Faculty Bibliography

BACKGROUND/UNASSIGNED:In this short review/perspective, we asked what the frequencies would be for both postoperative spinal epidural hematomas (SpEH) and postoperative surgical site infections (SSI) in predominantly posterior lumbar procedures performed with or without the placement of wound drains? METHODS/UNASSIGNED:Many spine surgeons are trained to use wound drains to decrease the risk of postoperative SpEH, despite the potential increased risk of SSI. Alternatively, avoiding drains may increase the risk of SpEH but likely decrease the potential for SSI. RESULTS/UNASSIGNED:Performing predominantly posterior lumbar procedures with or without wound drains resulted in largely comparable frequencies of postoperative spinal epidural hematomas (SpEH; range of 0.10%-0.69%) and postoperative surgical site infections (SSI: range of 0.75%-7.3%). Notably, however, two studies documented that drains increased transfusion requirements, with one study showing a prolongation of the in-hospital length of stay. Critically, these series emphasized the importance of early/emergent diagnosis (i.e., with MR) and surgical treatment of SpEH to minimize residual neurological deficits. CONCLUSION/UNASSIGNED:Here, we showed that patients undergoing predominantly lumbar spine surgery performed with or without wound drains demonstrated comparable frequencies of postoperative SpEH and SSI. Nevertheless, spine surgeons must assess on a case-by-case basis whether, based on their education, training, and experience, placing a wound drain is appropriate for their particular patient.

[This corrects the article DOI: 10.3389/fnut.2021.748847.].

BACKGROUND/UNASSIGNED:Pyridostigmine bromide is a short-acting carbamate acetylcholinesterase inhibitor that has been shown to acutely augment parasympathetic signaling in cardiovascular disease populations. OBJECTIVE/UNASSIGNED:This study was undertaken to characterize pharmacodynamics, safety, and tolerability of pyridostigmine during repeated dosing in patients with heart failure. METHODS/UNASSIGNED:A prospective ascending-dose, forced titration, double-blind Phase II randomized clinical trial was conducted to compare the effects of pyridostigmine bromide (15, 30, and 60 mg TID over 8 weeks) versus matching placebo on red blood cell (RBC) acetylcholinesterase activity, cholinergic side effects, and physiologic measures of parasympathetic heart rate modulation and sympathovagal balance in ambulatory patients with chronic systolic heart failure. RESULTS/UNASSIGNED:< 0.001 vs placebo). Physiologic measures of parasympathetic heart rate modulation and sympathovagal balance did not differ between treatment groups. In the pyridostigmine bromide group, RBC acetylcholinesterase activity was not significantly associated with postexercise parasympathetic heart modulation. CONCLUSIONS/UNASSIGNED:Pyridostigmine bromide administered over 8 weeks was associated with a significant reduction of RBC acetylcholinesterase activity and relatively mild symptoms of cholinergic excess, but changes in parasympathetic signaling in the sinoatrial node previously reported after acute administration were not observed. Further investigations are needed to delineate pharmacodynamic and pathobiological factors contributing to these findings. ClinicalTrials.gov identifier: NCT01415921.

BACKGROUND/UNASSIGNED:A central vestibular neural mechanism known as velocity storage may be inappropriately conditioned in mal de débarquement syndrome (MdDS), a rare chronic vestibular disorder with a continuous false sensation of self-motion described as non-spinning vertigo. Visual-vestibular therapy approaches designed to recondition the three-dimensional properties of velocity storage have yielded much clinical success, but not without limitations. An alternative therapeutic approach, designed to attenuate the contribution of malfunctioning velocity storage in higher-order neural processing, has also yielded positive results, but at a lower success rate. We sought a possible explanation for the latter shortcoming using a mathematical model. METHODS/UNASSIGNED:The three-dimensional orientation properties of velocity storage can be modeled as a dynamical system using a 3 × 3 system matrix. For normal upright, the system matrix is diagonal, with its eigenvectors aligning with the head-fixed roll, pitch, and yaw axes, and the yaw eigenvector with gravity. A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical. We manipulated the velocity storage's yaw time constant and output weight. RESULTS/UNASSIGNED:The model predicted that attenuating the velocity storage contribution could exaggerate the pull sensation. CONCLUSION/UNASSIGNED:The present model-based exploration points to a possible weakness in the MdDS treatment approach focused on velocity storage attenuation, while likely beneficial otherwise. When a pulling sensation is present, the treatment protocol may need to be supplemented with another approach that specifically counters this problem, such as optokinetic stimulation.

BACKGROUND/UNASSIGNED:There is a greater risk of complications from severe COVID-19 in immunocompromised patients with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs), as well as a diminished vaccine response. METHODS/UNASSIGNED:In this exploratory, observational study, we recruited 28 patients with Relapsing Remitting MS (RRMS, n=24) or Secondary Progressive MS (SPMS, n=4), that were receiving treatment with either natalizumab or fumarates (diroximel or dimethyl) prior to baseline sample collection. Blood samples were collected before vaccination (baseline), between 4 weeks and 6 months post vaccination, and post booster administration. A multiplex bead immunoassay (MBI) was used to measure anti-Spike IgG, while IFNγ and IL-2 ELISpot assays were used to determine T cell activation. A 35-color spectral flow cytometry panel was used to phenotype bulk B and T cells and SARS-CoV-2-specific T cells, while dimensionality reduction was performed for further phenotypic analysis. RESULTS/UNASSIGNED:We observed a significantly increased absolute lymphocyte count (ALC) (p=0.0003) in natalizumab-treated pwMS when compared to fumarate-treated pwMS primarily due to increased circulating CD19+ B cells. Fumarate-treated pwMS exhibited a diminished Th1/Th2 ratio when compared to natalizumab-treated pwMS (p=0.0004) or healthy controls (p=0.0745), while natalizumab treatment marginally increased the Th1/Th2 ratio compared to healthy controls (p=0.1311). The observed increase in B cells in natalizumab-treated pwMS were predominantly memory B cells, and double negative (DN) B cells. However, no significant differences between the treatment groups were seen in terms of Spike IgG titers following the initial vaccination course or booster dose, nor in SARS-CoV-2-specific CD4+ responses, all of which remained robust for at least 6 months post-vaccination. The magnitude of humoral and cellular immune responses in both treatment groups were comparable to vaccinated healthy controls. Additionally, SARS-CoV-2 spike-specific CD4+ T cell phenotyping revealed a Th2 dominant response to booster dose in natalizumab-treated pwMS (p=0.0485) but not fumarate-treated pwMS. CONCLUSION/UNASSIGNED:pwMS treated with natalizumab or fumarates exhibit similarly robust and durable SARS-CoV-2 specific T cell and humoral responses following vaccination and booster dose. DMT-treated pwMS showing comparable responses to healthy individuals following initial vaccination supports the notion that treatment with these specific DMTs does not diminish strong, long-lasting immunity conferred by COVID-19 vaccination, despite the phenotypic differences modulated by each therapy.

BACKGROUND/UNASSIGNED:Most patients with cervical synovial cysts (CSC) present with radiculopathy and/or myelopathy. MR studies are the gold standard for diagnosing CSC, and typically show hypointense T1/hyperintense T2 lesions, with occasional cyst-wall enhancement and additional cyst-wall calcification. Surgery typically warrants focal cyst resection/ decompression with/without an instrumented fusion. Here, we reviewed the diagnosis/treatment of a 76-year-old male with a CSC, and C5-C6/C6-C7 , and C7-T1 stenosis. We further provided a select review of the literature. METHODS/UNASSIGNED:For 3 months, a 76-year-old-male experienced progressive bilateral/arm pain (i.e., radiculopathy), and one week of increased right upper/right lower extremity weakness with loss of balance (i.e., myelopathy). The MR with/without contrast and non contrast CT studies documented moderate C5-C6/C6-C7 stenosis and a large, likely synovial cyst filling the right-side of the spinal canal at the C7-T1 level (i.e, 12 mm x 9 mmx 19 mm). RESULTS/UNASSIGNED:The patient urgently underwent excision of the large right C7-T1 synovial cyst, along with a C6-T2 laminectomy for stenosis, and a C4-T4 instrumented fusion. At 4-postoperative months, the patient was neurologically intact. The repeated X-rays performed at 2, 6, and 12 weeks postoperatively documented maintained alignment, while the MR scan confirmed adequate cord decompression without myelomalacia. CONCLUSION/UNASSIGNED:A 76-year-old male with increased right-sided myeloradiculopathy, successfully underwent resection of a right-sided C7-T1 synovial cyst filling the spinal canal, a C6-T2 laminectomy for stenosis, and a C4-T4 instrumented fusion. Four months postoperatively, the patient was neurologically intact, with postoperative X-rays showing stable alignment. Further, the follow-up MR documented no residual cord/root compression, or myelomalacia. Here, we have provided a review of this case and select literature regarding the diagnosis and surgery for CSC.

BACKGROUND:Binimetinib and selumetinib are two mitogen-activated protein kinase kinase (MEK) inhibitors used to treat low-grade gliomas and plexiform neurofibromas. Cutaneous toxicities are commonly associated with MEK inhibitors; however, limited studies have examined cutaneous effects in a pediatric population or whether toxicities vary between MEK inhibitors. METHODS:We conducted an IRB-approved, single-center, retrospective review of pediatric neuro-oncology patients on binimetinib or selumetinib who presented to NYU from April 2016 through July 2022. RESULTS:Forty-six children met inclusion criteria (23 females, 23 males) with a mean age of 11.7 years. Thirty-three were treated with binimetinib and 13 with selumetinib. Dermatologic adverse events were encountered in 97.8% of the cohort, and the most common were acneiform eruption (63.0%), paronychia (58.7%), and xerosis (54.3%). Children 12 years and older were more likely to have acneiform eruption (p < 0.001) and seborrheic dermatitis (p < 0.001), while children under 12 were more likely to have xerosis (p = 0.037). The incidence of cutaneous adverse events was significantly different between MEK inhibitors for folliculitis and hair pigment dilution (39.4% binimetinib, 0% selumetinib, p = 0.009). Significantly, more patients required MEK inhibitor dose reduction/hold on binimetinib (87.9%) than selumetinib (46.2%) (p = 0.006). Severity of cutaneous disease was not associated with tumor response. CONCLUSIONS:Our study confirms dermatologic adverse events are common in children on MEK inhibitors. Age appears to be associated with increased likelihood of certain cutaneous reactions. Overall, the selumetinib patients in our cohort presented with less severe adverse events and decreased risk of MEK inhibitor dose reduction/hold. Our results will aid clinicians in providing appropriate counseling, treatments, and improved preventive care.

BACKGROUND/UNASSIGNED:Focal task-specific dystonia of the musicians' arm (FTSDma) is an unusual and challenging disorder, often causing significant disability with loss of performing careers. The etiology and optimal management of this disorder remains unclear. METHODS/UNASSIGNED:We reviewed records and videos of 173 patients with FTSDma, 50 patients with writer's cramp (WC), and 16 with other forms of arm dystonia (OD), evaluated by a single examiner in clinical practice over a 25-year period. Detailed analysis of clinical features and videotaped examinations in slow motion (what we call "deep phenotyping") allowed separation of patients into four categories: "precision-grip" dystonia (groups I and III); "power-grip" dystonia (group II); and "proximal dystonia" (group IV). We compared these results to deep phenotyping of patients with FTSDma, WC and OD patients reported in the literature. RESULTS/UNASSIGNED:FTSDma usually affects men, involves the right hand, and begins in the fourth decade. The precision hand of pianists and guitarists (digits 1, 2, 3) was preferentially affected in the right arm, and many of the remaining patients involved the power hand of either arm (digits 3, 4, 5). The dystonic phenotype of the bow arm of string players and drumming arm of stick drummers bore striking resemblance to WC and racquet dystonia, almost always involving the wrist, forearm or shoulder. CONCLUSIONS/UNASSIGNED:Deep phenotyping of FTSDma reveals similarities in dystonic phenotype between instrument classes, likely related to shared technical demands, and unexpected similarities between other forms of task-specific upper extremity dystonia. A network model to explain these findings is proposed.