Persistent post-COVID-19 neuromuscular symptoms.

Neuromuscular symptoms may develop or persist after resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides residual sensorimotor symptoms associated with acute neuromuscular complications of coronavirus disease-2019 (COVID-19), such as Guillain-Barré syndrome, critical illness neuromyopathy, and rhabdomyolysis, patients may report persistent autonomic symptoms, sensory symptoms, and muscle symptoms in the absence of these acute complications, including palpitations, orthostatic dizziness and intolerance, paresthesia, myalgia, and fatigue. These symptoms may be associated with long COVID, also known as post-COVID-19 conditions or postacute sequelae of SARS-CoV-2 infection, which may significantly impact quality of life. Managing these symptoms represents a challenge for health-care providers. Recent advances have identified small-fiber neuropathy as a potential etiology that may underlie autonomic dysfunction and paresthesia in some long COVID patients. The pathogenic mechanisms underlying myalgia and fatigue remain elusive and need to be investigated. Herein we review the current state of knowledge regarding the evaluation and management of patients with persistent post-COVID-19 neuromuscular symptoms.

Small fiber neuropathy associated with SARS-CoV-2 infection.

INTRODUCTION/AIMS: The development and persistence of neurological symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is referred to as "long-haul" syndrome. We aimed to determine whether small fiber neuropathy (SFN) was associated with SARS-CoV-2 infection. METHODS: We retrospectively studied the clinical features and outcomes of patients who were referred to us between May 2020 and May 2021 for painful paresthesia and numbness that developed during or after SARS-CoV-2 infection and who had nerve conduction studies showing no evidence of a large fiber polyneuropathy. RESULTS: We identified 13 patients, Eight women and five men with age ranging from 38-67 y. Follow-up duration ranged from 8 to 12 mo. All patients developed new-onset paresthesias within 2 mo following SARS-CoV-2 infection, with an acute onset in seven and co-existing autonomic symptoms in seven. Three patients had pre-existing but controlled neuropathy risk factors. Skin biopsy confirmed SFN in six, all of whom showed both neuropathy symptoms and signs, and two also showed autonomic dysfunction by autonomic function testing (AFT). Of the remaining seven patients who had normal skin biopsies, six showed no clinical neuropathy signs and one exhibited signs and had abnormal AFT. Two patients with markedly reduced intraepidermal nerve fiber densities and one with normal skin biopsy had severe and moderate coronavirus disease 2019 (COVID-19); the remainder experienced mild COVID-19 symptoms. Nine patients received symptomatic neuropathy treatment with paresthesias controlled in seven (77.8%). DISCUSSION: Our findings suggest that symptoms of SFN may develop during or shortly after COVID-19. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.

MRI negative myelopathy post mild SARS-CoV-2 infection: vasculopathy or inflammatory myelitis?

Since the onset of the COVID-19 pandemic, there have been rare reports of spinal cord pathology diagnosed as inflammatory myelopathy and suspected spinal cord ischemia after SARS-CoV-2 infection. Herein, we report five cases of clinical myelopathy and myeloradiculopathy in the setting of post-COVID-19 disease, which were all radiographically negative. Unlike prior reports which typically characterized hospitalized patients with severe COVID-19 disease and critical illness, these patients typically had asymptomatic or mild-moderate COVID-19 disease and lacked radiologic evidence of structural spinal cord abnormality. This case series highlights that COVID-19 associated myelopathy is not rare, requires a high degree of clinical suspicion as imaging markers may be negative, and raises several possible pathophysiologic mechanisms.

Variant Median Nerve Anatomy: Ultrasound Evidence of a Pseudoconduction Block.

INTRODUCTION: A conduction block at a noncompressible site warrants further investigation. METHODS AND MATERIALS: A 36-year-old woman with a history of Hodgkin lymphoma and chemotherapy-induced polyneuropathy developed bilateral hand numbness and paresthesias. Workup revealed bilateral carpal tunnel syndrome and an apparent superimposed conduction block of the median nerve in the forearm. Given the history of cancer, there was concern for an infiltrative or an immune-mediated process. RESULTS: Neuromuscular ultrasound demonstrated that the median nerve descended the upper extremity along an atypical path, deep along the posteromedial aspect of the upper arm, and relatively medially in the forearm. Ultrasound-directed nerve stimulation revealed there was no conduction block. This anatomical variant has been rarely described and has not been reported previously to mimic conduction block or been documented via ultrasound. CONCLUSIONS: This case demonstrates that neuromuscular ultrasound may supplement the electrodiagnostic study and limit confounding technical factors because of rare anatomic variation.

A Case of Elsberg Syndrome in the Setting of Asymptomatic SARS-CoV-2 Infection.

ABSTRACT: Elsberg syndrome is a rare cause of lumbosacral radiculitis with concomitant thoracic and lumbosacral myelitis that can be seen after an acute or reactivated viral infection. After the initial coronavirus surge in New York City, a 68-year-old man developed progressive lower extremity weakness and a defined sensory level at the lower abdomen. He had highly elevated SARS-CoV-2 IgG antibodies despite an absence of preceding COVID-19 symptoms. Serial electrodiagnostic testing revealed absent lower extremity late responses, with otherwise normal distal sensorimotor conductions. Electromyography revealed active neurogenic changes and reduced motor unit recruitment in the L3-L4 myotomes. Treatment with methylprednisolone and intravenous immunoglobulin was followed by minimal clinical improvement but re-emergence of the lower extremity late responses on electrodiagnostic testing. We report here, to the best of our knowledge, the first case of suspected COVID-19-associated Elsberg syndrome, which expands the spectrum of neuromuscular manifestations associated with SARS-CoV-2 infection and sheds light on ways to approach diagnostic and treatment options for these patients.

Management of Neuropathic Pain in the Geriatric Population.

Neuropathic pain is common in the geriatric population. Diagnosis requires a thorough history and physical examination to differentiate it from other types of pain. Once diagnosed, further workup is required to elucidate the cause, including potential reversible causes of neuropathy. When treating neuropathic pain in the elderly, it is important to consider patients' comorbidities and other medications to avoid drug-drug interactions and iatrogenic effects given the physiologic changes of drug metabolism in the elderly. Nonsystemic therapies and topical medications should be considered. Systemic medications should be started at low dose and titrated up slowly with frequent monitoring for adverse effects.

A critical review of the capsaicin 8% patch for the treatment of neuropathic pain associated with diabetic peripheral neuropathy of the feet in adults.

INTRODUCTION: Diabetes is an increasingly prevalent disorder affecting nearly 1-in-5 adults, of which half will experience diabetic peripheral neuropathy (DPN) and a quarter will suffer from diabetic peripheral nerve pain (DPNP), severely impacting quality of life. The currently approved treatment options are typically centrally acting agents whose use is limited by systemic effects and drug interactions. The capsaicin 8% dermal patch was recently approved by the U.S. FDA for the treatment of DPNP. AREAS COVERED: The authors review the available literature regarding the use of high-concentration capsaicin 8% patch for the treatment of diabetic peripheral neuropathy and neuropathic pain and discuss implementing its use in clinical practice. EXPERT OPINION: The high-concentration capsaicin 8% patch is an effective and well-tolerated treatment option for treating DPNP. Capsaicin 8% patch may be used alone or in combination with other oral therapies and can provide rapid and sustained neuropathic pain relief following a single application and is safe and effective when used long term.

Severe rapidly progressive Guillain-Barré syndrome in the setting of acute COVID-19 disease.

There is concern that the global burden of coronavirus disease of 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might yield an increased occurrence of Guillain-Barré syndrome (GBS). It is currently unknown whether concomitant SARS-CoV-2 infection and GBS are pathophysiologically related, what biomarkers are useful for diagnosis, and what is the optimal treatment given the medical comorbidities, complications, and simultaneous infection. We report a patient who developed severe GBS following SARS-CoV-2 infection at the peak of the initial COVID-19 surge (April 2020) in New York City and discuss diagnostic and management issues and complications that may warrant special consideration in similar patients.

Safety of Therapeutic Plasma Exchange for the Treatment of Guillain-Barré Syndrome in Polycythemia Vera.

Polycythemia vera (PV) is a risk factor for systemic thromboses and ischemic stroke. This has been attributed to blood hyperviscosity, the result of increased blood cell production. Intravenous immunoglobulin, which is indicated for the treatment of numerous hematologic and neurological conditions also causes increased serum viscosity and has been associated with ischemic strokes in the setting of PV. Here we report a case of a 70-year-old man with prior stroke and PV who developed Guillain-Barré syndrome, an acute inflammatory demyelinating disorder of peripheral nerves causing ascending paresis, numbness, and paresthesia, who was treated safely with therapeutic plasma exchange. Plasma exchange may be preferable to administration of intravenous immunoglobulin for treatment of various medical conditions in patients with comorbid PV.

Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are capable of detecting drug-induced clinical arrhythmia, Torsade de Pointes (TdP), and QT prolongation. Efforts herein employ a broad set of structurally diverse drugs to optimize the predictive algorithm for applications in discovery toxicology and cardiac safety screening. The changes in the beat rhythm and rate of a confluent monolayer of hiPS-CMs by 88 marketed and 30 internal discovery compounds were detected with real-time cellular impedance measurement and quantified by measures of arrhythmic beating (IB20, lowest concentration inducing ≥ 20% arrhythmic [irregular, atypical] beats in 3 consecutive 20-s sweeps, and predicted proarrhythmic score [PPS]-IB20) or changes in beat rate (BR20, the lowest concentration inducing a reduction in beat rate of ≥ 20% at 3 consecutive sweeps compared with the time-matched vehicle control group, and PPS-BR20). Drug-induced arrhythmic beats and reductions in beat rates are predictive of clinical arrhythmia and QT prolongation, respectively. A threshold of ≤ 10 µM for class determination results in 82% in vitro-in vivo concordance for TdP prediction and 91% sensitivity for non-TdP arrhythmia detection, or 83% and 91% if clinically efficacious plasma (effective serum therapeutic concentration [C eff]) values are incorporated. This human cardiomyocyte arrhythmic risk (hCAR) model provides greater predictivity for torsadogenicity in humans compared with either human ether-a-go-go-related gene (hERG) inhibition (75%) or QT prolongation (81%). The concordance of beat rate reductions to predict clinical QT prolongation is 86%, or 87% when C eff is considered, which is greater than a hERG signal (80%). Further, arrhythmic beats resulting from cytotoxicity were identified by a distinct arrhythmic beating pattern, which occurred after the onset of cytolethality. This hCAR assay showed increased performance over existing preclinical tools in predicting clinical QT prolongation, arrhythmia, and TdP. Thus, hiPS-CMs are a relevant cell system to improve evaluating cardiac safety liabilities of drug candidates.

Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes.

Improved in vitro systems for predicting drug-induced toxicity are needed in the pharmaceutical and biotechnology industries to decrease late-stage drug attrition. One unmet need is an early screen for cardiotoxicity, which accounts for about one third of safety-based withdrawn pharmaceuticals. Herein, the first published report of a high-throughput functional assay employing a monolayer of beating human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is described, detailing a model that accurately detects drug-induced cardiac abnormalities. Using 96-well plates with interdigitated electrode arrays that assess impedance, the rhythmic, synchronous contractions of the iPSC-CMs were detected. Treatment of the iPSC-CMs with 28 different compounds with known cardiac effects resulted in compound-specific changes in the beat rate and/or the amplitude of the impedance measurement. Changes in impedance for the compounds tested were comparable with the results from a related technology, electric field potential assessment obtained from microelectrode arrays. Using the results from the set of compounds, an index of drug-induced arrhythmias was calculated, enabling the determination of a drug's proarrhythmic potential. This system of interrogating human cardiac function in vitro opens new opportunities for predicting cardiac toxicity and studying cardiac biology.