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

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.

Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days to 1 year), and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

Diagnosing viral encephalitis and emerging concepts.

PURPOSE OF REVIEW: This review offers a contemporary clinical approach to the diagnosis of viral encephalitis and discusses recent advances in the field. The neurologic effects of coronaviruses, including COVID-19, as well as management of encephalitis are not covered in this review. RECENT FINDINGS: The diagnostic tools for evaluating patients with viral encephalitis are evolving quickly. Multiplex PCR panels are now in widespread use and allow for rapid pathogen detection and potentially reduce empiric antimicrobial exposure in certain patients, while metagenomic next-generation sequencing holds great promise in diagnosing challenging and rarer causes of viral encephalitis. We also review topical and emerging infections pertinent to neuroinfectious disease practice, including emerging arboviruses, monkeypox virus (mpox), and measles. SUMMARY: Although etiological diagnosis remains challenging in viral encephalitis, recent advances may soon provide the clinician with additional tools. Environmental changes, host factors (such as ubiquitous use of immunosuppression), and societal trends (re-emergence of vaccine preventable diseases) are likely to change the landscape of neurologic infections that are considered and treated in clinical practice.

An Overview of Monkeypox Virus and Its Neuroinvasive Potential.

Monkeypox virus (MPV) is an orthopox virus in the Poxviridae family that is currently of international concern. It is endemic to Central and Western Africa with two known viral clades. Various African rodents and primates are likely the natural reservoirs. Zoonotic transmission occurs by direct contact with infected animals (e.g., bites, scratches, slaughtering). Human to human transmission occurs through close contact with infected persons (e.g., respiratory droplets, skin-on-skin, or sexual contact) or fomites. Classically, human MPV disease first has a febrile prodrome with lymphadenopathy followed by a diffuse maculopapular to vesiculopustular skin/mucosal lesion eruption. In the current 2022 outbreak, which is primarily affecting men who have sex with men (MSM) currently, the febrile prodrome may be absent and skin/mucosal lesions may be isolated to the genital and anal regions. Rarely, MPV likely has the potential to be neuroinvasive based on animal models, previous case series, and preliminary reports currently under investigation. Even though neurologic manifestations of human MPV infection are rare, given the sheer numbers of increasing cases throughout the world, neurologists should be prepared to recognize, diagnose, and treat potential neuroinvasive disease or other neurologic symptoms. ANN NEUROL 2022;92:527-531.

COVID-19 vaccination status and related process of care outcomes among U.S. adults with active epilepsy-National Health Interview Survey, United States, 2021.

Growing research has examined the effects of the COVID-19 pandemic on people with epilepsy. There are no published national estimates of COVID-19 vaccination status among U.S. adults with active epilepsy. The purpose of this study is to use 2021 National Health Interview Survey (NHIS) data to examine select COVID-19-related outcomes by epilepsy status in a nationally representative sample of US adults. The study sample met the criteria for operationalization of epilepsy status (i.e., active epilepsy vs. no epilepsy history) and select questions related to COVID-19 testing, vaccination, delays in care, or experience with virtual care during the COVID-19 pandemic. All analyses accounted for the NHIS complex sample design and response sampling weights. Our study found that in 2021 receipt of one COVID-19 vaccination among U.S. adults with active epilepsy was generally similar to that among adults without a history of epilepsy. By age, adults aged 18-44 years with active epilepsy (27.0%) were significantly less likely to have reported receiving two COVID-19 vaccinations compared with their peers with no epilepsy history (39.1%). Compared to adults with no epilepsy history, adults with active epilepsy reported similar experiences and outcomes regarding COVID-19 testing and obtaining health care during the COVID-19 pandemic. This study provides baseline estimates of select COVID-19 outcomes among US adults with active epilepsy to guide interventions and additional studies.

Seizure- or Epilepsy-Related Emergency Department Visits Before and During the COVID-19 Pandemic - United States, 2019-2021.

Seizures, transient signs or symptoms caused by abnormal surges of electrical activity in the brain, can result from epilepsy, a neurologic disorder characterized by abnormal electrical brain activity causing recurrent, unprovoked seizures, or from other inciting causes, such as high fever or substance abuse (1). Seizures generally account for approximately 1% of all emergency department (ED) visits (2,3). Persons of any age can experience seizures, and outcomes might range from no complications for those with a single seizure to increased risk for injury, comorbidity, impaired quality of life, and early mortality for those with epilepsy (4). To examine trends in weekly seizure- or epilepsy-related (seizure-related) ED visits† in the United States before and during the COVID-19 pandemic, CDC analyzed data from the National Syndromic Surveillance Program (NSSP).§ Seizure-related ED visits decreased abruptly during the early pandemic period. By the end of 2020, seizure-related ED visits returned almost to prepandemic levels for persons of all ages, except children aged 0-9 years. By mid-2021, however, this age group gradually returned to baseline as well. Reasons for the decrease in seizure-related ED visits in 2020 among all age groups and the slow return to baseline among children aged 0-9 years compared with other age groups are unclear. The decrease might have been associated with fear of exposure to COVID-19 infection in EDs deterring parents or guardians of children from seeking care, adherence to mitigation measures including avoiding public settings such as EDs, or increased access to telehealth services decreasing the need for ED visits (5). These findings reinforce the importance of understanding factors associated with ED avoidance among persons with epilepsy or seizure, the importance that all eligible persons be up to date¶ with COVID-19 vaccination, and the need to encourage persons to seek appropriate care for seizure-related emergencies** to prevent adverse outcomes.

Two Cases of Monkeypox-Associated Encephalomyelitis - Colorado and the District of Columbia, July-August 2022.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

Usutu virus disease: a potential problem for North America?

Usutu virus is an emerging mosquito-borne flavivirus initially identified in South Africa in 1959 that is now circulating throughout parts of Africa, Europe, and the Middle East. It is closely related to West Nile virus, and has similar vectors, amplifying bird hosts, and epidemiology. Usutu virus infection can occur in humans and may be asymptomatic or cause systemic (e.g., fever, rash, and hepatitis) or neuroinvasive (e.g., meningitis and encephalitis) disease. Given few reported cases, the full clinical spectrum is not known. No anti-viral treatment is available, but it can be largely prevented by avoiding mosquito bites. Because of similar mosquitoes, birds, and climate to Europe, the potential for introduction to North America is possible.

Five Emerging Neuroinvasive Arboviral Diseases: Cache Valley, Eastern Equine Encephalitis, Jamestown Canyon, Powassan, and Usutu.

There are many arthropod-borne viruses (arboviruses) capable of neuroinvasion, with West Nile virus being one of the most well known. In this review, we highlight five rarer emerging or reemerging arboviruses capable of neuroinvasion: Cache Valley, eastern equine encephalitis, Jamestown Canyon, Powassan, and Usutu viruses. Cache Valley and Jamestown Canyon viruses likely circulate throughout most of North America, while eastern equine encephalitis and Powassan viruses typically circulate in the eastern half. Usutu virus is not currently circulating in North America, but has the potential to be introduced in the future given similar climate, vectors, and host species to Europe (where it has been circulating). Health care providers should contact their state or local health departments with any questions regarding arboviral disease surveillance, diagnosis, treatment, or prevention. To prevent neuroinvasive arboviral diseases, use of insect repellent and other mosquito and tick bite prevention strategies are key.

Heartland Virus and Hemophagocytic Lymphohistiocytosis in Immunocompromised Patient, Missouri, USA.

Heartland virus is a suspected tickborne pathogen in the United States. We describe a case of hemophagocytic lymphohistiocytosis, then death, in an immunosuppressed elderly man in Missouri, USA, who was infected with Heartland virus.

Increase in Acute Flaccid Myelitis - United States, 2018.

In August 2018, CDC noted an increased number of reports of patients having symptoms clinically compatible with acute flaccid myelitis (AFM), a rare condition characterized by rapid onset of flaccid weakness in one or more limbs and spinal cord gray matter lesions, compared with August 2017. Since 2014, CDC has conducted surveillance for AFM using a standardized case definition (1,2). An Epi-X* notice was issued on August 23, 2018, to increase clinician awareness and provide guidance for case reporting.

People with epilepsy are diagnosed most often with unspecified epilepsy, followed by focal epilepsy, generalized convulsive epilepsy, and generalized nonconvulsive epilepsy-US MarketScan data, 2010-2015.

The distribution of epilepsy types varies by age, etiology, provider diagnostic capabilities, and assessment criteria. No recent US study has examined the distribution of epilepsy types in a large, population-based sample of people with epilepsy. We used MarketScan data from January 1, 2010 through September 30, 2015, to estimate the proportion of epilepsy types among all (N=370,570) individuals diagnosed with epilepsy. We identified cases of epilepsy as individuals with at least one International Classification of Disease, 9th version (ICD-9) diagnostic code of 345.X and the use of at least one antiseizure drug described in the 2015 MarketScan Redbook. Unspecified epilepsy was more common (36.8%) than focal-localized epilepsy (24.6%), generalized convulsive epilepsy (23.8%), generalized nonconvulsive epilepsy (8.9%), other forms of epilepsy (5.2%), infantile spasm (0.3%), and epilepsia partialis continua (0.3%). The high proportion of epilepsy classified as unspecified might be lowered by improved training in epilepsy diagnosis and coding.

Close to 1 million US adults aged 55 years or older have active epilepsy-National Health Interview Survey, 2010, 2013, and 2015.

Epilepsy is common in older adults because known risk factors-such as traumatic brain injury, stroke, cerebrovascular disease, neurodegenerative disorders, and neoplasms-increase with age. This study uses the most recent data from the 2010, 2013, and 2015 National Health Interview Survey (NHIS) to provide updated national estimates of epilepsy prevalence among US adults aged 55 years or older to help guide public health action. We used the following validated surveillance case definition for active epilepsy: adults with self-reported doctor-diagnosed epilepsy or seizure disorder who reported either currently taking medications to treat their epilepsy or seizure disorder or at least one seizure during the past 12 months. We estimated the prevalence of active epilepsy to be 1.4% (about 529,000) among US adults aged 55-64, 0.9% (225,000) for those aged 65-74, and 1.0% (178,000) for those aged ≥75 years. The prevalence of a history of epilepsy and active epilepsy among adults aged 55-64 years was significantly higher than the prevalence in older age groups. Collectively, close to 1 million adults aged 55 years or older reported active epilepsy. Epilepsy stakeholders should ensure that older adults with epilepsy have access to age-appropriate clinical preventive services, chronic disease self-management support, specialty care for epilepsy and other comorbidities, and appropriate community services to promote quality of life.

Zika Virus-Associated Guillain-Barré Syndrome in a Returning US Traveler.

Zika virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Roughly 60% of people in countries such as the U.S. live in areas at risk for seasonal spread of ZIKV. ZIKV belongs to a class of diseases that is not typically seen in hospital settings across the U.S. and Europe. We describe the case presentation, management, and treatment of ZIKV infection complicated by GBS. A 64-year-old woman with recent travel to the Dominican Republic presented with rash followed by an acute, ascending polyneuropathy consistent with GBS. She was confirmed to have an acute ZIKV infection by detection of ZIKV nucleic acid by reverse transcription-polymerase chain reaction. She met Brighton Collaboration criteria level 1 evidence for GBS. She received two courses of intravenous immunoglobulin and slowly improved, though still had weakness at discharge. More research is needed to identify the pathophysiology behind ZIKV-associated GBS and its optimal treatment. Prevention is fundamental to limiting infection and spread of ZIKV.

Investigation of Acute Flaccid Paralysis Reported with La Crosse Virus Infection, Ohio, USA, 2008-2014.

Infection with La Crosse virus can cause meningoencephalitis, but it is not known to cause acute flaccid paralysis (AFP). During 2008-2014, nine confirmed or probable La Crosse virus disease cases with possible AFP were reported in Ohio, USA. After an epidemiologic and clinical investigation, we determined no patients truly had AFP.

Guillain-Barré Syndrome and Healthcare Needs during Zika Virus Transmission, Puerto Rico, 2016.

To assist with public health preparedness activities, we estimated the number of expected cases of Zika virus in Puerto Rico and associated healthcare needs. Estimated annual incidence is 3.2-5.1 times the baseline, and long-term care needs are predicted to be 3-5 times greater than in years with no Zika virus.

Zika Virus Disease for the Neurointensivist.

Zika virus (ZIKV) is a mosquito-borne and sexually transmitted flavivirus currently spreading throughout the Pacific and Western Hemisphere. ZIKV infection is often either asymptomatic or causes a self-limiting illness with symptoms such as rash, fever, myalgia, arthralgia, headache, or conjunctivitis. Rarely, ZIKV infection has been associated with conditions such as severe thrombocytopenia, microcephaly and other developmental abnormalities, acute polyneuropathy/Guillain-Barré syndrome, myelitis, meningoencephalitis, transient encephalopathy, provoked seizures, and various ophthalmologic conditions. Optimal treatment of these ZIKV-associated conditions is currently unclear and is largely guided by expert opinion or case reports/series. Further studies are needed to establish best treatment practices. This review concentrates on caring by neurointensivists for the patient affected with Zika virus-expected to flare up again in the summer.

Zika Virus Infection Associated With Severe Thrombocytopenia.

We report two patients that developed severe thrombocytopenia after Zika virus (ZIKV) infection. The first patient had 1000 platelets/µL and died after multiple hemorrhages. The second patient had 2000 platelets/µL, had melena and ecchymoses, and recovered after receiving intravenous immunoglobulin. ZIKV may be associated with immune-mediated severe thrombocytopenia.