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A Case of Opsoclonus-Myoclonus-Ataxia With Neuronal Intermediate Filament IgG Detected in Cerebrospinal Fluid [Case Report]

Merati, Melody; Rucker, Janet C; McKeon, Andrew; Frucht, Steven J; Hu, Jessica; Balcer, Laura J; Galetta, Steven L
ABSTRACT:A 62-year-old man presented with headache, fever, and malaise. He was diagnosed with Anaplasma phagocytophilum, confirmed by serum polymerase chain reaction, and started on oral doxycycline. After 5 days of treatment, the patient began to experience gait imbalance with frequent falls, as well as myoclonus, and confusion. Examination was notable for opsoclonus-myoclonus-ataxia (OMA) and hypometric saccades. Cerebrospinal fluid (CSF) autoimmune encephalitis panel demonstrated a markedly elevated neuronal intermediate filament (NIF) immunoglobulin G antibody titer of 1:16, with positive neurofilament light- and heavy-chain antibodies. These antibodies were suspected to have been triggered by the Anaplasma infection. Repeat CSF examination 8 days later still showed a positive immunofluorescence assay for NIF antibodies, but the CSF titer was now less than 1:2. Body computed tomography imaging was unrevealing for an underlying cancer. Our patient illustrates a postinfectious mechanism for OMA and saccadic hypometria after Anaplasma infection.
PMID: 35594157
ISSN: 1536-5166
CID: 5283712

Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics

Hinson, Shannon R; Honorat, Josephe A; Grund, Ethan M; Clarkson, Benjamin D; Miske, Ramona; Scharf, Madeleine; Zivelonghi, Cecilia; Al-Lozi, Muhammad Taher; Bucelli, Robert C; Budhram, Adrian; Cho, Tracey; Choi, Ellie; Grell, Jacquelyn; Lopez-Chiriboga, Alfonso Sebastian; Levin, Marc; Merati, Melody; Montalvo, Mayra; Pittock, Sean J; Wilson, Michael R; Howe, Charles L; McKeon, Andrew
BACKGROUND AND OBJECTIVES/OBJECTIVE:We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. METHODS:Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. RESULTS:Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. INTERPRETATION/CONCLUSIONS:Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022.
PMID: 36053822
ISSN: 1531-8249
CID: 5340102

Multiple Cranial Nerve Palsies as the Presenting Sign of GCA

Merati, Melody; Radomski, Shana; Below, Alexandra; Lambert-Cheatham, Nathan; Keating, Ryan; Chang, Howard; Kaufman, David
PMID: 36892944
ISSN: 1536-5166
CID: 5456872

A Case of Pembrolizumab-Induced Papillitis With Transverse Myelitis

Lambert-Cheatham, Nathan A; Sakuru, Ragha; Merati, Melody; Tessema, Sophia T; Salbert, Luke R; Ward, Jayne H; Nagia, Lina
ORIGINAL:0016065
ISSN: 1536-5166
CID: 5340122

Validation of Histologic Bone Analysis Following Microfil Vessel Perfusion

Sarhaddi, D; Poushanchi, B; Merati, M; Tchanque-Fossuo, C; Donneys, A; Baker, J; Buchman, S R
The ability to examine bone vascularity using Micro-Computed Tomography (μCT) following vessel perfusion with Microfil® and to subsequently perform histologic bone analysis in the same specimen would provide an efficient method by which the vascular and cellular environment of bone can be examined simultaneously. The purpose of this report is to determine if the administration of Microfil® precludes accurate histologic assessment of bone quality via osteocyte count and empty lacunae count. Sprague-Dawley rats (n=6) underwent perfusion with Microfil®. Left hemi-mandibles were harvested, decalcified and underwent vascular analysis via μCT prior to sectioning and staining with Gomori's Trichrome. Quantitative Histomorphometric evaluation was performed. Ninety-five percent confidence intervals were used to determine statistical differences from an established set of controls (n=12). Histologic analyses were successfully performed on specimens that had undergone previous perfusion. Quantitative measures of bone cellularity of perfused versus control specimens revealed no statistical difference in osteocyte count per high-power field (95.33 versus 94.66; 95 percent CI,-7.64 to 6.30) or empty lacunae per high-power field (2.73 versus 1.89, 95 percent CI, -1.81 to 0.13). Here we report a statistical validation allowing for histological analysis of cell counts in specimens in which Microfil® perfusion has previously been performed.
PMCID:4508845
PMID: 26207077
ISSN: 0147-8885
CID: 5340112