Faculty Bibliography

Deep brain stimulation (DBS) is a surgical treatment for advanced Parkinson's disease (PD) that has undergone technological evolution that parallels an expansion in clinical phenotyping, neurophysiology, and neuroimaging of the disease state. Machine learning (ML) has been successfully used in a wide range of healthcare problems, including DBS. As computational power increases and more data become available, the application of ML in DBS is expected to grow. We review the literature of ML in DBS and discuss future opportunities for such applications. Specifically, we perform a comprehensive review of the literature from PubMed, the Institute for Scientific Information's Web of Science, Cochrane Database of Systematic Reviews, and Institute of Electrical and Electronics Engineers' (IEEE) Xplore Digital Library for ML applications in DBS. These studies are broadly placed in the following categories: (1) DBS candidate selection; (2) programming optimization; (3) surgical targeting; and (4) insights into DBS mechanisms. For each category, we provide and contextualize the current body of research and discuss potential future directions for the application of ML in DBS.

Laryngeal adductor reflex-continuous intraoperative neuromonitoring (LAR-CIONM) is a novel method of continuous intraoperative neuromonitoring. In contrast to other vagal nerve monitoring techniques, which elicit a laryngeal compound muscle action potential, LAR-CIONM elicits a laryngeal reflex response (LAR). In 300 nerves at risk monitored with LAR-CIONM, two patients have had postoperative permanent vocal fold immobility (VFI). Both patients exhibited a significant LAR amplitude increase prior to complete loss of signal. No other patients have exhibited LAR hyperexcitability. If confirmed in a larger sample, this represents the first time that a vagal intraoperative neuromonitoring technique can distinguish transient from permanent VFI, which could improve patient outcomes. Laryngoscope, 2019.

OBJECTIVE:To evaluate whether multiple sessions of transcranial direct current stimulation (tDCS) applied to the primary motor (M1) cortex paired with aerobic exercise can improve walking functions in multiple sclerosis (MS). METHODS:MS participants were recruited for a double-blind, parallel-arm, randomized, sham-controlled trial and assigned to 10 sessions (5 d/wk for 2 weeks) of either active or sham tDCS paired with unloaded cycling for 20 minutes. Stimulation was administered over the left M1 cortex (2.5 mA; anode over C3/cathode over FP2). Gait spatiotemporal parameters were assessed using a wearable inertial sensor (10-meter and 2-minute walking tests). Measurements were collected at baseline, end of tDCS intervention, and 4-week postintervention to test for duration of any benefits. RESULTS:A total of 15 participants completed the study, nine in the active and six in the sham condition. The active and sham groups were matched according to gender (50% vs. 40% female), neurologic disability (median EDSS 5.5 vs. 5), and age (mean 52.1 ± 12.9 vs. 53.7 ± 9.8 years). The active group had a significantly greater increase in gait speed (0.87 vs. 1.20 m/s, p < 0.001) and distance covered during the 2-minute walking test (118.53 vs. 133.06 m, p < 0.001) at intervention end compared to baseline. At 4-week follow-up, these improvements were maintained (baseline vs. follow-up: gait speed 0.87 vs. 1.18 m/s, p < 0.001; distance traveled 118.53 vs. 143.82 m, p < 0.001). INTERPRETATION/CONCLUSIONS:Multiple sessions of tDCS paired with aerobic exercise lead to cumulative and persisting improvements in walking and endurance in patients with MS.

This study examined the effect of increasing material-specific verbal and visual memory impairment severity on Rey 15-Item Test (RFIT) and RFIT/Recognition Trial performance. Data from 146 clinically referred patients (109 valid/37 invalid) who completed the RFIT, Brief Visuospatial Memory Test-Revised, and Rey Auditory Verbal Learning Test were analyzed. Rey Auditory Verbal Learning Test/BVMT memory impairment was operationalized as ≥40T (no memory impairment), 30T-39T (mild memory impairment), or ≤29T (severe memory impairment). Medium-to-large correlations emerged between the RFIT and memory measures. Significantly more patients with impaired visual memory, and to a lesser extent verbal memory, failed the RFIT and RFIT/Recognition. RFIT and RFIT/Recognition produced areas under the curve = .80-.90 for detecting invalidity and strong associated psychometric properties among patients without memory impairment, but both yielded low and largely unacceptable accuracy (areas under the curve = .57-.71) when verbal or visual memory impairment of any severity was present. In sum, RFIT performance was significantly affected by increasing material-specific memory deficits, such that it produced acceptable accuracy among unimpaired patients, but accuracy greatly diminished with memory impairment, which is antithetical to a sound performance validity test. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BACKGROUND:Some patients with chronic pain and implanted spinal cord stimulators (SCS) or intrathecal (IT) pumps fail to obtain significant pain relief. The use of dual-modality treatment with both therapies is understudied. This is the first study evaluating comprehensive outcomes in this patient population, and to report outcomes primarily using IT ziconotide. METHODS:We retrospectively analyzed 11 patients with chronic pain treated with both SCS and IT therapy. When a primary treatment failed to capture significant pain relief, a secondary device was trialed and implanted. Pain severity (measured by the numeric rating scale, NRS) was assessed by the change from baseline to after the first and second intervention. In a subset of patients (n=6), quality of life metrics were also assessed. Outcome measures were analyzed closest to the one-year follow-up date after implantation of the first modality, then at the most recent follow-up following implantation of the second modality. RESULTS:SCS leads were percutaneous (n=2) or paddle (n=9), and commonly covered T8-10. IT medication included ziconotide (n=8), baclofen (n=1), hydromorphone (n=1), or morphine-clonidine (n=1). There was a mean of 19.64±3.17 months between primary and secondary intervention. There was a significant improvement in pain severity from baseline to implantation of the second modality (p=0.032) at a mean follow-up of 50.18±11.83 months. CONCLUSIONS:We suggest dual-modality therapy is a potential treatment option in patients who have lost efficacy with a single neuromodulation modality. Further study is required to identify potential responders and non-responders.

OBJECTIVES/OBJECTIVE:To analyze and compare differences between epidemiological and clinical aspects, as well as radiologic findings and treatment, in a series of adult patients with traumatic intracranial hypotension (TIH) and spontaneous intracranial hypotension (SIH) treated at our institution in order to identify predictors of recurrence. BACKGROUND:Cerebrospinal fluid hypotension headache (CSF-HH) is often caused by orthostasis and relieved by recumbency. Etiology can be either traumatic or spontaneous. Indirect signs of CSF hypotension are often observed on brain MRI. The most common therapeutic approach is conservative management and, when necessary, the use of an epidural blood patch. METHODS:Medical history and brain MRI of adult patients consulting our institution with a diagnosis of CSF-HH between January 2010 and March 2019, were retrospectively reviewed. Clinical criteria as per the International Classification of Headache Disorders, 3rd edition, were applied. Presence of typical MRI findings were assessed by two experienced neuroradiologists, previously informed of patients' clinical characteristics. Patients were divided into two different groups, namely: Group A: Spontaneous Intracranial Hypotension (SIH) and Group B: Traumatic Intracranial Hypotension (TIH). Recurrence was defined as return of symptoms after one month of remission. In order to find predictors of recurrent intracranial hypotension the patients were divided into three groups: Recurrent Orthostatic headache (ROH); (33 cases; 25%); Non-Recurrent Orthostatic headache (NROH) (84; 61%) and Patients missing follow-up (20; 15%). The latter were excluded from the regression analysis. RESULTS:137 patients with CSF-HH were identified: 80 traumatic (54 women, age 33.8 ± 10.4 years) and 57 spontaneous (31 women, age 43.9 ± 15.2 years). Median follow-up was 35 months (range: 8 months-9 years). Compared with TIH, patients with SIH showed lower frequency of orthostatic headache and higher frequency of aural fullness. Also, in patients with SIH, brain MRI showed a higher frequency of pachymeningeal enhancement, ventricular collapse, cisternal obliteration, posterior fossa crowding, brainstem distortion, and a more likely presence of subdural collections. Patients with SIH required an epidural blood patch treatment more often, showed higher recurrence rates, and were more prone to develop subdural hematomas. RECURRENCE/UNASSIGNED:As more days elapsed between headache onset and clinical consultation, the presence of spontaneous intracranial hypotension, tinnitus, and thoraco-lumbo-sacral pain were all more common in patients with recurrence. Findings on brain MRI suggesting higher recurrence rates in patients included: ventricular collapse, brainstem distortion, and posterior fossa crowding. Patients treated with invasive therapy (epidural blood patch) presented a higher recurrence rate. In the multivariate regression analysis, the only independent predictor of recurrence after adjusting for age, sex and traumatic vs spontaneous cause of IH, was brainstem distortion diagnosed on MRI (OR 5.13, 95% CI: 1.2-21.7; p = 0.026). CONCLUSIONS:SIH and TIH can no longer be likened, since there is considerable variability in clinical presentation, imaging findings, response to treatment and recurrence rates. Anatomical abnormalities underlying SIH leaks are often complex and not simply a disruption of normal structures as encountered in TIH, which could explain why treatment success is poor and recurrence rates remain high.

BACKGROUND:Adverse effects of masticatory muscle injections of Botulinum Toxin (Btx) have been noted in animal and, less dramatically, human studies. OBJECTIVE:Among women treated in multiple community-based private practices, to compare TMJ bone density and mandibular condylar volume between patients with myofascial TMJD receiving multiple masticatory muscle Btx treatments and similarly diagnosed women not receiving such treatment. METHODS:Cohorts consisted of women whose treatment charts indicated a diagnosis of myofascial TMJD: 35 received at least 2 Btx treatment cycles; 44 received none. Bone density at prespecified regions of interest (ROI) was defined by grey scale values from Cone Beam CT, adjusting for a fixed density phantom included in each scan. Mean bone density and mandibular condyle volume were compared between groups. Dose response effects were tested within the Btx-exposed group. RESULTS:The mean density of primary and secondary ROIs was similar between exposure groups, as was condylar volume. Among Btx-exposed women, increasing dose of Btx to the temporalis muscle was inversely proportional to the density of the trabecular area of the mandible body. Many Btx-exposed women received smaller doses of Btx to the masseter muscles than in most TMJD Btx clinical trials. CONCLUSION/CONCLUSIONS:Masticatory muscle injections of Btx failed to produce clinically significant TMJ bone-related changes. Should Btx receive regulatory approval for treatment of myofascial TMJD, a phase IV study is recommended to evaluate potential adverse effects of Btx on bone and muscle when administered at higher doses and/or for more treatment cycles.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.