The virus might invade the nervous system, or the immune system's response might trigger the damage.
As monkeypox spread across continents in 2022, researchers at Queen Mary University of London turned to a quiet but consequential question: could this virus, like its poxvirus relatives before it, leave its mark not just on skin but on the brain itself? A study published in eClinicalMedicine found that between 2 and 3 percent of infected patients developed serious neurological complications — seizures, encephalitis, lasting disability — while many more reported headaches, fatigue, and psychological distress. The evidence points toward a link, but science has not yet closed the distance between association and cause, leaving physicians and researchers in the uncomfortable position of knowing something is happening without fully understanding why.
- A small but significant fraction of monkeypox patients — 2 to 3 percent — are developing seizures and brain inflammation severe enough to cause long-term disability, a finding that demands attention even amid a disease better known for its skin lesions.
- The data trail is frustratingly thin: earlier studies from West Africa focused on hospitalized cases and rarely tracked how long symptoms lasted, how severe they were, or whether psychiatric effects like anxiety and depression persisted after recovery.
- Researchers cannot yet determine whether the virus directly invades the nervous system, whether the immune response triggers the damage, or whether the psychological burden of a stigmatizing, disfiguring illness is itself driving psychiatric distress.
- Partial confirmation has arrived from multiple directions — a 16-country study found no encephalitis but documented headaches and mood disturbances in a substantial share of patients, while Spain reported two confirmed cases of monkeypox-related encephalitis.
- Scientists are now calling for longitudinal studies that follow uninfected individuals before exposure, the only method rigorous enough to establish causation and determine whether neurological symptoms endure long after the infection clears.
A research team led by James Brunton Badenoch from Queen Mary University of London began with a historical observation: smallpox and the vaccinia virus had both caused neurological complications in infected and vaccinated people. Could monkeypox do the same? Their study, published in eClinicalMedicine, suggests the answer is yes — though the full picture remains elusive.
Combing through evidence gathered before the current outbreak, mostly from hospitalized patients in West Africa, the researchers found that 2 to 3 percent of infected individuals developed severe neurological damage, including seizures and encephalitis — brain inflammation capable of leaving lasting disability. A broader group reported more common symptoms: headaches, muscle pain, and fatigue. Mood disturbances, particularly sadness, appeared in studies that examined psychiatric effects, though most research did not track these outcomes consistently or over time.
The central obstacle was causation. The data suggested a connection between monkeypox and neurological harm, but could not confirm one. Badenoch outlined several possible mechanisms — direct viral invasion of the nervous system, immune-driven damage, or the psychological weight of a stigmatizing illness marked by disfiguring skin lesions — without being able to distinguish between them.
Subsequent research offered partial corroboration. A New England Journal of Medicine study tracking more than 500 patients across 16 countries found no encephalitis or seizures, but headaches and fatigue appeared in over a quarter of patients and mood disturbances in roughly one in ten. Spain, meanwhile, confirmed two cases of monkeypox-related encephalitis, demonstrating that severe complications, however rare, do occur.
Badenoch's conclusion was measured: monkeypox is primarily a disease of flu-like symptoms and skin problems, and most patients will not experience serious neurological effects. But encephalitis and seizures can happen, and the mechanisms remain unknown. What the field needs now are studies that follow people before infection — tracking symptoms forward in time — to determine whether the virus is truly the cause and whether its neurological effects persist long after recovery.
A research team led by James Brunton Badenoch from Queen Mary University of London set out to answer a straightforward question: if smallpox and the vaccinia virus had caused neurological problems in infected and vaccinated people throughout history, could monkeypox do the same? The answer, according to a study published in eClinicalMedicine, appears to be yes—though the picture remains incomplete and the mechanisms remain mysterious.
The researchers combed through existing evidence of neurological and psychiatric complications in monkeypox patients from before the current outbreak. Most of the data came from West Africa and focused on hospitalized cases. What they found was striking in its specificity: between 2 and 3 percent of infected people developed severe neurological damage, including seizures and encephalitis, an inflammation of the brain that can leave lasting disability. Badenoch was careful to note that these figures came from small studies, a limitation that shadowed the entire analysis. Beyond the rare but serious cases, the team identified a broader pattern of common neurological symptoms—headaches, muscle pain, fatigue—reported across a larger group of patients. Yet even here, the data proved frustratingly vague. The studies did not consistently report how severe these symptoms were, how long they lasted, or how many patients experienced psychiatric effects like anxiety and depression. Among those that did examine mood, sadness emerged as the most frequently reported symptom.
The central problem facing Badenoch and his colleagues was causation. The evidence suggested a link, but could not prove one. They did not know whether different viral strains or the severity of infection affected neurological outcomes, because earlier studies had not tracked this information consistently. More fundamentally, they could not establish that monkeypox itself was responsible for the brain damage. Badenoch proposed several possibilities: the virus might directly invade the nervous system, or the immune system's response to infection might trigger the damage. He also raised a less biological but equally real possibility—that the psychological weight of infection itself, compounded by the stigma and the disfiguring skin lesions that characterize the disease, could drive psychiatric distress.
Other research published after Badenoch's work lent partial support to his findings. A study in the New England Journal of Medicine tracked more than 500 monkeypox patients across 16 countries during the current outbreak. It found no cases of encephalitis or seizures, but headaches and fatigue appeared in more than a quarter of the infected people, and mood disturbances in roughly one in ten. Yet Spain reported two confirmed cases of monkeypox-related encephalitis, suggesting that severe neurological complications, while rare, do occur.
Badenoch's final assessment captured the uncertainty that still defines the field. Monkeypox primarily causes flu-like symptoms and skin problems, he acknowledged. Neuropsychiatric symptoms are not uncommon, but serious brain complications appear to strike only a small fraction of patients. No one expects a wave of severe neurological disease. But encephalitis and seizures can happen. The critical next step is research that follows uninfected people before they contract monkeypox, tracking whether neurological symptoms persist and whether the virus itself is truly the cause. Until then, the question remains open.
Citações Notáveis
It is important to note that these findings are based on studies with few participants— James Brunton Badenoch, Queen Mary University of London
We do not expect a wave of serious brain problems, but complications like encephalitis and seizures can occur in a small proportion of people— James Brunton Badenoch
A Conversa do Hearth Outra perspectiva sobre a história
Why did researchers start looking at monkeypox's neurological effects in the first place?
They had historical precedent. Smallpox and the vaccinia virus—used in vaccines—had both caused neurological complications in people. Once monkeypox began spreading, it seemed logical to ask whether this virus might do the same.
And what did they find?
In 2 to 3 percent of infected patients, serious problems—seizures, brain inflammation. But the data came from small studies, mostly from West Africa and hospitalized patients. That's a real limitation.
What about the milder symptoms?
Headaches, muscle pain, fatigue showed up in larger groups. But the old studies didn't consistently report how bad these were or how long they lasted. That's the frustrating part—the evidence points somewhere, but not clearly.
Can they say the virus actually causes the damage?
Not yet. They can't rule out that the immune system's response is doing it, or that the psychological toll of infection—the stigma, the disfiguring lesions—is driving the psychiatric symptoms.
So what happens now?
They need longitudinal studies. Track people before infection, then after. See if symptoms stick around, see if the virus is really the culprit. Right now they're working with incomplete data.
Is this something people should worry about?
Not panic. Severe brain complications appear rare. But they do happen—Spain confirmed two cases of encephalitis. It's worth monitoring and researching, not ignoring.