41-Year-Old Male with Sub-Acute Encephalopathy, Seizures, and End Stage Renal Disease: A Unifying Diagnosis and Response to Therapy.

We describe a case of a 41-year-old male with a history of end-stage renal disease, hypertension, epilepsy, ischemic stroke, and traumatic brain injury transferred to our tertiary care center for subacute, progressive cognitive impairment. He was found to have disproportionate brain atrophy, focal seizures, and refractory hypertension. Given suspicion for an underlying genetic etiology, a genetic panel for progressive renal disease was sent, revealing two known pathogenic variants in a gene for a cobalamin metabolism disorder, Cobalamin C deficiency. He was started on targeted metabolic supplementation with subsequent improvement in his cognition. Our case highlights the crucial need to expand diagnostic workup to include genetic and metabolic causes in patients with neurologic disease, atypical features, relevant family history and multi-organ dysfunction.

Clinical and Radiographic Characteristics of Nocardia vs Non-Nocardia Brain Abscesses.

Background and Objectives: Diagnosis and treatment of CNS nocardiosis is challenging and often delayed, which increases morbidity and mortality. The primary objective was to compare the clinical and radiographic characteristics of patients with CNS nocardiosis with non-Nocardia bacterial brain abscesses. Methods: We performed a case-control study of patients with brain abscesses diagnosed between 1998 and 2018 at a tertiary academic center. We identified 56 patients with brain MRI demonstrating brain abscess from the institutional imaging database: 14 with culture-confirmed nocardiosis and 42 randomly selected prevalent controls with culture-confirmed non-Nocardia bacterial infection. The primary outcomes were the diagnosis of concomitant lung infection and history of immunosuppression. Secondary outcomes included abscess radiographic characteristics: multifocality, occipital lobe and/or infratentorial location, and bilobed morphology. Results: Compared with patients with non-Nocardia brain abscesses, patients with CNS nocardiosis were older (median 61 years [IQR 59-69] vs 48 years [IQR 34-61]; p = 0.03), more likely to be immunosuppressed [71% (10) vs 19% (8); p < 0.001), have diabetes (36% (5) vs 10% [4]; p = 0.03), or a concomitant lung infection (86% [12] vs 2% [1]; p < 0.001). Radiographically, more cases of CNS nocardiosis exhibited multifocal abscesses (29% [4] vs 2% [1]; p = 0.01), which were located in the infratentorial (43% [6] vs 10% (4); p = 0.01) or occipital (36% [5] vs 5% [2]; p = 0.008) regions and had a bilobed (as opposed to unilobed) morphology (79% [11] vs 19% [8]; p < 0.001). Blood and CSF cultures were negative in most of the cases and controls, whereas neurosurgical specimen culture yielded a diagnosis in 100% of specimens. Discussion: Patients with CNS nocardiosis were more likely to be older, have a history of diabetes or immunosuppression, or have a concomitant lung infection compared with those with non-Nocardia brain abscesses. Abscesses because of CNS nocardiosis were more likely to be multifocal, affect the infratentorial region or occipital lobe, or have a bilobed appearance. Neurosurgical specimen culture was most likely to yield a diagnosis for both Nocardia and non-Nocardia abscesses. The combination of clinical and imaging findings may suggest CNS nocardiosis and inform early initiation of targeted empiric treatment.

Cardiac Arrest and Neurologic Recovery: Insights from the Case of Mr. Damar Hamlin.

The association between brain injury after cardiac arrest and poor survival outcomes has led to longstanding pessimism. However, the publicly witnessed cardiac arrest, resuscitation, and acute management of Mr. Damar Hamlin and his favorable neurologic recovery provides some optimism. Mr. Hamlin's case highlights the neurologic advances of the last 2 decades and presents the opportunity to improve outcomes for all cardiac arrest patients in key areas: (1) effectively implementing the American Heart Association "Chain of Survival" to prevent initial brain injury and promote neuroprotection; (2) revisiting the process of neurologic prognostication and re-defining the brain recovery during the early periods, and (3) incorporating neurorehabilitation into existing cardiac rehabilitation models to support holistic recovery. ANN NEUROL 2023;93:871-876.

Amyloid-ß related angiitis presenting as eosinophilic meningitis: a case report.

BACKGROUND: Eosinophilic meningitis is uncommon and often attributed to infectious causes. CASE PRESENTATION: We describe a case of a 72-year-old man who presented with subacute onset eosinophilic meningitis, vasculitis, and intracranial hypertension with progressive and severe neurologic symptoms. Brain MRI demonstrated multifocal strokes and co-localized right temporo-parieto-occipital vasogenic edema, cortical superficial siderosis, and diffuse leptomeningeal enhancement. He ultimately underwent brain biopsy with immunohistochemical stains for amyloid-ß and Congo red that were extensively positive in the blood vessel walls and in numerous diffuse and neuritic parenchymal confirming a diagnosis of amyloid-ß related angiitis. He was treated with immunosuppression with clinical stabilization. CONCLUSIONS: Amyloid-ß related angiitis is an underrecognized cause of eosinophilic meningitis that can present fulminantly and is typically responsive to immunosuppression. The presence of eosinophils may provide additional clues to the underlying pathophysiology of amyloid-ß related angiitis.

Autoimmune Meningitis and Encephalitis.

Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of inflammation on tissue pathology or by cerebrocpinal fluid (CSF) analysis showing pleocytosis or intrathecal antibody synthesis. Clinicians evaluating undifferentiated meningitis or encephalitis should simultaneously consider autoimmune, infectious, and neoplastic causes, using patient risk factors, clinical syndrome, and diagnostic results including CSF and MRI findings to narrow the differential diagnosis. If an autoimmune cause is favored, an important early diagnostic question is whether a specific neural autoantibody is likely to be identified.

Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid.

Importance: Cerebrospinal fluid (CSF) cytologic testing and flow cytometry are insensitive for diagnosing neoplasms of the central nervous system (CNS). Such clinical phenotypes can mimic infectious and autoimmune causes of meningoencephalitis. Objective: To ascertain whether CSF metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, in difficult-to-diagnose cases of CNS malignant neoplasm. Design, Setting, and Participants: Two case-control studies were performed at the University of California, San Francisco (UCSF). The first study used CSF specimens collected at the UCSF Clinical Laboratories between July 1, 2017, and December 31, 2019, and evaluated test performance in specimens from patients with a CNS malignant neoplasm (positive controls) or without (negative controls). The results were compared with those from CSF cytologic testing and/or flow cytometry. The second study evaluated patients who were enrolled in an ongoing prospective study between April 1, 2014, and July 31, 2019, with presentations that were suggestive of neuroinflammatory disease but who were ultimately diagnosed with a CNS malignant neoplasm. Cases of individuals whose tumors could have been detected earlier without additional invasive testing are discussed. Main Outcomes and Measures: The primary outcome measures were the sensitivity and specificity of aneuploidy detection by CSF mNGS. Secondary subset analyses included a comparison of CSF and tumor tissue chromosomal abnormalities and the identification of neuroimaging characteristics that were associated with test performance. Results: Across both studies, 130 participants were included (median [interquartile range] age, 57.5 [43.3-68.0] years; 72 men [55.4%]). The test performance study used 125 residual laboratory CSF specimens from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases. The neuroinflammatory disease study enrolled 12 patients and 17 matched control participants. The sensitivity of the CSF mNGS assay was 75% (95% CI, 63%-85%), and the specificity was 100% (95% CI, 96%-100%). Aneuploidy was detected in 64% (95% CI, 41%-83%) of the patients in the test performance study with nondiagnostic cytologic testing and/or flow cytometry, and in 55% (95% CI, 23%-83%) of patients in the neuroinflammatory disease study who were ultimately diagnosed with a CNS malignant neoplasm. Of the patients in whom aneuploidy was detected, 38 (90.5%) had multiple copy number variations with tumor fractions ranging from 31% to 49%. Conclusions and Relevance: This case-control study showed that CSF mNGS, which has low specimen volume requirements, does not require the preservation of cell integrity, and was orginally developed to diagnose neurologic infections, can also detect genetic evidence of a CNS malignant neoplasm in patients in whom CSF cytologic testing and/or flow cytometry yielded negative results with a low risk of false-positive results.

Neurology podcast utilization during the COVID-19 pandemic.

BACKGROUND: As medical education shifted to a virtual environment during the early coronavirus disease 2019 (COVID-19) pandemic, we evaluated how neurology podcasting may have been utilized during this period, and which features of podcasts have been more highly sought by a medical audience. METHODS: We conducted a retrospective analysis of neurology-themed blogs and/or podcasts between April 2019 and May 2020. Programs were eligible if they reported mean monthly downloads > 2000, were affiliated with an academic society, or offered continuing medical education credit. Thirty-day download counts were compared between study months, with adjustment for multiple testing. Exploratory analyses were performed to determine which podcast features were associated with higher downloads. RESULTS: Of the 12 neurology podcasts surveyed, 8 completed the survey and 5 met inclusion criteria. The median monthly download count was 2865 (IQR 869-7497), with significant variability between programs (p < 0.001). While there was a 358% increase in downloads during April 2020 when compared to the previous month, this was not significant (median 8124 [IQR 2913-14,177] vs. 2268 [IQR 540-6116], padj = 0.80). The non-significant increase in overall downloads during April 2020 corresponded to an increase in unique episodes during that month (r = 0.48, p = 0.003). There was no difference in 30-day downloads among episodes including COVID-19 content versus not (median 1979 [IQR 791-2873] vs. 1171 [IQR 405-2665], p = 0.28). CONCLUSIONS: In this unique, exploratory study of academic neurology-themed podcasts, there was no significant increase in episode downloads during the early COVID-19 pandemic. A more comprehensive analysis of general and subspecialty medical podcasts is underway.

Neurological manifestations of polyarteritis nodosa: a tour of the neuroaxis by case series.

BACKGROUND: Heterogenous central nervous system (CNS) neurologic manifestations of polyarteritis nodosa (PAN) are underrecognized. We review three cases of patients with PAN that illustrate a range of nervous system pathology, including the classical mononeuritis multiplex as well as uncommon brain and spinal cord vascular manifestations. CASE PRESENTATION: Case 1 presented with mononeuritis multiplex and characteristic skin findings. Case 2 presented with thunderclap headache and myelopathy due to spinal artery aneurysm rupture. Both patients experienced disease remission upon treatment. Case 3 presented with headache and bulbar symptoms due to partially thrombosed intracranial aneurysms, followed by systemic manifestations related to visceral aneurysms. She demonstrated clinical improvement with treatment, was lost to follow-up, then clinically deteriorated and entered hospice care. CONCLUSIONS: Although the peripheral manifestations of PAN are well-known, PAN association with CNS neurovascular disease is relatively underappreciated. Clinician awareness of the spectrum of neurologic disease is required to reduce diagnostic delay and promote prompt diagnosis and treatment with immunosuppressants.

Facial Nerve Palsy: Clinical Practice and Cognitive Errors.

Facial paralysis is the most common cranial nerve paralysis and the majority of these are idiopathic. Idiopathic facial nerve paralysis, or Bell palsy, typically presents acutely, affects the entire face, may be associated with hyperacusis, a decrease in lacrimation, salivation, or dysgeusia, and typically resolves spontaneously. The diagnosis of idiopathic facial paralysis is made after a thorough history and physical examination to exclude alternative etiologies and follow-up to ensure recovery of facial function. Atypical presentation, recurrent paralysis, additional neurologic deficits, lack of facial recovery in 2-3 months, or a history of head and neck or cutaneous malignancy are concerning for alternative causes of facial paralysis requiring workup. The erroneous use of the eponym Bell palsy to refer to all causes of facial paralysis, regardless of the history and presentation, may result in cognitive errors, including premature closure, anchoring bias, and diagnosis momentum. Hence, we recommend replacing the eponym Bell palsy with idiopathic facial nerve paralysis.

Team conflict and the neurologist.

Collaboration within a complicated organization is inherently challenging and can be fraught with discord. Recent emphasis on interdisciplinary and collaborative teamwork in neurology has brought this issue to the forefront of daily practice. The health care system can be complex and opaque, and the stakes-human life-are high. Medical team conflict has been associated with decreased subjective effectiveness, less job satisfaction, and increase in errors. As specialists, neurologists are necessarily embedded within a network of providers and must be adept in the understanding and management of conflictual situations. For the practicing neurologist, it is important to understand team conflict dynamics. Here, management strategies are provided that illustrate how individual neurologists can serve as effective leaders who mitigate harmful effects and capitalize on benefits of team conflict on performance.