Neurological Effects of Orthopoxvirus Infections: Neurotropism and Neurovirulence Insights

Overview

Orthopoxviruses, including monkeypox virus (MPXV), variola virus (VARV), vaccinia virus (VACV), camelpox, and cowpox viruses, can cause neurological manifestations ranging from headaches to encephalitis. Recent outbreaks, especially of MPXV, have highlighted their neurotropic and neurovirulent potential, with evidence of central nervous system involvement and neurological complications.

Background

Orthopoxviruses are large, enveloped double-stranded DNA viruses capable of replicating in the cytoplasm of infected cells. Historically, variola virus caused smallpox, eradicated by vaccination, but other orthopoxviruses remain zoonotic threats. MPXV re-emerged as a global health emergency in 2022, causing mpox syndrome with systemic and neurological symptoms. Neurological manifestations include headaches, seizures, altered consciousness, and encephalitis, with MRI and cerebrospinal fluid findings supporting CNS infection.

Data Highlights

Key Findings

• MPXV infection can cause neurological syndromes including headaches, seizures, altered consciousness, and encephalitis.
• MRI findings in MPXV patients may show brain hyperintensities consistent with edema.
• Cerebrospinal fluid pleocytosis in MPXV cases suggests active CNS infection.
• Newborn rodents and immunodeficient animals demonstrate susceptibility to MPXV CNS infection, indicating the virus can cross the blood–brain barrier.
• Orthopoxviruses, though not classical neurotropic viruses, exhibit neurovirulence affecting both central and peripheral nervous systems.
• Neurological complications vary among orthopoxviruses but are increasingly recognized as clinically significant.

Clinical Implications

Clinicians should be vigilant for neurological symptoms in patients with orthopoxvirus infections, particularly MPXV, as early recognition of CNS involvement may impact management. Diagnostic evaluation including neuroimaging and cerebrospinal fluid analysis can aid in identifying neuroinvasive disease. Awareness of neurovirulence supports consideration of neurological monitoring and potential therapeutic interventions in severe cases.

Conclusion

Orthopoxviruses possess neurotropic and neurovirulent properties that contribute to a spectrum of neurological manifestations, underscoring the need for heightened clinical awareness and further research into their neuropathogenesis and management.

References

1. WHO 2022 -- Monkeypox Declared Global Health Emergency
2. Historical and Clinical Overview of Orthopoxviruses
3. Neurological Manifestations in MPXV Infection