Grand Rounds: Mass General Neurologists Respond to COVID-19

On April 23, 2020, neurologists at Massachusetts General Hospital discussed the neurologic sequelae of COVID-19 and the Department of Neurology's response to the pandemic in a virtual Grand Rounds presentation. Below are highlight key takeaways from the talks.

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Data-driven Guidance

Shibani Mukerji, MD, PhD, associate director of the Neuroimmunology and Neuro-Infectious Diseases Division at Mass General, described a new prospective database, created in less than three weeks, that will track neurologic complications of COVID-19. Some complications of infectious illnesses can last for years—or a lifetime. These complications may be subtle, such as cognitive changes, headache and depressive symptoms.

With the help of M. Brandon Westover, MD, PhD, a neurologist who directs the Clinical Data Animation Center at Mass General, Dr. Mukerji and colleagues from multiple departments will use machine learning and artificial intelligence (AI) to understand clusters of COVID-19 symptoms. Major goals are to understand how to treat COVID-19–associated neurologic disease, predict outcomes and care for survivors, including preparing for a potential new or worsening disease that may occur during any resurgence of SARS-CoV-2.

Neuroimmunology of COVID-19

Bart K. Chwalisz, MD, founding director of the Inflammatory Neuro-Ophthalmology and Skull Base Disorders Clinic at Mass General, addressed the cytokine storm as a potential mechanism of neurotoxicity in COVID-19. In most cases, the disease is controlled by the immune system, with the viral load and inflammation both decreasing. In severe cases, though, the virus is not cleared despite an exuberance of cytokines, including interleukin-6.

Several other conditions are characterized by a cytokine storm, notably cytokine release syndrome (CRS) that can develop after chimeric antigen receptor T-cell (CAR T) therapy for hematologic malignancies. A more concerning side effect is CAR T-cell–related encephalopathy syndrome (CRES), which can cause expressive aphasia, seizures, stroke, coma and death.

Tocilizumab, an interleukin-6 inhibitor, effectively treats CRS but not CRES. Now that tocilizumab is being investigated for COVID-19, there's concern the drug might not work in patients with neurologic complications and could even exacerbate them.

Neuromuscular Complications

Paloma Gonzalez-Perez, MD, PhD, director of the Muscle Disorder Clinic, reviewed neuromuscular complications of COVID-19. Viral rhabdomyolysis, a late complication, manifests as generalized or proximal muscle weakness in adults. It's unclear whether it is a direct effect of the viral infection or results from the cytokine storm. Rhabdomyolysis is life-threatening, as it commonly involves acute renal failure and can also be complicated by hyperkalemia, hypocalcemia, hepatic inflammation, arrythmia, cardiac arrest, disseminated intravascular coagulation and compartment syndrome.

The keys to management are to preserve renal function and discontinue drugs/toxins (e.g., statins). If a muscle biopsy is desired to determine etiology, it is best delayed until a few weeks after the episode.

Critical illness myopathy (CIM) is common and affects women more often than men (4:1), with the lower extremities more often affected than upper limbs in a symmetric limb–girdle pattern. The respiratory muscles are also involved. The most common form is a combination of CIM and critical illness polyneuropathy (CIP).

Prevention and treatment of CIM depend on early mobilization; minimization of sedation, paralytics and steroids; and blood glucose control. Diaphragmatic weakness and atrophy correlate with the duration of mechanical ventilation, so extubation should occur as soon as possible. About 28% of patients with CIM do not recover independent walking or spontaneous ventilation, especially when CIP is also present.

Other neuromuscular complications of COVID-19 include:

• Guillain–Barré syndrome (onset 5–10 days after COVID-19 symptoms) and Miller–Fisher syndrome (onset 3–5 days after)
• Metabolic myopathies (e.g., hypokalemia-induced myopathy in patients with severe diarrhea)
• Drug-related myopathies (e.g., acute steroid-induced myopathy; azithromycin + statin increases the risk of rhabdomyolysis; chronic use of hydroxychloroquine can cause myopathy)

Risk Prediction

Building on Dr. Mukerji's presentation, Dr. Westover explained Mass General's efforts to develop artificial intelligence to predict which COVID-19 patients are:

• At risk of admission
• At risk of ICU admission/intubation or death
• Safe to discharge home
• At risk of persistent neurologic complications

The goal is to deliver these results daily with different event horizons (risks within the next few hours, the next three days, etc.) The computer algorithms will be retrained regularly.

Dozens of faculty across multiple departments are consulting on the project and providing demographics, vital signs, lab values, ICD codes, chest radiographs, ECG reports and narrative notes. Already a deep neural network does as well as a radiologist at evaluating the severity of pneumonia on radiographs, and it can also predict fairly well who will be intubated.

The group is in the process of creating a secure website where frontline clinicians can see the predictions. The data will also be made available to researchers.

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