Grill, Marie

Introduction: Granulomatosis with polyangiitis (GPA) is a vasculitic process that can cause neurological dysfunction in addition to characteristic sinus and pulmonary manifestations. This case report highlights the spectrum of nervous system manifestations and includes rarely reported autonomic and pituitary involvement. Case Report: A 62-year-old woman presented with orthostatic intolerance, tachycardia, dry mouth, and temperature sensitivity; subsequent autonomic reflex study demonstrated widespread postganglionic sympathetic sudomotor, cardiovagal, and cardiovascular adrenergic impairment reflective of autonomic neuropathy and overall autonomic failure. Additional progressive symptoms included dysarthria, dysphagia, bilateral hearing loss, voice hoarseness, and right-sided facial numbness with multiple cranial neuropathies identified on neurological examination. The diagnosis of central diabetes insipidus was also confirmed. Pachymeningitis was present on brain magnetic resonance imaging. Pathologic review of the dural biopsy specimen revealed necrotizing granulomatous vasculitis consistent with GPA. She was treated with intravenous methylprednisolone and rituximab. Over the next 2 months, she had near-complete resolution of her symptoms with normalization on repeat autonomic testing. Conclusions: This is a unique GPA case presenting with autonomic failure and pituitary dysfunction with conclusive objective findings of autonomic dysfunction. Autonomic dysfunction and other disease manifestations were responsive to immunosuppressive therapy.

Abstract Background Coccidioidomycosis is often diagnosed with a collection of tests that measure a patient’s ability to mount an immune response to the fungus (antibody-based diagnostics) utilizing fungal protein preparations. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in diagnostic antigen preparations with potential for use in human serum. Methods An inhibition-based enzyme-linked immunoassay (ELISA) was developed that utilizes a monoclonal antibody specific for coccidioidal CTS1. CTS1 was quantified in commercial antigen preparations using recombinant CTS1 as a standard. Sera from 192 individuals from an endemic area were tested which included 78 patients (40.6%) with proven or probable coccidioidomycosis. Results The quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. Temporal constraints of availability of different lots of commercial antigens does not allow for immediate comparison of lot-to-lot variability. Assay results from patient serum samples correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Further analysis suggested that patient derived anti-CTS1 antibodies may overlap with the mouse monoclonal antibody used in the assay. This unexpected overlap in CTS1 binding suggests the assay can detect antigen, antibody, or both, which contributes to its high level of clinical sensitivity of 89.74% and specificity of 94.90%. Conclusions The CTS1 inhibition ELISA described in this report is a promising tool to aid in quality control of antigens used in the diagnosis of coccidioidomycosis. Further optimization is needed to harness its utility as a diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by “dancing” eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Abstract INTRODUCTION Opsoclonus–myoclonus syndrome (OMS) is a rare neurological disorder characterized by spontaneous multidirectional saccadic eye movements, myoclonus, and ataxia. It is suspected to be an autoimmune mediated process precipitated by a paraneoplastic or infectious trigger. Among the pediatric population, OMS is often associated with neuroblastoma and anti-Hu antibody. Paraneoplastic syndromes in adults manifesting as OMS are most commonly described in breast, gynecological and small cell lung cancer with associated anti-neuronal antibodies (ANNA-2; anti-Ri). We describe the first case of OMS associated with lung adenocarcinoma and Contactin-associated protein-like 2 (Caspr2) antibody. CASE REPORT: A 46-year-old-woman with history of limited small cell lung cancer (SCLC) status-post chemotherapy with cisplatin and etoposide and prophylactic whole brain radiation, presented with new onset gait instability, nausea, vomiting, vertigo, and opsoclonus. Two months prior to her presentation, a chest computed topography (CT) revealed no evidence of recurrent disease. Brain MRI revealed T2 hyperintensities in the white matter and central pons presumably related to chronic small vessel ischemic changes, unchanged from prior imaging. CSF studies revealed normal cell count, glucose, and protein. Gram stain, culture and meningoencephalitis panel were negative. Her paraneoplastic panel revealed a positive Caspr2 antibody. A repeat CT chest for cancer surveillance revealed a new lung mass. Immunotherapy treatment included plasmapheresis, corticosteroids, and intravenous immunoglobulin therapy. She underwent a biopsy of the new pulmonary lesion and the pathology was consistent with non-small cell lung carcinoma. Her symptoms slowly improved after treatment. Unfortunately, her disease progressed on repeat PET scan despite surgical resection of the lung mass. She ultimately elected for hospice. CONCLUSION We report a novel antibody, Caspr2, occurring in association with paraneoplastic OMS. While SCLC is the most common neoplasm associated with OMS among adults, non-small cell lung carcinoma should be considered. Prompt immunotherapy and neoplasm treatment may result in improvement.

Background and Purpose: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes. Methods: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years. Those with identified alternative inflammatory, infectious, or neoplastic causes of pachymeningitis or leptomeningitis were excluded. Results: Fourteen patients meeting inclusion/exclusion criteria were identified. All patients were positive for rheumatoid factor or cyclic citrullinated peptide. All patients had magnetic resonance imaging abnormalities characterized by pachymeningeal and/or leptomeningeal enhancement. Of the 10 patients who underwent biopsy, nonspecific findings were seen in 74%. All patients except one were treated with corticosteroids with subsequent symptomatic improvement. Radiographic improvement or resolution was seen in 10 (83%) of 12. Patients improved with corticosteroid treatment, including those who were diagnosed with RM on clinical basis without undergoing a biopsy as well. Conclusions: This retrospective review displays the myriad of clinical presentations of RM. It also suggests that with appropriate exclusion of infectious, neoplastic, and other autoimmune etiologies, biopsy may not be necessary to initiate treatment.

Purpose: Neuroinvasive West Nile virus (WNV) is rare, occurring in less than 1% of those infected, and may manifest as meningitis, encephalitis, and/or acute flaccid paralysis. Patients may present initially with nonspecific symptoms including fevers. Although rare, neuroinvasive WNV is associated with significant morbidity and mortality. The mainstay of treatment is supportive care. Electroencephalography (EEG) allows for identification of nonconvulsive status epilepticus and other epileptiform and nonepileptiform patterns suggestive of underlying cognitive dysfunction. Our aim was to describe specific EEG patterns observed in WNV neuroinvasive disease. Methods: A retrospective chart review was conducted. West Nile virus was confirmed with serum and/or cerebrospinal fluid markers. Patients with a history of abnormal EEG were excluded. Electroencephalography reports were classified into categories based on the presence of epileptiform activity, focal slowing, generalized periodic discharges with triphasic morphology, and frontally predominant generalized rhythmic delta activity. Results: In our cohort of 34 patients, 60% of focal EEG abnormalities were anterior-predominant, seen as epileptiform discharges, focal slowing, or frontally predominant generalized rhythmic delta activity. Nonepileptiform EEG patterns included nonspecific slowing and generalized periodic discharges with triphasic morphology. Two patients had electrographic seizures, one arising from the frontocentral head region. Conclusions: EEGs are important in the evaluation of WNV infection to rule out seizures or alternative causes of encephalopathy, and because of the risk of nonconvulsive seizures or status epilepticus in encephalitis. Although an anterior predominance of EEG abnormalities was seen in our cohort, this most likely is more correlative to encephalopathy than WNV itself. Although a specific correlative EEG pattern may not accompany all cases of WNV neuroinvasive disease, WNV should be considered as a possible etiology in patients presenting with an encephalitic or meningitic syndrome in the presence of abnormal EEG findings including encephalopathic patterns, particularly those with anterior predominant EEG changes.

Following acute West Nile virus (WNV) infection in humans, there is upregulation of pro-inflammatory molecules that promote neuroinflammation, including S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). The effects of S100B and HMGB1 are transduced by the receptor for advanced glycation end products (RAGE). Interestingly, the same immunoregulatory proteins that fuel neuroinflammation can also promote tumorigenesis. We present 2 cases of glial neuronal tumors, a glioblastoma multiforme and dysembryoplastic neuroepithelial tumor, in patients with severe West Nile neuroinvasive disease (WNND). In these cases, the viral infection was a precursor to the development of the aggressive brain tumors. We describe a potential mechanism where the presence of tumorigenic proteins in the microenvironment induced by WNV, and subsequent RAGE and OPN signaling, may contribute to development or aggressive growth of these tumors. Although it is certainly possible that the occurrence of primary brain tumors following WNND is coincidental, the ability of WNV to alter cellular signaling and increase expression of pro-inflammatory and tumorigenic molecules merits further investigations to determine whether there is an association between these disease processes or implications for brain tumor patients who develop WNV infection.

Abstract Little is known about the clinical presentation and outcomes associated with spinal implant infections. Here, we describe a single center's experience in a retrospective cohort of 109 individuals with spinal implant infections, including clinical, microbiological, therapeutic, and outcome data.