MOG antibody-associated encephalitis secondary to Covid-19: case report.

BACKGROUND: While Covid-19 predominantly affects the respiratory system, neurological manifestations including encephalitis occur in some patients, possibly affecting the course and outcome of the disease. Here, we describe a unique case of a young man with Covid-19 and transient MOG-positive encephalitis, with a benign course. CASE PRESENTATION: A 22-year-old male, with PCR confirmed Covid-19 infection was admitted because of persistent headache. The clinical examination was normal. Neuropsychological testing revealed distinct executive deficits. Brain MRI and cerebrospinal fluid (CSF) analysis were suggestive for encephalitis. Further laboratory examination revealed a serum MOG antibody titre. The headache improved with analgetic treatment and i.v. methylprednisolone. Consequently, the MOG antibody titer decreased and MRI lesions were resolving. The patient made a full recovery, with no signs of deterioration over the following months. CONCLUSIONS: Covid-19 manifestations in the CNS include encephalitis with variable course and prognosis. This case highlights a possible association between inflammation due to COVID-19 and transient secondary autoimmunity with transient MOG antibodies and atypical clinical presentation.

[Chemosensory disorders in Covid-19: Pathomechanisms and clinical relevance]. / Störungen der Chemosensorik bei Covid-19: Pathomechanismen und klinische Relevanz.

In this review article, current information on the frequency and relevance of chemosensory disorders in Covid-19 was recorded, assigned pathophysiologically and statements on prognostic significance were derived. The results are based on a comprehensive literature search of all literature on this topic and our own experience in the treatment of patients with smell and taste disorders since the beginning of the pandemic.Current study results indicate that clinically less affected Covid-19 patients without inpatient treatment and who do not require ventilation often have disorders of the chemosensory system. In young patients and women in particular, they seem to be an indicator of a favorable prognosis for the course of the disease. Smell disorders can appear early, as the sole symptom or together with other symptoms of Covid-19 disease. It has not yet been clarified whether ageusia can occur independently or whether it is also felt in the context of anosmia. In the pandemic, the new occurrence of anosmia without congestion / obstruction/runny nose is probably an expression of an infection with SARS-CoV-2 and should always give rise to quarantine and testing for SARS-CoV-2. The smell disorder in Covid-19 mostly seems to be temporary; It is not yet possible to conclusively assess whether there is usually a full restitution. The therapeutic approaches already established for other postviral olfactory disorders (e. g. olfactory training) are also used here.

Reliable Detection of Atrial Fibrillation with a Medical Wearable during Inpatient Conditions.

Atrial fibrillation (AF) is the most common arrhythmia and has a major impact on morbidity and mortality; however, detection of asymptomatic AF is challenging. This study sims to evaluate the sensitivity and specificity of non-invasive AF detection by a medical wearable. In this observational trial, patients with AF admitted to a hospital carried the wearable and an ECG Holter (control) in parallel over a period of 24 h, while not in a physically restricted condition. The wearable with a tight-fit upper armband employs a photoplethysmography technology to determine pulse rates and inter-beat intervals. Different algorithms (including a deep neural network) were applied to five-minute periods photoplethysmography datasets for the detection of AF. A total of 2306 h of parallel recording time could be obtained in 102 patients; 1781 h (77.2%) were automatically interpretable by an algorithm. Sensitivity to detect AF was 95.2% and specificity 92.5% (area under the receiver operating characteristics curve (AUC) 0.97). Usage of deep neural network improved the sensitivity of AF detection by 0.8% (96.0%) and specificity by 6.5% (99.0%) (AUC 0.98). Detection of AF by means of a wearable is feasible in hospitalized but physically active patients. Employing a deep neural network enables reliable and continuous monitoring of AF.

The association between collateral status, recanalization and long term outcome in stroke patients treated with stent retrievers - Are there indications not to perform thrombectomy based on CT angiography?

BACKGROUND AND PURPOSE: To investigate the association between baseline pial collateral status on computed tomography angiography (CTA) with recanalization and functional outcome in patients with acute anterior circulation stroke treated with stent retriever thrombectomy. MATERIAL AND METHODS: Retrospective analysis of 87 patients from a prospective thrombectomy registry. Collateral status on CTA source images was categorized into good, moderate, and poor with the Tan and Miteff scores by two-blinded readers. Association between CTA collateral status and successful recanalization was investigated with univariate regression analysis. Multivariate logistic regression was used to analyse the association between collateral score and favourable clinical outcome (mRS 0-2) and death at follow-up. RESULTS: Mean age was 72.5 years and baseline median NIHSS score was 15. Patients with poor collaterals on Tan score had a significant higher mortality compared with moderate or good collaterals during a mean follow-up period of 5.2 months (85.7% vs. 30.6% vs. 25.7%, P<0.001). Univariate logistic regression analysis did not show a significant association between Tan score (OR 1.681, 95% CI 0.683-4.140) and successful recanalization. Higher age (OR 1.067, 95% CI 1.013-1.124; P=0.015) and lower Tan score (OR 0.421, 95% CI 0.192-0.922; P=0.031) were independent predictors of death at follow-up on multivariate analysis. The Miteff collateral score could be assessed only in 65 of the 87 patients and the Tan collateral score had a higher interrater reliability. CONCLUSIONS: Poor collaterals on CTA were associated with a very high rate of fatal outcome in anterior circulation stroke patients despite a high rate of successful recanalization with stent retrievers.

Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome.

INTRODUCTION: Postural tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Our objective in this study was to evaluate the correlation between C-fiber involvement as shown by skin biopsy and adrenergic cardiac metaiodobenzylguanadine (MIBG) uptake in POTS patients. METHODS: Skin biopsies of 84 patients with POTS were examined by Protein Gene Product 9.5 (PGP9.5) immunohistochemistry and were compared with MIBG myocardial scintigraphy imaging data. RESULTS: Mean intraepidermal nerve fiber (IENF) density was in the lower normal age-adjusted range, 7.2 ± 2.9/mm (normal ≥ 7/mm), and was slightly below the normal range in 45% of POTS patients. MIBG uptake was reduced in 21% of patients. Low IENF density correlated with reduced cardiac MIBG uptake (r = 0.39, P = 0.001). CONCLUSIONS: A subset of neuropathic POTS patients may harbor mild small fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin associated with reduced myocardial postganglionic sympathetic innervation.

Dysphagia risk assessment in acute left-hemispheric middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. METHODS: We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. RESULTS: 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. CONCLUSIONS: In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.

Cerebral hypoxia, missing cortical somatosensory evoked potentials and recovery of consciousness.

BACKGROUND: Bilaterally absent N20 components of the sensory evoked potentials (SEP) from the median nerve are regarded as accurately predicting poor outcome after cardiac arrest. CASE PRESENTATION: We are reporting on a patient, who regained consciousness despite this ominous finding. Early after cardiac arrest, MRI showed signal alterations in diffusion weighted imaging (DWI) bilaterally in the primary visual and sensorimotor cortex and in the basal ganglia. SEP were repeatedly absent. The patient survived shut out form sensory and visual experience and locked in for voluntary movements, but kept her verbal competence in several languages. CONCLUSION: SEP inform about integrity only of a narrow cortical strip. It is unguarded, but common practice, to conclude from absent SEP, that a patient has suffered diffuse cortical damage after cardiac arrest. Cerebral MRI with DWI helps to avoid this prognostic error and furthers understanding of the sometimes very peculiar state of mind after cardiac arrest.

Using routine data for quality assessment in NeuroNet telestroke care.

BACKGROUND: Systematic clinical trials are often unavailable to evaluate and optimize operational telestroke networks. In a complementary approach, readily available routine clinical data were analyzed in this study to evaluate the effect of a telestroke network over a 4-year period. METHODS: Routine clinical data from the HELIOS hospital information system were compared before and after implementation of the NeuroNet concept, including neurologic acute stroke teleconsultations, standard operating procedures, and peer review quality management in 3 hospital cohorts: 5 comprehensive stroke centers, 5 NeuroNet hospitals, and 5 matched control hospitals. RESULTS: During the study period, the rate of thrombolytic therapy increased by 4.8% in NeuroNet hospitals, while ischemic stroke in-hospital mortality decreased (relative risk reduction ~29% in NeuroNet and control hospitals). The odds ratio for thrombolytic therapy in comprehensive stroke centers compared to NeuroNet hospitals was reduced from 3.7 to 1.3 between 2006 and 2009. Comprehensive stroke care coding according to German Diagnosis Related Groups definitions increased by 45% in NeuroNet (P < .0001) and by 18% in control hospitals. CONCLUSIONS: Routine clinical data on in-hospital mortality, the rate of thrombolytic therapy, and comprehensive stroke care coding reflect different aspects of acute stroke care improvement related to the implementation of the telemedical NeuroNet concept and unified quality management (standard operating procedure teaching concept, peer review process). Similar evaluation processes could contribute to quality monitoring in other telestroke networks.

Cell-replacement therapy and neural repair in the retina.

Visual impairment severely affects the quality of life of patients and their families and is also associated with a deep economic impact. The most common pathologies responsible for visual impairment and legally defined blindness in developed countries include age-related macular degeneration, glaucoma and diabetic retinopathy. These conditions share common pathophysiological features: dysfunction and loss of retinal neurons. To date, two main approaches are being taken to develop putative therapeutic strategies: neuroprotection and cell replacement. Cell replacement is a novel therapeutic approach to restore visual capabilities to the degenerated adult neural retina and represents an emerging field of regenerative neurotherapy. The discovery of a population of proliferative cells in the mammalian retina has raised the possibility of harnessing endogenous retinal stem cells to elicit retinal repair. Furthermore, the development of suitable protocols for the reprogramming of differentiated somatic cells to a pluripotent state further increases the therapeutic potential of stem-cell-based technologies for the treatment of major retinal diseases. Stem-cell transplantation in animal models has been most effectively used for the replacement of photoreceptors, although this therapeutic approach is also being used for inner retinal pathologies. In this review, we discuss recent advances in the development of cell-replacement approaches for the treatment of currently incurable degenerative retinal diseases.

Greater occipital nerve neuralgia caused by pathological arterial contact: treatment by surgical decompression.

Occipital nerve neuralgia is a rare cause of severe headache, and may be difficult to treat. We report the case of a patient with occipital nerve neuralgia caused by pathological contact of the nerve with the occipital artery. The pain was refractory to medical treatment. Surgical decompression yielded complete remission.

Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterised by excessive tachycardia of unknown aetiology. Whether this condition involves abnormal cardiac sympathetic innervation or function remains elusive. Meta-iodobenzylguanidine (MIBG) resembles guanethidine and is a pharmacologically inactive analogue of norepinephrine, which is similarly metabolised in noradrenergic neurons. MIBG myocardial scintigraphy is used clinically to estimate local myocardial sympathetic nerve damage in some forms of heart disease and autonomic neuropathy. The objective of this study was to evaluate cardiac sympathetic innervation in patients with POTS. METHODS: 20 patients with POTS were studied using (123)I-MIBG-single photon emission computed tomography, standardised autonomic testing, assessment of catecholamine plasma levels and sympathetic skin response. RESULTS: In four POTS patients (20.0%), myocardial MIBG uptake was markedly decreased. The mean heart to mediastinum ratio was reduced to 1.22+/-0.08 compared with the normal range of >1.7. No correlation was found between myocardial MIBG uptake and degree of postural tachycardia, baroreflex sensitivity, catecholamine plasma levels or other autonomic parameters. Sympathetic skin responses were normal in all patients. CONCLUSIONS: These findings suggest that POTS may be, in part, a manifestation of autonomic cardiac neuropathy. MIBG myocardial scintigraphy may be helpful to distinguish patients with neuropathic POTS from patients with orthostatic intolerance of other origin.

[COVID-19: Variable symptoms in mild course: olfactory loss and increased resting heart rate]. / COVID-19: Symptome und Frühzeichen auch bei leichten Verlaufsformen ­ Bedeutung von Riechstörungen und Ruhepuls.

HISTORY: A 56-year-old, previously healthy male and long distance runner noticed short episodes of parosmia, followed by anosmia. Few days later, he monitored an increase in his resting heart rate. This was followed by a dry cough, fatigue, and myalgia. At the same time, symptoms occurred in all four family members. CLINICAL FINDINGS: The patient had a dry cough. The medical examination was normal. Heart rate was 60/min, sinus rhythm, body temperature 36.6 °C. Complete anosmia was present. The RT-PCR for SARS-CoV-2 from a deep pharyngeal swab was positive in all five family members. THERAPY AND COURSE: Symptoms were present for almost two weeks. All family members had anosmia, that started earlier and lasted longer than the other symptoms, and myalgia. Reduced taste sensation, fatigue, dry cough and sore throat were present in four of five persons. Shortness of breath at rest or gastrointestinal symptoms were absent. Four affected persons had sleep disturbances in the later course of the disease. None of the affected persons had raised temperature at any time during the disease. Specific medical or drug treatment was not necessary. All patients made full recoveries without signs of organ dysfunction, and with full restitution of physical strength. DISCUSSION: We describe a family of 5 previously healthy persons with a mild course of COVID-19 disease. The symptoms and course are described in detail. Anosmia can precede other symptoms by several days and can indicate an early phase of infection. An increase in resting heart rate can occur in the absence of raised temperature or fever. The symptoms and course are discussed in the context of the ongoing pandemic, and efforts to control infection chains.

"Neurological manifestations of COVID-19" - guideline of the German society of neurology.

Infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a previously unknown clinical picture, which is known as COVID-19 (COrona VIrus Disease-2019) and was first described in the Hubei region of China. The SARS-CoV-2 pandemic has implications for all areas of medicine. It directly and indirectly affects the care of neurological diseases. SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of the new infection. This S1 guideline provides guidance for the care of patients with SARS-CoV-2 infection regarding neurological manifestations, patients with neurological disease with and without SARS-CoV-2 infection, and for the protection of healthcare workers. This is an abbreviated version of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

Interdisciplinary Decision Making in Hemorrhagic Stroke Based on CT Imaging-Differences Between Neurologists and Neurosurgeons Regarding Estimation of Patients' Symptoms, Glasgow Coma Scale, and National Institutes of Health Stroke Scale.

Background and Purpose: Acute intracerebral hemorrhage (ICH) requires rapid decision making toward neurosurgery or conservative neurological stroke unit treatment. In a previous study, we found overestimation of clinical symptoms when clinicians rely mainly on cerebral computed tomography (cCT) analysis. The current study investigates differences between neurologists and neurosurgeons estimating specific scores and clinical symptoms. Methods: Overall, 14 neurologists and 15 neurosurgeons provided clinical estimates and National Institutes of Health Stroke Scale (NIHSS) as well as Glasgow Coma Scale (GCS) based on cCT images and basic information of 50 patients with hypertensive and lobar ICH. Subgroup analyses were performed for the different professions (neurologists vs. neurosurgeons) and bleeding subtypes (typical location vs. atypical). The differences between the actual GCS and NIHSS scores and the cCT-imaging-based estimated scores were depicted as Bland-Altman plots and negative and positive predictive value (NPV and PPV) for prediction of clinical relevant items. ΔNIHSS points (ΔGCS points) were calculated as the difference between actual and rated NIHSS (GCS) including 95% confidence interval (CI). Results: Mean ΔGCS points for neurosurgeons was 1.16 (95% CI: -2.67-4.98); for neurologists, 0.99 (95% CI: -2.58-4.55), p = 0.308; mean ΔNIHSS points for neurosurgeons was -2.95 (95% CI: -12.71-6.82); for neurologists, -0.33 (95% CI: -9.60-8.94), p < 0.001. NPV and PPV for stroke symptoms were low, with large differences between different symptoms, bleeding subtypes, and professions. Both professions had more problems in proper rating of specific clinic-neurological symptoms than rating scores. Conclusion: Our results stress the need for joint decision making based on detailed neurological examination and neuroimaging findings also in telemedicine.

Primary cCT Imaging Based Clinico-Neurological Assessment-Calling for Addition of Telestroke Video Consultation in Patients With Intracerebral Hemorrhage.

Background and Purpose: Intracerebral hemorrhage (ICH) requires rapid decision making to decrease morbidity and mortality although time frame and optimal therapy are still ill defined. Ideally, specialized neurologists, neurosurgeons, and (neuro-) radiologists who know the patient's clinical status and their cerebral computed tomography imaging (cCT) make a joint decision on the clinical management. However, in telestroke networks, a shift toward cCT imaging criteria used for decision making can be observed for practical reasons. Here we investigated the "reverse correlation" from cCT imaging to the actual clinical presentation as evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). Methods: CCT images and basic information (age, sex, and time of onset) of 50 patients with hypertensive and lobar ICH were presented to 14 experienced neurologists and 15 neurosurgeons. Based on this information, the NIHSS and GCS scores were estimated for each patient. The differences between the actual GCS and NIHSS scores and the cCT-imaging-based estimated scores were plotted in a bland-Altman plot. Results: The average estimated GCS score mainly based on cCT imaging was 12. 4 ± 2.8 (actual value: 13.0 ± 2.5; p = 0.100), the estimated NIHSS score was 13.9 ± 9.1 (actual value: 10.8 ± 7.3; p < 0.001). Thus, in cCT-imaging-based evaluation, the neurological status of patients especially employing the NIHSS was estimated poorer, particularly in patients with lobar ICH. "Reverse clinical" evaluation based on cCT-imaging alone may increase the rate of intubation and secondary transferal and neurosurgical treatment. Telestroke networks should consider both, videoassessment of the actual clinical picture and cCT-imaging findings to make appropriate acute treatment decisions.

Impaired development of the Harderian gland in mutant protein phosphatase 2A transgenic mice.

Although Harderian glands are especially large in rodents, many features of this retroocular gland, including its development and function, are not well established. Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes expressed in this gland. PP2A substrate specificity is determined by regulatory subunits with leucine 309 of the catalytic subunit playing a crucial role in the recruitment of regulatory subunits into the complex in vitro. Here we expressed an L309A mutant catalytic subunit in Harderian gland of transgenic mice. We found a delayed postnatal development and hypoplasia of the gland, causing enophthalmos. To determine why expression of the L309A mutant caused this phenotype, we determined the PP2A subunit composition. We found an altered subunit composition in the transgenic gland that was accompanied by pronounced changes of proteins regulating cell adhesion. Specifically, cadherin and beta-catenin were dramatically reduced and shifted to the cytosol. Furthermore, we found an inactivating phosphorylation of the cadherin-directed glycogen synthase kinase-3beta. In conclusion, the carboxy-terminal leucine L309 of the PP2A catalytic subunit determines PP2A heterotrimer composition in vivo. Moreover, our data demonstrate that PP2A subunit composition plays a crucial role in regulating cell adhesion and as a consequence in the development of the Harderian gland.

Statin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins.

PURPOSE: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders. METHODS: We carried out a medline search on statin actions, with respect to biochemical pathways and signal transduction on the one hand, and clinical studies in neurologic and retinal diseases on the other hand. Novel experimental data obtained in a rat model of axonal CNS injury were also included. RESULTS: Statins exert multiple effects on endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" are independent of cholesterol lowering and appear to be beneficial in the context of brain injury. Several mechanisms of statin actions underlying neuroprotective effects may also involve heat shock proteins and the survival-related PI-3K/Akt pathway. CONCLUSIONS: Available data suggest that statins may be of potential therapeutic use in a variety of diseases of the CNS including ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of retinal and eye diseases. Before general recommendations can be made and specific therapeutic approaches can be developed, more reliable clinical data and studies are required, and possible side effects must be carefully evaluated.

Improved high-capacity adenoviral vectors for high-level neuron-restricted gene transfer to the CNS.

Adenovirus-based (Ad) vectors are used widely for experimental gene transfer to the CNS. Ad transduce many cell types including postmitotic neurons. However, their use for CNS gene transfer is limited due to the host immune response elicited. Furthermore, the extensive distribution of the primary cellular receptor for Ad, the coxsackievirus and adenovirus receptor (CAR), allows adenoviral vectors to infect a broad range of host cells which may be disadvantageous in tissues with various different cell types, like the CNS. The use of tissue-specific promoters allows for neuron-restricted gene expression, even though gene expression driven by these promoters is often very weak. Accordingly, increased transgene expression levels from viral transcription units are needed in order to improve the overall performance of Ad vectors. We designed a high-capacity Ad vector (HC-Ad) that allows for high-level, neuron-restricted transgene expression and shows no obvious signs of immunogenicity or toxicity in the mouse brain.