Introduction
The most important recommendations and statements of this guideline (all with approval rates between 90 and 100%)
Encephalopathy
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Encephalopathies are quite common in COVID-19, especially in severe cases.
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Symptoms and clinical course are highly heterogeneous.
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For encephalopathies triggered by SARS-CoV-2 are discussed as pathomechanisms: hypoxia, sepsis, severe systemic inflammation, renal failure and cytokine storm.
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Biomarkers found in this context in patients with severe COVID-19 were IL-2, IL-6, IL-7, GCSF, TNF-alpha1.
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A solid basis for specific therapeutic measures does not yet exist.
Meningoencephalitis
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In the case of newly occurring central neurological symptoms, especially in the case of disturbances of consciousness, acute cognitive deficits and epileptic seizures, further diagnosis with cerebral imaging (MRI), EEG examination and cerebrospinal fluid diagnostics is necessary.
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The use of corticosteroids in high doses may be attempted if symptoms persist.
Risk of COVID-19 under immunotherapy
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It is advisable to continue immunotherapy. Individual risk factors such as patient age, morbidity and regional prevalence of COVID-19 should be taken into account to assess the individual patient risk and in individual cases de-escalation strategies such as a change of therapy or an extension of the interval should be evaluated.
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In case of COVID-19 disease, aspects such as disease activity of the underlying neurological disease as well as the previous course of therapy should be considered and the immune therapy should be paused if necessary.
Guillain-Barré syndrome (acute inflammatory demyelinating polyneuritis - AIDP)
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Guillain-Barré syndrome (GBS) is a serious complication of COVID-19 disease and can occur within days of the first respiratory symptoms.
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Clinically, mild courses up to severe tetraparesis and cranial nerve involvement are possible.
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Electroneurographically, a demyelinating pattern of damage usually dominates, although axonal processes are also reported.
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CSF diagnosis is necessary to exclude an infectious etiology. In most cases a cytoalbuminous dissociation appears.
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Serological testing of ganglioside antibodies is recommended.
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Intravenous immunoglobulins as well as plasma exchange procedures are to be regarded as equivalent and should be initiated promptly.
Acute disseminated encephalomyelitis
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Newly occurring multifocal neurological symptoms suggest acute disseminated encephalomyelitis (ADEM), so that rapid diagnosis including MRI and CSF analysis should be initiated.
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MRI imaging with contrast agent administration is essential for the detection of inflammatory lesions. A complementary hemorrhage-sensitive sequence helps to detect a hemorrhagic component.
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A normal CSF finding does not exclude the diagnosis of ADEM.
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A 3–5-day cycle with methylprednisolone 1 g/day should be administered intravenously. If symptoms persist intravenous immunoglobulins should be administered.
Stroke
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Worldwide, the number of patients hospitalized for stroke has fallen under the COVID 19 pandemic. In the pandemic, it is important for all physicians involved in stroke care to maintain the best possible quality of care for cerebrovascular diseases even under the current difficult conditions.
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Ischemic strokes and, more rarely, intracerebral hemorrhage (ICH) occur in patients with COVID-19 disease and are associated with a more severe course of the disease.
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When treating COVID-19 patients, it is important to detect possible cerebrovascular complications and immediately initiate the necessary diagnostic procedures.
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A confirmed or presumed infection with SARS-CoV-2 in patients with acute stroke should not lead to different treatment than for other stroke patients. They should receive the same acute diagnostics and acute treatment as all stroke patients, provided that appropriate hygiene measures are observed.
Epilepsy
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If epileptic seizures or a status epilepticus (SE) occur in patients with COVID-19 disease, it should be clarified whether it is a first-time seizure or a recurrence of previously known epilepsy.
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In case of unclear disturbance of consciousness, an EEG should be performed to detect and localize activity typical for epilepsy and to detect or exclude a non-convulsive SE.
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The treatment of seizures or SE should be performed according to the respective guidelines.
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Contraindications and interactions of anticonvulsants with substances used for COVID-19 disease should be taken into account.
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In patients with known fever-associated seizures, an NSAID (e.g. paracetamol) should be given.
Chemosensory disturbances
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Infection with SARS-CoV-2 can lead to chemosensory disorders, with hyposmia and often anosmia.
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During the pandemic, a suddenly appearing olfactory disorder (anosmia) during free nasal breathing is very likely an expression of an infection with SARS-CoV-2.
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Olfactory disturbances can precede other disease symptoms and are therefore epidemiologically relevant (early identification of new “hot spots”).
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The olfactory disorder in COVID-19 seems to be mostly temporary. Whether or not a complete restitution is regularly achieved cannot yet be conclusively assessed.
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-Should the olfactory function does not return to normal within 3–4 weeks, a neurological and ENT presentation with further diagnostics is recommended.
Nerve and muscle affections
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Myalgia, fatigue and hyper-CK-emia are the most common triad forms (40–70%) of skeletal muscle affection in COVID-19 cohorts.
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A COVID-19 disease requiring intensive care with invasive ventilation can lead to ICUAW (“ICU-acquired weakness” [ICU: intensive care unit]), a clinical picture in which CIP (“critical illness polyneuropathy”) and CIM (“critical illness myopathy”) intertwine.
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There seems to be no massively increased risk for neuromuscular patients suffering from SARS-CoV-2 infection.
Neurological intensive care medicine
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Neurological manifestations of COVID-19 can easily remain masked in the severe, pulmonally dominated intensive care setting. Therefore, an active search for involvement of the central or peripheral nervous system is necessary.
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Invasive ventilation with PEEP (Positive End-Exspiratory Pressure), a permissive hypercapnia or in abdominal position can lead to an increase of the intracranial pressure, but still be necessary.
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If cerebral or spinal involvement by COVID-19 is suspected, a CT or MRI should be performed. In some patients who cannot be reliably examined clinically due to severe intensive care and/or analgosedation, this may also be indicated prophylactically (e.g. cerebral CT before ECMO).
Neuroimmunological manifestations of COVID-19
(Infectious) inflammatory complications - (Meningo-)encephalitis
Diagnosis
Therapy
(Autoimmune) inflammatory diseases
Substance | Diseases | General Recommendation during pandemic | Specific recommendations in case of infection |
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DNA-synthesis Interference strategies | |||
Azathioprin | MG, NMOSD, PACNS, IIM, AIE, Vasculitis, Neurosarcoidosis | Continuation | Discontinuation |
Methotrexate | MG, NMOSD, PACNS, IIM, AIE, Vasculitis, Neurosarcoidosis | Continuation | Discontinuation |
Cyclophosphamid | PACNS, AIE, Vasculitis, Collagene vascular disease | Continuation, in case of longterm stable disease de-escalation | Discontinuation |
Mitoxantron | SPMS | Alternative treatments, in case of longterm stable disease: dose-reduction or termination | Discontinuation |
Teriflunomid | RRMS | Continuation | Continuation, in case of severe lymphopenia discontinuation |
Mycophenolat-Mofetil | MG, NMOSD, PACNS, IIM, Vasculitis, Neurosarcoidosis | Continuation | Continuation, in case of severe lymphopenia discontinuation |
Cladribin | RRMS | Delay next treatment cycle | Discontinue, look for alternate treatment |
Immune cell depletion strategies | |||
Rituximab | MG, NMOSD, PACNS, IIM, AIE, CNS-Vasculitis, CIDP | Delay next treatment cycle; CD19-B-Zell-Monitoring | Discontinue, look for alternate treatment |
Ocrelizumab | RRMS, PPMS | Delay next treatment cycle; CD19-B-Zell-Monitoring | Discontinue, look for alternate treatment |
Inebilizumab | NMOSD | Delay next treatment cycle; CD19-B-Zell-Monitoring | Discontinue, look for alternate treatment |
Alemtuzumab | RRMS | Delay next treatment cycle; CD19-B-Zell-Monitoring | Discontinue, look for alternate treatment |
Leucocyte sequestration | |||
Fingolimod/Ozanimod | RRMS | Continuation | Continue, or discontinuation for a few weeks |
Siponimod | SPMS | Continuation | Continue, or discontinuation for a few weeks |
Natalizumab | RRMS | Continuation or delay of treatment cycle | Continuation or delay of treatment cycle |
Pleiotropic Immunomodulation | |||
Glatirameracetat | RRMS | Continuation | Continuation |
Dimethylfumarat | RRMS | Continuation Severe Lymphopenia: Discontinue | Continuation Severe Lymphopenia: Discontinue |
Cytokines | |||
IFN-β | RRMS, SPMS | Continuation | Continuation |
Tocilizumab/Satralizumab | NMOSD | Continuation | Continuation |
Complement inhibitors | |||
Eculizumab | MG, NMOSD | Continuation | Continuation |
Intracellular pathway Blockers | |||
Ciclosporin A | MG, IIM | Continuation | Continuation, dose reduction |
Acute therapies | |||
Steroid pulse therapy | MS, MG, NMOSD, PACNS, IIM, AIE, Vasculitis, Neurosarcoidosis | Only in case of high disease activity | Discontinuation or dose reduction |
Chronic glucosteroid therapy | NMOSD, MG, PACNS, IIM, CIDP, Vasculitis, Neurosarcoidosis | Dose reduction | Stable disease: Dose reduction |
IVIG | MG, IIM, CIDP, GBS | Continuation or delay of treatment cycle | Continuation or delay of treatment cycle |
Plasmapheresis/Immuno-adsorption | MS, MG, NMOSD, AIE, IIM, GBS | Continuation | Continuation |
Acute encephalopathy and acute encephalitis associated with COVID-19
Diagnosis
Therapy
Cerebrovascular diseases
SARS-CoV-2 as a risk factor for stroke
Effects of the SARS-CoV-2 pandemic on the care of stroke patients
Diagnosis
Therapy
Epileptic seizures and epilepsy in adults
Definition and classification
Diagnosis
Therapy
Disorders of the chemosensory system: anosmia, ageusia
Definition and classification
Disturbances of the chemosensory system in COVID-19
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Self-isolation/quarantine
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Testing for SARS-CoV-2 (via telephone contact with family doctor/health office)
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Use of personal protective equipment in professional contact with affected persons