New guidelines for assessing and managing neurologic symptoms of long-COVID

COVID-19 can cause multi-organ damage during the acute stage of infection. It also has the potential to cause long-term complications, as part of post-acute sequelae of SARS-CoV-2 infection (PASC; also called long-COVID syndrome). The most prevalent neurologic symptoms remaining three to four weeks after the initial infection are “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%) and myalgias (55%).1 An increased risk of various neurologic sequelae has also been found 12 months following acute COVID-19, including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (e.g., migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy. The risks and burdens of these sequelae are elevated even in people who did not require hospitalization during acute COVID-19.1 To date, only limited guidance exists on the assessment and treatment of neurologic sequelae in patients with long-COVID. To address this issue, a U.S. multi-disciplinary group (PASC Collaborative) has developed guidance in this area. The PASC Collaborative consists of experts in physical medicine and rehabilitation, neurology, internal medicine, family practice, pediatric specialties, cardiology, physical therapy, occupational therapy, social work and other disciplines.1 The new guidance statement focuses on the neurologic sequelae of PASC, including headaches, neuropathies and neuropathic pain, sleep disturbances, muscular pain/weakness and tremors, and cranial nerve conditions.1 The guidance document is consensus-based, built on expert opinion from healthcare professionals who regularly care for PASC patients. Scientific evidence regarding effective assessment and treatment of PASC is currently limited, which prevented the creation of evidence-based clinical guidelines. The PASC Collaborative notes that fatigue, autonomic dysfunction and cognitive function changes are reviewed in separate American Academy of Physical Medicine and Rehabilitation (AAPM&R) guidance statements.2-4 An AAPM&R consensus document focusing on mental health sequelae is also in development.1 The current guidance statement highlights the initial evaluation and initial treatment options for neurologic sequelae in patients with PASC. The document also includes a section on “red flag” presentations that require prompt escalation of care. Examples of red flags include sudden or progressive weakness or sensory changes, bladder/bowel incontinence or retention, transient loss of consciousness, or acute neuropsychiatric symptoms/psychosis. The bulk of the guidance statement reviews signs, symptoms, patient history and evaluation, additional studies to consider for differential diagnosis, initial treatment approach, referral options and resources for common neurologic sequelae. A focus on initial treatment approaches is provided below.1 Initial treatment approaches 1. Cranial nerve abnormalities Loss of smell or taste: Recommend avoidance of tobacco, alcohol, spicy foods, and foods with extreme temperature Consider educating on and recommending smell therapy Recommend hydration (at least 1.9 L of fluids/day) Consider recommending mouth moisturization products. Changes in vision: Recommend avoidance of medications that can worsen symptoms (e.g., anticholinergics or antihistamines) Consider antiviral therapy and an infectious disease evaluation, if acute herpetic infection is identified Consider vision rehabilitation by an occupational therapist Consider steroids or immunotherapy if an autoimmune etiology is suspected Consider steroids or referral to an emergency department for optic neuritis. Dizziness/vertigo/tinnitus/loss of hearing: Recommend adequate hydration (at least 1.9 L of fluids/day) Recommend use of compression stockings (if postural) Consider vestibular rehabilitation with a neurological or vestibular trained physical therapist Consider a trial of white noise for tinnitus or hearing loss Consider referral for hearing aids for tinnitus or hearing loss. Changes in facial expressions (e.g., facial droop, inability to smile), chewing or swallowing: Recommend oral moisturizing or lubricating agents that contain carboxymethylcellulose or saliva substitutes with xylitol. 2. Headaches Recommend lifestyle modifications—SEEDS (sleep, exercise, eat, diary, stress). Recommend counselling on the negative effects of medication overuse (> 3x/week, including acetaminophen and ibuprofen) and how it can cause rebound headaches. Recommend counselling for alcohol and drug use effects Patients may benefit from a multidisciplinary approach to treatment that includes both pharmacologic and nonpharmacologic approaches Consider OTC supplements for prophylaxis (e.g., magnesium, melatonin, coenzyme Q10, riboflavin, feverfew) Nonpharmacologic therapies (acupuncture, relaxation therapies with deep breathing exercises, biofeedback) may be beneficial for patients with sensitivity, resistance or inability to tolerate medication. Relaxation strategies include gentle stretching, ergonomics (positioning at work, headset), trigger point injections, nerve blocks, neuromodulation devices The statement also outlines treatment and referral approaches based on headache phenotype (migraine, moderate–severe headache and tension-type headache). 3. Sleep disturbances First-line approach for insomnia should include cognitive behavioural therapy (CBT) for insomnia, whenever it is available Manage underlying conditions that may impact sleep (e.g., asthma, heart failure, hyperthyroidism, acid reflux, anxiety) Educate on behavioural strategies: create a sleep routine, avoid stimulants, stop electronic screens for at least an hour prior to bedtime, journal thoughts before bedtime, relaxation techniques Consider short-term use of OTC medications and aids (e.g., melatonin, chamomile tea) Consider drug therapy when OTC medications/aids and behavioural strategies are unsuccessful (e.g., trazodone, zolpidem, eszopiclone, doxepin, temazepam). Use these medications with caution in the older population and advise patients regarding potential for habituation over time Consider medications based on other symptoms. However, the following medications often have side effects and should be used cautiously: gabapentin for headaches or anxiety; tizanidine or baclofen for muscle aches or spasms; mirtazapine for anorexia; amitriptyline or gabapentin for pain; and quetiapine for psychiatric disorders. 4. Neuropathies and neuropathic pain Consider use of pain management strategies for neuropathic pain (gabapentin, pregabalin, duloxetine, nortriptyline, topical capsaicin, dry needling, heat, ultrasound) Consider use of “Evidence-based pain medicine for primary care physicians” as an evidence-based resource for pain management.5 5. Muscular pain/weakness/tremors Refer to neurology for significant myopathy, progressive weakness or worsening gait instability Refer to rheumatology for inflammatory myopathy or consideration for rheumatologic conditions Refer to orthotist for joint protection or stabilization, improved functional safety; night-time splinting and positioning (as needed) Refer to pain management for treatment strategies for myalgias Refer to physical therapy for strengthening, stretching (muscular and neural tension), balance retraining, gait training, aquatic therapy, adjunct therapies such as yoga or sports Refer to occupational therapy for strengthening, stretching (muscular and neural tension), pacing strategies, functional skills training including safety and compensatory strategies for pain, tremor and activities of daily living, myofascial pain techniques Refer to speech language pathology/therapy to perform focal exercises for facial or cervical muscles, dysphagia therapy, voice. Summary Healthcare providers caring for patients with neurological complications of long-COVID syndrome should conduct an appropriate diagnostic workup, pursue initial treatment of new and/or worsening central and peripheral nervous system disorders and provide referrals to multidisciplinary clinical teams, when needed. References 1. Melamed E, Rydberg L, Ambrose AF, et al. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R 2023; published online March 29, 2023 ahead of print. (accessed May 25, 2023). 2. Herrera JE, Niehaus WN, Whiteson J, et al. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients. PM R 2021;13(9):1027-43. (accessed May 25, 2023). 3. Fine JS, Ambrose AF, Didehbani N, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R 2022;14(1):96-111. (accessed May 25, 2023). 4. Blitshteyn S, Abramoff B, Azola A, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of autonomic dysfunction in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R 2022;14(10):1270-91. (accessed May 25, 2023). 5. Owen GT, Bruel BM, Schade CM, et al. Evidence-based pain medicine for primary care physicians. Proc (Bayl Univ Med Cent) 2018;31(1):37-47. (accessed May 25, 2023).

New guidelines for assessing and managing neurologic symptoms of long-COVID

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