Faculty Bibliography

PURPOSE/OBJECTIVE:Up to 25% of patients diagnosed as idiopathic Parkinson's disease (IPD) have an atypical parkinsonian syndrome (APS). We had previously validated an automated image-based algorithm to discriminate between IPD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). While the algorithm was accurate with respect to the final clinical diagnosis after long-term expert follow-up, its relationship to the initial referral diagnosis and to the neuropathological gold standard is not known. METHODS:F-fluorodeoxyglucose (FDG) PET to classify patients as IPD or as APS based on the automated algorithm. Patients were followed by a movement disorder specialist and subsequently underwent neuropathological examination. The image-based classification was compared to the neuropathological diagnosis in 15 patients with parkinsonism. RESULTS:At the time of referral to PET, the clinical impression was only 66.7% accurate. The algorithm correctly identified 80% of the cases as IPD or APS (p = 0.02) and 87.5% of the APS cases as MSA or PSP (p = 0.03). The final clinical diagnosis was 93.3% accurate (p < 0.001), but needed several years of expert follow-up. CONCLUSION/CONCLUSIONS:The image-based classifications agreed well with autopsy and can help to improve diagnostic accuracy during the period of clinical uncertainty.

Background/UNASSIGNED:The ictal examination is crucial for neuroanatomic localization of seizure onset, which informs medical and neurosurgical treatment of epilepsy. Substantial variation exists in ictal examination performance in epilepsy monitoring units (EMUs). We developed and implemented a standardized examination to facilitate rapid, reliable execution of all testing domains and adherence to patient safety maneuvers. Methods/UNASSIGNED:Following observation of examination performance, root cause analysis of barriers, and review of consensus guidelines, an ictal examination was developed and disseminated. In accordance with quality improvement methodology, revisions were enacted following the initial intervention, including differentiation between pathways for convulsive and nonconvulsive seizures. We evaluated ictal examination fidelity, efficiency, and EMU staff satisfaction before and after the intervention. Results/UNASSIGNED:We identified barriers to ictal examination performance as confusion regarding ictal examination protocol, inadequate education of the rationale for the examination and its components, and lack of awareness of patient-specific goals. Over an 18-month period, 100 ictal examinations were reviewed, 50 convulsive and 50 nonconvulsive. Ictal examination performance varied during the study period without sustained improvement for convulsive or nonconvulsive seizure examination. The new examination was faster to perform (0.8 vs 1.5 minutes). Postintervention, EMU staff expressed satisfaction with the examination, but many still did not understand why certain components were performed. Conclusion/UNASSIGNED:We identified key barriers to EMU ictal assessment and completed real-world testing of a standardized, streamlined ictal examination. We found it challenging to reliably change ictal examination performance in our EMU; further study of implementation is warranted.

Background/UNASSIGNED:People living with multiple sclerosis (MS) experience a high symptom burden that interferes with daily functioning. Virtual reality (VR) is an emerging technology with a range of potential therapeutic applications that may include ameliorating the experience of some common MS symptoms. Objective/UNASSIGNED:We tested the feasibility and tolerability of a VR intervention and its preliminary effects on affect. Methods/UNASSIGNED:Participants with MS were recruited to complete a pilot study of eight sessions of VR over four weeks. Results/UNASSIGNED: = 0.040). Conclusion/UNASSIGNED:VR interventions are feasible, safe, and tolerable for individuals living with MS and may improve affect.

Inflammatory peripheral neuropathies can be disabling for any patient. Selecting the most appropriate agent for treatment, especially in the elderly, is no simple task. Several factors should be considered. Herein, we discuss immunotherapeutic options for peripheral nerve diseases and the important considerations required for choosing one in the geriatric population.

OBJECTIVE:To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort. METHODS:We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes. RESULTS:There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge. CONCLUSIONS:Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.

OBJECTIVE:Cognitive deficits following a traumatic brain injury (TBI) are a leading cause of disability in young adults and there is a critical need for novel approaches to improve cognitive outcomes in TBI survivors. Transcranial direct current stimulation (tDCS) paired with cognitive remediation has emerged as a viable, cost-effective, noninvasive approach for treating cognitive impairments in a wide variety of neurological conditions. Here, we report the first case study utilizing remotely supervised tDCS (RS-tDCS) protocol paired with cognitive remediation in a 29-year-old man with persisting cognitive and emotional sequelae following TBI. METHOD/METHODS:Neuropsychological measures were administered before and after the patient completed 20 daily sessions of RS-tDCS (2.0 mA × 20 minutes, left anodal dorsolateral prefrontal cortex montage). During the daily stimulation period, he completed adaptive cognitive training. All treatment procedures were delivered at home and monitored in real time via videoconference with a study technician. RESULTS:Following 20 RS-tDCS and cognitive training sessions, he had significant improvements (>1 SD) on tests of attention and working memory, semantic fluency, and information processing speed. Mood was also improved. CONCLUSIONS:This is the first demonstration of at-home telerehabilitation with RS-tDCS and cognitive training to improve cognitive outcomes following TBI.

Neocortical heterotopia consist of ectopic neuronal clusters that are frequently found in individuals with cognitive disability and epilepsy. However, their pathogenesis remains poorly understood due in part to a lack of tractable animal models. We have developed an inducible model of focal cortical heterotopia that enables their precise spatiotemporal control and high-resolution optical imaging in live mice. Here, we report that heterotopia are associated with striking patterns of circumferentially projecting axons and increased myelination around neuronal clusters. Despite their aberrant axonal patterns, in vivo calcium imaging revealed that heterotopic neurons remain functionally connected to other brain regions, highlighting their potential to influence global neural networks. These aberrant patterns only form when heterotopia are induced during a critical embryonic temporal window, but not in early postnatal development. Our model provides a new way to investigate heterotopia formation in vivo and reveals features suggesting the existence of developmentally modulated, neuron-derived axon guidance and myelination factors.

DSA is the standard imaging technique for evaluation of cerebrovascular conditions. However, One drawback is its limitation in depicting a single angiographic phase at a time. We describe a new 3D-DSA algorithm, which we call arterial and venous-3D-DSA, which allows the concurrent yet distinct display of the arterial and venous structures, which may be useful for different clinical and educational purposes.

Voluntary rapid eye movements (saccades) redirect the fovea toward objects of visual interest. The saccadic system can be considered as a dual-mode system: in one mode the eye is fixating, in the other it is making a saccade. In this review, we consider two examples of dysfunctional saccades, interrupted saccades in late-onset Tay-Sachs disease and gaze-position dependent opsoclonus after concussion, which fail to properly shift between fixation and saccade modes. Insights and benefits gained from bi-directional collaborative exchange between clinical and basic scientists are emphasized. In the case of interrupted saccades, existing mathematical models were sufficiently detailed to provide support for the cause of interrupted saccades. In the case of gaze-position dependent opsoclonus, existing models could not explain the behavior, but further development provided a reasonable hypothesis for the mechanism underlying the behavior. Collaboration between clinical and basic science is a rich source of progress for developing biologically plausible models and understanding neurological disease. Approaching a clinical problem with a specific hypothesis (model) in mind often prompts new experimental tests and provides insights into basic mechanisms.