Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

[Herpes zoster and postherpetic neuralgia]. / Herpes zoster und postzosterische Neuralgie.

Herpes zoster develops by endogenous reactivation of varizella zoster virus (VZV). Incidence increases with age. Females are more frequently affected than males. The reactivation rate in seropositive individuals is about 20 %. After a short prodromal stage, herpetiform-grouped vesicles appear in segmental arrangement. Pain and paresthesia are typical zoster symptoms. Complications like bacterial superinfections, vasculopathy, paresis, and oculopathy may occur. During pregnancy herpes zoster is a threat for mother and child. Among elderly patients, cardiovascular risk is increased during the first week of herpes zoster infection. Postherpetic neuropathy is feared. Diagnosis can be made clinically and by the use of polymerase chain reaction. First-line treatment is systemic antiviral drug therapy with either acyclovir or brivudine. Adjuvant therapies consist of pain management and topical treatment.

[Non-cardiac and non-pulmonary causes of dyspnea]. / Nichtkardiale und nichtpulmonale Ursachen der Dyspnoe.

In addition to cardiac and pulmonary diseases there is a broad variety of different underlying causes of dyspnea. The spectrum includes the different forms of anemia, all causes of upper airway obstructions, neuromuscular diseases and psychopathological disorders. This article gives a brief review of the entire spectrum by providing information about differential diagnostics as well as the main therapeutic principles. A field of growing interest is dyspnea in the context of palliative care.

[Vertigo and syncope: a clinically oriented introduction to the problem]. / Schwindel und Synkope: Eine klinisch orientierte Hinführung zum Problem.

Vertigo and syncope are frequently occurring clinical presentations in the physician's practice as well as in the emergency room. Therefore, many physicians and institutions have formulated diagnostic protocols that they follow when a patient with vertigo or syncope presents. This kind of blanket routine may lead to over-diagnosis in many cases, as well as to under-diagnosis in some. The purpose of the following article is to show that a well-focused history based on clear cut concepts of disease and a sound pathophysiological understanding will guide the physician precisely through the diagnostic process in both clinical presentations and will help to avoid manifold diagnostic procedures. Finally, a description of the most frequent pitfalls of the diagnostic work-up is given, along with measures to avoid these.

[Vertigo/dizziness and syncope from a neurological perspective]. / Schwindel und Synkope aus Sicht des Neurologen.

Vertigo/dizziness and syncope are among the most frequent clinical entities encountered in neurology. In patients with presumed syncope, it is important to distinguish it from neurological and psychiatric diseases causing a transient loss of consciousness due to another etiology. Moreover, central nervous disorders of autonomic blood pressure regulation as well as affections of the peripheral autonomic nerves can be responsible for the onset of real syncope. This is particularly relevant in recurrent syncope. Vertigo occurs in the context of temporary disorders, relatively harmless diseases associated with chronic impairment, as well as in acute life-threatening states. Patient history and clinical examination play an important role in classifying these symptoms. It is of crucial importance in this context, e.g., to establish whether the patient is experiencing an initial manifestation or whether such episodes have been known to occur recurrently over a longer period of time, as well as how long the episodes last. Clinical investigations include a differential examination of the oculomotor system with particular regard to nystagmus. The present article outlines the main underlying neurological diseases associated with syncope and vertigo, their relevant differential diagnoses as well as practical approaches to their treatment.

[Diseases of the peripheral vestibular system: contribution of ENT medical diagnostics and therapy]. / Erkrankungen des peripher-vestibulären Systems: HNO-ärztliche Diagnostik und Therapie.

The most common types of vertigo caused by diseases of the peripheral vestibular system are benign paroxysmal positional vertigo (BPPV), Meniere's disease and vestibular neuritis. A thorough examination of the medical history and clinical examination are usually sufficient for the differential diagnostics. Treatment includes differentiated repositioning maneuvers, medicinal treatment and physiotherapy.

[Reflex syncope and syncope secondary to orthostatic hypotension]. / Reflexsynkopen und Synkopen bei orthostatischer Hypotonie.

BACKGROUND: Reflex syncope predominantly occurs in younger patients and is the most common type of syncope. Typical contributors to reflex syncope are orthostatic stress, followed by a delayed and inadequate circulatory response consisting of bradycardia (cardioinhibitory type) and hypotension (vasodepressor type). Comparably, syncope may occur after direct activation of the vagus nerve, after emotional distress or pain, and in specific situations, such as coughing and post-micturition. The latter situations are mediated by indirect vagus nerve activation by usually unknown mediators. Syncope mediated by orthostatic hypotension occurs in elderly patients and is mediated by insufficient sympathoadrenergic vasoconstriction, occurring shortly after the onset of the orthostatic situation. DIAGNOSTICS: A thorough examination of the patient history is the mainstay of diagnostics. Specific testing is only required in uncertain and recurrent cases. In addition to standard diagnostics, tilt table testing can be helpful. A negative tilt test is, however, not definitive. Implanted loop recorders are helpful to diagnose the cardioinhibitory component of reflex syncope and are more sensitive than tilt testing. THERAPY: Treatment of both types of syncope consists of avoiding known situations leading to syncope, early reaction to prodromal syndromes, and physical counterpressure manoeuvers. Drug treatment (e.g. alpha-adrenergic agonists and fludrocortisone) are effective only in patients with orthostatic syncope. In selected patients with reflex syncope of a predominantly cardioinhibitory type, pacemaker implantation may be considered in selected patients.

[Cardiogenic syncope]. / Die kardiogene Synkope.

BACKGROUND: Cardiogenic syncope is a serious clinical event and the cause has to be clarified as rapidly and definitively as possible. DIAGNOSTICS: With knowledge of the pathophysiological background the reason for syncope can mostly be clarified by taking a thorough medical history. In most cases a physical examination, electrocardiogram (ECG) and echocardiography can provide sufficient evidence for most of the causes. Rhythmogenic syncope, however, often tends to be extremely difficult to diagnose which is why many different instruments have been developed for the detection of changes in heart rhythm. Several drugs can induce syncope by different modes of action and is the reason why particular attention should always be paid to this aspect.

[Leg swelling]. / Das geschwollene Bein.

Leg swelling is an extremely frequent symptom with a broad variety of largely differing causes. The most important mechanisms behind the symptom include venous and lymphatic pathology, volume overload, increased capillary permeability, and lowered oncotic pressure. Therefore, the most frequent diseases associated with leg swelling are deep vein thrombosis and chronic venous insufficiency, primary or secondary lymphedema, cardiac failure, hypoproteinemia due to liver or renal failure, idiopathic cyclic edema, and drug-induced edema. Lipedema as a misnomer represents an important differential diagnosis. History and physical examination, when based on a sound knowledge of the diseases of interest, enable a conclusive diagnosis in most cases. Additional test are required in only a minority of patients. The present review discusses pathophysiology and clinical features of the most prevalent types of leg swelling. Finally, a brief guide to differential diagnosis is given.

[Foot lesions]. / Fußläsionen.

The foot is the target organ of a variety of internal diseases. Of upmost importance is the diabetic foot syndrome (DFS). Its complex pathophysiology is driven by the diabetic neuropathy, a vastly worsening effect is contributed by infection and ischemia. Seemingly localised lesions have the potential for phlegmone and septicaemia if not diagnosed and drained early. The acral lesions of peripheral artery occlusive disease (PAOD) have unique features as well. However, their life-threatening potential is lower than that of DFS even if the limb is critical. Notably, isolated foot lesions with a mere venous cause may arise from insufficient perforator veins; the accompanying areas of haemosiderosis will lead the diagnostic path. Cholesterol embolization (blue toe syndrome, trash foot) elicits a unique clinical picture and will become more frequent with increasing numbers of catheter-based procedures. Finally, descriptions are given of podagra and of foot mycosis as disease entities not linked to perfusion. The present review focuses on the depiction of disease and its diagnosis, leaving therapeutic considerations untouched.

[Leg pain]. / Das schmerzhafte Bein.

Leg pain is a very common complaint in clinical medicine which deserves thorough investigation. All tissues of the lower leg are able to cause pain, each of them by different pathomechanisms. In the current review, all the different types of tissue, i.e., spine, neural plexus, peripheral nerves, muscles, and vasculature, are systematically covered. The different disease entities are explained in terms of pathophysiology and clinical picture. Diagnostic measures and pathways are sketched, as well as therapeutic approaches in some instances. Diseases of the bone and joint are omitted since they are the subject of orthopedic surgery.

[Leg ulcers]. / Ulcus cruris.

The lower leg is in particular prone to the development of ulceration. Many different causes may lead to ulceration. Thus, a thorough diagnosis is mandatory, and a biopsy is often required. By far the most common type is the classical venous ulcer due to chronic venous insufficiency, located at the medial ankle. A more complicated-and more difficult to treat-type of venous ulcer is arthrogenic congestion syndrome with its extreme variant of a "legging" ulcer. In cases with severe peripheral arterial disease, an arterial ulcer may develop. The hypertensive ulcer Martorell is associated with arterial hypertension and diabetes; the underlying pathology is occlusion of arteriolar vessels. A typical diabetic ulceration is the necrobiosis lipoidica. Important differential diagnoses of leg ulceration include pyoderma gangrenosum and the calciphylactic ulcer. Due to a long-standing course, an ulceration may turn malignant. Vice versa, ulceration may occur as sign of a primary malignant lesion.

[Leg discoloration]. / Das verfärbte Bein.

Many patients present with discolouration of the legs or with non-ulcerating skin lesions, the most frequent causes being chronic venous insufficiency or other chronic or acute states of congestion. Erysipelas (cellulitis) is also a frequent example of a bacterial skin infection. A complex differential diagnosis arises from all types of immune-mediated skin lesions, opening up the broad spectrum of inflammatory systemic disease, such as vasculitis and sarcoidosis. Livedo like lesions and skin involvement in borreliosis are challenging to classify but of considerable clinical importance. The present review focuses on the description of underlying diseases as well as on diagnosis and differential diagnosis. Therapeutic considerations are discussed in less detail.

[Pseudomigraine with pleocytosis]. / Pseudomigräne mit Pleozytose.

We report two cases of male patients aged 32 and 34 presenting with headache, neurological deficits, and fever. Neither the patients nor their families had a history of migraine. Analysis of the CSF revealed lymphocytic pleocytosis, but no causative infectious agent could be identified. During the attacks, EEG showed focal slowing and was normal afterwards. Computed tomography, MRI, Doppler sonography, and routine blood parameters were normal. In both patients, the focal deficits and the headache vanished within a few hours. We diagnosed a pseudomigraine with pleocytosis (PMP), recently described as an entity. This disorder is characterized by brief relapsing attacks with headache, nausea, vomiting, focal neurological deficits, and a lymphocytic pleocytosis in the CSF. The differentiation from vascular disorders is important because angiography should be avoided due to a high rate of complications in patients with PMP.

Bilateral cerebellar infarctions caused by a stenosis of a congenitally unpaired posterior inferior cerebellar artery.

Bilateral symmetrical cerebellar infarcts in the territory supplied by the medial posterior inferior cerebellar artery (PICA) branches are extremely rare. In the few cases published, it has not been possible to clearly pinpoint the cause of this infarct pattern. The authors present the case history of a 58-year-old man who had acute headaches accompanied by pronounced rotatory vertigo with nausea and vomiting. The neurological examination revealed bilateral cerebellar signs. Cranial magnetic resonance imaging showed bilateral, nearly symmetrical infarcts in the territory of the medial branches of both PICAs. These bilateral PICA infarctions were caused by a stenosis of an unpaired PICA originating from the left vertebral artery supplying both cerebellar hemispheres.

Reorganization of human motor cortex after hand replantation.

In 10 patients, reorganizational changes of the motor cortex contralateral to a replanted hand (MCreplant) were studied one to 14 years after complete traumatic amputation and consecutive successful replantation of the hand. The organizational state of MCreplant was assessed for the deafferentated and peripherally deefferentated hand-associated motor cortex and the adjacent motor representation of the proximal arm. For this, response maps were established for the first dorsal interosseus and biceps brachii muscle using focal transcranial magnetic stimulation (TMS) on a skull surface grid. Characteristics of the maps were center of gravity (COG), number of effective stimulation sites, amplitude sum, and amplitudes and response threshold at the optimal stimulation point. The COG is defined by the spatial distribution of response amplitudes on the map and lies over the cortex region with the most excitable corticospinal neurones supplying the recorded muscle. The COG of the biceps map in MCreplant was shifted laterally by 9.8 +/- 3.6 mm (range 5.0-15.7 mm). The extension of the biceps map in MCreplant was increased and the responses were enlarged and had lowered thresholds. For the muscles of the replanted hand, the pattern of reorganization was different: Response amplitudes were enlarged but thresholds, COG, and area of the cortical response map were normal. The different reorganizational phenomena observed for the motor cortical areas supplying the replanted hand and the biceps brachii of the same arm may be influenced by a different extent of deafferentation and by their different role in hand motor control.

Evaluation of clinical, electrophysiologic, and computed tomographic parameters in replanted hands.

OBJECTIVE: To compare clinical, electrophysiologic, and computed tomography (CT) imaging correlates of reinnervation in replanted limbs. DESIGN: Patients were assessed between 8 and 194 months after replantation of completely severed hands. SETTING: University hospital, departments for neurology and for plastic and reconstructive surgery. PARTICIPANTS: Thirteen patients, 10 with total and 3 with subtotal type V amputation, whose hands had been reattached. INTERVENTIONS: Clinical assessment of function of hand and finger muscles; electromyographic tests of sensory nerve action potentials (SNAPs) of median, ulnar, and radial nerves; and compound motor action potentials (CMAPs) of abductor pollicis brevis, first dorsal interosseus, and abductor digiti minimi muscles. CT assessment of motor unit action potentials. Measurements of both replanted and normal hands. MAIN OUTCOME MEASURES: Medical Research Council scale of force; sensory functions of anatomic areas of nerves; SNAP and CMAP amplitudes; CT area, mean absorption, standard deviation (SD) from mean absorption, and root mean square SD of absorption. RESULTS: Correlates of reinnervation were evidenced by all methods, except by surface recordings of SNAPs, which could not be elicited even in hands with good sensory function. CMAP amplitudes were the electrophysiologic parameter that correlated best with the clinical restoration. Of the CT measures, the cross-sectional area was the most useful parameter for the detection of denervation, but no CT parameter was sufficiently sensitive to detect reinnervation. In cases with good functional recovery, CMAP amplitudes were superior to clinical rating in showing incomplete reinnervation. CONCLUSION: The combination of clinical and electrophysiologic methods supplied sufficient data for a reliable evaluation of reinnervation. Usually, CT parameters did not add useful information.

Comparison of various coils used for magnetic stimulation of peripheral motor nerves: physiological considerations and consequences for diagnostic use.

We compared the ability of 4 magnetic coils to activate peripheral nerves in healthy subjects. No differences in motor threshold intensities were found between the coils, but the intensities needed to elicit maximum compound muscle action potential (CMAP) amplitudes were different. For superficial nerves maximum CMAPs in comparison with electrical stimulation were usually but not always found. CMAPs were at their maximum only when the direction of induced current flowed from proximal to distal and when a certain part of the coil was over the nerve. Distal nerve stimulation was time consuming. Due to artifacts many stimuli were necessary and sometimes no maximum CMAP could be elicited. CMAPs were much less sensitive to position changes of the coil than to changes in an electrical stimulator. Small circular coils were superior to larger coils in terms of the lower intensities necessary to elicit maximum CMAPs, better focusing of the stimulus, and less artifacts. For deep nerves amplitudes were always submaximal. Coactivation of nearby nerves and underlying muscles was another main drawback especially at proximal sites and for coils of large diameter. Despite better focusing, double coils are less useful due to their great diameter. Magnetic stimulation cannot replace electrical neurography at the moment, even if different coils are used at different sites of stimulation.