Faculty Bibliography

Migraine is a neurovascular disorder that affects over 1 billion people worldwide. Its widespread prevalence, and associated disability, have a range of negative and substantial effects not only on those immediately affected but also on their families, colleagues, employers, and society. To reduce this global burden, concerted efforts are needed to implement and improve migraine care that is supported by informed health-care policies. In this Series paper, we summarise the data on migraine epidemiology, including estimates of its very considerable burden on the global economy. First, we present the challenges that continue to obstruct provision of adequate care worldwide. Second, we outline the advantages of integrated and coordinated systems of care, in which primary and specialist care complement and support each other; the use of comprehensive referral and linkage protocols should enable continuity of care between these systems levels. Finally, we describe challenges in low and middle-income countries, including countries with poor public health education, inadequate access to medication, and insufficient formal education and training of health-care professionals resulting in misdiagnosis, mismanagement, and wastage of resources.

BACKGROUND:In the post-Carotid Occlusion Surgery Study (COSS) era, multiple reviews suggested subset groups of patients as potential candidates for superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Among them are patients with recurrent strokes despite optimal medical therapy. There is a paucity of data on the outcome of bypass in these specific patients. OBJECTIVE:To examine the safety and efficacy of direct STA-MCA bypass in patients with nonmoyamoya, symptomatic steno-occlusive disease with impaired distal perfusion, who failed optimal medical management or endovascular treatment. METHODS:A retrospective review was performed to identify patients with cerebrovascular steno-occlusive disease who underwent bypass after symptomatic recurrent or rapidly progressive strokes, despite optimal conservative or endovascular treatment. RESULTS:A total of 8 patients (mean age 60 ± 6 yr) underwent direct or combined direct/indirect STA-MCA bypass between 2016 and 2019. All anastomoses were patent. One bypass carried slow flow. There were no procedure-related permanent deficits. One patient developed seizures which were controlled by medications. A total of 7 out of 8 patients were stable or improved clinically at last follow-up (mean 27.3 ± 13.8 mo) without recurrent strokes. One patient did not recover from their presenting stroke, experienced severe bilateral strokes 4 mo postoperatively, and subsequently expired. Modified Rankin Scale (mRS) improved in 6 patients (75%), remained stable in 1 patient (12.5%), and deteriorated in 1 (12.5%). Good long-term functional outcome was achieved in 5 patients (63%, mRS ≤ 2). CONCLUSION/CONCLUSIONS:Patients with symptomatic, hypoperfused steno-occlusive disease who fail optimal medical or endovascular treatment may benefit from cerebral revascularization. Direct or combined STA-MCA bypass was safe and provided favorable outcomes in this small series.

We present a case of acute transverse myelitis associated with presumed Covid-19 infection.Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). The full spectrum of neurological involvement of Covid-19 has not been characterized.Design/Methods: Case report and review of literature.Results: A 52-year-old man from New York City with hypertension, diabetes, and diabetic peripheral neuropathy presented after two days of progressive bilateral leg weakness and urinary retention. He reported fever, cough, and low back pain that started three weeks prior to this presentation. On arrival, he was febrile and hypoxic on room air (SpO2 88%). Neurological examination showed bilateral hip flexion weakness (Medical Research Council grade 3/5), stable length-dependent sensory loss in the lower extremities, and generalized hyporeflexia. Laboratory studies were notable for leukocytosis (15.9 103/uL), lymphopenia (13%), hyponatremia (126 mmol/L), and elevated inflammatory markers: Lactate dehydrogenase (390 IU/L), erythrocyte sedimentation rate (120 mm/hr), C-reactive protein (195 mg/L), and interleukin-2 receptor (1383 pg/mL). Chest radiography revealed interstitial opacities in both lungs. Magnetic resonance imaging of the total spine revealed increased T2 signal in the spinal cord at the level of the T3 vertebra (Figure 1B–D). Cerebrospinal fluid (CSF) analysis revealed normal cell count (1 cell/mL) with elevated protein (91 mg/dL) and negative RT-PCR for SARS-COV-2. Early mobility was encouraged and antipyretics successfully controlled the patient’s fever. Spontaneous voiding returned on day three of hospitalization. His respiratory status also improved, and he was discharged home.Conclusions: Neuroinvasion has been demonstrated to be a common feature of many coronaviruses. This case provides insight into the potential mechanisms by which SARS-CoV-2 can affect the central nervous system, highlights acute transverse myelitis as a neurological manifestation of Covid-19, and demonstrates an example of an affected individual with good potential for neurologic recovery.Disclosure: Dr. Valdes has nothing to disclose. Dr. Zakin has nothing to disclose.

BACKGROUND:Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis. METHODS:We investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19-38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a). RESULTS:Overall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures. CONCLUSIONS:These neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.

How do people form their political beliefs? In an effort to address this question, we adopt a neuropsychological approach. In a natural experiment, we explored links between neuroanatomy and ideological preferences in two samples of brain lesion patients in New York City. Specifically, we compared the political orientations of patients with frontal lobe lesions, patients with amygdala lesions and healthy control subjects. Lesion type classification analyses revealed that people with frontal lesions held more conservative (or less liberal) beliefs than those with anterior temporal lobe lesions or no lesions. Additional analyses predicting ideology by extent of damage provided convergent evidence that greater damage in the dorsolateral prefrontal cortex-but not the amygdala-was associated with greater conservatism. These findings were robust to model specifications that adjusted for demographic, mood, and affect-related variables. Although measures of executive function failed to mediate the relationship between frontal lesions and ideology, our findings suggest that the prefrontal cortex may play a role in promoting the development of liberal ideology. Our approach suggests useful directions for future work to address the issue of whether biological developments precede political attitudes or vice versa-or both. This article is part of the theme issue 'The political brain: neurocognitive and computational mechanisms'.

BACKGROUND:Non-slip socks are sometimes used in an attempt to prevent falls in hospitals despite limited evidence of benefit. We critique the current literature on their risks, benefits and effects. METHODS:A rapid review was conducted following the Cochrane Rapid Review Methods Group Guidelines. To be included, studies needed to have data on single or multifactorial interventions that used non-slip socks in hospitals or their safety, risks or effects in a laboratory setting. Six electronic databases were searched: Medline, Embase, Cinahl, Cochrane, AMED and Proquest Central. RESULTS:Fourteen articles met the inclusion criteria. Nine used non-slip socks as an intervention in hospitals. Three assessed their effects in laboratory settings. Two reported risks in relation to bacterial transfer. Most studies that used non-slip socks to prevent hospital falls had negative or equivocal results and were of comparatively low method quality, with a high risk of bias. Two of the laboratory tests reported traction socks to be no safer than walking barefoot and to have similar slip resistance. The laboratory studies had a low risk of bias and showed that bacteria can sometimes be acquired from socks. CONCLUSION/CONCLUSIONS:Non-slip socks carry an infection control risk that requires careful management. There was no strong or conclusive evidence that they prevent hospital falls.

Importance/UNASSIGNED:Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse. Objective/UNASSIGNED:To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice. Design, Setting, and Participants/UNASSIGNED:This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching. Interventions/UNASSIGNED:Mechanical thrombectomy or standard medical treatment with or without IVT. Main Outcomes and Measures/UNASSIGNED:Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up. Results/UNASSIGNED:Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P = .06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P = .04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P = .005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort. Conclusions and Relevance/UNASSIGNED:This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.

OBJECTIVES/OBJECTIVE:To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. DESIGN/METHODS:The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. METHODS:Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. RESULTS:The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? CONCLUSIONS:Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.