomes of two CVT patients who chose to underwent anticoagulation with rivaroxaban instead of warfarin. One was a 39-year-old female attorney who had been taking oral contraceptives for a year, in addition to smoking. Brain magnetic resonance venography (MRV) showed thrombosed left lateral and sigmoid sinuses (Fig. 1a). The other was a 32-year-old male laborer who presented with thunderclap headache. MRV showed thrombosis of the right lateral and sigmoid sinuses, as well as the internal jugular vein (Fig. 1c). Exam and hypercoagulable state workup in both patients were normal. After three-months of therapy with rivaroxaban, follow-up MRV of the first patient showed partial to complete recanalization of the left lateral sinus (Fig. 1b), and on the second patient, partial to complete recanalization of the right lateral and sigmoid sinus (Fig. 1d). Neither patient reported any bleeding complications. Both were taken off rivaroxaban after threeto four-months. There was no evidence of recurrence at 6and 12-month follow-up. The use of rivaroxaban in CVT has been reported in a small series by Geisbüsch et al. (3). Among 16 patients with CVT, seven were treated with rivaroxaban. All patients showed at least partial recanalization with no major bleeding within a median follow-up period of eightmonths. Rivaroxaban may be an effective anticoagulation strategy in patients with benign/uncomplicated CVT who do not require long-term anticoagulation. Correspondence: Réza Behrouz*, Medical Arts and Research Center, University of Texas Health Science Center San Antonio, 3800 Floyd Curl Drive, San Antonio, TX 78229, USA. E-mail: behrouz@uthscsa.edu

Impact of oral health in patients with multiple sclerosis and epilepsy: A survey in a neurology clinic

This study investigated the impact of oral health on neurological disorders using the Oral Health Impact Profile (OHIP). A total of 460 subjects completed the OHIP, including 141 control subjects who did not have any neurological conditions. Of the 319 subjects with a neurological diagnosis who were enrolled in the study, 31% had multiple sclerosis (MS), 34% had epilepsy, and 34% had other neurological conditions. Compared to the control group, mean age (p = .001), education (p = .003), and household income levels (p ≤ .001) were statistically significantly lower among subjects with epilepsy than in the other two groups. The majority of the study populations were Caucasian and the percentage was highest in those with MS (87%). Patients with any neurologic diagnosis had greater physical pain and disability than controls. Adjusting for demographic variables, the impact of physical disability was statistically significantly higher in patients with any neurological diagnosis (including MS and epilepsy) (OR = 4.49). In multinomial regression, the strongest association of physical disability impact was noted in patients with epilepsy (OR = 5.17). The physical disability domain of the OHIP is more commonly associated with a neurological diagnosis, including MS, and the association is strongest in patients with diagnosis of epilepsy.

Intracerebral hemorrhage patients presenting with normal blood pressure

There are patients with intracerebral hemorrhage (ICH) who present with blood pressure (BP) values below the standard treatment threshold recommended by the American Heart Association/American Stroke Association (AHA/ASA; systolic o150mmHg). Specific data on this category of ICH patients is, however, scarce. In this study, we looked at the proportion of ICH patients who present with systolic BP o150mmHg, their clinical/radiological features, initial severity and discharge outcomes. We determined that ~ 1 in 10 ICH patients presents with systolic BP o150mmHg, and the majority are lobar. Moreover, presentation with systolic BP lower than the standard treatment threshold has no association with initial severity or discharge outcomes. The cornerstone of acute therapy for patients with intracerebral hemorrhage (ICH) is BP control, notwithstanding the absence of convincing evidence that acute BP lowering has a positive impact on outcomes. Currently, it is the recommendation of the AHA/ASA that BP be lowered in ICH patients presenting with a systolic value ⩾ 150mmHg. This leaves a management gap with regard to patients who present with systolic BP o150mmHg. The aim of this study was to determine the proportion of ICH patients who present with systolic BP o150 mmHg, their clinical features, severity and discharge outcomes. An institutional review board approval was obtained for this study. A retrospective review of the medical records of consecutive patients with nontraumatic ICH treated at the Ohio State University between January 2011 and December 2013 was conducted. The International Classification of Diseases, Ninth Revision, diagnosis code for ICH (431) was used to compile a list of patients for analysis. Patients with ICH related to tumor, aneurysm or arteriovenous malformation were excluded. To prevent the confounding effects of surgery on outcomes, we also excluded patients who underwent emergency craniotomy for hematoma evacuation. All ICH patients were managed in accordance with the ASA/AHA guidelines, including timely initiation of intravenous antihypertensive medications. The following data were recorded: presentation systolic BP and Glasgow Coma Scale (GCS) score, age, gender, admission International Normalization Ratios (INRs), hourly systolic BP values for up to 24 h, hematoma volume and location, intraventricular hemorrhage and length of stay (LOS). The ICH Score, a clinical grading scale that allows risk stratification on presentation with ICH, was a used to estimate clinical severity. An ICH score ⩾ 3 was considered severe. Hematoma volume was measured on the initial head computed tomography scan using the ABC/2 method. Outcomes on hospital discharge were recorded as scores on the modified Rankin Scale (mRS), a stroke outcome scale with scores ranging from 0 (no symptoms at all) to 6 (dead). At the Ohio State University Medical Center, based on institutional policy, mRS scores at discharge are documented for all stroke patients. For the purpose of this study, systolic BP of o150 mmHg was considered ‘normal’. A dichotomy was created between hypertensive (systolic BP ⩾ 150 mmHg) and normotensive (systolic BP o150mmHg). Student’s t-test was used to measure any significant difference between the two groups in relation to continuous variables (age, systolic BP, GCS, ICH volume and LOS). The following features were also dichotomized to create categorical variables: good outcome and poor outcome (mRS ⩾ 4), and high (41.4) and normal INR, and severe (ICH Score ⩾ 3) and non-severe presentation. The equality of proportions was compared with the use of Fisher’s exact test and the χ-test. A P-value of 0.05 or less was considered significant. Of the 433 patients gathered via the initial query, 128 patients met our inclusion criteria; 16 (12.5%) presented with systolic BP o150 mmHg (Po0.0001). The mean age for this group was 67.4 ± 15.4. There were 11 lobar, 3 basal ganglia and 2 cerebellar hematomas. Mean systolic BP for the normotensive and hypertensive groups were 136.3 ± 7.8 and 188.3 ± 18.4 mmHg, respectively (Po0.0001). Between the normotensive and the hypertensive groups, there was no difference in admission severity (P= 0.39) or poor outcomes on discharge (P= 0.89). Hematomas in the normotensive group were mostly lobar (P= 0.01). Table 1 displays the characteristic differences between the two groups in more detail. Overall, there was no significant difference between any clinical or radiological features between the normotensive and hypertensive ICH patients. Although it seemed that INR 41.4 was more prevalent in normotensive (37.5%) than hypertensive patients (16.9%), this difference was not significant (P= 0.085). Following systolic BP values for 24 h for each normotensive patient showed elevation above 150mmHg in only two patients. Each of these patients received an intravenous antihypertensive bolus with good response; neither were started on continuous infusion. This study showed that ~ 1 in every 10 patients with ICH presents with systolic BP o150mmHg; a significant fraction statistically. Clinical characteristics of these patients were no different than those presenting with high BP. Moreover,

Letter by Behrouz et al Regarding Article, “Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion”

The study by Coutts et al1 on intravenous tenecteplase for minor strokes is a reminder, once again, that a large-scale trial involving this drug in acute ischemic stroke is needed. Although the study was small and uncontrolled, it reiterated what earlier investigations have suggested about the safety and efficacy of tenecteplase.2 In tenecteplase–tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion-1, no comparison to historical alteplase cases could be made because, as the authors acknowledged, patients with minor strokes are excluded or under-represented in most of the stroke thrombolysis trials. The investigators could, nonetheless, compare their results to a matched control group of patients who did not receive any …

Practice Diversity among US Stroke Physicians with Respect to the 3- to 4·5-h Window

In 2009, the American Heart Association/ American Stroke Association (AHA/ASA) endorsed the extension of the intravenous (IV) tissue plasminogen activator (tPA) window to 4·5 h from symptom onset for acute ischemic stroke (AIS) (1). This is now a Class Ib recommendation (2). There are two implications of this extended therapeutic window. First, IV tPA is not approved by the US Food and Drug Administration for that particular window. This raises the question whether off-label administration of IV tPA, which has more than minimal risk, requires an informed consent. Second, there are four additional exclusion criteria: age >80 years, baseline National Institutes of Health Stroke Scale (NIHSS) score >25, warfarin use (despite International Normalization Ratio of 1·7 or less), and a combined history of prior stroke and diabetes (2). These four characteristics were part of the main exclusion criteria for the third European Cooperative Acute Stroke Study (ECASS III) (3). They were not established based on a lack of benefit or poor outcomes. Therefore, in practice, precluding patients meeting these criteria is based on the absence of evidence, not evidence of absence. Since the advisory, there has been a significant increase in the use of tPA between 3 and 4·5 h (4). In the Minnesota Stroke Registry, patients who received IV rt-PA within the 3to 4·5-h window comprised 17% of all IV tPA cases treated (5). Still, it is unknown how the overall practice of AIS care has evolved over the past fiveyears, particularly in relation to the two issues discussed. Through an online survey targeting colleagues in the Stroke Council, we sought the answers to two questions: (1) Does the off-label prescription of IV tPA within the 3 to 4·5-h window require an informed consent? and (2) considering the lack of evidence that patients who meet the additional four exclusions do not benefit from IV tPA, how strongly do stroke practitioners adhere to the those criteria? An approval was obtained by the Institutional Review Board (IRB) at our University. We used the AHA/ASA online member directory to identify and gather e-mail addresses for potential participants. The following filters were used in our search: Council: Stroke, Specialty: Neuro/Stroke, Classification: Physician, and Country: USA. A questionnaire targeting our research questions was generated using the Survey MonkeyTM (SM) online service. A link to the survey was e-mailed to each member whose address was available, totaling 1027 members. The survey included an electronic consent form, followed by six questions (Table 1). The consent form had a check box for respondents to agree to participate, and the survey would not appear unless the ‘agree’ box was checked. The respondents were asked to indicate their respective subspecialties and to answer questions pertaining to the 3 to 4·5-h window. Answer options were divided based on frequency of performance: always, often (>50% of the time), seldom (<50% of the time), and never. In accordance with the IRB guidelines, we were also included ‘decline to answer’. The survey was only sent once to each member, and after completing it once, it could not be retaken. All answers received were completely anonymous. The survey was available online for fivedays. For analysis, SM filters were used to exclude respondents who did not agree to participate and those who skipped or declined to answer any of the six questions. Consequently, we only included answers from colleagues who consented and completed the questionnaire in its entirety. In total, there were 260 (25%) responses. After applying the SM filters, 230 participants were selected for analysis. The majority (83·5%) identified their practice as vascular neurology, 13·5% as general neurology, and 3% as other neurology subspecialty. One-third (33·5%) of the participants stated that they always obtained informed consents. Almost the same proportion (28·3%) claimed they never did. Twentytwo percent did so often, and 16·1% chose seldom. The average percentage of participants always following all four exclusions was 32·1%; often = 22%, seldom = 24·8%, and never = 23·2%. Results for individual questions are displayed in Table 2. Correspondence: Réza Behrouz*, Division of Cerebrovascular Diseases & Neurosciences Critical Care, Department of Neurology, Ohio State University College of Medicine, 333 West 10th Avenue, Columbus, OH 43210, USA. E-mail: Reza.Behrouz@osumc.edu