Post-coronavirus disease 2019 polyneuropathy with significant response to immunoglobulin therapy: a case report

Background The symptoms of coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2, were originally assumed to be mainly respiratory. With increasing knowledge, however, it turned out that the spectrum of complaints varies broadly with age and concomitant diseases. While many neurological symptoms were reported in the context of the disease, ranging from permanent fatigue to recurrent headaches and concentration disturbance, treatment approaches are still in development. This case discusses a possible treatment approach with immunoglobulin therapy and its outcomes. Case presentation We present the case of a 56-year-old Caucasian female patient who, following coronavirus disease 2019, developed peripheral sensory and autonomic disturbances that fell within subacute demyelinating neuropathy. Because a significant improvement in symptoms as well as in the results of clinical and electrophysiological examination was reported after immunoglobulin therapy, long-term therapy does not appear to be necessary. Conclusion Given the significant subjective and objective improvement reported, this case provides additional evidence that immunoglobulin therapy can be considered in post-coronavirus disease 2019 syndrome.

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia

Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance. These disturbances involve almost all autonomic functions and might contribute to poor medication compliance, worsened quality of life and increased mortality. Therefore, it has a great importance to find a potential therapeutic solution to improve the autonomic disturbances. The altered level of kynurenines (e.g., kynurenic acid), as tryptophan metabolites, is almost the most consistently found biochemical abnormality in schizophrenia. Kynurenic acid influences different types of receptors, most of them involved in the pathophysiology of schizophrenia. Only few data suggest that kynurenines might have effects on multiple autonomic functions. Publications so far have discussed the implication of kynurenines and the alteration of the autonomic nervous system in schizophrenia independently from each other. Thus, the coupling between them has not yet been addressed in schizophrenia, although their direct common points, potential interfaces indicate the consideration of their interaction. The present review gathers autonomic disturbances, the impaired kynurenine pathway in schizophrenia, and the effects of kynurenine pathway on autonomic functions. In the last part of the review, the potential interaction between the two systems in schizophrenia, and the possible therapeutic options are discussed.

The 2021 Carl Ludwig Lecture. Unsympathetic autonomic regulation in heart failure: patient-inspired insights

Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; that basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response, becomes maladaptive; and, that the magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: that the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy; and, that serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. I précis 6 elements of our current synthesis of the causes and consequences of maladaptive sympathetic disequilibrium in heart failure, shaped by patient-inspired epiphanies: arterial baroreceptor reflex modulation; excitation stimulated by increased cardiac filling pressure; paradoxical muscle sympathetic activation as a peripheral neurogenic constraint on exercise capacity; renal sympathetic restraint of natriuresis; co-existing sleep apnea; and, augmented chemoreceptor reflex sensitivity, then conclude by envisaging translational therapeutic opportunities.

IMPACT OF HIRDOTHERAPY ON VEGETATIVE DIS-ABILITIES AFTER CORONAVIRUS INFECTION

Вегетативно сосудистые и вегетативнотрофические изменения наблюдались у абсолютного большинства пациентов с ПКВИ с преобладанием частоты эмоциональных нарушений (страха смерти) 100%, генерализованный гипергидроз у 75,9%, наличие гипервентиляционного синдрома 71%, субфебрилитет, наличие вегетососудистых кризов, мигрени, склонности к обморокам 50,6%, боли в икроножных мыщах 48,1%, чувствительность к перемене климатических условий при ПКВИ наличие ухудшения самочувствия при смене погоды у 48,1% пациентов. Дисдинамические и дизритмические расстройства лабильности артериального давления (АД) с тенденцией к повышению и сердечного ритма с тенденцией к тахикардии 46,9% больных с ПКВИ. Под влиянием пятикратной и десятикратной применение грудотерапии обшое количество баллов симптомов вегетативных расстройств после перенесенной КВИ составили 557 баллов и 31 баллов и снизились на 82,4% и 99,1%. Индекс выраженности вегетативных нарушении сизились от 2,23±0,11 условных единиц (уе) на 0,39±0,01 и 0,02±0,001 уе.Результаты нейропсихологического тестирования у больных, принимавших гирудотерапии, показали объективное улучшение у них вегатативных нарушении, средний балл индекс выраженности вегетативных нарушении достоверно снизился после пятикратного и 10 дненого применение на 82,6% и 99,1% (р < 0,001) по сравнению с фоновым показателем.Таким образом, у больных с ПКВИ, принимавших 10 дневный курс гирудотерапии, показали объективное улучшение у них вегатативных функций. Autonomic vascular and autonomictrophic changes were observed in the vast majority of patients with PCVI with a predominant frequency of emotional disturbances (fear of death) 100%, generalized hyperhidrosis in 75.9%, the presence of hyperventilation syndrome 71% , subfebrile, presence of vegetovascular crises, migraine, tendency to fainting 50.6% , calf pain 48.1% , sensitivity to changes in climatic conditions in PCVI presence of worsening of wellbeing at a change of weather in 48.1% patients. Dysdynamic and dysrhythmic disorders of arterial pressure (BP) lability with a tendency to increase and cardiac rhythm with a tendency to tachycardia 46.9% of patients with PKVI. Under the influence of fivefold and tenfold application of chest therapy, the total score of symptoms of autonomic disorders after CPVI was 557 and 31 and decreased by 82.4% and 99.1%, respectively. The index of severity of autonomic disturbances sized up from 2.23±0.11 conventional units (ue) by 0.39±0.01 and 0.02±0.001 ue.The results of neuropsychological testing in the patients who took hirudotherapy showed the objective improvement of vegetative disturbances in them, the average index score of vegetative disturbances expression reliably decreased after 5 and 10 day application by 82,6 % and 99,1 % (p <0,001) in comparison with the background index.Thus, patients with PKVI who underwent hirudotherapy for 10 days showed objective improvement of vegetative functions.

Dystonin loss-of-function leads to impaired autophagy-endolysosomal pathway dynamics

The neuronal dystonin protein (DST-a) is a large cytoskeletal linker important for integrating the various components of the cytoskeleton. Recessive <i></i>Dst<i></i> mutations lead to a sensory neuropathy in mice known as <i></i>dystonia musculorum<i></i> (<i></i>Dstdt<i></i>). The disease is characterized by ataxia, autonomic disturbances, and ultimately death, which are associated with massive dorsal root ganglion (DRG) sensory neuron degeneration. Recent investigation of <i></i>Dstdt<i></i> sensory neurons revealed an accumulation in autophagosomes and a disruption in autophagic flux, which was believed to be due to insufficient motor protein availability. Motor protein levels and the endolysosomal pathway were assessed in pre-symptomatic (postnatal day 5; P5) and symptomatic (P15) stage wild type and <i></i>Dstdt<i></i> DRGs. Levels of mRNA encoding molecular motors are reduced, although no significant reduction protein level is detected. An increase in lysosomal marker LAMP1 in medium-large size <i></i>Dstdt-27J<i></i> sensory neurons is observed, along with an accumulation of electron-light single-membraned vesicles in <i></i>Dstdt-27J<i></i> DRG tissue at late stages of disease. These vesicles are likely to be autolysosomes, and their presence in only late stage <i></i>Dstdt-27J<i></i> sensory neurons is suggestive of a pathological defect in autophagy. Further investigation is necessary to confirm vesicle identity, and to determine the role of Dst-a in normal autophagic flux.

Concomitant Congenital Horner and Harlequin Syndromes: Case Report and Review of Literature

Harlequin syndrome is a condition characterized by autonomic dysfunction leading to hemifacial flushing on one side with pallor and impaired sweating on the other side. It is a rare condition that can be both congenital and acquired, with congenital cases being rarer, comprising ∼6% of all Harlequin syndrome cases. Harlequin syndrome is usually associated with other autonomic disturbances including Horner syndrome especially when presenting as a congenital condition. We reported the findings of a rare case of concomitant congenital Horner and Harlequin syndromes in an otherwise healthy 4-month-old male infant patient and provided a review of the current literature.

0803 Clinical and Polysomnographic Features of Trauma Associated Sleep Disorder (TASD)

Introduction Trauma associated sleep disorder (TASD) is an emerging parasomnia that develops after trauma with clinical features of trauma related nightmares (TRN), disruptive nocturnal behaviors (DNB), and autonomic disturbances. The purpose of this study is to characterize the clinical and polysomnographic (PSG) features of TASD. Methods Clinical history and detailed video-PSG review, to include post-PSG nightmare reports, of a cohort of patients with TASD. Results Patients (n=40, 32 men, 8 women) were active duty service members with a median age of 38.9 yrs (range 24-57 yrs). Dream content typically related to combat (n=37, 92.5%), with 75% (n=30) reporting TRN and 60% (n=24) reporting dream enactment at least weekly. Self-reported DNB included vocalizations, violent limb movements, thrashing, defensive posturing, and jumping from bed. There was a high rate of comorbid insomnia (n=35, 87.5%), PTSD (n=23, 63.9%), anxiety (n=25, 62.5%), depression (n=20, 50%), OSA (n=19, 47.5%), chronic pain (n=12, 30%), and TBI (n=13, 32.5%). Most patients had REM sleep without atonia (RSWA) (n=33, 82.5%), though a minority had purposeful DNB (n=11, 27.5%). Vocalizations were present in seven (17.5%) patients. Patients with PTSD were more likely to have purposeful DNB (n=9, 100%) than those without PTSD (n=13, 50%; p=0.013), whereas patients with purposeful DNB had markedly less N3 sleep (1.0±11.4%) than those without purposeful DNB (13.8±16.2%; p=0.002). There was no significant difference in medications between DNB groups. Conclusion TASD is frequently comorbid with other sleep and behavioral health disorders. Characteristics of TASD are often captured on video-PSG during REM sleep, though DNB may be less pronounced than what patients report in their habitual sleeping environment. Clinical and video-PSG correlations are invaluable in assessing patients with TASD. This study, which is the largest cohort to date, provides a further basis for establishing TASD as a unique REM-related parasomnia. Support N/A

Insula stroke: the weird and the worrisome

Infarction of the insula is a common scenario with large tissue-volume strokes in the middle cerebral artery territory. Considered to be part of the central autonomic network, infarction of this region is associated with autonomic disturbances, in particular cardiovascular dysregulation. Risk of aspiration following stroke is also associated with involvement of the insula, consistent with its purported participation in complex functions of the mouth and pharynx. Strokes restricted to the insula are rare and present with a broad range of symptoms that offer a window of insight into the diverse functionality of the insular cortex. Chemosensory, autonomic, vestibular, auditory, somatosensory, language and oropharyngeal functional deficits are all recognised, among others. Long-term sequelae are unknown but profound symptoms, such as hemiparesis, are usually transient. Understanding the patterns of dysfunction highlighted provides the basis for future strategies to optimise stroke management on the discovery of insula involvement.