Investigation on Gender Differences in Leadership of Stroke-Related Clinical Trials.

BACKGROUND: Gender disparities among principal investigators of clinical trials (CT) can have implications regarding the areas of investigation, methods, conduct, trial enrollment, and interpretation of results. An estimation of the gender gap in the leadership of stroke-related CTs from North America has to date not been undertaken. METHODS: We extracted information about stroke-related CTs between 2011 and 2020 from www. CLINICALTRIALS: gov and PubMed. We examined the gender distribution according to the academic credentials and the trial type. The gender of PIs and authors was determined using gender package in R, which identifies gender using historical data from the United States. Additionally, we obtained information from Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education data resource books on the gender composition of full-time neurology faculty, neurology residents and vascular neurology fellows. RESULTS: In these analyses of 821 CTs registered on Clinicaltrials.gov and 110 trials published on PubMed, we found that gender disparity among the PIs, first and last authors have persisted over the last decade without any significant trend toward parity (P>0.05). On examining the gender distribution according to academic credentials and trial type, we found that men were over-represented in the sub-group of PIs with an MD degree (78.11% versus 21.87%; P<0.01) and those leading acute stroke trials (86.04% versus 13.89%; P<0.01). We also found that a lower proportion of women neurology residents pursued a vascular neurology fellowship during this period (33.5% versus 42.5%; P<0.05). CONCLUSIONS: Our results show that the favorable trend toward gender parity seen in Neurology faculty over the last decade has not translated to the same in the leadership of CTs. Our findings merit further investigation and a re-examination of efforts toward inclusion of women as leaders of stroke-related CTs.

Ataxia and ophthalmoplegia: an atypical case of Miller Fisher syndrome (MFS) with anti-GAD antibody.

BACKGROUND: Miller Fisher syndrome (MFS) is frequently encountered variant of Gillian Barre Syndrome (GBS). It has distinct clinical and serological features. Here we describe an atypical GQ1b seronegative case with significantly elevated anti-glutamic acid decarboxylase antibody (GAD-Ab). CASE DESCRIPTION: A 24-year-old previously healthy Caucasian male presented with rapidly progressive ascending weakness, binocular diplopia and autonomic instability for 2 days. Examination was remarkable for asymmetrical facial weakness (L > R), opthalmoplegia and truncal ataxia without areflexia. MRI brain was normal. CSF analysis showed elevated protein. Electromyography/Nerve Conduction Study (EMG/NCS) within the first week was normal. Antiganglioside antibodies were negative. Extended serological and neoplastic workup revealed negative anti-GQ1b antibody, but significant increase of GAD-Ab, Voltage Gated Calcium Channel (VGCC) Ab, and mild elevation of TPO Ab IgG and Thyroglobulin (Tg) Ab IgG. Clinical diagnosis of partial MFS was made. He received a course of IVIg (2 g/kg over 5 days) and had complete recovery in 3 months. CONCLUSION: There are incomplete or atypical forms of MFS. Recognition of its various clinical presentations is essential for early diagnosis and optimal management. Further investigation is needed to elucidate the role of anti-GAD-ab and other autoimmune antibodies in the pathogenesis of GQ1b-seronegative MFS patients.

A case of COVID-19 with multiple cranial neuropathies.

Various neurological manifestations involving the central and peripheral nervous system have been reported in association with COVID-19. Most common associations reported are encephalopathy, headache, ischemic, hemorrhagic stroke and transient ischemic attack, Miller Fisher syndrome, cranial neuropathies and Guillain-Barre syndrome. Of the cranial neuropathies, anosmia, and dysgeusia are the most common reported symptoms. This is a case of COVID-19 with ipsilateral fifth and seventh cranial nerve involvement with complete resolution of symptoms over a period of 3 weeks. The neurological symptoms started within 5 days of respiratory symptoms. We conclude that isolated cranial neuropathies can be the manifestations of SARS-CoV-2 infection.

Bihemispheric Cortical Infarcts in an Adult Secondary to Escherichia coli K1 Meningitis.

Cerebral ischemia is a known complication of meningitis. Most Escherichia coli meningitis-induced infarcts have been reported in the neonatal and pediatric population. To the best of our knowledge, there have been no previous reports describing bilateral cortical infarcts in an adult secondary to a K1 strain of E. coli meningitis, and herein we report a case in a 25-year-old female. The challenge in treating this patient was determining the duration of systemic antibiotic treatment and whether or not to use steroids. This study demonstrates the necessity of early diagnosis and treatment of E. coli meningitis to prevent neurological complications, including stroke.

Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman.

Background: Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS). Case Description: We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot. There are coexisting long-tract disturbance and lower-extremity weakness. Treatment with diazepam provided symptomatic relief while plasma exchange (PLEX) did not lead to significant clinical improvement. The patient was bedridden within 3 months and passed away within 6 months from symptom onset. Conclusion: This case highlights the importance of recognition of uncommon presentation of SPS and its oncological significance. This entity requires a high degree of suspicion for initiation of the proper workup. The rapid identification and treatment of the underlying tumor might offer the best chance for recovery.

Neuromodulation in Intractable Epilepsy Through Responsive Vagal Nerve Stimulation: A Three-Year Retrospective Study at the University of Texas Medical Branch, Galveston.

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.

EEG Characteristics in COVID-19 Survivors and Non-survivors With Seizures and Encephalopathy.

The objective of this study is to report EEG findings in both COVID-19 survivors and non-survivors who underwent EEG either due to seizure or encephalopathy. Out of total 1468 COVID-19-positive patients, 19 patients underwent EEG. Eight out of 19 patients had a history of seizure disorder and in the remaining 11 with no prior history of seizures, four had a clinical seizure during their hospital stay. Only one had new-onset complex focal status epilepticus on EEG. Amongst the survivors (13/19), the most common EEG findings were normal followed by mild diffuse slowing. Amongst the non-survivors (6/19), the most common EEG finding was moderate to severe slowing in 50% of the patients. It can be deduced that COVID-19 infection does not increase the propensity of epileptiform discharges on EEG. There is perhaps a trend towards increased risk of new-onset status epilepticus in patients with encephalopathy and focal lesions.

Impact of Acute Confusional State in Patients With COVID-19 and a Predictive Score.

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.

Gabapentin-Induced Myokymia: A Case Report.

BACKGROUND: Gabapentin is a commonly used medication for neuropathic pain and epilepsy that is prescribed by a wide range of medical specialties. Adverse effects including asterixis and myoclonus have been described in patients with chronic kidney disease, but myokymia has not been previously reported. CASE PRESENTATION: A 69-year-old man with a history of traumatic brain injury, peripheral neuropathy, amnesia, and posttraumatic stress disorder presented to the hospital after multiple falls attributed to acute onset muscle spasms. He reported taking a total daily dose of 9600 mg of gabapentin, as prescribed. Physical examination demonstrated stimulus-sensitive myoclonus, painful muscle spasms in all extremities, and myokymia in his bilateral calves. Diffuse action tremors, as well as tongue tremors, were also observed.Initial workup, including basic laboratory investigations, brain imaging, and electroencephalogram, was unrevealing. Gabapentin toxicity was suspected, and a gabapentin holiday was initiated with the improvement of myokymia by hospital day 3. The patient was found to have a high gabapentin level (25.8 µg/mL; reference range, 2.0-20.0 µg/mL) measured the morning after hospital presentation. After restarting on a lower dose of gabapentin with multimodal pain control, the patient continued to improve with diminution of his myoclonus, tremor, and gait instability. CONCLUSIONS: Myokymia is a newly described motor symptom associated with gabapentin toxicity. The mechanism of gabapentin-associated myokymia is currently unknown. A brief medication holiday resulted in the resolution of motor symptoms without significant withdrawal symptoms. Knowledge of this newly reported adverse manifestation can aid physicians in the diagnosis of gabapentin toxicity and prompt treatment, as gabapentin levels are not widely or immediately available.

Tumefactive multiple sclerosis (TMS): A case series of this challenging variant of MS.

BACKGROUND: Tumefactive MS is a rare variant of multiple sclerosis that poses a diagnostic and a therapeutic challenge due to its close resemblance to central nervous neoplasms on MRI. TMS is defined as acute large >2 cm, tumour like demyelinating lesion in the CNS that may occur with surrounding edema, mass effect and ring enhancement. Some of the known mimickers are CNS lymphoma, metastasis, primary brain tumour such as glioblastoma, brain abscesses. The prevalence of TMS is estimated to be 1-3/1000 cases. There are also reported cases of drug induced TMS cases especially with fingolimod and natalizumab therapy. We report the occurrence of tumefactive MS at our institution. METHODS: We retrospectively reviewed the chart of the patients with multiple sclerosis including initial visits, hospitalizations, clinic follow up notes and collected data on demographic, ethnicity, presenting signs and symptoms, imaging modalities, cerebrospinal fluid analysis results, disease progression. After reviewing the charts, we isolated the patients with tumefactive multiple sclerosis from the group and summarized the cases. Four of these patients were managed with Glatiramer acetate, 2 on dimethyl fumarate and 1 on beta interferon with 0-2 clinical flare ups on subsequent years. RESULTS: Out of 323 patients reviewed with multiple sclerosis or possible multiple sclerosis, 7 carried a diagnosis of tumefactive MS. The age range of these patients were 19 to 62 years old with 4 females and 3 males. Five patients were Caucasian and 2 were Hispanic. Out of seven patients, 6 were newly diagnosed MS following biopsy of the lesion. The histological findings in 3 patients who underwent biopsy demonstrated include reactive gliosis and inflammatory cells predominantly macrophages and lymphocytes while 1 patient showed hypercellular brain tissue with perineuronal satellosis. CONCLUSION: Tumefactive MS remains a challenging disease to diagnosis and often times requires a biopsy for definitive diagnosis or to exclude neoplasms, other inflammatory conditions such as neurosarcoidosis. The demographic of the patients in this case series is no different than patients with relapsing remitting multiple sclerosis (RRMS). However, based on our experience, the patients with TMS do respond to disease modifying agents such as Glatiramer acetate and Dimethyl fumarate with similar progression as of RRMS.

Intracranial Hemorrhage in a Patient With COVID-19: Possible Explanations and Considerations.

Some of the reported neurological manifestations of COVID-19 are encephalopathy, headache, ischemic, hemorrhagic stroke, Miller Fisher syndrome, cranial neuropathies, and Guillain-Barre syndrome. We report a case of a 75-year-old COVID-19 patient with life-threatening intracranial hemorrhage. The initial labs on admission showed D-dimer of 1.04 µg/mL, which increased to 3.74 µg/mL the next day, PT/INR of 13.7 seconds/1.2, aPTT of 22 seconds, fibrinogen of 386 mg/dL, WBC of 9.71 K/µL, Hgb of 14.1 g/dL, platelet of 315 x 103/µL, LDH of 965 U/L, and CRP of 35.2 mg/dL. In addition to aspirin and Plavix (clopidogrel), the patient was started on a therapeutic dose of enoxaparin due to elevated D-dimer. A few days later, the patient had a change in the neurological examination. The CT of the head without contrast revealed a left-sided acute subdural hematoma, causing left to right midline shift, a large left temporal intraparenchymal, and subarachnoid hemorrhage with transtentorial herniation, leading to death. This case illustrates a combination of factors including hypertension, triple therapy (aspirin, clopidogrel, and enoxaparin), and underlying coagulopathy due to COVID-19, which contributed to the life-threatening intracranial hemorrhage in this patient. Therefore, this raises a concern about the safety of starting these patients preemptively on a therapeutic dose of anticoagulation.

Overlapping autoimmune syndrome: A case of concomitant anti-NMDAR encephalitis and myelin oligodendrocyte glycoprotein (MOG) antibody disease.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that commonly manifests as a complex neuropsychiatric syndrome. Antibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis. The concurrence of NMDAR encephalitis and demyelinating syndromes is rare. We describe the case of a 29-year-old male with NMDAR encephalitis and overlapping MOG antibody disease. The aim of this report is to add to the growing knowledge of phenotypic characteristics of overlap syndromes as their clinical and prognostic features may differ from those of single antibody disease.

Use of noninvasive induction techniques in the diagnosis of PNES.

The diagnosis of psychogenic nonepileptic seizures (PNES) remains challenging. In the correct clinical setting with prolonged electroencephalography (EEG) monitoring, the specificity of provocative techniques to distinguish induced epileptic event from a nonepileptic event approaches 90%. We report our epilepsy monitoring unit (EMU) experience with the use of noninvasive verbal suggestion (VS) during hyperventilation (HV), photic stimulation (PS) as induction technique in making the diagnosis of PNES. In total, 189/423 patients were diagnosed with PNES during the EMU evaluation. Of the 189, 20 had mixed disorder and 169 patients had only PNES, 80 patients (47.3%) had a PNES with induction, and the remaining 89 of 169 patients (52.7%) had a spontaneous PNES episode that did not require induction. Verbal suggestion during HV and PS confirmed the diagnosis of PNES in 47% of the patients who otherwise did not have spontaneous events. Within the group who was diagnosed with PNES following induction, antiepileptic drugs (AEDs) were stopped in 53% of the patients. We believe that this is a large proportion of patients that would possibly remain undiagnosed if no induction were performed.

Anti-glutamic acid decarboxylase (GAD) positive cerebellar Ataxia with transitioning to progressive encephalomyelitis with rigidity and myoclonus (PERM), responsive to immunotherapy: A case report and review of literature.

We present a case of a 65-year-old African American male, immunosuppressed on Tacrolimus, who initially presented with cerebellar ataxia and rapidly developed Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with positive anti-glutamic acid decarboxylase (GAD65) antibodies, no underlying malignancy, and normal neuroimaging. PERM is a rare spectrum of Stiff Person Syndrome (SPS), which is strongly associated with anti-GAD antibodies and characterized by flare-ups and remissions of encephalopathy, myelopathy and rigidity with myoclonus. PERM is diagnosed clinically and has been successfully treated with both Intravenous Immunoglobulin (IVIg) and plasmapheresis. Our patient was successfully treated with IVIg. On day 14 after starting IVIg treatment, his neurological symptoms started to improve and ultimately returned to baseline.

Embryonal Tumor with Multilayered Rosettes, C19MC-Altered: Clinical, Pathological, and Neuroimaging Findings.

BACKGROUND AND PURPOSE: Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered, is a recently described, rare central nervous system tumor. To our knowledge, the imaging findings of this tumor have not been systematically evaluated in the neuroradiology literature. We present here the clinical, radiological, and pathological correlation of a case series of this very rare tumor, including the full range of anatomic compartment presentations (supratentorial, infratentorial, and spinal). METHODS: We retrospectively analyzed 7 (4M, 3F) pathologically-proven cases of ETMR referred to our institution between 2007 and 2017. We demonstrate the imaging characteristics of this tumor on CT and MRI with advanced imaging. RESULTS: All of the patients are children (ages 1-12). On MR imaging of ETMR, contrast enhancement is often heterogeneous and minimal if any, and there is no significant surrounding T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity to suggest edema. The lesions were often expansile with no evidence of infiltration of the fiber tracks that were displaced by the tumor mass. Diffusion-weighted imaging often demonstrated restricted diffusion within ETMRs. On magnetic resonance spectroscopy (MRS), the choline/creatine (Cho/Cr) ratio is increased, with low N-acetylaspartate (NAA) or NAA/Cho ratio, typical of high-grade tumors. CONCLUSION: We demonstrate the conventional and advanced imaging characteristics of ETMR, including MRS and diffusion tensor imaging, which, to our knowledge, have not been systematically evaluated in the radiology literature. The knowledge gained may potentially impact patient management, especially in inoperable cases and in locations where it is risky to perform a biopsy.

MRI venous architecture of insula.

PURPOSE: The purpose of this paper is to describe the venous anatomy of the insula using conventional MR brain imaging and confocal reconstructions in cases with glioma induced venous dilatation (venous gliography). METHODS: Routine clinical MRI brain scans that included thin cut (1.5-2 mm) post contrast T1 weighted imaging were retrospectively reviewed to assess the insular venous anatomy in 19 cases (11 males and 8 females) with insular gliomas. Reconstruction techniques (Anatom-e and Osirix) were used to improve understanding of the venous anatomy. RESULTS: We identified the following insular and peri-insular veins on MRI: the superficial middle cerebral vein (SMCV), peri-insular sulcus vein, vein of the anterior limiting sulcus, the precentral, central, and posterior sulcus veins of the insula, the communicating veins and deep MCV. CONCLUSIONS: We concluded that venous anatomy of insula is complicated and is often overlooked by radiologists on MR brain imaging. Use of confocal imaging in different planes helped us to identify the superficial and deep middle cerebral veins and their relationship to the insula. The understanding of the insular venous architecture is also useful to distinguish these vessels from insular arteries. This knowledge may be helpful for presurgical planning prior to insular glioma resection.

MRI venous architecture of the thalamus.

PURPOSE: Our purpose is to describe the thalamic veins using a novel approach named venous gliography in cases with primary or secondary gliomas of the thalamus. Venous gliography is defined by authors as a method to visualize veins on MRI Brain T1-weighted post contrast scans containing gliomas which have induced regional venous congestion. METHODS: Routine clinical MR Imaging studies were reviewed to assess the presence of thalamic veins in 29 glioma cases. In addition, confocal reconstruction techniques (Anatom-e and Osirix) were used in cases that had thin sections (1.0-1.5mm) post contrast T1 weighted sequences. Multiplanar MIP and confocal volume rendered images were generated to evaluate the thalamic veins in those cases. RESULTS: Using venous gliography and confocal reconstruction techniques, two patterns in the venous architecture of the thalamus were documented. First, the branching pattern created by the tributaries of the internal cerebral vein, namely the superior thalamic vein and the anterior thalamic vein, which together formed the superior group of thalamic veins. Second, the pattern created by the un-branched vertically oriented veins, namely the inferior thalamic veins and the posterior thalamic veins, which joined the basal vein of Rosenthal and constituted the inferior group of thalamic veins. CONCLUSIONS: Venous gliography combined with the use of confocal reconstruction techniques provided a novel approach to display the thalamic veins that are usually not seen. The understanding of the venous architecture is mandated by the recent research where veins have taken on an important role in the perivenular spread of gliomas.