Table 2.
Neuro-PASC symptoms
| Neuro PASC symptom | Presentation | Frequency | Neurodiagnostic testing | Pathogenesis | Therapies |
|---|---|---|---|---|---|
| Cognitive dysfunction | “Brain fog”, decreased attention, concentration, multitasking abilities, forgetfulness | 8% of all patients; 50% of critically ill patients |
NIH Toolbox, PROMIS inventory, MoCA and neuropsychological testing may be abnormal MRI, MRA, EEG, CSF may show elevated protein or non-CNS specific oligoclonal bands Screen for B12, folate deficiency, HIV infection, thyroid dysfunction, sleep apnea |
Fatigue, sleep disruption, aberrant immune response, and potential persistent infection and auto-immune reaction | Cognitive rehabilitation, adjusted work schedule, list-making, vitamin supplementation |
| Fatigue | Early fatiguing with normal activities, exercise intolerance, sleepiness | 13% of all Covid-19 survivors; 39% of hospitalized patients | Sleep study in those with daytime sleepiness, snoring | Dysfunction in sleep and wakefulness centers in the brainstem | Amantadine 100 mg upon awakening and 100 mg at noon; modafinil 100–200 mg daily |
| Anosmia/ageusia | Impaired or absent smell and/or taste | 77% of patients during initial infection; 31% prolonged | Patient self-reporting; hypometabolism of the olfactory/rectus gyrus on 18F-FDG brain PET | Injury to the nasal epithelium/supporting cells of olfactory bulb; damage to areas of the brain involved in olfaction and taste (parahippocampal gyrus, orbitofrontal cortex and insula) | Smell therapy (repeatedly smelling various strongly-scented odors) twice daily for 3–6 months. Intranasal fluticasone and/or oral triamcinolone paste for 5 days may have mild benefit |
| Dysautonomia | Heart rate and/or blood pressure variability, orthostasis, bladder and/or bowel dysfunction and fatigue | Overall rates unknown; 30% of patients seen in a neuro-COVID clinic | POTS is diagnosed by an increase in heart rate of 30 bpm, or over 120 bpm, within 10 min of standing, in the absence of orthostatic hypotension. Orthostatic hypotension is diagnosed if the systolic blood pressure drops 20 mmHg or diastolic pressure drops 10 mmHg after 3 min of standing | Damage to autonomic ganglia, vagus nerve, autoantibodies have been postulated | Maintain proper hydration, compression stockings, abdominal binders, and participate in graded exercise programs on the patient’s back. Propranolol or ivabradine for tachycardia. Midodrine or fludrocortisone may be helpful for orthostasis |
| Headache | Bilateral throbbing, persistent headaches | 47% of COVID-19 patients at onset and 10% at 30 days | MRI brain with and without contrast and vessel imaging is indicated in patients with confusion, headaches and focal neurologic deficit | Cytokine release irritating meninges; binding of ACE2 increases angiotension II and CGRP leading to trigemino-vascular activation | Indomethacin 50 mg twice a day for 5 days. Nortriptyline 25 mg nightly or propranolol 20 mg TID may be helpful |
| Neuropathy | Small fiber neuropathy (persistent tingling, burning); numbness in peripheral distribution | Overall incidence unknown; up to 60–90% of patients seen in neuro-Covid clinic | 17% had abnormal electrodiagnostic tests, 63% had abnormal skin biopsies confirming small fiber neuropathy and 50% had abnormal autonomic testing | Small fiber neuropathy may be due to autoimmune neuritis; critical illness neuropathy and compression neuropathy in hospitalized patients | Gabapentin or other neuropathic agents. IVIG has led to improvement in a small number of patients |
| Audio-vestibular symptoms | Vertigo, hearing loss, and tinnitus | Vertigo (7.2%), hearing loss (7.6%), tinnitus (4.8%) | MRI brain with internal auditory canal and VNG | Post-viral vestibular neuronitis, BPPV, PPPD. Direct viral invasion, immune dysregulation or microthrombi have been postulated | Anti-vertiginous drugs (meclizine, benzodiazepines). SSRI or SNRI for PPPD. Neuro-otology or ENT referral |
NIH National Institutes of Health, PROMIS Patient Reported Outcome Measurement Information System, MoCA Montreal Cognitive Assessment, MRI magnetic resonance imaging, MRA magnetic resonance angiography, EEG electroencephalogram, CSF cerebrospinal fluid, POTS postural orthostatic tachycardia syndrome, VNG videonystagmography, BPPV benign paroxysmal positional vertigo, PPPD persistent postural perceptual dizziness, SSRI selective serotonin reuptake inhibitor, SNRI serotonin and norepinephrine reuptake inhibitor