From HIV to COVID-19, experts in neuroinfectious diseases… : Neurology Today

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While neuro-infectious disease experts have made progress over the past 20 years in treating diseases that were once deadly, such as HIV, the COVID-19 pandemic has brought a wave of potential neurological problems, especially in so-called long-term patients. Additionally, as research has shown an association of infectious diseases with other neurological conditions, neuroinfectious disease specialists see a greater role for the subspecialty in the coming years.

With increasing reports of cognitive problems and other potentially neurological problems in patients with COVID-19, particularly among so-called long-distance cases, the spectrum of brain and central nervous system complications due to the infection bears uncanny similarities to the experiences of HIV patients some 20 years ago, neuro-infectious disease experts have said neurology today.

Like COVID-19, an array of cognitive problems emerged in people living with HIV early in AIDS, according to David B. Clifford, MD, FAAN, professor of clinical neuropharmacology at Washington University School of Medicine in St Louis. But 20 years later, Dr Clifford says progress against HIV and its neurological sequelae has been his biggest and most rewarding breakthrough.

“Over the past 20 years, there have been tremendous advances in the development of effective therapies for HIV and its neurological complications. The researchers really got their act together on that, and today most patients have near-normal life expectancies,” he said. neurology today.

“Twenty years ago, the cART T cell therapy (cART) that was available was more complicated to take and more toxic. Although the dramatic improvement in the ability to maintain sustained viral load control was exciting and positive, the early years of cART using stavudine and didanosine included very noticeable problems with distal neuropathy, and sometimes dramatic cosmetic complications. and unpleasant that would often identify an HIV patient from across the room,” he says.

“Furthermore, the medications routinely required multiple doses per day, often with quite a few pills. However, for those able to comply with cART, neurocognitive status often improved somewhat early and then was relatively stable. It felt like a huge accomplishment. “

In terms of therapy, he said HIV-directed therapy with cART remains the key to achieving stability. “We are now focusing much more on comorbidities that likely contribute to ongoing disability, making recommendations for optimal care for hypertension, diabetes, cholesterol, and weight. Additionally, healthier lifestyles emphasizing the importance of quitting smoking, adequate high-quality sleep, and exercise have rightly become important messages for our patients, noted Dr. Clifford. .

“The neurocognitive impairment we see now is generally quite mild and not very progressive in most patients. Optimizing cART remains central to therapy as it has been, but now that HIV is not the more the limiting factor, we draw attention to broader measures of health, and I think that still makes a difference when the importance of healthy living is embraced.

Progress has also been made in treating the immune system complications of progressive multifocal leukoencephalopathy (PML), Dr. Clifford said. “Twenty years ago, PML was almost always fatal. Today, exciting advances have been made in recognizing and understanding the disorder so that we can define and monitor risk.

Lyme disease

Karen Roos, MD, FAAN, professor emeritus of neurology at Indiana University School of Medicine, said fewer infectious diseases over the past 20 years have seen greater clarity in diagnosis and treatment than Lyme disease. The initial confusion arose from the fact that in the first weeks of Lyme disease, serology can be falsely negative. This has since been clarified and resolved and specific guidelines for serologic testing and interpretation of serologic testing are well established. It’s also clear that patients don’t need years of intravenous antimicrobial therapy, she said.

The spirochete, Borrelia burgdorferi, is eradicated after four weeks or less of antimicrobial treatment. The diagnosis of ‘chronic Lyme disease’ in patients with fatigue, cognitive impairment, depression and pain, and no history of characteristic symptoms or laboratory evidence of Lyme disease, has been discouraged, it said. she noted, adding that a similar situation may be true with the current pandemic.

“Early and aggressive” treatment

The past 20 years have also seen increased acceptance of dexamethasone as an adjunct therapy by non-neurologists, Dr. Roos said. “It was a long uphill battle because only neurologists fully understood the critical importance of preventing neurological complications of bacterial meningitis and not just eradicating the pathogen.”

The opponents’ argument was that steroids would suppress the immune response to an infectious disease and make that disease worse, until it was clear that the immune response itself was detrimental to the patient, she said.

Today, neurologists treat herpes simplex virus encephalitis as soon as the diagnosis is suspected and before it is confirmed. “This aggressive approach reduced neurological morbidity and mortality,” Dr. Roos continued.

“Over the past 20 years, there have been tremendous advances in the development of effective therapies for HIV and its neurological complications. The researchers really cooperated on this, and today most patients have an almost normal life expectancy. —DR. DAVID B. CLIFFORD

“Despite the considerable advances made in antiretroviral treatment, leading to a decrease in both the incidence of opportunistic infections in HIV-infected persons and the neurotoxicity associated with older nucleoside reverse transcriptase inhibitors, there is no had no advances in the antiviral treatment of arthropod-borne infections, such as West Nile virus and eastern equine encephalitis virus, or JC virus despite the increasing risk of infection with the latter due to the immunomodulatory therapies.

Dr. Roos said the topic of progress – as well as failures in the diagnosis and management of neurological infectious diseases – is particularly timely in relation to the current pandemic. She said the biggest advance in the diagnosis of neurological infectious diseases in the past 20 years, for example, is the widespread availability of polymerase chain reaction (PCR) to detect viral and bacterial pathogens, a- she continued.

“PCR tests, antigens and antibodies have become household terms during the pandemic,” Dr Roos said. “There is promise that home testing for SARS-CoV-2 will soon be more readily available. Unfortunately, what neurological infectious diseases, and especially viral infectious diseases, and the pandemic have in common is the lack of therapeutics,” she said.

“Why it took so long to develop an antiviral therapy for SARS-CoV-2 is inexcusable and frustrating,” Dr. Roos said. “Less than 1% of the $1.9 trillion in the COVID relief fund has been spent on developing therapies.”

Dr Roos added: “It is disappointing that patients without serological evidence of SARS-CoV-2, but suffering from fatigue, pain and cognitive impairment, are now being diagnosed with ‘long-haul COVID’. »

The current state of things

Elyse Singer, MD, FAAN, a professor of neurology at the University of California, Los Angeles and a member of the school’s Brain Research Institute, said neurology today that she is also troubled by the lack of therapies for COVID-19.

“We are seeing a potential deluge of cognitive symptoms in long-haul COVID patients. Some of them are quite weakened and there are some interesting autoimmune issues, but we don’t have a good idea what might be causing these symptoms.

Figure 2

“Neurologists treat herpes simplex virus encephalitis as soon as the diagnosis is suspected and before it is confirmed. This aggressive approach reduced neurological morbidity and mortality. —DR. KAREN ROOS

Although patients have so far reported mostly milder cognitive problems, these are younger people and the long-term impact of the disability on their lives could be significant unless the cause is clear. be better understood, she said. neurology today.

Waiting for more data

Dr. Clifford agreed that the biggest emerging concern is the still unresolved issue of COVID-19 and the brain. “The evidence is slowly emerging, but the evidence seems to be that the virus doesn’t invade the brain,” he said. “Early fears based on the reported loss of sense of smell have not arisen since the [initial] reports. We know the infection can cause vascular damage, but whether the brain is at risk remains unclear. This is a major area for data collection and investigation,” he said.

“The potential for long-term post-acute neurological sequelae is of great concern,” Dr. Clifford agreed. “Some patients seem to have immune-mediated changes, but more research is needed, and we’re all waiting for more information.”

More research is also needed, experts say, into potential associations between infectious diseases and other neurological disorders. Dr. Singer cited a recent study from Harvard University, published in the journal Sciencewhich suggests that multiple sclerosis could be caused by the Epstein Barr virus (EBV).

“The hypothesis has been studied for several years, but this is the first study providing convincing evidence of causation. This could be very important because although there is no cure for EBV, we can potentially treat the symptoms,” she said.

Coupled with recent research suggesting that infection may play a role in both multiple sclerosis and Parkinson’s disease, specialists in neuro-infectious diseases are seeing their role become increasingly important, and the under- specialty looks set to play a bigger role in the years to come.

“All these [cases] are interesting,” said Dr. Singer, which speaks to the value of neuroinfectious disease experts. “For a long time, there were very few specialists in neuro-infectious diseases,” she said. “We’re not really represented in professional societies and there’s really not a high demand at many universities. I think these recent developments show the value of what they are doing because many neurological diseases can turn out to be infectious.

Dr. Roos agreed, adding: “The greatest achievement in the field of neurological infectious diseases in 20 years has been the growing number of neurologists specializing in improving patient care, there is no greater success .

Disclosures

Drs. Roos, Singer and Clifford had no disclosures related to the article.

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