Management of cognitive impairment associated with post-COVID-19 syndrome: recommendations for primary care.

Introduction: Although post-COVID-19 syndrome (PCS) with cognitive impairment is increasingly encountered in primary care, evidence-based recommendations for its appropriate management are lacking. Methods: A systematic literature search evaluating the diagnosis and treatment of cognitive impairment associated with PCS was conducted. Practical recommendations for the management of PCS-associated cognitive impairment in primary care are summarized, based on an evaluation of pharmacological plausibility and clinical applications. Results: Currently, the pathology of cognitive impairment associated with PCS remains unclear with no high-quality data to support targeted interventions. Existing treatment approaches are directed towards symptom relief where counseling on the chronicity of the disease and regular reassessments at 4- to 8-week intervals is considered reasonable. Patients should be informed and encouraged to adopt a healthy lifestyle that centers around balanced nutrition and appropriate physical activities. They may also benefit from the intake of vitamins, micronutrients, and probiotics. The administration of Ginkgo biloba extract could offer a safe and potentially beneficial treatment option. Other non-pharmacological measures include physiotherapy, digitally supported cognitive training, and, if indicated, ergotherapy or speech therapy. In most patients, symptoms improve within 8 weeks. If serious, ambiguous, or when new symptoms occur, specialized diagnostic measures such as comprehensive neurocognitive testing or neuroimaging should be initiated. Very few patients would require inpatient rehabilitation. Conclusion: PCS with cognitive impairment is a debilitating condition that could affect daily functioning and reduce work productivity. Management in primary care should adopt a multidisciplinary approach, centering around physical, cognitive, and pharmacological therapies.

Alleviation of Post-COVID-19 Cognitive Deficits by Treatment with EGb 761®: A Case Series.

BACKGROUND Cognitive symptoms persisting longer than 3 months after infection, such as memory loss, or difficulties concentrating, have been reported in up to one-third of patients after COVID-19. Evidence-based therapeutic interventions to treat post-COVID-19 symptoms (also called "Long-COVID symptoms") have not yet been established, and the treating physicians must rely on conjecture to help patients. Based on its mechanism of action and its efficacy in treating cognitive impairment, as well as its good tolerability, the Ginkgo biloba special extract EGb 761 has been suggested as a remedy to alleviate cognitive post-COVID-19 symptoms. In many studies, EGb 761 has been demonstrated to protect endothelial cells, to have potent anti-inflammatory effects, and to enhance neuroplasticity. CASE REPORT Here, we report for the first time the application of EGb 761 in the therapy of post-COVID-19-related cognitive deficits. Three women and 2 men, aged 26 to 59 years (average age 34.6 years), presented with concentration and attention deficits, cognitive deficiencies, and/or fatigue 9-35 weeks after infection. A daily dose of 2×80 mg of EGb 761 did not cause any detectable adverse effects, and it substantially improved or completely restored cognitive deficits and, when initially present, also other symptoms, such as fatigue and hyposmia, within an observation period of up to 6 months. CONCLUSIONS Our observations support the hypothesis that EGb 761 might be a low-risk treatment option for post-COVID-19 patients with cognitive symptoms. Moreover, we derive recommendations for randomized controlled clinical trials to confirm efficacy in that indication.

Covid-19: Involvement of the nervous system. Identifying neurological predictors defining the course of the disease.

The main objective of this study was to analyse neurological symptoms during a Covid-19 infection and determine the pattern of symptoms by comparing outpatients with inpatients. A further goal was to identify possible predictors, such as pre-existing conditions and neurological symptoms. We recorded the clinical data of 40 inpatients and 42 outpatients in this retrospective, cross sectional study. Of them, 68 patients (83%), evenly distributed between the two groups, suffered from neurological symptoms. We identified the onset of neurological symptoms and the related time ranges in 41 patients (36 outpatients and 5 inpatients). Of these, 63.4% reported neurological symptoms on the first or second day of illness. 49 patients (72%) showed combinations of at least two to a maximum of seven different neurological symptoms. A more severe course of disease was correlated with age and male sex, but age was not identified as a predictor for the occurrence of neurological symptoms. Women suffered from central and neuromuscular symptoms more often than men (p = 0,004). The most common symptoms were fatigue (54%), headache (31%), loss of taste (31%), and loss of smell (27%). Pre-existing dementia was associated with increased lethality; similarly, pre-existing stroke was associated with a more severe course of Covid-19 infection. Hallucinations and confusion were related to an increased likelihood of death. The present data demonstrate the importance of comprehensive neurological support of inpatients and outpatients affected by Covid-19.

Spontaneous bilateral diaphragmatic paralysis: a rare cause of respiratory failure.

Bilateral diaphragmatic paralysis (BDP) can occur in the course of motor neuron disease, myopathy, or from mechanical damage or the use of "ice slush" during cardiac surgery. BDP has been observed during and after infections, associated with systemic lupus erythematosus and mediastinal tumors, or may have idiopathic etiology. It is a serious and life-threatening condition. A 62-yr-old man presented with slowly progressive dyspnoea that worsened in the supine position and on bending forward. Chest X-rays, fluoroscopy, lung-function parameters and blood-gas analysis revealed respiratory failure. BDP was confirmed from a phrenic nerve stimulation test and measurement of transdiaphragmatic pressure (Pdi). Since there was no evidence of an obvious etiology, BDP was considered idiopathic. Other muscles were not involved. The pathological basis was probably focal demyelination in segments of the phrenic nerve. Because of increasing diaphragmatic muscle fatigue, the patient was treated with a nasal mask providing bi-level positive airway pressure (BiPAP) ventilation during the night. Clinical suspicion of BDP should always be raised in patients suffering slowly progressive dyspnoea without any obvious cardiac, metabolic or traumatic predisposing factors, and orthopnoea and dyspnoea on bending forward. Electromyographic tests and measurement of Pdi can reveal the correct diagnosis.

Management of fatigue in patients with multiple sclerosis.

As long as no causal treatment is available for multiple sclerosis (MS), and as long as only some patients with MS respond to immunomodulators, symptomatic treatment is of paramount importance. Fatigue is the most common symptom of MS and is associated with a reduced quality of life. It is described as the worst symptom of their disease by 50-60% of patients. The first step in managing MS-related fatigue is identifying and eliminating any secondary causes. Primary fatigue syndrome can be alleviated with drug treatment in many cases. Modafinil has been shown to be effective in some studies, and amantadine is an alternative for patients who do not respond to or cannot tolerate modafinil. The nonpharmacological management of fatigue in MS includes inpatient rehabilitation and aerobic endurance exercise. This article describes the pathophysiology, diagnosis and treatment of MS-related fatigue--the most common symptom of MS.

[Therapy of day time fatigue in patients with multiple sclerosis]. / Therapie der Tagesmüdigkeit bei Patienten mit multipler Sklerose.

Fatigue is the most common symptom of multiple sclerosis. 75%-90% of patients with multiple sclerosis report having fatigue, and 50%-60% describe it as the worst symptom of their disease. Fatigue is significantly associated with reduced quality of life and is also a major reason for unemployment, especially for patients with otherwise minor disability. The mechanisms underlying abnormal levels of fatigue in multiple sclerosis are poorly understood. To date, drug treatment has been only partially successful in alleviating fatigue, and effects vary widely from patient to patient. Amantadine and modafinil showed to be effective in the treatment of fatigue in some studies. Non-pharmacological management of fatigue in multiple sclerosis includes inpatient rehabilitation and endurance training. There is also evidence, that pulsing electromagnetic fields may improve fatigue associated with multiple sclerosis. This paper summarizes the recent literature on pathophysiology, diagnosis and therapy of the most common symptom of multiple sclerosis.

Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label study.

BACKGROUND: Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants. Results of a placebo-controlled study showed it to improve fatigue in multiple sclerosis (MS) at a dose of 200 mg daily, but not at a dose of 400 mg daily. OBJECTIVE: To establish the efficacy, safety and appropriate dose of modafinil in the treatment of fatigue and sleepiness in patients with multiple sclerosis. METHOD: A total of 50 patients diagnosed with MS (mean age 40.4 +/- 10.3 years, 30 females/20 males; MS type: 36 relapsing remitting, 1 primary progressive, 13 secondary progressive; mean disability level 3.8 +/- 1.5 on the Kurtzke EDSS) and complaining of chronic fatigue were enrolled in a prospective 3-month, two-center, open-label study. Efficacy was evaluated with the Fatigue Severity Scale (FSS, score range 0-42), the Epworth Sleepiness Scale (ESS, score range 0-24) and by subjective patient appraisal of change of fatigue, quality of life and overall satisfaction with treatment. Adverse effects (AEs) were recorded throughout the study. Treatment was started with a single daily dose of 100 mg in all patients. In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg. RESULTS: Three patients discontinued modafinil because of AEs (nervousness, dizziness). Two patients (4 %) were treated with 50 mg, 25 (50 %) with 100 mg, 21 (42 %) with 200 mg and 2 (4 %) with 300 mg daily. No patient required 400 mg daily. Mean FSS scores were 30.3 +/- 8.5 at baseline and 25.4 +/- 3.7 at 3 months (p < 0.0001). Mean ESS scores were 9.7 +/- 3.9 at baseline and 4.9 +/- 2.9 at 3 months (p < 0.0001). Self-appraisal of change of fatigue showed clear improvement in 41 patients (87.2 %), some improvement in 4 (8.5 %) and no change in 2 (4.3 %). Overall clinical condition was clearly improved in 43 patients (91.5 %), somewhat improved in 1 patient (2.1 %), and unchanged in 3 patients (6.4 %). No patient reported worsening of overall clinical condition. CONCLUSIONS: Treatment with modafinil significantly improves fatigue and sleepiness and is well tolerated by patients with MS. Unlike the higher dose regimen required in narcolepsy, a low-dose regimen of modafinil is effective in MS.