Background: Transverse myelitis (TM) is a rare, acquired neuro-immunological spinal cord disorder that occurs with rapid onset of motor weakness, sensory deficits with bowel and bladder dysfunction. Patients being treated with immune checkpoint inhibitors (ICIs) for advanced malignancy have a known higher propensity of developing neuro immune complications. With the advent of COVID-19 pandemic there have been reported cases of TM with COVID-19 immunization. The reported infrequency of TM with both of the aforementioned causes makes delineation of the etiology challenging.Methods: We present a patient with metastatic small cell lung cancer (SCLC) on maintenance Atezolizumab immunotherapy who developed longitudinal extensive transverse myelitis (LETM) after administration of second dose of COVID-19 mRNA vaccine one day prior to presenting symptoms of acute paralysis of the lower extremity, sensory loss from chest down with overflow incontinence. A clinical diagnosis of myelopathy was supported by MRI of the spine illustrating enhancing lesions from C7-T7 concerning for LETM.Results: A 5-day course of pulsed methylprednisolone followed by therapeutic plasma exchange for 3 days resulted in only minimal improvement in the neurologic exam with increased strength in his lower extremities while the sensory level remained unchanged.Conclusions: This case demonstrates the complication and symptomatology of TM in the setting of anti-PD-L1 monoclonal antibody with coincidental COVID-19 mRNA vaccine administration. The causal relationship between the vaccine and LETM is difficult to establish. However, the presence of a known inciting factor hints at a possible exaggeration of the existing neuro-inflammatory process.

Nummular headaches are a rare and relatively newly characterized primary headache disorder. The epidemiology is largely unknown due to likely underdiagnosis and a small population of all headache patients in outpatient presentation. Though our understanding of nummular headaches continues to evolve, they remain a diagnostic challenge for physicians and the underlying pathophysiology is poorly understood. Hypotheses consider neuralgia stemming from epicranial tissues as well as undergoing observation of varying prevalence of autoimmune markers. Peripheral nociception versus central sensitization needs to be evaluated as well, with cases not having consistent direction. Selecting treatment options can be challenging due to limited efficacy, the vague nature of reported symptoms, the rarity of the diagnosis, and the range of presentations. Several treatment modalities have been utilized including non-steroidal anti-inflammatory drugs (NSAIDs), beta-blockers, botulinum toxin injection, transcutaneous nerve stimulation, or even simple reassurance. A case-by-case analysis must be undertaken to best develop treatment options for affected individuals as high-quality randomized quality trials for nummular headaches are very few. We detail two novel cases of patients presenting with nummular headaches that highlight the challenges and importance of making the diagnosis and weighing treatment options for improved levels of patient care, which is followed by a literature review.

Background: Vitamin B6 (pyridoxine) is an important cofactor in the process by which glutamic acid decarboxylase (GAD) converts the excitatory, pro-epileptogenic neurotransmitter, glutamate, into the inhibitory, anti-epileptogenic neurotransmitter, gamma-aminobutyric acid (GABA). This concept has been established in infants with pyridoxine-dependent epilepsy as well as adult patients with other epilepsy subtypes who presented with medication-resistant status epilepticus, with both patient groups experiencing cessation of seizure activity following pyridoxine administration. Given our knowledge of the role of vitamin B6 in the conversion of glutamate to GABA, its effect on seizure control in infants with specific epilepsy subtypes, reports of adult-onset seizures associated with vitamin B6 deficiency, and vitamin B6's role in terminating status epilepticus in adult patients with other types of epilepsy, we suspect that low vitamin B6 levels in adult epilepsy patients may correlate with poor seizure control across all epilepsy subtypes. This study seeks to determine whether there is a relationship between pyridoxine levels and the level of seizure control in adults with epilepsy, regardless of their seizure type. Methods: After obtaining institutional review board approval, we prospectively enrolled 32 patients (age range: 25-57 years) with epilepsy who presented to our clinic. Patients who did not meet the study criteria or who were diagnosed with psychogenic non-epileptic seizures (PNES) were excluded from the study (n = 2). Patients were classified as well-controlled (WC) or poorly controlled (PC) based on the absence or presence of a seizure within the last three months, respectively. After classification as WC or PC, pyridoxine serum levels and anti-seizure medication (ASM) levels were drawn in that clinic visit, following patient consent. All patients were contacted regarding pyridoxine and serum ASM levels, and patients that were found to be deficient in pyridoxine were treated with appropriate supplementation. At the end of the recruitment period, we performed analyses to determine if there was a statistically significant relationship between PC status and serum pyridoxine levels. Results: Of 32 patients, two patients were diagnosed with psychogenic non-epileptic events and were subsequently excluded. Of 30 patients, 10 had PC epilepsy. Median (interquartile range) serum B6 levels were 35.8 (26.8-54.2) in patients with WC epilepsy and 17.5 (10.1-41.3) in patients with PC epilepsy (P = 0.11). In the PC group, 6/10 (60%) of the patients demonstrated low serum pyridoxine compared to 3/20 (15%) in the WC group (P = 0.03). Conclusion: There was a statistically significant relationship between serum pyridoxine levels and seizure control. If appropriate, pyridoxine supplementation should be considered, especially in critically ill adult patients with refractory or PC seizures despite good adherence to ASMs.

The objective is to describe a rare case of lumbar lipomyelomeningocele presenting as progressive urinary incontinence. Lipomyelomeningocele is a type of closed spinal dysraphism typically presenting as a lipomatous mass contiguous with a neural defect above the gluteal crease. Tethered cord syndrome is defined as symptoms and signs caused by excessive spinal cord tension from an abnormally low conus medullaris, with an abnormally thick filum terminale attached to the lower sacral region. A 19-year-old male with no remarkable medical history presented with low back pain and urinary incontinence for the past one year. On physical exam patient had normal motor strength, sensory testing to all modalities was intact. The rectal tone was normal, and no saddle anesthesia was noted. MRI lumbar spine revealed lumbar lipomyelomeningocele with associated tethered cord syndrome. The patient underwent tethered cord release surgery with lipoma excision. Pathology of the soft tissue showed fibrovascular tissue and mature adipose tissue consistent with lipoma. The majority of cases of tethered cord syndrome are related to spinal dysraphism, a rare pediatric syndrome. It is potentially treatable if caught early, and MRI can help with an accurate diagnosis of the condition. Older adults are more likely to present with urological and neurological complaints. Surgical un-tethering is indicated in patients with progressive symptoms. In our case, the only presenting symptom was urinary incontinence, and the neurological exam was normal other than lower lumbar paraspinal tenderness.

To report an acute presentation of long extensive transverse myelitis (LETM) in the setting of Atezolizumab monotherapy and COVID-19 mRNA immunization

Coronavirus disease (COVID-19) is an infectious disease caused by a novel coronavirus impacting more than 75 million people across 220 countries. The pharma and biotech industries, along with research institutes, strive to develop an effective vaccine against the novel coronavirus. Efforts are also underway for finding drugs through drug repurposing and novel drug discovery methods. In this study, we have used a multi-target drug approach. The objective is to identify phytochemicals from plant sources effective against novel coronavirus. Natural products having good medicinal properties are known to have minimal side effects compared to synthetic drugs. Therefore, the medicinal products from natural sources are of significance in drug discovery research. In this study, compounds from three common plants were selected for analysis, namely, Tinospora cordifolia, Withania somnifera, and Punica granatum. The primary target selected for this study was glycoprotein. Glycoproteins are known to play a key role in the regulation of cell proliferation, growth, and signaling pathways. We also investigated the effect of screened compounds on other targets in order to have a multi-target therapy. The target proteins chosen for drug design are Spike glycoprotein, Main Protease, and uridylate-specific Endoribonuclease (EndoU). The spike glycoprotein (S) of coronavirus, is a trimeric transmembrane protein, which facilitates entry into cells and is the main target of antibodies. The spike glycoprotein is highly sensitive to mutation. The main protease (MPro) of SRAS-CoV-2 plays an essential role in disease propagation by processing the polyproteins necessary for its replication. Inhibiting the main protease by designing agonists/antagonists can serve in the repair mechanism-the uridylate-specific Endoribonuclease (EndoU) of SRAS-CoV-2 causes a delay in the host sensor system. The objective of this study was to identify potential natural hit compounds which could target multiple proteins of coronavirus. Compounds that can target all the three, namely, Spike glycoprotein, EndoU, and MPro will have better therapeutic index and efficacy than a single target approach. Therefore, the compounds were screened against all these three structural targets. The compounds targeting only one of the proteins were filtered and only those compounds showing activity against all the three structural proteins were retained for further analysis. Drug design methods, including Absorption, Distribution, Metabolism and Elimination (ADME) profiling and molecular docking studies, have been used in the study to identify potential hit molecules. The twenty four hits obtained targeted all the three selected proteins. This will pave the way for developing lead molecules from the screened compounds effective against all three proteins of novel coronavirus: Main protease, Spike glycoprotein, and Endoribonuclease.

Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a type of acquired immune-mediated disorder that affects the peripheral nervous system. Although it has diverse clinical presentations, the classical presentation includes symmetric proximal and distal sensory and motor involvement. CIDP can be monophasic, relapsing, or progressive, which develops over more than eight weeks. The time course of 8 weeks as well as the duration to reach nadir help distinguish CIDP from Guillain-Barre syndrome (GBS) or other acute inflammatory demyelinating polyneuropathies (AIDP). The first case was described by Eichhorst Burns in 1890. About 16% of the patients present with acute GBS.

Background: Vagus nerve stimulation (VNS) functions through neuromodulatory mechanisms to provide quality of life improvements to those with drug-resistant epilepsy. Responsive VNS (rVNS) generators are designed to further reduce seizure burden by detecting ictal tachycardia and aborting seizures soon after their onset. Methods: Electronic medical records were accessed from January 2015 to December 2018 to identify patients with epilepsy managed with rVNS generators. Data were collected on seizure burden before and after rVNS implantation. Seizure burden was compared using t-tests, and monthly seizure reductions were gauged with the McHugh scale. Twenty-seven individuals met inclusion criteria; 10 were eliminated due to prior VNS implantation or undocumented seizure frequencies. Results: The average seizure burden prior to rVNS implantation was 24.78 seizures/month. Following generator placement, the mean seizure frequencies at three months, six months, 12 months, and 18 months were 6.81, 16.57, 5.65, and 5.78 seizures/month, respectively. However, despite documented reductions in the average monthly seizure frequency, we found no statistically significant differences in seizure frequency relative to baseline. Conclusion: While many participants showed individual reductions in seizure burden, this study was unable to definitively conclude that rVNS therapy leads to statistically significant reduction in seizure burden.

To evaluate the relationship between AutoStim frequency and seizure control in patient with new detect and response VNS mode.

Background: Acute confusional state (ACS) in COVID-19 is shown to be associated with poor clinical outcomes. Methods: We assessed the impact of ACS - defined as a documented deterioration of mental status from baseline on the alertness and orientation to time, place, and person - on inpatient mortality and the need for intensive care unit (ICU) transfer in inpatient admissions with active COVID-19 infection in a single-center retrospective cohort of inpatient admissions from a designated COVID-19 tertiary care center using an electronic health record system. Furthermore, we developed and validated a neurological history and symptom-based predictive score of developing ACS. Results: Thirty seven out of 245 (15%) patients demonstrated ACS. Nineteen (51%) patients had multifactorial ACS, followed by 11 (30%) patients because of hypoxemia. ACS patients were significantly older (80 [70-85] years vs 50.5 [38-69] years, p < 0.001) and demonstrated more frequent history of dementia (43% vs 9%, p < 0.001) and epilepsy (16% vs 2%, p = 0.001). ACS patients observed significantly higher in-hospital mortality (45.9% vs 1.9%, aOR [adjusted odds ratio]: 15.7, 95% CI = 3.6-68.0, p < 0.001) and need for ICU transfer (64.9% vs 35.1%, aOR: 2.7, 95% CI = 1.2-6.1, p = 0.015). In patients who survived hospitalization, ACS was associated with longer hospital stay (6 [3.5-10.5] days vs 3 [2-7] day, p = 0.012) and numerically longer ICU stay (6 [4-10] days vs 3 [2-6] days, p = 0.078). A score to predict ACS demonstrated 75.68% sensitivity and 81.73% specificity at a cutoff of ≥3. Conclusion: A high prevalence of ACS was found in patients with COVID-19 in our study cohort. Patients with ACS demonstrated increased mortality and need for ICU care. An internally validated score to predict ACS demonstrated high sensitivity and specificity in our cohort.

46% had left-sided disease (n=7), 33% had right-sided disease (n=5), and 20% had bilateral disease (n=3). The majority were male (n=10). Average age at the start of treatment was 1 year 5.5 months. A total of 66 treatments were performed, with a median of 4 per patient or 3.5 per involved eye. Of the 18 eyes treated, 12 (66%) initially had anterograde ophthalmic artery flow. Drug delivery was accomplished using direct ophthalmic catheterization (n=35), ICA balloon technique (n=18), ECA balloon technique (n=7), and via ECA branch catheterization (n=6). A flow reversal event was observed a total of 5 times (28% of eyes), each necessitating a change in drug delivery technique. All 5 events were in patients receiving multi-agent chemotherapy. These events occurred in 4 patients and involved 5 separate eyes, never more than once per eye. Flow reversal events were seen in both eyes (left=3, right=2). On average, events occurred between the third and fourth treatment (range 2 to 6). No correlation was found between reversal event and treatment technique. Conclusions Ophthalmic artery flow is variable in RB patients treated with IAC. Further, mid-treatment shifts between anterograde and retrograde ophthalmic artery filling are common and necessitate variation in delivery methods throughout a single treatment course. In our analysis all flow reversal events were associated with multi-agent chemotherapy (as opposed to Melphalan alone). Although the correlation was not statistically significant,our analysis is limited by power. Future investigation is necessary to elucidate the nature of these variations, such as if they are a direct response to the number of chemotherapy agents utilized. Regardless, interventionalists should be comfortable and prepared to use various techniques independent of a given patient’s treatment history. Disclosures M. Feldman: None. H. Grimaudo: None. S. Roth: None. H. Vance: None. A. Daniels: None. M. Froehler: 1; C; Genentech, Medtronic, Stryker, Microvention, and Penumbra. 2; C; Genentech, Medtronic, Stryker, Balt USA, Viz.ai, and Corindus.