Paraneoplastic Calmodulin Kinase-Like Vesicle-Associated Protein (CAMKV) Autoimmune Encephalitis.

OBJECTIVES: To report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase-like vesicle-associated (CAMKV). METHODS: Serum and cerebrospinal fluid (CSF) samples harboring unclassified antibodies on murine brain-based indirect immunofluorescence assay (IFA) were screened by human protein microarray. In 5 patients with identical cerebral IFA staining, CAMKV was identified as top-ranking candidate antigen. Western blots, confocal microscopy, immune-absorption, and mass spectrometry were performed to substantiate CAMKV specificity. Recombinant CAMKV-specific assays (cell-based [fixed and live] and Western blot) provided additional confirmation. RESULTS: Of 5 CAMKV-IgG positive patients, 3 were women (median symptom-onset age was 59 years; range, 53-74). Encephalitis-onset was subacute (4) or acute (1) and manifested with: altered mental status (all), seizures (4), hyperkinetic movements (4), psychiatric features (3), memory loss (2), and insomnia (2). Paraclinical testing revealed CSF lymphocytic pleocytosis (all 4 tested), electrographic seizures (3 of 4 tested), and striking MRI abnormalities in all (mesial temporal lobe T2 hyperintensities [all patients], caudate head T2 hyperintensities [3], and cortical diffusion weighted hyperintensities [2]). None had post-gadolinium enhancement. Cancers were uterine adenocarcinoma (3 patients: poorly differentiated or neuroendocrine-differentiated in 2, both demonstrated CAMKV immunoreactivity), bladder urothelial carcinoma (1), and non-Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All treated patients (4) demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]), though 3 died from cancer. INTERPRETATION: CAMKV-IgG is a biomarker of immunotherapy-responsive paraneoplastic encephalitis with temporal and extratemporal features and uterine cancer as a prominent oncologic association. ANN NEUROL 2024;96:21-33.

Detection of High-Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins.

OBJECTIVE: Co-occurring anti-tripartite motif-containing protein 9 and 67 autoantibodies (TRIM9/67-IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67-IgG detection are not known. METHODS: We performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67-IgG cases by tissue-based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell-based assay (CBA), and immunoblot. Cases in which TRIM9/67-IgG was detected by at least 2 assays were considered TRIM9/67-IgG positive. RESULTS: Among these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67-IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. INTERPRETATION: TRIM9/67-IgG is a rare but likely high-risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086-1101.

Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline.

A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia.

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.

Controlled Fabrication of Micropatterned Supramolecular Gels by Directed Self-Assembly of Small Molecular Gelators.

Herein, the micropatterning of supramolecular gels with oriented growth direction and controllable spatial dimensions by directing the self-assembly of small molecular gelators is reported. This process is associated with an acid-catalyzed formation of gelators from two soluble precursor molecules. To control the localized formation and self-assembly of gelators, micropatterned poly(acrylic acid) (PAA) brushes are employed to create a local and controllable acidic environment. The results show that the gel formation can be well confined in the catalytic surface plane with dimensions ranging from micro- to centimeter. Furthermore, the gels show a preferential growth along the normal direction of the catalytic surface, and the thickness of the resultant gel patterns can be easily controlled by tuning the grafting density of PAA brushes. This work shows an effective "bottom-up" strategy toward control over the spatial organization of materials and is expected to find promising applications in, e.g., microelectronics, tissue engineering, and biomedicine.

Baylisascaris procyonis-Associated Meningoencephalitis in a Previously Healthy Adult, California, USA.

After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.

First US experience following FDA approval of the ABBOTT vascular bioresorbable vascular scaffold for the treatment of coronary artery disease.

Drug eluting stents are considered the "gold standard" for the percutaneous treatment of coronary artery disease. Recent publications have suggested that a reasonable alternative, in well selected cases, may be the ABSORBTM bioresorbable vascular scaffold (BVS) stent. © 2016 Wiley Periodicals, Inc.

Inpatient Neurologic Consultation in Solid Organ Transplant Patients.

A third of solid organ transplant recipients experience neurologic complications after transplantation. In this article the author reviews common and uncommon complications of the perioperative period including stroke and peripheral neuropathy, neurotoxicity associated with immunosuppressant medications such as calcineurin inhibitors, and opportunistic infections that target the nervous system. A careful clinical history, neurologic examination, and medication review are vital in generating a differential diagnosis that will guide diagnostic testing and decisions regarding treatment and management, and early recognition of many disorders is imperative to prevent irreversible neurologic morbidity and death.

Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention.

BACKGROUND: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention, is predictive of death and rehospitalization for heart failure. METHODS AND RESULTS: IMR was measured immediately after primary percutaneous coronary intervention in 253 patients from 3 institutions with the use of a pressure-temperature sensor wire. The primary end point was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared with coronary flow reserve, TIMI myocardial perfusion grade, and clinical variables. The mean IMR was 40.3±32.5. Patients with an IMR >40 had a higher rate of the primary end point at 1 year than patients with an IMR ≤40 (17.1% versus 6.6%; P=0.027). During a median follow-up period of 2.8 years, 13.8% experienced the primary end point and 4.3% died. An IMR >40 was associated with an increased risk of death or rehospitalization for heart failure (hazard ratio [HR], 2.1; P=0.034) and of death alone (HR, 3.95; P=0.028). On multivariable analysis, independent predictors of death or rehospitalization for heart failure included IMR >40 (HR, 2.2; P=0.026), fractional flow reserve ≤0.8 (HR, 3.24; P=0.008), and diabetes mellitus (HR, 4.4; P<0.001). An IMR >40 was the only independent predictor of death alone (HR, 4.3; P=0.02). CONCLUSIONS: An elevated IMR at the time of primary percutaneous coronary intervention predicts poor long-term outcomes.

Time from onset of SIRS to antibiotic administration and outcomes after subarachnoid hemorrhage.

INTRODUCTION: The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population. METHODS: We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients' baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS). RESULTS: Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86%, 95% CI 78-95%). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95% CI 0.987-1.001). CONCLUSIONS: In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.

Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6.

Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.

Morbidity pattern in hospitalized under five children with sickle cell disease.

BACKGROUND & OBJECTIVES: Children with sickle cell disease require more frequent hospital care and younger children (<5 yr of age) are more vulnerable to mortality. There are limited data on the events leading to hospitalizations and death in younger children with sickle cell disease from India. This study was, therefore, undertaken to evaluate the morbidity pattern in hospitalized under five children with sickle cell disease in a tertiary care hospital in Maharashtra, India. METHODS: This was a prospective observational study carried out from July 2007 to June 2009. Hospitalized children below five years of age with sickle cell disease were enrolled for the study and evaluated for morbid event/s leading to hospitalization. Haematological indices were noted at baseline (most recent past when patient was not acutely sick) and at the time of hospitalization. RESULTS: Eighty five children with sickle cell disease were hospitalized during the study period. Hospitalization with acute febrile illness (31%) was the most common morbid event followed by severe anaemia (30%) and acute painful events (20%). Majority (62%) of the events occurred between August and October. Forty five patients had foetal haemoglobin (HbF) more than 20 per cent (26.80 ± 4.81%) and morbidity was significantly less in these patients. INTERPRETATION & CONCLUSION: Acute febrile illness was the most common morbid event followed by severe anaemia and acute painful event hospitalized children with sickle cell disease. There was significant seasonal variation with maximum events occurring in the monsoon season.

Clinical Reasoning: A Young Adult With New Seizures and Chapeau de Gendarme.

The evaluation of new seizures is a common clinical query for neurologists. It can be challenging to delineate between the numerous etiologies of new focal or generalized seizures and, if focal, to localize their onset. In this case report, we present a 26-year-old patient with a new onset of stereotyped events concerning for seizures featuring facial grimacing, dystonic left-hand posturing, and convulsions with immediate return to baseline. Throughout the case, we highlight a stepwise diagnostic approach to the evaluation of new-onset seizures, discuss clues that seizure semiology can provide for localization of ictal onset, and review a novel and atypical presentation of a disease entity frequently encountered by neurologists.

Application of the ABCD2 score to identify cerebrovascular causes of dizziness in the emergency department.

BACKGROUND AND PURPOSE: Dizziness can herald a cerebrovascular event. The ABCD(2) score predicts the risk of stroke after transient ischemic attack partly by distinguishing transient ischemic attack from mimics. We evaluated whether this score would also identify cerebrovascular events among emergency department patients with dizziness. METHODS: We retrospectively identified consecutive adults presenting to a university emergency department with a primary symptom of dizziness, vertigo, or imbalance. Two neurologists independently reviewed medical records to determine whether the presenting symptom was caused by a cerebrovascular event (ischemic stroke, transient ischemic attack, or intracranial hemorrhage). ABCD(2) scores were then assigned using clinical information from the medical record. The ability of the score to discriminate between patients with cerebrovascular events and those with other diagnoses was quantified using the c statistic. RESULTS: Among 907 dizzy patients (mean age, 59 years; 58% female), 37 (4.1%) had a cerebrovascular cause, the majority of which were ischemic strokes (n=24). The median ABCD(2) score was 3 (interquartile range, 3-4). The ABCD(2) score predicted ultimate diagnosis of a cerebrovascular event (c statistic, 0.79; 95% CI, 0.73-0.85). Only 5 of 512 (1.0%) patients with a score of ≤ 3 had a cerebrovascular event compared to 25 of 369 patients (6.8%) with a score of 4 or 5 and 7 of 26 patients (27.0%) with a score of 6 or 7. CONCLUSIONS: The ABCD(2) score may provide useful information on dizzy emergency department patients at low-risk for having a cerebrovascular diagnosis and may aid frontline providers in acute management if validated prospectively.

Xience side branch access stent for treatment of bifurcation coronary disease: a review of preclinical data.

The Xience Side Branch Access (SBA) stent is an everolimus-eluting stent designed specifically for branching coronary geometry, providing wire access into the side branch (SB) regardless of the planned treatment strategy. The stent is delivered via a low-profile, dual-lumen, and single-tip catheter. A single inflation deploys the stent in the main branch (MB) and opens a portal into the SB. It is through this portal opening, allowing wire access into the SB, that this device differentiates itself from certain other dedicated bifurcation devices currently in various stages of development and testing. The Xience SBA stent was compared with a standard Multi-Link Vision® stent using a provisional T-stenting strategy in an ovine beating heart model. The Xience SBA stent tended to be deployed with less mean contrast usage (21.05 vs. 43.23 mL; P = 0.09), shorter fluoroscopy time (2.55 vs. 4.52 minute; P = 0.12), and lower rates of guidewire entanglement (16% vs. 100%) compared with the workhorse stent. As a result, the total procedure time with the Xience SBA stent was significantly shorter than that with the standard stent (5.46 vs. 8.65 minute; P = 0.01). The Xience SBA stent was also evaluated by four recently trained interventionalists who had no previous experience with the device. Using a perfused synthetic heart model, SB access time was reduced by 54%, average fluoroscopy time was reduced by 46%, and average contrast usage was lowered by 39% with the Xience SBA compared with the standard stent. Initial experience in the ovine model suggests that the Xience SBA stent is also amenable for use in distal left main coronary artery disease, regardless of whether it is deployed in the left ascending coronary artery or left circumflex artery and the portal opened in the opposing vessel. On the basis of these experimental results, the Xience SBA stent is an easy to use and versatile device for the purpose of SB access and potentially for the treatment of bifurcation coronary artery lesions.

Approach to Myelopathy and Myelitis.

Myelopathy can present acutely or more insidiously and has a broad differential diagnosis. In addition to the clinical history and neurologic examination, diagnostic testing, including MRI and cerebrospinal fluid analysis, as well as thorough review of patient comorbidities, risk factors, and potential toxic exposures, can help neurohospitalists distinguish between various causes and potentially start appropriate empiric therapy while awaiting definitive testing. This article focuses on how imaging can help in determining the most likely cause of myelopathy and highlights a range of causes, including compressive, vascular, metabolic and toxic, infectious, autoimmune, neoplastic, and paraneoplastic causes of spinal cord dysfunction.

Clinical Problem Solving: An Older Woman With Weakness from Head to Toe.

A 67-year-old woman was admitted to our hospital for progressive weakness, dysphagia, muscle pain, and weight loss. Here we detail the clinical problem solving involved in diagnosing and treating her immune-mediated necrotizing myopathy caused by anti-HMGCoA reductase autoantibodies. Interestingly, this diagnosis coincided with discovery of a gastrointestinal stromal tumor (GIST) and positivity for anti-nuclear matrix protein (anti-NXP2), another myositis specific autoantibody.

An Elusive Seizure.

We present a case of a healthy 62-year-old woman who developed recurrent seizures preceded by subacute cognitive slowing, ataxia, night sweats, and weight loss. She was found to have cytopenias, multifocal T2/FLAIR hyperintensities on magnetic resonance imaging (MRI), and magnetic susceptibility artifact lesions on susceptibility weighted imaging (SWI). Her symptoms, imaging and laboratory abnormalities all improved with high-doses of steroids and intravenous immunoglobulin (IVIG). But recurred several weeks after completing treatment. Despite extensive work-up, she required multiple hospitalizations and repeat diagnostic studies to arrive at a diagnosis. With an expert discussant in hematology and oncology, we review the differential diagnosis and stepwise approach of unexplained neuro-inflammatory syndromes with cytopenias and systemic symptoms. Our case highlights how time, empiric treatment response, and repeated diagnostic studies refine differential diagnoses and subsequent evaluation. After revealing the diagnosis, we discuss the heterogenous clinical manifestations of this disease process.

Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS).

The first international colloquium on basal cell nevus syndrome (BCNS) was held at Saint Louis University School of Medicine and supported by the Basal Cell Carcinoma Nevus Syndrome (BCCNS) Life Support Network (www.gorlinsyndrome.org). The foremost goal of the conference was to review and revise the prior diagnostic criteria and define the surveillance recommendations for affected pediatric and adult patients to allow for early intervention. The invited consensus group participants included geneticists, dermatologists, orthopedists, neurologists, and dental/oral medicine specialists, who treat patients with BCNS or related disorders. This group also included individuals who have a research interest in BCNS and who additionally serve on the medical advisory board of the BCCNS Life Support Network. Expert opinion was based on the collective clinical and research experience of the consensus group participants after presentation and review of the previously published literature regarding diagnosis and treatment of BCNS. A consensus was achieved and agreed upon by open roundtable discussion of the group participants. The consensus statement outlines the proposed diagnostic and management protocols that will hopefully limit morbidity and mortality for affected individuals until more specific and targeted therapies are widely available.