Neurologists around the world say that a small subset of patients with COVID-19 are developing serious impairments of the brain.

Although fever, cough and difficulty breathing are the typical hallmarks of infection with the new coronavirus, some patients exhibit altered mental status, or encephalopathy, a catchall term for brain disease or dysfunction that can have many underlying causes, as well as other serious conditions. These neurological syndromes join other unusual symptoms, such as diminished sense of smell and taste as well as heart ailments.

In early March, a 74-year-old man came to the emergency room in Boca Raton, Florida, with a cough and a fever, but an X-ray ruled out pneumonia and he was sent home. The next day, when his fever spiked, family members brought him back. He was short of breath, and could not tell doctors his name or explain what was wrong — he had lost the ability to speak.

The patient, who had chronic lung disease and Parkinson’s, was flailing his arms and legs in jerky movements, and appeared to be having a seizure. Doctors suspected he had COVID-19, and were eventually proven right when he was finally tested.

On Tuesday, doctors in Detroit reported another disturbing case involving a female airline worker in her late 50s with COVID-19. She was confused, and complained of a headache; she could tell the physicians her name but little else, and became less responsive over time. Brain scans showed abnormal swelling and inflammation in several regions, with smaller areas where some cells had died.

Physicians diagnosed a dangerous condition called acute necrotizing encephalopathy, a rare complication of influenza and other viral infections.

“The pattern of involvement, and the way that it rapidly progressed over days, is consistent with viral inflammation of the brain,” Dr. Elissa Fory, a neurologist with Henry Ford Health System, said through an email. “This may indicate the virus can invade the brain directly in rare circumstances.” The patient is in critical condition.

These domestic reports follow similar observations by doctors in Italy and other parts of the world, of COVID-19 patients having strokes, seizures, encephalitislike symptoms and blood clots, as well as tingling or numbness in the extremities, called acroparesthesia. In some cases, patients were delirious even before developing fever or respiratory illness, according to Dr. Alessandro Padovani, whose hospital at University of Brescia in Italy opened a separate NeuroCovid unit to care for patients with neurological conditions.

The patients who come in with encephalopathy are confused and lethargic and may appear dazed, exhibiting strange behavior or staring off into space. They may be having seizures that require immediate medical care, and experts are warning health care providers who treat such patients to recognize that they may have COVID-19 and to take precautions to protect themselves from infection.

Much is still unknown about the neurological symptoms, but efforts are underway to study the phenomena, said Dr. Sherry H-Y. Chou, a neurologist at the University of Pittsburgh School of Medicine, who is leading a team of investigators for the Neurocritical Care Society.

“We absolutely need to have an information finding mission, otherwise we’re flying blind,” Chou said. “There’s no ventilator for the brain. If the lungs are broken we can put the patient on a ventilator and hope for recovery. We don’t have that luxury with the brain.”

Experts have emphasized that most COVID-19 patients appear to be normal neurologically.

“Most people are showing up awake and alert, and neurologically appear to be normal,” said Dr. Robert Stevens, a neurologist at the Johns Hopkins School of Medicine in Baltimore who is tracking neurological observations.

Neurological specialists also say that it is too early to make definitive statements or identify the specific mechanisms by which the new coronavirus is affecting the neurological system.

In one recent paper, Chinese scientists noted that there was some evidence that other coronaviruses were not confined to the respiratory tract and invaded the central nervous system, and the authors speculated that this may potentially play a role in acute respiratory failure in COVID-19.

Stevens emphasized that all mechanistic explanations at this point are hypotheses because so little is known: “It could be as simple as low levels of oxygen in the bloodstream,” resulting from respiratory failure, along with an increase in carbon dioxide, which “can have significant impact on the function of the brain, and lead to states of confusion and lethargy,” he said.

“We are still in the early days of this, and we don’t really know for sure.”

Neurologists in Wuhan, China, where the outbreak started, were among the first to report the symptoms in a preliminary paper published online in February.

Since that report, specialists observed similar symptoms in Germany, France, Austria, Italy and Holland as well as the United States, including among patients under 60, Stevens said.

Some doctors have reported cases of patients who were brought in for treatment because of their altered mental state, and who ultimately tested positive for COVID-19, although they had none of the classic symptoms like fever or cough.

Four elderly patients who came into Danbury Hospital in Connecticut with encephalopathy ultimately tested positive for COVID-19, although they had no other symptoms, said Dr. Paul Nee, an infectious disease specialist at the hospital. Two of the four went on to develop low grade fevers and needed oxygen briefly, but two did not, he said.

While it is not unusual for elderly people to experience confusion when they develop other infections, “the striking thing is we have not seen any real respiratory illness in these patients,” Nee said. They have continued to test positive and cannot be discharged, even though they are not really ill, he said.

But earlier reports had indicated that severely ill individuals with more typical symptoms were more likely to exhibit the rare neurological conditions, which ranged from dizziness and headaches to impaired consciousness, stroke and musculoskeletal injury. The Chinese study in February said that about 15% of those patients with severe illness experienced a change in mental status, compared with 2.4% of those who did not have severe illness, according to that study.

Another study, published in the British Medical Journal in late March, found that of 113 patients from Wuhan who died of COVID-19, 22% had experienced disorders of consciousness, ranging from somnolence to deep coma, compared with only 1% of another group of patients who recovered from the illness.

For potential COVID-19 patients and the people caring for them, the Centers for Disease Control and Prevention includes “new confusion or inability to rouse” among the warning signs that should prompt a decision to seek immediate medical care.

Patients who have encephalopathy and seem confused or incoherent are prone to having seizures, and should receive treatment as soon as possible, said Dr. Jennifer Frontera, a neurologist at NYU Langone Health who is working with Chou. She added that seizures can manifest in more subtle ways than the dramatic presentations often depicted in movies and television shows.

“Seizures are not always big things where people fall down and are shaking on the ground,” Frontera said. “Some could be just veering off, not paying attention, making repetitive nonpurposeful movements, or just mental status changes where people are just not themselves.”

But even if seizures are not observed, people who are sick should be aware of other potential mental symptoms.

“You don’t feel your best when you have a fever, but you should be able to interact normally,” Frontera said. “You should be able to answer questions and converse in a normal fashion.”

She added: “I don’t want everyone calling 911 because they’re overly concerned. We just don’t have the capacity. But if someone is really out of it, they probably need medical attention.”

Medical reference: technologyreview