Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24496
Transcallosal inhibition does not influence subacute motor recovery in mild-to-moderate stroke
After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to definitively confirm or refute a maladaptive role of contralesional TI in subacute motor recovery. We assessed 30 mild-to-moderately impaired subjects over the six months following ischemic stroke. We tracked contralesional TI and motor functions in the proximal and distal segments of the paretic UE. We used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP) in an arm and hand muscle. We used quantitative and clinical testing to examine deficits in muscle strength, motor control, and individuation; UE segmental impairment; and UE activity limitation. We assessed the relationships of contralesional TI to motor functions in the subacute period. Despite recovery of most motor functions in the proximal and distal UE, contralesional TI was largely static and unrelated to recovery of any motor function. There were inconsistent associations between stronger TI, less hand impairment, and less activity limitation in the subacute period overall. We found no compelling evidence to suggest a maladaptive role of contralesional TI in UE motor recovery in mild-to-moderately impaired stroke subjects. The scattered associations between stronger TI and better levels of paretic UE function suggest a potential supportive role rather than a limiting one. These findings challenge the validity of the interhemispheric competition model in the subacute recovery period, and prompt reconsideration of neuromodulatory strategies that subacutely target contralesional TI.
PMID: 40066755
ISSN: 1460-2156
CID: 5808302
The cerebellum in epilepsy
The cerebellum, a subcortical structure, is traditionally linked to sensorimotor integration and coordination, although its role in cognition and affective behavior, as well as epilepsy, is increasingly recognized. Cerebellar dysfunction in patients with epilepsy can result from genetic disorders, antiseizure medications, seizures, and seizure-related trauma. Impaired cerebellar function, regardless of cause, can cause ataxia (imbalance, impaired coordination, unsteady gait), tremor, gaze-evoked nystagmus, impaired slow gaze pursuit and saccade accuracy, as well as speech deficits (slurred, scanning, or staccato). We explore how cerebellar dysfunction can contribute to epilepsy, reviewing data on genetic, infectious, and neuroinflammatory disorders. Evidence of cerebellar dysfunction in epilepsy comes from animal studies as well as human neuropathology and structural magnetic resonance imaging (MRI), functional and diffusion tensor MRI, positron emission and single photon emission computerized tomography, and depth electrode electro-encephalography studies. Cerebellar lesions can infrequently cause epilepsy, with focal motor, autonomic, and focal to bilateral tonic-clonic seizures. Antiseizure medication-resistant epilepsy typically presents in infancy or before age 1 year with hemifacial clonic or tonic seizures ipsilateral to the cerebellar mass. Lesions are typically asymmetric benign or low-grade tumors in the floor of the fourth ventricle involving the cerebellar peduncles and extending to the cerebellar hemisphere. Electrical stimulation of the cerebellum has yielded conflicting results on efficacy, although methodological issues confound interpretation. Epilepsy-related comorbidities including cognitive and affective disorders, falls, and sudden unexpected death in epilepsy may also be impacted by cerebellar dysfunction. We discuss how cerebellar dysfunction may drive seizures and how genetic epilepsies, seizures and seizure therapies may drive cerebellar dysfunction, and how our understanding of epilepsy-related comorbidities through basic neuroscience, animals models and patient studies can advance our understanding and improve patient outcomes.
PMID: 40079849
ISSN: 1528-1167
CID: 5808732
Impact of phenobarbital when used in combination with benzodiazepines for the treatment of alcohol withdrawal syndrome: A retrospective analysis
BACKGROUND AND OBJECTIVE/OBJECTIVE:Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol use disorder. Although benzodiazepines are the mainstay of treatment, some patients may be resistant to them, requiring rapidly escalating doses. Phenobarbital has emerged as an effective adjunct therapy in severe alcohol withdrawal, but studies have yielded inconsistent results and carry safety risks. The purpose of our study was to examine the effectiveness and the potential harm of phenobarbital in AWS. METHODS:In this multi-center, retrospective cohort study, patients who were admitted for AWS and received phenobarbital with benzodiazepine were compared to patients who received benzodiazepine monotherapy. The primary outcome was time to AWS resolution. Other secondary and safety outcomes included length of stay (LOS), rate of mechanical ventilation, and incidence of aspiration pneumonia. RESULTS:The phenobarbital group received significantly higher doses of benzodiazepines compared to the benzodiazepine monotherapy group (660 mg vs 340 mg, p < 0.0001). After adjustment, the use of phenobarbital was associated with significantly reduced time to AWS resolution (141.65 h vs 165.72 h, p < 0.0001). However, the use of phenobarbital was associated with the likelihood of mechanical ventilation (19.42 %vs. 0.96 %, p < 0.0001), aspiration pneumonia (22.33 % vs 5.77 %, p = 0.0006), and increased hospital LOS (8 days vs. 6 days, p = 0.0197). In the combination group, earlier phenobarbital initiation (within 24 h) was associated with significantly lower cumulative benzodiazepine dose (530 mg vs 887.50 mg, p = 0.002) and hospital LOS (6 days vs 10 days, p = 0.0017). CONCLUSION AND RELEVANCE/CONCLUSIONS:In our study, patients who received phenobarbital in combination with benzodiazepines had a quicker resolution of AWS but also had a higher incidence of mechanical ventilation, prolonged hospital LOS, and an increased risk of aspiration pneumonia. For patients at high risk of severe alcohol withdrawal, earlier initiation of phenobarbital appeared to yield the most optimal benefit.
PMID: 40080990
ISSN: 1532-8171
CID: 5808812
Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome
OBJECTIVE:We analyzed the long-term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open-label extension (OLE) study after participating in randomized controlled trials (RCTs) or commencing FFA de novo as adults. METHODS:Patients with DS who participated in one of three RCTs or were 19 to 35 years of age and started FFA de novo were included. Key endpoints were: incidence of treatment-emergent adverse events (TEAEs) in the safety population, and median percentage change in monthly convulsive seizure frequency (MCSF) from the RCT baseline to end of study (EOS) in the modified intent-to-treat (mITT) population. Post hoc analyses compared effectiveness in patients on concomitant stiripentol (STP) vs those not taking STP, and assessed safety (TEAEs) and effectiveness (Clinical Global Impression-Improvement [CGI-I] scale ratings) in patients enrolled as adults. RESULTS:A total of 374 patients, including 45 adults, received ≥1 FFA dose. Median FFA exposure was 824 days (range, 7-1280). TEAEs occurring in ≥10% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiography (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection; no valvular heart disease or pulmonary arterial hypertension was observed over the OLE. In the mITT population (n = 324), median percentage change in MCSF from baseline to EOS was -66.8% (p < .001). The post hoc analyses of MCSF change from baseline to EOS in patients on concomitant STP (n = 75) was -36.2% vs -71.6% in those not on concomitant STP (n = 234) (p < .0001). In adult patients, 29 of 41 (70.7%) and 29 of 42 patients (69.1%) demonstrated clinically meaningful improvement on CGI-I at last visit as rated by caregivers and investigators, respectively. SIGNIFICANCE/CONCLUSIONS:Our OLE study of FFA in patients with DS confirmed previous positive findings and extended the exposure up to 3.5 years. No new or unexpected safety signals were observed and FFA demonstrated sustained and clinically meaningful reduction in MCSF.
PMID: 40072476
ISSN: 1528-1167
CID: 5808502
Clinical Reasoning: A 56-Year-Old Woman With New-Onset Hoarseness and Dysphagia [Case Report]
STATEMENT OF THE CLINICAL PROBLEM ADDRESSED BY THE CASE/UNASSIGNED:We report an atypical clinical presentation of a rapidly progressive neurologic emergency that required prompt investigation and treatment of impending respiratory failure. We discuss the differential diagnosis, evaluation, emergency management, and treatment options of patients with atypical variants of this disorder. BRIEF DESCRIPTION OF CASE PRESENTATION/UNASSIGNED:A 56-year-old woman with a history of hypothyroidism, anxiety, and depression presented to the emergency department 3 weeks after an upper respiratory and ear infection with cough, pain with sinus palpation, tingling in her fingers bilaterally and right foot, hives, and an episode of blurry vision on awakening. She was discharged home with antibiotics. That evening, she developed rapidly progressing hoarseness and dysphagia and returned to the emergency department. An initial examination and laryngoscopy revealed complete left vocal cord paralysis, consistent with a left cranial nerve X palsy, which prompted a neurologic evaluation. Her examination progressively worsened over the next day requiring mechanical ventilation and ICU admission. SUMMARY OF THE KEY TEACHING POINT IN THE CASE/UNASSIGNED:New-onset bulbar cranial neuropathies should raise concern for neurologic disorders that can be rapidly progressive and result in respiratory failure. Urgent diagnosis and treatment are warranted.
PMID: 40063858
ISSN: 1526-632x
CID: 5808222
Unplanned extubation prevention in the neuroscience ICU at a High Reliability Organization
BACKGROUND:Intubated neuroscience ICU patients are at risk for unplanned extubation (premature removal of the endotracheal tube by the patient or during patient care). The incidence of unplanned extubation is an indicator of the quality of ICU care. Unplanned extubation is a risk factor for pneumonia, increased ventilator days, the need for tracheostomy and increased ICU and hospital length-of-stay. After serial unplanned extubations, we introduced a multidisciplinary unit-based practice standard to reduce unplanned extubations as part of a quality improvement initiative in the neuroscience ICU in a large academic medical center at a High Reliability Organization in May 2021. The unit-based practice standard to guide care of intubated neuroscience ICU patients focused on communication, timely escalation of concerns, use of sedation/analgesia targeting RASS ≤ -1, soft wrist restraints (unless specified exclusion criteria met) and continuous observation for patients at high risk of agitation/restlessness. We sought to determine the impact of this initiative on the incidence of unplanned extubations. METHOD/METHODS:Unplanned extubations were identified via retrospective audit of prospective incident reports from our Patient Safety Incident registry pre-initiative (June 2020-May 2021) and prospective audit of incident reports post-initiative (July 2021-March 2024). Chart review facilitated collection of data on patient age, sex, diagnosis, intubation day, RASS goal, sedation/analgesia, restraints, constant observation, shift, and reintubation. The total number of intubated patients and ventilator days during these timeframes was identified retrospectively via an electronic medical record report of all patients on ventilators in the neuroscience ICU. RESULTS:During the pre-initiative audit period, there were 214 intubated patients (968 ventilator days). The audit identified 9 unplanned extubations (0.93/100 ventilator days; 8 males, median age 63-years-old (IQR 47-67)). There were 4 patients who were not ordered for sedation/analgesia or had a RASS goal of 0 and no patients were in nonviolent soft wrist restraints. During the post-initiative audit period, there were 576 intubated patients (2,730 ventilator days). The audit identified 6 unplanned extubations (0.22/100 ventilator days; 6 males, median age 53-years-old (IQR 27-78)). All 6 patients had a RASS goal ≤ -1 and were in nonviolent soft wrist restraints. CONCLUSION/CONCLUSIONS:This quality improvement initiative effectively reduced the incidence of unplanned extubations in our neuroscience ICU.
PMID: 40068249
ISSN: 1532-2653
CID: 5808362
Spontaneous Spinal Cord Infarction in a Young Patient: An Overview of Clinical Features and Management
PMID: 39781784
ISSN: 1524-4628
CID: 5805182
X-chromosome-wide association study for Alzheimer's disease
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-
PMID: 39633006
ISSN: 1476-5578
CID: 5804132
Severe intracranial hypotension secondary to cerebrospinal-venous fistula in a patient with remote history of spinal decompression and fusion
PMID: 39733505
ISSN: 1532-2653
CID: 5805402
Treatment of Acute Iatrogenic Cerebrovascular Injury Using Flow Diverter Stents
BACKGROUND AND OBJECTIVES/OBJECTIVE:Iatrogenic cerebrovascular injury can cause intracranial hemorrhage and pseudoaneurysm formation, putting patients at high risk for postoperative bleeding. No consensus for management exists. This study describes endovascular treatment of these acute injuries with flow diverter stents. METHODS:Electronic medical records were retrospectively reviewed for injury type and etiology, timing of diagnosis, and endovascular management, including antiplatelet regimens, embolization results, and clinical outcome. RESULTS:Six patients were included. Three suffered an injury to the internal carotid artery, 1 suffered an injury to the left anterior cerebral artery, 1 suffered an injury to the right posterior cerebral artery, and 1 suffered an injury to the basilar artery. Four of the 6 injuries occurred during attempted tumor resection, 1 occurred during cerebrospinal fluid leak repair, and 1 occurred during an ophthalmic artery aneurysm clipping. All injuries resulted in pseudoaneurysm formation. Four were immediately detected on angiography; 2 were initially negative on imaging. Five were treated with a pipeline embolization device, and 1 was treated with a Silk Vista Baby. Two were treated with 2 pipeline embolization devices telescopically overlapped across the pseudoaneurysm. All devices deployed successfully. No pseudoaneurysm recurrence or rebleeding occurred. No parent artery occlusion or stenosis was observed, and complete pseudoaneurysm occlusion was observed in 4 patients (in 2 patients, follow-up imaging could not be obtained). CONCLUSION/CONCLUSIONS:With proper antiplatelet regimens, flow diverter stents can be used safely to successfully treat complex acute iatrogenic injuries. Early repeat angiogram is needed when immediate postinjury imaging does not discover the point of vessel injury.
PMID: 39311570
ISSN: 2332-4260
CID: 5802862
