Human metapneumovirus (hMPV) is a respiratory virus that primarily causes upper and lower respiratory tract infections. However, emerging evidence suggests that hMPV can also have neurological effects in some cases.
## Neurological Manifestations
The neurological manifestations associated with hMPV infection can range from mild to severe and include:
**Seizures:** Febrile and afebrile seizures have been reported in children with hMPV infection[1][20]. Some studies have found a higher frequency of seizures in hMPV cases compared to respiratory syncytial virus (RSV) infections[11].
**Encephalitis:** There have been case reports of encephalitis associated with hMPV infection in both children and adults[1][3][15]. Symptoms can include altered mental status, seizures, and focal neurological deficits.
**Status epilepticus:** Prolonged seizures or status epilepticus have been observed in some severe cases of hMPV infection[1][20].
**Encephalopathy:** Acute encephalopathy has been reported, particularly in young children with severe hMPV respiratory disease[1][20].
## Potential Mechanisms
The exact mechanisms by which hMPV affects the central nervous system (CNS) are not fully understood, but several possibilities have been proposed:
**Direct viral invasion:** Some studies have detected hMPV RNA in cerebrospinal fluid (CSF) and brain tissue, suggesting the virus may be able to directly invade the CNS in rare cases[3][5][15].
**Neuroinflammation:** hMPV infection can trigger the release of pro-inflammatory cytokines and chemokines that may contribute to neurological symptoms[1][20]. Elevated levels of IL-6, IL-8, CCL2, and CCL4 have been found in the CSF of some patients with hMPV-associated neurological complications[20].
**Blood-brain barrier disruption:** Animal studies have shown that hMPV infection can increase blood-brain barrier permeability, potentially allowing viral particles or inflammatory mediators to enter the CNS[21].
**Immune-mediated effects:** In some cases, neurological symptoms may result from an excessive immune response triggered by the viral infection rather than direct viral invasion[2].
## Clinical and Diagnostic Considerations
Neurological complications appear to be relatively rare in hMPV infections, but they may be underrecognized due to limited awareness and testing. Some key points to consider include:
– Neurological symptoms can occur with or without significant respiratory involvement[3][15].
– CSF analysis may show normal or mildly elevated protein levels with minimal pleocytosis[15].
– MRI findings in hMPV-associated encephalitis can include cortical and subcortical T2/FLAIR hyperintensities[12][15].
– PCR testing of respiratory samples and CSF can help confirm hMPV infection and CNS involvement[3][15].
## Long-term Effects and Prognosis
The long-term neurological effects of hMPV infection are not well-characterized. However, some concerning findings from animal studies include:
– Impaired cognitive performance observed in mice several weeks after hMPV infection[21].
– Potential for long-term behavioral changes following hMPV-induced neuroinflammation[21].
More research is needed to determine if these findings translate to human patients and to assess the risk of long-term neurological sequelae following severe hMPV infections.
## Conclusion
While hMPV is primarily a respiratory pathogen, clinicians should be aware of its potential to cause neurological complications, particularly in young children, older adults, and immunocompromised individuals. The exact mechanisms of CNS involvement remain to be fully elucidated, but likely involve a combination of direct viral effects and immune-mediated processes. Further research is needed to better understand the neurological impact of hMPV, develop targeted therapies, and assess long-term outcomes in affected patients.
As our understanding of hMPV’s neurological effects grows, it may be prudent to consider testing for this virus in cases of unexplained encephalitis or seizures, especially during peak respiratory virus seasons. Additionally, ongoing surveillance and research will be crucial to monitor for any changes in the neurological manifestations of hMPV as the virus continues to evolve and circulate globally.
Citations:
[1] https://journals.aai.org/jimmunol/article/210/1_Supplement/236.22/263946/Pneumoviruses-can-impair-the-central-nervous
[2] https://www.financialexpress.com/life/how-does-hmpv-infection-affects-brain-symptoms-complications-and-treatment-explained-3709201/
[3] https://pubmed.ncbi.nlm.nih.gov/19755929/
[4] https://pmc.ncbi.nlm.nih.gov/articles/PMC11404324/
[5] https://pmc.ncbi.nlm.nih.gov/articles/PMC3298257/
[6] https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00386/full
[7] https://pmc.ncbi.nlm.nih.gov/articles/PMC7188429/
[8] https://jamanetwork.com/journals/jamaneurology/fullarticle/1149696
[9] https://www.mdpi.com/1999-4915/12/1/14
[10] https://journals.lww.com/ccejournal/fulltext/2020/04000/neurologic_manifestations_of_severe_respiratory.7.aspx
[11] https://europepmc.org/article/med/19755929
[12] https://wwwnc.cdc.gov/eid/article/21/11/15-0608_article
[13] https://www.astrazeneca.com/our-therapy-areas/vaccines-and-immune-therapies/hMPV.html
[14] https://www.who.int/news-room/questions-and-answers/item/human-metapneumovirus-(hmpv)-infection
[15] https://pmc.ncbi.nlm.nih.gov/articles/PMC4622250/
[16] https://pmc.ncbi.nlm.nih.gov/articles/PMC10986691/
[17] https://pmc.ncbi.nlm.nih.gov/articles/PMC7107938/
[18] https://www.sciencemediacentre.org/expert-comments-about-hmpv-human-metapneumovirus-following-media-reports-about-cases-in-china/
[19] https://www.cnn.com/2023/05/29/health/human-metapneumovirus-explainer-wellness/index.html
[20] https://pmc.ncbi.nlm.nih.gov/articles/PMC6212673/
[21] https://journals.aai.org/jimmunol/article/210/1_Supplement/236.22/263946/Pneumoviruses-can-impair-the-central-nervous
[22] https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00386/full
[23] https://journals.lww.com/pidj/fulltext/2024/04000/epidemiology_and_clinical_characteristics_of_human.25.aspx
