Scholarly Activity

Neurology Publications

Scholarly journal articles and meeting abstracts authored by members of the Department of Neurology at Henry Ford Health.

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Neurology Articles

  • 5/1/2025 7:00 AM

    BACKGROUND: Synesthesia is a condition in which the stimulation of one sensory modality triggers unusual experiences in a second sensory modality such as colors or shapes. Synesthesia has been linked to specific conditions such as autism spectrum disorder, although the mechanisms underlying synesthesia remain largely unclear.

    OBJECTIVE: This pilot study aimed to investigate the prevalence of grapheme-color synesthesia (GCS) in patients with epilepsy and to characterize the epilepsy features associated with GCS experiences.

    METHODS: Participants were asked whether they reported experiences suggesting GCS. Those reporting GCS underwent a standard online consistency and congruency battery test (http://www.synesthete.org). Epilepsy features, electroencephalogram (EEG) findings, and magnetic resonance imaging (MRI) findings were collected and analyzed.

    RESULTS: Of the 40 study participants, 21 reported GCS experiences and 3 (7.5 %) resulted synesthetes from the battery test. Analysis of the test results showed that participants with focal seizures had lower median consistency scores (indicating they were less consistent in their color assignments) and higher congruency scores (indicating they were more accurate in quickly identifying matching color and letter/number combinations) compared to patients with generalized-onset seizures (2.9 and 51.4 respectively; p = 0.006, p = 0.001). Participants with non-motor seizures had lower median consistency scores (1.1) and higher congruency scores (79.2) compared to patients with motor seizures (2.8 and 52.8, respectively; p = 0.011, p = 0.036).

    CONCLUSION: GCS may be more prevalent in patients with epilepsy than the general population. Focal and non-motor seizures may be associated with predisposition to GCS. Further larger scale studies are needed to confirm and expand these observations.

  • 4/29/2025 7:00 AM

    BackgroundIntravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are the standard of care for select stroke patients with acute large vessel occlusion (LVO). Fibrinogen levels may drop after IVT, and a significant decrease in fibrinogen is associated with an increased risk of intracranial hemorrhage (ICH). Our pilot study aimed to explore the relationship between fibrinogen levels and the development of ICH in MT-treated patients and whether bridging with IVT further increases that risk.MethodsThis is a prospective pilot study that enrolled adults presenting with a diagnosis of LVO stroke and eligible to receive MT with or without IVT between April 2020 and May 2023. Fibrinogen levels were drawn before treatment with IVT or MT and immediately following MT.ResultsForty-one patients were enrolled. Median age was 68 years [interquartile range 56-79], 58.5% were females and 56.1% were black. Nineteen patients (46.3%) were treated with MT + IVT, and 22 (53.6%) were treated with MT-only. There was no difference in baseline characteristics between the two groups. Baseline fibrinogen levels were similar between MT + IVT and MT-only groups [391 vs. 352 mg/dL, p = 0.4]. Post MT, the MT + IVT group had lower fibrinogen levels compared to the MT-only group [224 vs. 303 mg/dL, p <  0.001]. Similarly, there was a significant change between baseline and follow-up levels in the MT + IVT vs. MT-only group [106 vs. 39.5 mg/dL, p = 0.001]. Eight patients (19.5%) developed ICH; 5 (26.3%) in the MT + IVT group and 3 (13.6%) in the MT-only group. No significant differences were seen in baseline, follow-up, or change in fibrinogen levels between patients who developed ICH and those who did not. However, when stratified by treatment group, postintervention fibrinogen levels were significantly lower in patients who developed an ICH in the MT + IVT group compared to those without ICH in the MT group (200 vs. 301 mg/dL, p = 0.006). There was also a negative correlation between the change in fibrinogen levels and the rate of first-pass recanalization (Spearman CC -0.33, p = 0.03).ConclusionThis pilot study's preliminary data showed an association between fibrinogen depletion and hemorrhagic transformation in MT-treated patients. Since intracerebral hemorrhage is the most dire side effect in stroke treatment, fibrinogen monitoring in patients undergoing MT after IVT may help identify patients with an increased risk of ICH. Larger, prospective, and multicenter studies are needed to confirm these findings and if fibrinogen repletion should be considered for dysfibrinogenemia.

  • 4/4/2025 7:00 AM

    Introduction: The decision to intervene with mechanical thrombectomy (MT) for anterior cerebral artery (ACA) strokes is often made based on anticipated long-term functional outcomes using modified Rankin scores (mRS) which is primarily based on ambulatory status. Here, we review our single-center experience with ACA MT and evaluate the utility of various functional outcomes reporting.

    Methods: A case series of 15 patients undergone MT for ACA stroke using the Solitaire or Trevo stent-retrievers was completed. The data retrieved included patient demographics, initial National Institute of Health Stroke Scale (NIHSS), thrombolysis in cerebral infarction (TICI) scores and number of passes, post-procedure 24-hour NIHSS, intra-operative or post-operative complications, discharge NIHSS and mRS, and 90-day mRS.

    Results: There were 87 % favorable ACA TICI scores (i.e. 2B/C and 3) and 80 % first pass recanalization rate. The Solitaire 4 mm stent-retriever was employed in the majority of cases (60 %). No procedural complications were noted in 73 % of cases and no hemorrhagic conversion in 87 % of cases. 90-day mRS scores of 0–2 were noted in 26 % of patients. Using an adjusted outcomes index, 80 % of patients had favorable outcomes based on the 24-hour baseline-adjusted NIHSS score decrease of ≥ 41 %.

    Conclusion: Our preliminary findings here highlight successful radiographic and favorable functional outcomes using the Solitaire and Trevo stent-retrievers (3–6 mm luminal diameter) for ACA MT when reporting with the adjusted outcomes index as compared to the 90-day mRS score. Further studies comparing these outcomes reporting metrics with a larger sample size will be needed to further elucidate this notable difference.

  • 4/3/2025 7:00 AM

    BACKGROUND: There are no data on the effect size and timing of plasma exchange (PLEX) in patients with myasthenic crisis (MC).

    METHODS: We retrospectively analyzed measurements of forced vital capacity (FVC) and negative inspiratory force (NIF) in the days before and after PLEX (administered every other day) in patients with MC admitted to a tertiary hospital over 4 years. For multiple measurements in one day, the average value was used. The day immediately before the first treatment with PLEX was considered baseline. Using time as a continuous or categorical variable in mixed-effects multiple linear regressions, we estimated predicted values for these tests.

    RESULTS: Twenty-two patients (mean age 67.3 years, 51.9% male patients) with 27 MC episodes and 508 measurements (234 FVC and 274 NIF; from 5 days before to 20 days after PLEX) were included. Presence of antibodies was detected in 70.4%. Intubation and mechanical ventilation occurred in 36.6% of patients. The mean number of PLEX was 5.1 (range 3-11). NIF values decreased before the first PLEX but increased after by on average 1 cm H(2)O/day (95% confidence interval [CI] 0.68-1.32, p <  0.001). FVC fluctuated before the first PLEX but then increased by on average 51.2 mL/day (95% CI 35.8-66.1, p <  0.001). The maximum increase in NIF occurred during the day of the first PLEX (9.2 cm H(2)O, 95% CI 3.3-15.1, p = 0.002) and rather slowed after day 10. FVC increase compared to baseline became significant the second day after the first PLEX (287 mL, 95% CI 7.5-567.6, p = 0.04) and continued overall to increase (with fluctuations) up to day 17.

    CONCLUSIONS: Significant increases in bedside respiratory measurements are observed as soon as the first PLEX day but with more variability on FVC than NIF, which may either reflect more FVC technique inconsistencies or more consistent effect of the treatment on NIF.

  • 4/2/2025 7:00 AM

    BACKGROUND AND OBJECTIVES: Times to clinically relevant events are a valuable outcome in observational and interventional studies, complementing linear outcomes such as functional rating scales and biomarkers. In ALS, there are several clinically relevant events. We developed dynamic prediction models for several of these times to events that can be used for clinical trial modeling and personal planning.

    METHODS: Landmark time-to-event analysis was implemented to determine the effect of patient characteristics on disease progression. Longitudinal data from 1557 participants in the ALS Natural History Consortium dataset were used. Five outcomes in the ALS disease progression were considered: loss of ambulation, loss of speech, gastrostomy, noninvasive ventilation (NIV) use, and continuous NIV use. Covariates in our models include age at diagnosis, sex, onset location, riluzole use, diagnostic delay, ALSFRS-R scores at the landmark time, and ALSFRS-R rates of change from baseline. Internal and external validation techniques were used.

    RESULTS: For each of our models and landmark times, we present risk prediction intervals for random sets of patient characteristics. We demonstrate our models' application for an individual's personal predicted time-to-event. Our internal and external validation metrics indicate good concordance and overall performance. The time to loss of speech models perform the best for each metric in terms of both internal and external validation.

    DISCUSSION: Landmarking is an efficient, individualized risk prediction model that is intuitive for both clinicians and patients. Importantly, landmarking can be used for clinical trial modeling, personal planning, and development of real-world evidence of the impacts of treatment interventions.

  • 4/1/2025 7:00 AM

    IMPORTANCE: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.

    OBJECTIVE: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.

    DESIGN SETTINGS AND PARTICIPANTS: Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.

    INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.

    MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale-Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.

    RESULTS: A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR < 1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.

    CONCLUSIONS AND RELEVANCE: Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.

    TRIAL REGISTRATION: Clinical Trial Identifiers: NCT04297683 and NCT04436510.

  • 4/1/2025 7:00 AM

    Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in reports on EAE across animal strains/studies, limiting the utility of these biomarkers for predicting disease activity. In this study, we investigated blood-based analyte profiles, including neural markers (NFL and GFAP) and cytokines (IL-6, IL-17, IL-12p70, IL-10, and TNF-α), in two clinically distinct EAE models: relapsing-remitting (RR)-EAE and chronic-EAE. Ultrasensitive single-molecule array technology (SIMOA, Quanterix) was used to profile the analytes in the blood plasma of mice at the acute, chronic, and progressive phases of disease. In both models, NFL was substantially increased during post-disease onset across all phases, with a pronounced increase observed in chronic-EAE. The leakage of GFAP into peripheral blood was also greater after disease onset in both EAE models, especially in the acute phase of chronic-EAE. Among all cytokines, only IL-10 had consistently lower levels in both EAE models throughout the course of disease. This study suggests NFL, GFAP, and IL-10 as potential translational predictors of disease activity in EAE, making them potential candidates as surrogate markers for the preclinical testing of therapeutic interventions in animal models of MS.

  • 3/1/2025 8:00 AM

    Dendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN(+)) and CaMKIIa positive (CaMKIIa(+)) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke. Neuronal mitochondria were then selectively isolated from the fresh brain tissues excised from the ischemic core (IC), ischemic boundary zone (IBZ), as well as from the homologous contralateral hemisphere (CON) by anti-HA magnetic beads for functional analyses. We found that the bead pulled neuronal specific mitochondria were co-precipitated with GFP and enriched with mitochondrial markers, e.g. voltage-dependent anion channel, cytochrome C, and COX IV, but lacked the Golgi protein RCAS1 as well as endoplasmic reticulum markers: Heme‑oxygenase 1 and Calnexin, indicating that specific neuronal mitochondria have been selectively isolated. Western-blot data showed that oxidative phosphorylation (OXPHOS) components in SYN(+) and CAMKII(+) neuronal mitochondria were significantly decreased in the IBZ and further decreased in the IC compared to the contralateral tissue, which was associated with the significant reductions of mitochondrial function indicated by oxygen consumption rate (OCR) (p < 0.05, respectively, for both neuron types). These data suggest dysfunction of neuronal mitochondria post stroke is present during the stroke recovery stage. Collectively, for the first time, we demonstrated that using a Mito-tag mouse line combined with AAV9 carrying Cre recombinase approach, neuronal specific mitochondria can be efficiently isolated from the mouse brain to investigate their functional changes post stroke.

  • 3/1/2025 8:00 AM

    Neuronal circuitry remodelling, which comprises excitatory and inhibitory neurons, is critical for improving neurological outcomes after a stroke. Preclinical studies have shown that small extracellular vesicles (sEVs) have a therapeutic effect on stroke recovery. However, it is highly challenging to use sEVs to specifically target individual neuronal populations to enhance neuronal circuitry remodelling after stroke. In the present study, using a chemogenetic approach to specifically activate peri-infarct cortical interneurons in combination with the administration of sEVs derived from cerebral endothelial cells (CEC-sEVs), we showed that the CEC-sEVs were preferentially taken up by the activated neurons, leading to significant improvement of functional outcome after stroke, which was associated with augmentation of peri-infarct cortical axonal/dendritic outgrowth and of axonal remodelling of the corticospinal tract. The ultrastructural and Western blot analyses revealed that neurons with internalization of CEC-sEVs exhibited significantly reduced numbers of damaged mitochondria and proteins that mediate dysfunctional mitochondria, respectively. Together, these data indicate that the augmented uptake of CEC-sEVs by activated peri-infarct cortical interneurons facilitates neuronal circuitry remodelling and functional recovery after stroke, which has the potential to be a novel therapy for improving stroke recovery.

  • 2/27/2025 8:00 AM

    BACKGROUND: Neurological complications in patients with infective endocarditis (IE), such as ischemic and hemorrhagic stroke, are well described; however, predicting which patients are most likely to experience stroke remains uncertain.

    AIMS: We conducted a systematic review and meta-analysis to identify the factors associated with the risk of stroke in patients hospitalized with IE.

    METHODS: A systematic search of Ovid MEDLINE, EMBASE, and Web of Science up to 27 June 2024 was conducted. Articles evaluating risk of acute ischemic stroke (AIS) or intracranial hemorrhage (ICH) in patients with IE were included. Meta-analysis of odds ratios was feasible for only some predictive factors due to study heterogeneity. Cochrane's Risk of Bias in Non-Randomized Studies of Exposure tool was used for risk-of-bias assessment.

    SUMMARY OF REVIEW: Of 3538 studies identified, 35 were included: 9 prospective and 26 retrospective cohort.

    CONCLUSION: Our study has identified factors which are associated with increased stroke risk in IE and may help physicians predict risk. While echocardiographic and neuroimaging findings may be particularly informative, underlying comorbidities and various laboratory values may also contribute to predicting IE-associated strokes.



Neurology Abstracts

  • 11/1/2024 7:00 AM

    BACKGROUND: OncoPath provides a visual analysis of a brain tumor patient's longitudinal clinical data overlayed on disease specific pathways with the goal of reducing knowledge discordant care and insurance authorization burden. By ingesting, curating and visually presenting the patient experience on guidelines, OncoPath aims to streamline clinical decision making and related processes. Understanding the patient's journey compared to treatment guidelines is of value in addressing health equity and guideline adoption in real world settings. METHODS: Data from 44 glioma patients diagnosed and treated between 2016-2021 were uploaded to OncoPath using natural language processing and other tools to capture abstractable data elements. The data was overlayed on guidelines using recursive graph modeling. Using the knowledge graph of a patient's history, the model also recommends treatment options in an interactive visual dashboard representing NCCN guidelines. The dashboard includes the guidelines in graphical format with associated references and notation. RESULTS: 28 males and 16 females age 21-38 years at diagnosis were abstracted. Cases represented 4 oligodendrogliomas, 13 astrocytomas, and 27 glioblastomas. Data was available through second line therapy, discharge to hospice or death. Cases were matched to the NCCN 2021 guidelines which was used for treatment decisions until November 2022. The patient data matched OncoPath except in 3 cases where KPS was not available resulting in premature pathway truncation. For these cases we inferred KPS based on subsequent treatment received to optimize the historic data. CONCLUSION: To our knowledge, this is a first-of-a-kind technology in neuro-oncology that may improve time to treatment, reduce health utilization resources and can serve as a benchmarking tool for care delivery. The feasibility of clinically implementing such tools for decision support was demonstrated. This type of tool could be particularly useful in low-resource areas where disease specific expertise may not be available or to illuminate care discrepancies.

  • 6/1/2024 7:00 AM

    Purpose : Traumatic optic neuropathy (TON) has been regarded a vision threatening condition caused by either ocular or blunt/penetrating head trauma which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. TON results optic nerve damage that leads to profound loss of central vision. There is stiil a lack of TON managment. Here, we used remote ischemic post-conditioning (RIC) therapy to reduce TON related retinal dysfunction. Earlier, we have demonstrated that RIC therapy is protective in TON via AMPKα1 activation in mice. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Methods : We generated myeloid specific AMPKα1 KO mice by using LysMcre to carry out the study. We induced TON in mice by using controlled impact system as reported previously. RIC therapy was given every day (5-7 days following TON). Western blotting, Immunohistochemistry, Flow cytometry and TEM technique, and Unisense sensor system for retinal oxygenation were used to generate research data. Results : Immunofluorescence and western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in TON [AMPKα1F/F] vs Sham group but TON+RIC [AMPKα1F/F] attenuated expression level of these markers. Interestingly, higher microglia activation was observed in myeloid AMPKα1F/F KO group with TON and RIC didn't show any significant difference. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers and increased anti-inflammatory markers, and improved oxygen level however, myeloid AMPKα1 KO mice didn't show any changes after TON with RIC. Transmission electron microscopy (TEM) data of optic nerve showed increased demyelination and axonal degeneration in TON [AMPKα1F/F] group and TON+RIC [AMPKα1F/F] showed improved myelination. RIC has no significant effect in myeloid AMPKα1 KO group following TON. Conclusions : Overall, these data suggested that RIC therapy provides protection against inflammation and neurodegeneration via myeloid AMPKα1. Further investigation of RIC and AMPKα1 signaling is warranted in TON.

  • 6/1/2024 7:00 AM

    Background: GBM AGILE (NCT03970447) is a phase 2/3 Bayesian adaptive registration platform trial testing multiple therapies efficiently against a common control (C) with a primary endpoint of overall survival (OS). VAL-083 (VAL) is a DNA targeting agent that, independent of O6-methylguanine DNA methyltransferase promoter methylation status, targets the N7 position of guanine residues and facilitates inter-strand DNA crosslinks, leading to DNA doublestrand breaks and cell death. It entered the trial in January 2021, and it is the 2nd arm (of 6) to complete its evaluation. Methods: Patient subtypes considered in GBM AGILE are newly diagnosed methylated (NDM), ND unmethylated (NDU), & recurrent disease (RD). C is temozolomide (in ND) & lomustine (in RD). Arms open to all 3 subtypes are evaluated in = prospectively defined signatures (sig): NDU, NDM, RD, all ND and All. Randomization to C is 20% in each subtype. Exp arms in GBM AGILE have 1 or 2 stages. Efficacy is based on OS hazard ratio (HR) of arm/C. Efficacy goal is a final Bayesian probability ≥ 98% for HR <1.00 in combined Stages 1 & 2. Arms stop accruing in Stage 1 if they reach max sample size (N) or drop for futility or safety. Exp arms in Stage 1 are adaptively randomized with allocation being proportional to an arm's current probability of having ≥ 30% benefit in OS, P(HR <0.70). In stage 1, exp arms are evaluated monthly, and arms showing Bayesian predictive power (PP) ≥ 0.8, graduate into Stage 2 with fixed randomization in one sig. For all exp arms, follow up continues for 12 mos after accrual stops (clinical cutoff). Arms are declared futile at any monthly analysis when PP is <0.25 for all sigs. Open to all 3 subtypes, VAL entered as the 1st arm in NDM and was randomized 1:1 to C in this subtype until additional arms entered. The target max N for VAL in its Stages 1 & 2 were 150 and 50, resp. Results: At the interim after VAL reached max sample size in Stage 1, the PP for all signatures was <0.8 and >0.25 for at least one sig. Thus, VAL did not graduate nor drop for futility, but accrual stopped for maximum N in Stage 1 (see table). Final results will be presented at the meeting. Columns 2-5 show results at the interim after which VAL stopped for max N. Columns 6-8 show near final results. Conclusions: GBM AGILE is an efficient & effective model for phase 3 drug development. VAL did not increase OS compared to C in any glioblastoma subtype. GBM AGILE evaluated this agent in less time, at lower cost, & with fewer patients than typical registration trials & is currently evaluating several other arms. (Table Presented).

  • 5/1/2024 7:00 AM

    Background: We determined the efficacy, safety, and tolerability of ND0612, an investigational, continuous 24-hours/day subcutaneous infusion of levodopa/carbidopa (LD/CD), versus oral immediate-release (IR) LD/CD in people with Parkinson’s disease (PwP) experiencing motor fluctuations.

    Methods: This is a phase 3, double-blind, double-dummy (DBDD) trial (NCT04006210). PwP on ≥4 oral LD/CD doses/day (≥400mg/day LD) and experiencing ≥2.5h of daily OFF-time underwent 4-6 weeks of open-label IR-LD/CD dose adjustment followed by 4-6 weeks of open-label ND0612 conversion (+ IR-LD/CD as needed). Patients were randomized (1:1) to 12-week DBDD treatment with either their optimized ND0612 or IR-LD/CD regimens.

    Results: In the open-label adjustment/conversion phases, mean ON-time without troublesome dyskinesia (OTwoTD) increased from 9.4h (both arms) at enrollment to 11.8h (ND0612) and 12.1h (IR-LD/CD) following optimization of the ND0612 regimen. During the 12-week DBDD treatment OTwoTD was maintained in the ND0612 group (11.5h at endpoint) but decreased in the IR-LD/CD group who had their ND0612 infusion withdrawn (9.8h at endpoint). The study met its primary endpoint, with the ND0612 regimen providing an additional 1.72h [95%CI: 1.08h, 2.36h] of OTwoTD compared with IR-LD/CD (p<0.0001). Significant treatment effects (TE) vs. IR-LD/CD were also seen in the hierarchical secondary endpoints: OFF-time (TE: -1.40 [-1.99, -0.80]h, p<0.0001), MDS-UPDRS Part II (TE: -3.05 [-4.28, -1.81], p<0.0001) and global impressions by patients (Odds ratio [OR] of improvement: 5.31 [2.67, 10.58], p<0.0001) and clinicians (OR: 7.23 [3.57, 14.64], p<0.0001). Infusion site reactions were the most reported adverse events (82.6% during open-label conversion to infusion, during the DBDD period the rates were 57.0% for ND0612 vs. 42.7% for IR-LD/CD). Discontinuation rates after randomization (DBDD phase; ND0612 vs IR-LD/CD) were 6.3% vs 6.1% overall, and 5.5% vs 3.1% due to adverse events.

    Conclusions: ND0612 treatment led to clinically meaningful improvement in motor fluctuations and functional endpoints vs oral IR-LD/CD and was generally well tolerated.

  • 4/9/2024 7:00 AM

    Objective: Intracranial dural arteriovenous fistula (AVF) is a rare condition; it is usually described as an arterio-venous shunt within the dura with sinus or cortical drainage. AVFs can occur anywhere in the central nervous system. Most commonly, they are found at the transverse sinus, and this location is reported in 50% of all cases. Symptoms of the Dural AVFs vary widely according to their location. Progressive thalamic dementia due to venous hypertension of thalamic draining veins is an example. Herein, we present a patient with reversible progressive encephalopathy due to this pathology. Background: This is a 55-year-old man who was admitted for progressive encephalopathy for 3 months. Inpatient work-up included a negative Computed Tomography of the head, unremarkable infectious, toxic and metabolic abnormalities including cerebrospinal fluid analysis, patient underwent MRI of the brain with contrast showing bilateral thalamic infarcts. MR angiography showed dural AVF at the torcular herophili, with high-grade stenosis of the junction of straight sinus and torcula Herophili. The patient underwent cerebral angiography showing a complex dural AVF at the tentorium and left sigmoid sinus, this was with a retrograde venous arterialization through the internal cerebral veins, the straight vein and vein of Galen. Embolization of the fistula was done intra-procedurally, with a gradual improvement of his mental status over 4 months when followed up on in the office. Design/Methods: N/A Results: N/A Conclusions: Bilateral thalamic infarcts due to underlying venous hypertension caused by dural AVF can present as a subacute or even a chronic encephalopathy. Since the symptoms are not specific, the diagnosis might be challenging. This condition must be added to the differential list when no other obvious etiology can be found. Early diagnosis and management are generally associated with good prognosis. .

  • 4/9/2024 7:00 AM

    Objective: To present a case of Ramsey hunt syndrome that presented with SUNCT type of headache Background: Ramsay Hunt syndrome represents reactivation of latent varicella zoster virus in the geniculate ganglion, but sometimes extends to involve other cranial nerves Frequently reported symptoms are unilateral and ipsilateral facial paralysis, and painful vesicles in the auditory canal or on the auricle. Design/Methods: Case report Results: A health 55-year-old female who presented initially with acute-onset pressure-like right ear pain associated with rhinorrhea. On day 4 of symptoms, she reported worsening of symptoms, with change of pain to be excruciating, and sharp limited to 5 seconds or less per attack, innumerable times throughout the day, with associated symptoms of increased lacrimation and ipsilateral conjunctival injection. On examination, she exhibited mild scleral injection of the right eye, reduced sensation to pinprick over the right (V2) and (V1), which appeared worse during attacks, with subtle right lower motor neuron facial weakness. CT head without contrast and CTA were unremarkable. A presumed diagnosis of SUNCT was made, and patient was provided with Lamotrigine and Indomethacin, which improved symptom partially then was discharged. 3 days later she noticed facial weakness and was prescribed a course of oral steroids for 6 days. The following day, she noticed a vesicular rash developing in the pinna of the right ear, for which she was given ten-day course of Valacyclovir then All of her symptoms gradually improved till completely resolved over the next 4 weeks. Conclusions:The patient did meet the criteria for a SUNCT diagnosis according to the (ICHD-3) criteria. Additionally, she symptomsconsistent with Ramsey-Hunt syndrome with findings of vesicular rash, facial pain and facial weakness. Our case broadensthe understanding of SUNCT, allowing one to consider RHS or herpes zoster as part of the differential for SUNCT.

  • 4/9/2024 7:00 AM

    Objective: Report an unusual case of recurrent falls secondary to obstructive hydrocephalus, attributed to tumefactive perivascular spaces. Background: Perivascular spaces also known as Virchow Robin spaces are benign, fluid-filled structures surrounding blood vessels in the white matter of the brain. They are usually small and not easily identified on brain imaging. Tumefactive Perivascular Spaces (TPVS) are characterized by the significant dilation and enlargement of these perivascular spaces. When the dilation is large enough, they can be visualized on MRI. The appearance of TPVS can resemble the appearance of more serious conditions like brain tumors and demyelinating disease making them clinically significant. Additionally, in 43% of giant TPVS, hydrocephalus can be seen. Obstructive hydrocephalus can be due to a myriad of conditions, but enlarged perivascular spaces is unusual. Most common presentation of obstructive hydrocephalus secondary to TPVS is headaches; however, as our case illustrates, poor balance and recurrent falls can be the presenting complaint. Design/Methods: NA Results: A 36-year-old man with no significant medical history presented to the Emergency Department with recurrent falls and imbalance for 6 weeks. Neurological exam was unremarkable with intact brainstem, normal strength, sensation, and reflexes; but, he had extreme difficulty maintaining a steady posture. MRI showed cystic foci filled with CSF in the right midbrain, cerebral peduncle, thalamus, and dentate nucleus but without transependymal flow on FLAIR sequences, suggestive of chronic TPVS. These lesions were causing mass effect and hence, an obstructive hydrocephalus. DWI and apparent diffusion coefficient sequences did not reveal any signal restriction. The patient was admitted and underwent endoscopic third ventriculostomy. After three months, he showed remarkable improvement of his symptoms. Conclusions: TPVS are oftentimes easily misinterpreted as a sinister process given the complications patients present with. Surgery is the mainstay of treatment and remarkable improvement can be achieved after third ventriculostomy for patients who are symptomatic.

  • 4/9/2024 7:00 AM

    Objective: Neurosyphilis can mimic different diseases, not only in its clinical presentation but also on imaging. Treponema Pallidum is also known as the great imitator . Having an ultimate diagnosis of neurosyphilis is quite critical as this can affect management drastically. Herein, we discuss the case of a 69-year-old female who was treated for neurosyphilis, while having an atypical imaging finding of anterior temporal lobe enhancement that simulated an infection with HSV. Background: A 69-year-old female with untreated syphilis infection (diagnosed almost 20 years prior presentation), was brought in with progressive decline in memory and confusion over one month. According to the family, the patient was unable to recall the name of her children or attend to her daily activities. On initial examination, she was alert but not oriented to herself, family members, location nor time, she had perseveration while answering questions, was able to only mimic commands. The rest of her examination was otherwise unremarkable. MRI of the brain with contrast showed anterior temporal lobes, insular cortex and pons T2 and FLAIR hyperintensities, that were all enhancing. Syphilis serology was positive and reactive for IgG/IgM. Treponema pallidum hemagglutination test was positive, and HIV was negative. CSF studies showed protein of 94.6 mg/dL, WBC of 15 cells/mm3 with lymphocytic predominance, RBC of 35 cu/mm, VDRL in the CSF was negative. Viral studies in the CSF were all negative. Benzathine penicillin G 24 million units was given for the total of 14 days with improvement in her mental status on follow up at one and two months. Design/Methods: N/A Results: N/A Conclusions:This unusual imaging finding of anterior temporal lobe hyperintensities with enhancement, plus the clinical presentationmake it worth listing neurosyphilis next to many disease processes including HSV on the differential list.

  • 4/9/2024 7:00 AM

    Objective: Minimally invasive and surgical spine procedures are commonplace with various risks and complications. Cranial nerve palsies, however, are infrequently encountered, particularly after procedures such as lumbar punctures, epidural anesthesia, or intrathecal injections and are understandably worrisome for clinicians and patients as they may be interpreted as secondary to a sinister etiology. However, a less commonly considered source is pneumocephalus which may, in rare cases abut cranial nerves and cause a palsy as a benign and often self-resolving complication. Background: A middle-aged patient with a new diagnosis of high-grade mature T-cell non-Hodgkin lymphoma was admitted to the hospital for chemotherapy initiation. The patient received the first cycle of CHOP chemotherapy and a first infusion intrathecal methotrexate infusion and post-procedurally, she developed a new onset of painless right-sided horizontal diplopia. The intrathecal injection was performed in prone positioning using a fluoroscopic guided 20-gauge spinal needle into the L2-L3 space. Next, approximately 10ml of CSF fluid was collected followed by 12mg of methotrexate injection. CSF studies returned unremarkable. Upon physical examination, there was a notable partial right-sided abducens palsy without any other focal neurological deficits. Non-contrast CT scan of the head demonstrated a pneumocephalus anterior to the pons and at the level of the clivus abutting the right abducens nerve (Figure 1). Follow-up brain MRI with contrast was unremarkable for other potential causes of this acute palsy presentation, including infections, stroke, or herniation from intracranial hypotension. The patient was monitored and managed expectantly without any acute interventions and upon follow-up in 24 hours there was complete resolution of her symptoms. Design/Methods: N/A Results:N/AConclusions:Pneumocephalus causing a cranial nerve palsy is very rare. Its complications may be as trivial as headaches, to morecomplex presentations such a cranial nerve palsy, to exceedingly dangerous complications like tension pneumocephalus.Signs and symptoms resolve spontaneously with conservative management.

  • 4/9/2024 7:00 AM

    Objective: To conduct a literature review using real-world evidence on the most common pharmacotherapies used in treating essential tremor (ET). Background: ET is among the most common movement disorders in the US. Current treatments include pharmacological treatments and surgical interventions, though many patients continue to lack adequate tremor control. Syntheses of published real-world evidence on ET pharmacotherapies are lacking. Design/Methods: We conducted a comprehensive literature review of English-language studies published between 1966-2022 using PubMed. The review targeted non-clinical trial studies of adults with ET evaluating propranolol, primidone, gabapentin, and/or topiramate, and reporting at least upper limb tremor efficacy, safety/adverse events, tolerability, and/or treatment patterns. Studies reporting 10 subjects were excluded. Results: We identified 236 studies. Following title and screening, 75 full-text studies were assessed, with 15 included in data extraction. Patient- or clinician-validated scales were used in 2/15 studies. Activities of daily living and quality of life outcomes were not commonly reported. Up to 81% and 55% of patients used propranolol and primidone, respectively. Gabapentin (30%) and topiramate (20%) were used less frequently. Though clinical response definitions varied, propranolol demonstrated response in 37-56% of patients, and primidone in 43-55% of patients among studies with 50 evaluable patients. Approximately one-quarter of patients reported responding to gabapentin or topiramate. Discontinuation rates varied widely across studies, from 10-70% for both propranolol and primidone. Gabapentin and topiramate had discontinuation rates from 26-86% and 26-58%, respectively. Usage, efficacy, and discontinuation were not characterized by line of therapy (i.e. initial vs subsequent treatments) in the assessed studies. Conclusions: Currently available ET pharmacotherapies may not provide adequate efficacy for many patients, highlighting substantial unmet need. We identified several gaps in the published evidence base, including evaluation of commonly-used ET medications by line of therapy and reporting on validated measures to enable comparisons to new ET pharmacotherapies.

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