Powassan virus (POWV), a tick-borne flavivirus transmitted primarily by Ixodes ticks, poses a significant threat as it can lead to severe neuroinvasive illness. This review delves into the nuanced clinical presentation of Powassan infection, a challenge in diagnosis exacerbated by the absence of an available vaccine. Over the past decade, the prevalence of POWV has surged in North America, necessitating a thorough examination of its neurological manifestations alongside tick-borne encephalitis virus (TBEV). A comprehensive literature search conducted up to January 2024 revealed 135 cases of neurological symptoms associated with either Powassan or TBEV infection. Notably, severe occipital headache emerged as the most prevalent symptom (22.75%), followed by meningoencephalitis (10.34%), seizures (8.27%), and flaccid paresis (6.8%). Additional manifestations included poor balance, wide gait, dysarthria, facial nerve palsy, seizure, slurred speech, and absent deep tendon reflexes. Tragically, nine cases resulted in fatal outcomes attributed to POWV infection. This analysis highlights the intricate spectrum of neurological symptoms associated with Powassan infection and underscores the necessity for heightened awareness among medical practitioners, particularly in regions with a higher prevalence of the virus. The complexity of symptoms emphasizes the need for further research to unravel the factors contributing to this diversity. Additionally, exploring potential treatment avenues and vaccine development is crucial in addressing the rising threat posed by POWV, ultimately enhancing our ability to manage and prevent severe neurological outcomes.

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