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. 2022 Mar 1;9(3):e1146.
doi: 10.1212/NXI.0000000000001146. Print 2022 May.

Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

Anne Louise Oaklander  1 , Alexander J Mills  2 , Mary Kelley  2 , Lisa S Toran  2 , Bryan Smith  2 , Marinos C Dalakas  2 , Avindra Nath  2
Affiliations

Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

Anne Louise Oaklander et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins).

Discussion: Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.

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Figures

Figure 1
Figure 1. Case 15: Prolonged COVID-Incident Multifocal Motor Neuropathy
CMAP = compound motor action potential; D = day; EDX = electrodiagnostic testing; IVIg = IV immunoglobulin therapy; MMN = multifocal motor neuropathy; SNAP = sensory nerve action potential. Three weeks after 12/04/1920 onset of mild COVID-19, this previously healthy 65-year-old developed progressive R > L hand weakness and atrophy. Three months later, he could not hold eating utensils or a pen and noted hand “limpness” tingling and pain, and finger cramps without lower limb symptoms. Neurosurgical referral prompted cervical MRI showing unrelated degenerative changes. A local neurologist's EDX suggesting MMN or lower motor neuron disease prompted our neuromuscular evaluation on post-COVID D67. This revealed weakness in the distal ulnar and median nerve distributions, 4/5 finger abduction strength, and R > L interosseus and thenar eminence atrophy. He could not make a fist or hold utensils; sensory self-examination was normal. EDX on D122 documented demyelinating neuropathy with conduction blocks in both ulnar nerves at the forearms and across the elbows and prolonged latencies and reduced conduction in both median nerves. F waves were prolonged in the upper and lower limbs, and the right peroneal CMAP was low amplitude. SNAP velocities were normal, with slightly diminished amplitude in the median, ulnar, and sural nerves. Serum immunoglobulins and immunofixation were normal, and GM1 antibodies were absent. He met the diagnostic criteria for MMN and began standard treatment, IVIg 2 g/kg/4 weeks, on D146. A few weeks later, he noticed improved hand dexterity with ability to fully open hands and use utensils and decreased hand cramps, with 90% improvement after the 3rd cycle. Then, expiration of IVIg orders caused regression. After 2 missed cycles, D292 evaluation documented R > L increasing difficulty opening his hands and return of hand and forearm tingling. He self-reported hair loss on legs, muscle difficulties, skin color changes, tingling, itching, and needing to move legs for comfort (eFigure 1, links.lww.com/NXI/A697). Same-dose IVIg was restarted, and after 2 cycles with improvement, clinic return on D341 documented 80% improved weakness, hand opening, finger dexterity, and hand cramps. He had bilateral 4/5 finger abduction strength, and this image documented significant remaining R > L interossei muscle atrophy. IVIg was continued, and he was referred for interosseus exercises.
See this image and copyright information in PMC

References

    1. World Health Organization A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus. 2021. Accessed October 1, 2021. WHO/2019-nCoV/Post_COVID-19_condition/Clinical_case_definition/2021.1.
    1. Oaklander AL, Nolano M. Scientific advances in and clinical approaches to small-fiber polyneuropathy: a review. JAMA Neurol. 2019;76(10):1240-1251. - PMC - PubMed
    1. Davis HE, Assaf GS, McCorkell L, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019. - PMC - PubMed
    1. Treister R, Lodahl M, Lang M, Tworoger SS, Sawilowsky S, Oaklander AL. Initial development and validation of a patient-reported symptom survey for small-fiber polyneuropathy. J Pain. 2017;18(5):556-563. - PMC - PubMed
    1. Zirpoli G, Downs S, Farhad K, Oaklander AL. Initial validation of the Mass General neuropathy exam tool (MAGNET) for diagnosing small-fiber polyneuropathy. Ann Neurol. 2018. Proccedings of the 2018 meeting of the American Neurological Association.

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