Faculty Bibliography

Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Undiagnosed and untreated obstructive sleep apnea (OSA) is associated with health comorbidities and negatively affects quality of life. Alternative treatments should be considered in patients who are unable to tolerate or benefit from positive airway pressure treatment. When properly indicated, positional devices, oral appliances, airway surgery, and hypoglossal nerve stimulation have been shown to be effective in treating OSA. Hypoglossal nerve stimulation is a successful second-line treatment with low associated morbidity and complication rate.

Purpose of Review/UNASSIGNED:In 2019, over 50 million Americans were expected to use wearables at least monthly. The technologies have varied capabilities, with many designed to monitor health conditions. We present a narrative review to raise awareness of wearable technologies that may be relevant to the field of neurology. We also discuss the implications of these wearables for our patients and briefly discuss issues related to researching new wearable technologies. Recent Findings/UNASSIGNED:There are a variety of wearables for neurologic conditions, e.g., stroke (for potential arrhythmia capture), epilepsy, Parkinson disease, and sleep. Research is being performed to capture the risk of neuropsychiatric relapse. However, data are limited and adherence to these wearables is often poorly studied. Summary/UNASSIGNED:The care of neurology patients may ultimately be improved with the use of wearable technologies. More research needs to examine efficacy and implementation strategies.

BACKGROUND:Elevated systolic blood pressure (SBP) in the acute phase after endovascular therapy (EVT) is associated with worse outcome. However, the association between systolic blood pressure reduction (SBPr) and the outcome of EVT is not well understood. OBJECTIVE:To determine the association between SBPr and clinical outcomes after EVT in a prospective multicenter cohort. METHODS:A post hoc analysis of the Blood Pressure after Endovascular Stroke Therapy (BEST) prospective observational cohort study was carried out. SBPr was defined as the absolute difference between admission SBP and mean SBP in the first 24 hours after EVT. Logistic regression was used to assess the association between SBPr and poor functional outcome (modified Rankin Scale score 3-6) at 90 days. RESULTS:A total of 259/433 (58.5%) patients had poor outcome. SBPr was higher in the poor outcome group than in the good outcome group (26.6±27.4 vs 19.0±22.3 mm Hg; p<0.001). However, in adjusted models, SBPr was not independently associated with poor outcome (OR=1.00 per 1 mm Hg increase, 95% CI 0.99 to 1.01) or death (OR=0.9 per 1 mm Hg increase; 95% CI 0.98 to 1.00). No association remained when SBPr was divided into tertiles. Subgroup analyses based on history of hypertension, revascularization status, and antihypertensive treatment yielded similar results. CONCLUSION/CONCLUSIONS:The reduction in baseline SBP following EVT was not associated with poor functional outcomes. Most of the cohort (88%) achieved successful recanalization, and therefore, these results mainly apply to patients with successful recanalization.

KEY POINTS/CONCLUSIONS:The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans. ABSTRACT/UNASSIGNED:The corticoreticulospinal tract (CReST) is a major descending motor pathway in many animals, but little is known about its innervation patterns in proximal and distal upper extremity muscles in humans. The contralesional CReST furthermore reorganizes after corticospinal tract (CST) injury in animals, but it is less clear whether CReST innervation changes after stroke in humans. We thus examined CReST functional connectivity, connection strength, and modulation in an arm and hand muscle of healthy (n = 15) and chronic stroke (n = 16) subjects. We delivered transcranial magnetic stimulation to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs) from the paretic biceps (BIC) and first dorsal interosseous (FDI) muscle. We operationalized CReST functional connectivity as iMEP presence/absence, CReST projection strength as iMEP size and CReST modulation as change in iMEP size by head rotation. We found comparable CReST functional connectivity to the BICs and FDIs in both subject groups. However, the pattern of CReST connection strength to the muscles diverged between groups, with stronger connections to FDIs than BICs in healthy subjects and stronger connections to BICs than FDIs in stroke subjects. Head rotation modulated only FDI iMEPs of healthy subjects. Our findings indicate that the healthy CReST does not have a proximal innervation bias, and its strong FDI connections may have functional relevance to finger individuation. The reversed CReST innervation pattern in stroke subjects confirms its reorganization after CST injury, and its strong BIC connections may indicate upregulation for particular upper extremity muscles or their functional actions.

This study evaluated multiple previously-identified Continuous Performance Test-Third Edition (CPT-3) scores as embedded validity indicators (EVIs) among 201 adults undergoing neuropsychological evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD) divided into valid (n = 169) and invalid (n = 32) groups based on seven criterion measures. Although 6/10 CPT-3 scores accurately detected invalidity, only two reached minimally acceptable classification accuracy of ≥0.70. The remaining four had unacceptably low accuracy (AUCs = 0.62-0.69) with 0.19-0.41 sensitivity at ≥0.90 specificity. Composite scores did not provide better classification accuracy than individual CPT-3 scores. In sum, CPT-3 individual and composite scores generally are not accurate PVTs among adults undergoing clinical evaluation for ADHD.

PURPOSE/OBJECTIVE:By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). METHODS:We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. RESULTS:We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. CONCLUSION/CONCLUSIONS:The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.

Objective/UNASSIGNED:Little is known about how symptom severity in the various neurologic domains commonly affected by multiple sclerosis (MS) varies by age, sex, and race/ethnicity. Methods/UNASSIGNED:This was a retrospective study of patients with MS attending 2 tertiary centers in the New York City metropolitan area, who self-identified as White, African American (AA), or Hispanic American (HA). Disability was rated with Patient-Determined Disability Steps (PDDS) and symptom severity, with SymptoMScreen (SyMS), a validated battery for assessing symptoms in 12 domains. Analyses comparing race, sex, and age groups were performed using analysis of variance models and Tukey honestly significant difference tests to control the overall type I error. A multivariable model was constructed to predict good self-rated health (SRH) that included demographic variables, PDDS, and SyMS domain scores. Results/UNASSIGNED:= 0.012), but similar total SyMS scores. Women reported higher fatigue and anxiety scores, whereas men had higher walking and dexterity scores. AAs and HAs had higher symptom domain scores than Whites in each of the 12 domains and worse SRH. In a multivariable logistic model, only pain, walking, depression, fatigue, and global disability (PDDS), but not sex or race/ethnicity, predicted good SRH. Conclusions/UNASSIGNED:AA and HA race/ethnicity was associated with higher overall disability, higher symptom severity in each of the 12 domains commonly affected by MS, and worse SRH relative to Whites. However, only symptom severity and disability, and not demographic variables, predicted good SRH.

INTRODUCTION/BACKGROUND:Many patients admitted to hospitals with acute trauma have positive serum blood alcohol levels. Published associations between alcohol use, injury patterns, and outcomes are inconsistent. We sought to further delineate the impact of alcohol use and alcohol withdrawal on hospital outcomes amongst acute trauma patients. METHODS:We performed a retrospective analysis of adult trauma patients hospitalized at a suburban level 1 trauma center between January 2015 and September 2019 with a blood alcohol level measurement and/or classification as alcohol withdrawal syndrome (AWS). Patients were separated into three groups: BAL ≤10 mg/dL, BAL >10 mg/dL, and alcohol withdrawal syndrome (AWS). RESULTS:Overall, 3896 patients met study criteria with 75.6% BAL ≤10, 23.2% BAL >10, and 1.2% AWS. The median age was significantly different (BAL ≤ 10: 59 years, BAL > 10: 44 years, AWS: 53.5 years). Alcohol withdrawal was experienced by patients with BAL ≤10 and BAL >10. While injury severity and mortality were similar across all 3 groups, AWS patients experienced significantly longer hospital and ICU lengths of stay, unplanned ICU admission, need for mechanical ventilation, and higher rates of complications. Patients with AWS had high rates of acute neuropsychiatric symptoms, complicating their management. CONCLUSIONS:Except for mortality, AWS patients experienced worse outcomes. The complex nature of alcohol withdrawal cases, including the possibility of developing AWS despite a negative BAL on admission, emphasizes the need for early assessment for alcohol withdrawal risk factors and input from specialists.