Evaluation of ischemic stroke patients associated with COVID-19

Aims: Many neurological symptoms and complications, including stroke, may develop during Coronavirus disease-2019 (COVID-19). This study evaluated the risk, timing, prognosis, relationship between stroke and COVID-19, and treatment modalities of stroke due to COVID-19 by examining stroke patients with COVID-19. Methods: This retrospective cross-sectional study included 12 patients aged ≥18 years with acute ischemic stroke and who were hospitalized with a confirmed diagnosis of COVID-19. In this study, demographic findings, clinical and stroke symptoms, stroke time, comorbid conditions that could pose a risk for stroke, inflammatory markers, D-dimer levels, imaging results, cardiologic evaluations, O2 need, administered treatments, intensive care support, and prognosis were recorded retrospectively from patient files. Results: Of the patients, 50% were male and 50% were female. The mean age was 70.6±9.3 (range, 55-84) years. The most common comorbid conditions were hypertension (58.3%) and diabetes mellitus (41.7%). Stroke developed at a median of 10.5 [interquartile range (IQR), 5-19.5] days after symptoms COVID-19. The mean National Institutes of Health Stroke Scale score was 7.8±4.7 (range, 3-18) (1-25). The average D-dimer and IL-6 levels of the patients were measured as 3.7 (IQR, 2.7-7.6) mg/L and 44.1±41.2 (range, 4.0-117) pg/mL, respectively. Most patients (66.7%) required oxygen during their hospitalization. Conclusions: Patients with a stroke due to COVID-19 infection have several risk factors, particularly diabetes mellitus and hypertension. They had increased D-dimer levels, and most patients had severe disease. These results suggested that COVID-19 triggered or facilitated stroke rather than being an independent cause.

Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Greater occipital nerve block efficacy in COVID‑19 associated headache: a preliminary study

COVID‑19 is an infection caused by the new coronavirus SARS‑CoV‑2. Headache is one of the most common neurological findings. In the treatment of various chronic headaches, the greater occipital nerve (GON) block is often used as a safe and effective method. The aim of our study was to investigate the effectiveness of the GON block in the treatment of headaches observed in COVID‑19 patients. Between March and May 2020, 27 patients (with laboratory‑confirmed 2019‑nCoV infection by next‑generation sequencing confirmation of real‑time PCR) that had moderate or severe headache associated with COVID‑19 and treated with a single session of GON block were retrospectively analyzed. The visual analogue scale (VAS) values and the number of analgesic usage of patients were recorded before and after the blockade on the 1st and 10th days. Fifteen (55.6%) patients included in the study were male and twelve (44.4%) were female. In terms of VAS values, the difference between pre‑treatment and post‑treatment values on the 1st and 10th days was found statistically significant. Likewise, the difference between analgesic use before and after the procedure was statistically significant. GON block appears to be an effective pain management method in COVID‑19 related headache, and it revealed promising reductions in pain scores and analgesic usage. As well as we know, this is the first study of "COVID‑19 associated headache treated with GON blockade". More long term and well‑designed prospective studies with more participants are needed to better define this headache and develop effective treatment strategies.

Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19.

BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.

EEG changes in intensive care patients diagnosed with COVID-19: a prospective clinical study.

INTRODUCTION: Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was declared a pandemic on March 11th, 2020, by the World Health Organization (WHO). There has been a substantial increase in the epileptic seizures and status epilepticus reported in the pandemic period. In this context, it is aimed with this study to identify the electroencephalography (EEG) features of patients admitted to the intensive care unit with the diagnosis of COVID-19 and to look for any specific patterns in these features. MATERIAL AND METHOD: The material of this study primarily comprised the neurological evaluations and continuous EEG recordings of 87 intensive care patients who were diagnosed with COVID-19. In addition, demographic and clinical features and comorbid conditions of these patients were also analyzed, and any correlation thereof was investigated. RESULTS: The EEG data of 87 patients who were diagnosed with COVID-19 and were followed up in the intensive care unit were recorded and then analyzed. Abnormal EEG findings were detected in 93.1% (n = 81) of the patients, which were found to increase significantly with age (p < 0.001). The mean age of patients with specific epileptiform abnormalities on EEG was found to be significantly higher than those with non-specific abnormalities. Epileptiform discharges were seen in 37.9% (n = 33) of the patients. Nonconvulsive status epilepticus (NCSE) was detected in 5.7% of the patients, and antiepileptic drugs were started in 25 (28.7%) of the patients. DISCUSSION: Statistically significant EEG changes were observed in the continuous EEGs of the patients followed up in the intensive care unit due to COVID-19 infection. However, further studies are needed to associate the EEG changes observed in the COVID-19 patients with the epileptogenesis of COVID-19 infection.

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism.

BACKGROUND AND AIM: Pathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache. METHODS: This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied. RESULTS: The mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. CONCLUSION: Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.

Latent class cluster analysis identified hidden headache phenotypes in COVID-19: impact of pulmonary infiltration and IL-6.

BACKGROUND AND OBJECTIVE: Clinical studies on COVID-19 headache are limited. This prospective study aimed to define headache characteristics, associated clinical and laboratory factors, and treatment response in COVID-19. METHODS: Cross-sectional study enrolled 287 patients diagnosed with COVID-19 and hospitalized on a regular ward during the pandemic. All patients were examined face to face and followed by a neurologist during their stay in the hospital. The characteristics, concomitant symptoms, treatment responses, and laboratory findings of COVID-19-associated headaches were recorded. RESULTS: Eighty-three COVID-19 patients reported headache (28.9%), in which 85.5% had no prior headaches. Mean age was 48.40 ± 15.90 and 58% was men. Compared to COVID-19 patients without headache (n = 204), patients with headache showed significantly higher frequency of pulmonary involvement (76%) and increased D-dimer levels. Fifty-nine percent of headaches responded iv paracetamol 1000 mg, and 85% of the paracetamol unresponsive headaches were relieved by greater occipital nerve (GON) blocks. Latent class cluster analysis identified 2 distinct class of bilateral, frontal, throbbing headaches: severe (VAS > 84), longer (> 14 h), frequent (> 7 headache days), paracetamol unresponsive-GON responsive headaches (85%), with pulmonary involvement (100%), and higher IL-6 levels (> 90 pg/mL) were classified in cluster 1. Cluster 2 included moderately affected patients (VAS > 54, > 6 h, > 4 days, 60% pulmonary involvement, > 20 pg/mL IL-6) and paracetamol responsive headaches (96%). VAS scores showed positive linear correlation with IL-6 levels (p < 0.001; r = 0.567). CONCLUSION: The intensity, duration, frequency, bilateral frontal location, and treatment response of COVID-19 headache was related to pulmonary involvement and IL-6 levels, which indicated a role of inflammation in determining the headache manifestations in moderately affected hospitalized patients. ROC curve cutoff values pointed that VAS > 70 severity, > 9 h duration, > 5 headache days, and IL-6 > 43 pg/mL levels can be diagnostic for COVID-19 headache. GON blocks can effectively abort headache when patients are unresponsive to paracetamol, and other NSAIDs are avoided during the SARS-CoV-2 infection.

Cerebral hemodynamic alterations in patients with Covid-19

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.

A prospective clinical study of detailed neurological manifestations in patients with COVID-19.

BACKGROUND: COVID-19 is a virus pandemic. According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail. This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19. METHODS: Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated. Detailed neurological examinations and evaluations of all patients were performed. All evaluations and examinations were performed by two neurologists who have at least five-year experience. RESULTS: This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19. Neurological findings were present in 83 of 239 patients (34.7%). The most common neurological finding was a headache (27.6%). D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 0.05). IL-6 level was found to be significantly higher in patients with headache than without headache (p < 0.05). Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 0.05). CONCLUSION: Neurological symptoms are often seen in patients with COVID-19. Headache was the most common seen neurological symptom in this disease. Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache. It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread.