A New Solution for Long-COVID Brain Fog?

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Noninvasive brain stimulation (NIBS) that uses alternating microcurrents appears to rapidly and effectively improve cognitive and visual deficits related to "long COVID," a small case series shows.

SARS-CoV-2 infections impair blood flow to the eyes and brain, causing visual and cognitive deficits, and the stimulation restores normal blood flow, lead study investigator Bernhard A. Sabel, PhD, professor of medical psychology, University of Magdeburg, Germany, told Medscape Medical News.

"Oxygen and glucose is delivered again to nerve cells, so they can do their job of firing electric signals to the brain, and the patient can think better, their cognition is better, and their vision is improved."

The benefits for those affected with long-term cognitive problems occur within days, said Sabel. "This Is the fastest solution that I'm aware of ― much faster than with the standard neurological rehabilitation."

The study was published in a recent issue of Restorative Neurology and Neuroscience.

No Effective Treatments

Many COVID-19 patients report ongoing fatigue, shortness of breath, and cognitive dysfunction, a syndrome often referred to as "long COVID." Symptoms may be of new onset following recovery from acute COVID-19 or persist from the initial illness and may fluctuate or relapse over time.

An estimated 20% to 30% of COVID-19 patients develop significant cognitive problems long after acute symptoms of the infection resolve. However, the risk is higher in hospitalized COVID-19 patients, with about 60% experiencing cognitive decline within 4 months.

COVID-19 causes swelling of the blood vessels, reducing their diameter, which leads to abnormal neuronal response, said Sabel.

"When a neuron fires a signal, it needs oxygen and glucose, but if the blood vessel doesn't open up, it's like you're stepping on the accelerator but the car isn't driving because it's not getting gas."

If patients are stressed, that could reduce the blood vessel diameter even further, added Sabel.

There are no effective treatments to improve cognitive and visual impairment in patients with long COVID. Physiotherapy and rehabilitation are the only current approaches, but they take weeks or months, and improvement is less than satisfactory.

The study included two relatively healthy and active women, one age 40 and the other 72, experiencing long-COVID-19 symptoms. One of them had a history of migraines, but neither had any other significant comorbidities.

One patient developed symptoms after SARS-Cov-2 infection, although she didn't require hospitalization, while the other noticed symptoms after vaccination. For both patients, there was the typical delay before long-COVID symptoms presented.

"Dramatic" Symptoms

These symptoms included headache, fever, fatigue, visual changes, loss of balance, and cognitive impairment, which involved compromised memory, concentration, attention deficits, and difficulty finding words, making it difficult to participate in conversation.

The symptoms were "quite dramatic" and affected the patients' everyday function and quality of life, said Sabel. He added that both women found it difficult to carry out daily household and other tasks and had to stop working.

NIBS has been used to enhance or suppress specific neurologic function, such as locomotor behavior. It has also been shown to enhance visual and cognitive dysfunction.

Sabel and his colleagues have had previous success in improving vision in glaucoma patients using NIBS treatment and hypothesized that the treatment could induce visual and cognitive recovery in COVID patients.

The intervention involved transcranial alternating current stimulation (tACS) using a neuromodulation device. During the procedure, the patients were seated comfortably in a chair, and an electrode was placed on the side of each eye near the forehead.

This area, said Sabel, is close to the frontal cortex, which MRI studies show is most affected by reduced blood flow.

The electric current rapidly alternates between electrodes, "so it kind of flips back and forth," said Sabel. "It basically passes from one eye to the other but also goes through the skull into the frontal cortex."

Potential Mechanism

Each stimulation session lasted 30 to 45 minutes. One patient received 13 sessions and the other, 10. Sabel noted that both patients underwent stress reduction therapy prior to the stimulation sessions.

Both patients tolerated the treatment well and reported feeling only a tingling sensation. There were no adverse or serious adverse events.

Before and after therapy, researchers assessed cognition subjectively by interview and quantified visual fields using perimetry. They also assessed one patient with a cognitive test battery and with a retinal dynamic vascular analyzer, a surrogate marker of vascular dysregulation in the brain.

In both patients, the visual problems caused by lack of blood supply to the eyes markedly improved, said Sabel.

They also experienced improved cognitive performance. "What was completely astonishing was that within 3 to 4 days, cognitive impairment improved significantly," he said.

One patient requested and underwent objective cognitive testing. Her results showed a greater than 30% improvement in reaction time in a test for alertness and greater than 60% improvement in reaction time for testing of executive function. She also experienced improved memory.

The second patient reported subjective cognitive improvements, including being more alert, no longer struggling for words, and being better able to plan and remember things.

Recovery from vascular dysregulation (central and peripheral retinal vessel dilation and constriction response to flicker light) was done on one patient. Observations from this test provided evidence that blood flow was restored to a normal level. This, said Sabel, indicates a mechanism for the positive visual and cognitive effects.

Restor Neurol Neurosci. 2021:39:393-408. Full text

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