Kay E. Wellik

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

Caffeine for the prevention and treatment of postdural puncture headache: debunking the myth.

Objective:Is caffeine effective in preventing and treating postdural puncture headache (PDPH)? Methods:The question was addressed with a structured evidence-based clinical neurologic practice review via videoconferencing between 3 academic institutions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, starting with a clinical scenario and structured question. Participant groups at each of the 3 institutions independently devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:Three directly relevant randomized controlled trial articles were selected as the best available evidence for the clinical questions. Two investigated caffeine [oral and intravenous (IV)] as PDPH prophylaxis and 1 (oral) as PDPH treatment. One additional quasirandomized trial (IV) and 1 open-label trial (IV) of caffeine for PDPH treatment were located by reviewing bibliographies. Articles describing the pharmacological basis for caffeine therapy were also identified. No valid pharmacological rationale for caffeine as an antinociceptive agent for PDPH exists. The clinical trials are few in number, small in sample size, methodologically weak or flawed, and either demonstrate no effectiveness, contradictory and conflicting results, or invalid answers. Conclusions:The wide endorsement for caffeine to prevent and treat PDPH found in textbooks and review articles appears to be unwarranted and insufficiently supported by the available pharmacological and clinical evidence.

Does cervical manipulative therapy cause vertebral artery dissection and stroke

Objective:Does cervical manipulative therapy (CMT) cause vertebral arterial dissection (VAD) and subsequent ischemic stroke? What is the best estimate of the incidence of CMT associated with VAD and ischemic stroke? Methods:The questions were addressed with a structured evidence-based clinical neurologic practice review. Participants included neuroscience students, consultant neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, starting with a clinical scenario and structured question. The participant group devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:The search yielded 169 citations, of which 55 were deemed most relevant. From this return, we selected 26 publications of the highest evidence available: 3 case-control studies, 8 prospective and retrospective case series studies, 4 illustrative case reports, 1 survey, 1 systematic review of observational research, 5 reviews, and 4 opinion and expert commentary pieces. Five of the applicable 7 criteria for causation were satisfactorily met and supported weak to moderate strength of evidence for causation between CMT and VAD and associated stroke, especially in young adults. Young vertebrobasilar artery territory stroke patients were 5 times more likely than controls to have had CMT within 1 week of the event date (OR 5.03, 95% CI, 1.32–43.87). No significant associations were found for those ≥45 years of age. The best available estimate of incidence is approximately 1.3 cases of VAD or occlusion attributable to CMT for every 100,000 persons <45 years of age receiving CMT within 1 week of manipulative therapy. Conclusions:Weak to moderately strong evidence exists to support causation between CMT and VAD and associated stroke. Ultimately, the acceptable level of risk associated with a therapeutic intervention like CMT must be balanced against evidence of therapeutic efficacy. Further research, employing prospective cohort study designs, is indicated to uncover both the benefits and the harms associated with CMT.

Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of central nervous system sarcoidosis.

Background:Sarcoidosis is a multisystem granulomatous disease that may involve the central nervous system (CNS) in many ways, leading to diagnostic difficulties. An accurate diagnostic laboratory test would enhance the evaluation and management of these patients. Objective:To determine the diagnostic accuracy of cerebrospinal fluid angiotensin-converting enzyme (ACE) for CNS neurosarcoidosis. Methods:The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuroimmunology. Results:Two primary articles were selected for review. Cerebrospinal fluid ACE assay is insensitive (24%–55%) but may be reasonably specific (94%–95%) for CNS neurosarcoidosis. However, existing data are derived from studies with significant methodological and reporting limitations. Conclusions:The diagnostic accuracy of cerebrospinal fluid ACE for CNS neurosarcoidosis is not clearly established and the test cannot replace tissue diagnosis. Despite its insensitivity, some clinicians might consider the specificity of cerebrospinal fluid ACE, based on existing data, high enough to warrant inclusion in the diagnostic evaluation of patients in whom CNS neurosarcoidosis is being considered. A well-designed prospective diagnostic study seems warranted.

Establishing a diagnosis of benign paroxysmal positional vertigo through the dix-hallpike and side-lying maneuvers: a critically appraised topic.

Background:Many patients consult neurologists because of vertigo. Benign paroxysmal positional vertigo (BBPV) is one of the most common types of vertigo. Although the clinical presentation of this common condition is straightforward, the diagnosis and diagnostic maneuvers can be challenging. Objectives:How useful is the Dix-Hallpike test in establishing the diagnosis of BPPV? How useful is an alternative positional test, such as the side-lying maneuver, in the diagnosis of BPPV? Methods:We addressed the question through development of a structured critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content expert in the field of otolaryngology. Participants started with a clinical scenario and structured questions, devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:A single study comparing the Dix-Hallpike and side-lying tests was identified. For the Dix-Hallpike test, the estimated sensitivity was 79% [95% confidence interval (CI) 65–94], specificity was 75% (33–100), positive likelihood ratio (LR) was 3.17 (95% CI 0.58–17.50), negative LR was 0.28 (95% CI 0.11–0.69). For the side-lying test, the estimated sensitivity was 90% (95% CI 79–100), specificity was 75% (33–100), positive LR was 3.59 (95% CI 0.65–19.67), negative LR was 0.14 (95% CI 0.04–0.46). The study employed very weak methodology, and therefore the results had limited validity. Conclusions:The Dix-Hallpike test is the standard from which the diagnosis of posterior semicircular canal BPPV is made. Hence evaluations of its diagnostic test properties and utility are challenging. For patients unable to move into the Dix-Hallpike test positions, alternative tests such as the side-lying test can be attempted. These modifications, however, are rarely necessary.

Clinical predictors of psychogenic nonepileptic seizures: a critically appraised topic.

Background:Psychogenic nonepileptic seizures (PNES) are often disabling and usually associated with psychiatric disorders and reduced quality of life. Although often suspected based on historical and clinical features, the gold standard for diagnosis of PNES is video electroencephalography. Identification of clinical features that reliably distinguish PNES from ES would be valuable in acute care settings, for patients that have coexisting disorders, and those with multiple event types. Objective:To determine the diagnostic value of putative clinical symptoms or signs of PNES against the gold standard of video electroencephalography. Methods:We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of epileptology. Results:There were wide variations in the rates of coexisting PNES and epilepsy and study methodology. Ictal stuttering and the “teddy bear” sign were associated with moderate specificity for PNES. However, the presence of pelvic thrusting or ictal eye closure did not accurately distinguish PNES from ES. Conclusions:The presence of either ictal stuttering or the teddy bear sign is moderately specific but poorly sensitive for PNES. Pelvic thrusting and ictal eye closure are not reliable indicators of PNES. Future studies should establish more precise and reliable definitions of clinical signs and evaluate combinations of such signs in a broad spectrum of patients with PNES and ES spell phenotypes that may be difficult to distinguish, such as spells of unresponsiveness with motor manifestations. Because PNES and ES may coexist, analysis of diagnostic accuracy of clinical features should be performed for individual spells.

Is obstructive sleep apnea an independent risk factor for stroke? A critically appraised topic.

Background:Obstructive sleep apnea (OSA) is associated with hypertension, atrial fibrillation, coronary artery disease, congestive heart failure, and diabetes. These disorders are also risk factors for stroke. Objective:To determine whether OSA increases the risk of stroke independently of other cerebrovascular risk factors. Methods:The objective was addressed through the development of a structured critically appraised topic. This evidence-based methodology included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of sleep medicine and vascular neurology. Results:A large observational cohort study was selected and appraised to address this prognostic question. The unadjusted analysis revealed that OSA (apnea-hypopnea index >5) was associated with stroke or death from any cause (hazard ratio, 2.24; 95% confidence interval [CI], 1.30–3.86; P = 0.004). The adjusted OSA analysis retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95% CI, 1.12–3.48; P = 0.01). In separate unadjusted analyses, OSA was associated with death and stroke with relative risks of 1.68 (95% CI, 1.10–2.25) and 5.16 (95% CI, 3.72–6.60), respectively. Conclusions:OSA independently contributes to stroke risk.

Telemedicine versus telephone for remote emergency stroke consultations: a critically appraised topic.

Background:The rate of patients being treated with thrombolytic therapy is low, in part, due to a shortage of vascular neurologists, especially in rural communities. Two-way audio-video communication through telemedicine has been demonstrated to be a reliable method to assess neurologic deficits due to stroke and maybe more efficacious in determining thrombolytic therapy eligibility than telephone-only consultation. Objective:To determine the efficacy of telemedicine versus telephone-only consultations for decision making in acute stroke situations. Methods:The objective was addressed through the development of a structured, critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content experts in the fields of vascular neurology, emergency medicine, and telemedicine. Participants started with a clinical scenario and a structured question, devised search strategies, located and compiled the best evidence, performed a critical appraisal, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:A single randomized, blinded, prospective trial comparing telephone-only consultations to telemedicine consultations for acute stroke was selected and appraised. Correct acute stroke treatment decisions were made more often in the telemedicine group versus the telephone-only group (98% vs. 82%, [number needed to assess = 6]). Stroke telemedicine when compared with telephone-only consultations was more sensitive (100% vs. 58%), more specific (98% vs. 92%), had a more favorable positive likelihood ratio (LR: 41 vs. 7) and negative likelihood ratio (LR: 0 vs. 0.5), and had higher predictive values (positive predictive value 94% vs. 76%, and negative predictive value 100% vs. 84%) for the determination of thrombolysis eligibility. Conclusion:Stroke telemedicine when compared with telephone-only consultations is an effective method to determine thrombolysis eligibility for acute stroke patients who do not have immediate access to a stroke neurologist.

Adjunctive haloperidol prophylaxis reduces postoperative delirium severity and duration in at-risk elderly patients.

Background:Delirium is a potentially life-threatening syndrome that is particularly common in elderly hospitalized patients, especially those with preexisting neurologic disorders. Nonpharmacological tactics can reduce the incidence and severity of delirium in acute care settings and antipsychotic drugs are widely used to treat established delirium. More effective preventive strategies could notably impact morbidity, mortality, and health care costs. Objective:To determine whether antipsychotic drug prophylaxis reduces the incidence and severity of postoperative delirium in at-risk elderly patients. Methods:We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of cognitive disorders. Results:One randomized controlled trial addressed the question. In at-risk patients aged >70 years, oral haloperidol 0.5 mg TID, administered from up to 72 hours preoperatively until the third postoperative day, did not alter the incidence of postoperative delirium (15.1%) compared with placebo (16.5%; relative risk 0.91; 95% confidence interval 0.59–1.44). However, the study was underpowered for this primary outcome, possibly because both groups received nonpharmacological delirium prevention strategies. Haloperidol significantly reduced delirium severity ratings, delirium duration (from a mean of 11.8 to 5.4 days), and length of hospital stay in affected participants (from 22.6 to 17.1 day). Conclusion:Adjunctive low-dose haloperidol prophylaxis reduces delirium severity, duration, and subsequent hospitalization length in elderly at-risk patients. Further study is needed to determine the optimal pharmacological approach, combination with nonpharmacological strategies, and generalizability to other settings.

A systematic review of telestroke.

Abstract Background: The use of 2-way audiovisual (AV) technology for delivery of acute stroke evaluation and management, termed “telestroke,” is supported by a rapidly growing literature base. A systematic review that provides a comprehensive, easily digestible overview of telestroke science and practice is lacking. Purpose: To conduct a systematic review of the published literature on telemedical consultation for the purposes of providing acute stroke evaluation and management. Data Sources: The Ovid Medline, Embase, PsychINFO, CINAHL, PubMed, and Cochrane databases were searched with numerous keywords relevant to telestroke from January 1996 through July 2012. Study Selection: Studies were included if the title or abstract expressed use of 2-way AV communication for acute stroke evaluation and management. Data Extraction: Each article was classified using a novel scoring rubric to assess the level of Functionality, Application, Technology, and Evaluative stage (FATE). Data Analysis: The search yielded 1405 potentially eligible articles, which were independently reviewed by 2 investigators. There were 344 unique studies that met eligibility criteria and underwent full–text review. Ultimately, 145 unique studies underwent FATE assessment and scoring. Results: Most telestroke studies evaluated functionality in the context of acute stroke assessment of adults in emergency departments. Nearly half of all published articles on telestroke were narrative reviews. After exclusion of these reviews, the median FATE score for telestroke primary data was 4. Conclusion: Telestroke technology is now part of mainstream clinical stroke practice in North America and internationally. Telestroke reliability, validity, efficacy, safety, clinical, and cost–effectiveness studies reflect maturity in the field, and new post–implementation studies in the pre–hospital setting present welcome and sophisticated advancements in the field.