Monkeypox‐Associated Central Nervous System Disease: A Case Series and Review

Abstract

Objective Monkeypox virus (MPXV) disease has been declared a public health emergency by the World Health Organization, creating an urgent need for neurologists to be able to recognize, diagnosis, and treat MPXV‐associated neurologic disease. Methods Three cases of MPXV‐associated central nervous system (CNS) disease occurring during the 2022 outbreak, and their associated imaging findings are presented, with 2 cases previously published in a limited capacity in a public health bulletin. Results Three previously healthy immunocompetent gay men in their 30s developed a febrile illness followed by progressive neurologic symptoms with presence of a vesiculopustular rash. MPXV nucleic acid was detected by polymerase chain reaction (PCR) from skin lesions of 2 patients, with the third patient having indeterminate testing but an epidemiologic link to a confirmed MPXV disease case. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis, elevated protein, and negative MPXV‐specific PCR. In 2 patients, magnetic resonance imaging of the brain and spine demonstrated partially enhancing, longitudinally extensive central spinal cord lesions with multifocal subcortical, basal ganglia, thalamic, cerebellar, and/or brainstem lesions. The third patient had thalamic and basal ganglia lesions. All patients received 14 days of tecovirimat, and 2 patients also received multiple forms of immunotherapy, including intravenous immunoglobulin, pulsed high‐dose steroids, plasmapheresis, and/or rituximab. Good neurologic recovery was observed in all cases. Interpretation MPXV can be associated with CNS disease. It is unclear whether this is from a parainfectious immune‐mediated injury or direct CNS viral invasion. ANN NEUROL 2023;93:893–905

A Rare Co-occurrence of Monkeypox Encephalitis and Neurosyphilis

“…To our knowledge, only one case has been reported with MPOX and suspected neurosyphilis as RPR was positive (1:64) while CSF-VDRL was negative [ 5 ]. Limited cases of MPOX have been known to have neurological involvement [ 10 ]. The central nervous system (CNS) complications in these cases are thought to occur either by an autoimmune process triggered by the infection or by an indirect inflammation in the CNS as a result of an exaggerated immune response by the body [ 10 , 11 ].…”

“…Limited cases of MPOX have been known to have neurological involvement [ 10 ]. The central nervous system (CNS) complications in these cases are thought to occur either by an autoimmune process triggered by the infection or by an indirect inflammation in the CNS as a result of an exaggerated immune response by the body [ 10 , 11 ]. However, it is not possible to rule out the possibility of direct viral invasion in the CNS in our case due to a lack of data on the sensitivity and specificity of MPOX nucleic acid or serology tests available for use in the CSF.…”

Current Evidence and Practice Guidelines of Systemic Complications of 2022 Mpox Outbreak: A Scoping Review

“…Frequently observed neurological symptoms include headaches (most common -50 % prevalence), followed by myalgia, anorexia, and fatigue [ 19 , 20 ]. Photophobia, numbness, extremity weakness, and bowel/bladder incontinence can also be seen, rapidly advancing to more severe manifestations in rare instances, such as confusion, disorientation, seizures, agitation, and encephalitis [ 21 ]. Neurological complications occur mostly in unvaccinated MSM patients [ 20 ], although the available evidence remains limited due to the scarcity of cases.…”

MOG‐IgG‐Associated Bilateral Optic Neuritis in Temporal Relation to Monkeypox Vaccination

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With great interest, we read the article by Money et al reporting 3 cases of monkeypox virus disease (MPXV) associated central nervous system (CNS) disease which raised the question if this reflects a para-infectious injury or a viral invasion of the CNS. 1 The reported cases strikingly resemble antibody-mediated CNS myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) in many aspects 2 : (1) patients presented with typical phenotypes, including prodromal phases with fever and myalgia followed by acute disseminated encephalomyelitis (ADEM), longitudinally extensive transverse myelitis (LETM), or encephalopathy with seizures, (2) cerebrospinal fluid (CSF) pleocytosis, (3) prompt treatment response to plasma exchange only, and (4) almost complete clinical and radiographic recovery. The authors' differential diagnosis included MOGAD, but myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) was negative (tested in 2/3), however, crucial information regarding the timepoint and method are lacking.

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“…Recent criteria have been proposed for diagnosis of MOG antibody-associated disease, with MOG immunoglobulin G (IgG) positivity as a core criterion. 1 Previously utilized enzyme-linked immunosorbent assay and immunoblot-based assays relied on non-native conformation (eg, linear or refolded recombinant) MOG protein as assay substrate, which was found to produce inconsistent results. 2 However, assays that utilize native conformation MOG protein as substrate (eg, radioimmunoprecipitation assays and cell-based assays) provide greater sensitivity with increasingly improved specificity with assay refinement and higher positive threshold.…”