Mononeuropathy Multiplex After Severe SARS-CoV-2 Infection: A Case Series and Literature Review.

INTRODUCTION: Peripheral nerve injuries are being increasingly recognized in patients recovering from severe SARS-CoV-2 infections. Axonal neuropathies can occur, leading to lasting and disabling deficits. CASE REPORTS: We present the cases of 3 patients who developed weakness and sensory symptoms after severe SARS-CoV-2 pneumonia. The clinical deficits revealed various patterns of injury including a mononeuropathy multiplex (MNM) in the first patient, a brachial plexopathy with superimposed MNM in the second patient, and a mononeuropathy superimposed on a polyneuropathy in the third patient. Electrodiagnostic studies revealed axonopathies. The patients with MNM were left with severe disability. The third patient returned to his baseline level of functioning. CONCLUSIONS: Severe SARS-CoV-2 infections can result in disabling axonopathies. Possible explanations include ischemic nerve damage from the profound inflammatory response and traumatic nerve injuries in the ICU setting. Preventing severe disease through vaccination and antivirals may therefore help reduce neurologic morbidity.

A Rare Presentation of a Rare Disease: Oropharyngeal Dysphagia as The Main Manifestation of Myasthenia Gravis.

Oropharyngeal dysphagia is defined as the inability or difficulty to initiate swallowing. It has a wide array of etiologies including structural and neurologic diseases. Myasthenia gravis (MG) is a rare autoimmune condition caused by antibodies against the post-synaptic membranes of the neuromuscular junction, leading to fatigable weakness of skeletal muscles. Bulbar symptoms are less prevalent than ocular symptoms or limb weakness but can be particularly morbid. Non-neurologists are more likely to be the first providers to evaluate patients with dysphagia and should be familiar with MG. We report a unique case of newly diagnosed MG with the initial presentation of solid food and liquid dysphagia.

Metabolic and Toxic Myelopathies.

Metabolic and toxic causes of myelopathy form a heterogeneous group of disorders. In this review, we discuss the causes of metabolic and toxic myelopathies with respect to clinical presentation, pathophysiology, diagnostic testing, treatment, and prognosis. This review is organized by temporal course (hyperacute, acute, subacute, and chronic) and etiology (e.g., nutritional deficiency, toxic exposure). Broadly, the myelopathies associated with dietary toxins (neurolathyrism, konzo) and decompression sickness present suddenly (hyperacute). The myelopathies associated with heroin use and electrical injury present over hours to days (acutely). Most nutritional deficiencies (cobalamin, folate, copper) and toxic substances (nitrous oxide, zinc, organophosphates, clioquinol) cause a myelopathy of subacute onset. Vitamin E deficiency and hepatic myelopathy cause a chronic myelopathy. Radiation- and intrathecal chemotherapy-induced myelopathy can cause a transient and/or a progressive syndrome. For many metabolic and toxic causes of myelopathy, clinical deficits may stabilize or improve with rapid identification and treatment. Familiarity with these disorders is therefore essential.

COVID-19 in patients with myasthenia gravis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG). METHODS: We studied the clinical course of COVID-19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle-specific tyrosine kinase antibodies) between April 1, 2020-April 30-2020. RESULTS: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID-19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications. DISCUSSION: Our findings suggest that the clinical course and outcomes in patients with MG and COVID-19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.

Neural coding of sound envelope in reverberant environments.

Speech reception depends critically on temporal modulations in the amplitude envelope of the speech signal. Reverberation encountered in everyday environments can substantially attenuate these modulations. To assess the effect of reverberation on the neural coding of amplitude envelope, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic and reverberant environments. Although reverberation degraded both rate and temporal coding of AM in IC neurons, in most neurons, the degradation in temporal coding was smaller than the AM attenuation in the stimulus. This compensation could largely be accounted for by the compressive shape of the modulation input-output function (MIOF), which describes the nonlinear transformation of modulation depth from acoustic stimuli into neural responses. Additionally, in a subset of neurons, the temporal coding of AM was better for reverberant stimuli than for anechoic stimuli having the same modulation depth at the ear. Using hybrid anechoic stimuli that selectively possess certain properties of reverberant sounds, we show that this reverberant advantage is not caused by envelope distortion, static interaural decorrelation, or spectral coloration. Overall, our results suggest that the auditory system may possess dual mechanisms that make the coding of amplitude envelope relatively robust in reverberation: one general mechanism operating for all stimuli with small modulation depths, and another mechanism dependent on very specific properties of reverberant stimuli, possibly the periodic fluctuations in interaural correlation at the modulation frequency.

Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways.

Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals.

Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach.

Middle ear function and cochlear input impedance in chinchilla.

Simultaneous measurements of middle ear-conducted sound pressure in the cochlear vestibule P(V) and stapes velocity V(S) have been performed in only a few individuals from a few mammalian species. In this paper, simultaneous measurements of P(V) and V(S) in six chinchillas are reported, enabling computation of the middle ear pressure gain G(ME) (ratio of P(V) to the sound pressure in the ear canal P(TM)), the stapes velocity transfer function SVTF (ratio of the product of V(S) and area of the stapes footplate A(FP) to P(TM)), and, for the first time, the cochlear input impedance Z(C) (ratio of P(V) to the product of V(S) and A(FP)) in individuals. mid R:G(ME)mid R: ranged from 25 to 35 dB over 125 Hz-8 kHz; the average group delay between 200 Hz and 10 kHz was about 52 mus. SVTF was comparable to that of previous studies. Z(C) was resistive from the lowest frequencies up to at least 10 kHz, with a magnitude on the order of 10(11) acoustic ohms. P(V), V(S), and the acoustic power entering the cochlea were good predictors of the shape of the audiogram at frequencies between 125 Hz and 2 kHz.

Middle-ear pressure gain and cochlear partition differential pressure in chinchilla.

An important step to describe the effects of inner-ear impedance and pathologies on middle- and inner-ear mechanics is to quantify middle- and inner-ear function in the normal ear. We present middle-ear pressure gain G(MEP) and trans-cochlear-partition differential sound pressure DeltaP(CP) in chinchilla from 100 Hz to 30 kHz derived from measurements of intracochlear sound pressures in scala vestibuli P(SV) and scala tympani P(ST) and ear-canal sound pressure near the tympanic membrane P(TM). These measurements span the chinchilla's auditory range. G(MEP) had constant magnitude of about 20 dB between 300 Hz and 20 kHz and phase that implies a 40-micros delay, values with some similarities to previous measurements in chinchilla and other species. DeltaP(CP) was similar to G(MEP) below about 10 kHz and lower in magnitude at higher frequencies, decreasing to 0 dB at 20 kHz. The high-frequency rolloff correlates with the audiogram and supports the idea that middle-ear transmission limits high-frequency hearing, providing a stronger link between inner-ear macromechanics and hearing. We estimate the cochlear partition impedance Z(CP) from these and previous data. The chinchilla may be a useful animal model for exploring the effects of non-acoustic inner-ear stimulation such as "bone conduction" on cochlear mechanics.