Nervous system involvement after infection with COVID-19 and other coronaviruses.

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

Early Neurorehabilitation and Recovery from Disorders of Consciousness After Severe COVID-19.

BACKGROUND: Early neurorehabilitation improves outcomes in patients with disorders of consciousness (DoC) after brain injury, but its applicability in COVID-19 is unknown. We describe our experience implementing an early neurorehabilitation protocol for patients with COVID-19-associated DoC in the intensive care unit (ICU) and evaluate factors associated with recovery. METHODS: During the initial COVID-19 surge in New York City between March 10 and May 20, 2020, faced with a disproportionately high number of ICU patients with prolonged unresponsiveness, we developed and implemented an early neurorehabilitation protocol, applying standard practices from brain injury rehabilitation care to the ICU setting. Twenty-one patients with delayed recovery of consciousness after severe COVID-19 participated in a pilot early neurorehabilitation program that included serial Coma Recovery Scale-Revised (CRS-R) assessments, multimodal treatment, and access to clinicians specializing in brain injury medicine. We retrospectively compared clinical features of patients who did and did not recover to the minimally conscious state (MCS) or better, defined as a CRS-R total score (TS) ≥ 8, before discharge. We additionally examined factors associated with best CRS-R TS, last CRS-R TS, hospital length of stay, and time on mechanical ventilation. RESULTS: Patients underwent CRS-R assessments a median of six (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients recovered to MCS after a median of 8 days (IQR 2-14) off continuous sedation; they had lower body mass index (p = 0.009), lower peak serum C-reactive protein levels (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028), and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time, and the best CRS-R TS was significantly higher than the last CRS-R TS (median 8 [IQR 5-23] vs. 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with a higher last CRS-R TS. CONCLUSIONS: More than half of our cohort of patients with prolonged unresponsiveness following severe COVID-19 recovered to MCS or better before hospital discharge, achieving a clinical benchmark known to have relatively favorable long-term prognostic implications in DoC of other etiologies. Hypoxia, systemic inflammation, sedation, and neuromuscular blockade may impact diagnostic assessment and prognosis, and fluctuations in level of consciousness make serial assessments essential. Early neurorehabilitation of these patients in the ICU can be accomplished but is associated with unique challenges. Further research should evaluate factors associated with longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.

COVID-19 and hospital restrictions: physical disconnection and digital re-connection in disorders of consciousness.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic forced hospitals to adopt tighter restrictions, the most impacting is no access to visitors. Disorder of consciousness (DOC) due to severe acquired brain injury is a condition needing neurorehabilitation and the role of relatives is essential, hence besides physical "disconnection" digital "re-connection" is crucial. We aimed to assess whether digital communication benefits in patients with DOC, considering the sensorial and emotional deprivation due to the COVID-19 emergency lock-down.Methods: For eleven consecutive patients with DOC admitted to our Intensive Neurorehabilitation Care (mean age: 45; females: 9), two observers registered neurobehavioral changes during a video-calls with their relatives. Heart-rate variability was measured before and during the calls. The video-call was performed by using two displays of different sizes: tablet (T-video-call) and large screen (LS-Video-call).Results: The video-calls impacted on the patients' vigilance and in the relationship with relatives. Moreover, positively impacted on their relatives. The current results showed significant greater impact on patients during the LS-video-call than when they are exposed to T-video-call.Conclusions: During the COVID-19 pandemic, besides the physical disconnection to stop the contagion spread, a "digital re-connection" is needed for all and especially for fragile population groups as patients with DOC.

Letter to the editor: COVID in patients with brain injury with a disorder of consciousness: a pathogenetic theory.

We recently published in this journal (Caronni and colleagues, Brain Injury, 2021-04-16) the first description of the spread of the SARS-CoV-2 infection in a cohort of brain injured patients with a disorder of consciousness (DOC). Surprisingly enough we showed that, in these patients, the COVID was moderate and did not result in fatalities. The pathogenesis of the COVID is characterized by the profound dysregulation of the immune system. To explain our findings, we speculated that the immunosuppression due to the brain injury could be protective against the development of the COVID in patients with DOC. More recently, a second group of authors (Marino and colleagues, PLoSOne, 2021-06-30) described the course of the COVID in an independent cohort of patients with DOC. Since our results were quite unexpected, we have been very comforted by the data reported by Marino and colleagues. Moreover, these data also offer a unique opportunity to further evaluate our theory regarding the COVID pathogenesis in patients with DOC. In the current Letter to the Editor it is shown that the independent data presented by Marino and colleagues do support our theory. Waiting for larger cohorts to further test it (and in case falsify it), our interpretation seems to remain valid.

Posterior reversible encephalopathy syndrome (PRES) associated with COVID-19.

The novel human coronavirus disease (COVID-19) has been associated with vascular and thrombotic complications, some of which may result from endothelial dysfunction, including the posterior reversible encephalopathy syndrome (PRES). We report a case series of 8 patients with COVID-19 and PRES diagnosed at two academic medical centers between March and July of 2020. The clinical, laboratory and radiographic data, treatment, and short-term outcomes were retrospectively analyzed. The mean age was 57.9 ± 12 years, and 50% were women. Four patients had previous vascular comorbidities. All the patients suffered from severe pneumonia, requiring intensive care unit admission. Five patients were not hypertensive at presentation (all SBP < 127 mmHg). Neurologic symptoms included seizures in 7 patients; impaired consciousness in 5 patients; focal neurological signs in 3 patients; and visual disturbances in 1 patient. All patients underwent brain magnetic resonance imaging which indicated asymmetric T2 prolongation or diffusion changes (50%), extensive fronto-parieto-occipital involvement (25%), vascular irregularities (12.5%) and intracranial hemorrhage (25%). Four patients were treated with tocilizumab. Three patients were discharged without neurologic disability, 2 patients had persistent focal neurologic deficits and 2 expired. One patient's prognosis remains guarded. Together, these data support the relationship between PRES and endothelial dysfunction associated with severe COVID-19. In patients with severe COVID-19, PRES can be triggered by uncontrolled hypertension, or occur independently in the setting of systemic illness and certain medications. Like other infectious processes, critically ill patients with COVID-19 may be at greater risk of PRES because of impaired vasoreactivity or the use of novel agents like Tocilizumab.

Characteristic of Parkinson's disease with severe COVID-19: a study of 10 cases from Wuhan.

Information about Parkinson's disease (PD) patients with severe COVID-19 is scarce. We aimed to analyze the clinical characteristics, outcomes, and risk factors affecting the prognosis of PD patients with severe COVID-19 infection. Clinical data of severe COVID-19 patients admitted at the Union Hospital, Wuhan between 28th January and 29th February 2020 were collected and analyzed. 10 patients (1.96%) had a medical history of PD with a mean (SD) age of 72.10 (± 11.46) years. The clinical characteristics and outcomes of severe COVID-19 with and without PD patients were then compared. There was no significant difference in overall mortality between the PD and non-PD patients with severe COVID-19 (p > 0.05). In PD patients with severe COVID-19, the proportion of patients with critical type, disturbance of consciousness, incidence of complications, white blood cells count and neutrophils counts on admission seem higher in the non-survivors. PD patients with older age, longer PD duration, and late stage PD may be highly susceptible to critical COVID-19 infection and bad outcome. The PD patients with consciousness disorders and complications that progressed rapidly are at increased risk of death.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

[Utility and prognosis value of the electroencephalogram in COVID-19 and encephalopathy: electroencephalographic patterns in a case series]. / Utilidad y valor pronóstico del electroencefalograma en la COVID-19 y la encefalopatía: patrones electroencefalográficos en una serie de casos.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused a collapse situation in many hospitals around the world. The aim of this study is to analyse the utility of the electroencephalogram (EEG) in the management of the neurological patient during the COVID-19 pandemic. PATIENTS AND METHODS: The Clinical Neurophysiology Department of the Hospital Central de la Defensa Gomez Ulla was dissolved due to the hospital collapse situation. Therefore, the EEG was performed exceptionally in those cases with the greatest probability of providing a benefit in its management. We describe seven patients (four in ICU and three hospitalized) diagnosed with COVID-19, who underwent through an EEG. RESULTS: The EEG showed abnormalities in all cases, including one case of brain death. The EEG resulted in a change in clinical management in four of the patients (57%) and helped the clinician provide information to the family. In the other three cases, a toxic-metabolic origin was suspected before the EEG was performed, so it did not imply a change in the clinical management already proposed, although it facilitated a prognostic orientation. Slow polymorphic waves were evident in five cases. Five patients were unresponsive. Currently, one patient remain hospitalized and four have died. CONCLUSIONS: The EEG was useful and facilitated decision making in COVID-19 patients in whom it was requested. It guided the diagnosis in cases where CT was non-contributory and led to a change in therapeutic management in most patients. The most frequent findings were signs of encephalopathy and epileptiform discharges.

TITLE: Utilidad y valor pronóstico del electroencefalograma en la COVID-19 y la encefalopatía: patrones electroencefalográficos en una serie de casos.Introducción. La enfermedad por coronavirus 2019 (COVID-19) causó el colapso de muchos hospitales. El objetivo de este estudio es analizar la utilidad del electroencefalograma (EEG) en el tratamiento del paciente neurológico durante la pandemia de COVID-19. Pacientes y métodos. El Servicio de Neurofisiología Clínica del Hospital Central de la Defensa Gómez Ulla fue disuelto debido a la situación de saturación hospitalaria. En consecuencia, se realizó un EEG excepcionalmente a los pacientes a los que tenía mayor probabilidad de aportar un beneficio en su tratamiento. Se describen siete pacientes (cuatro en cuidados intensivos y tres hospitalizados) diagnosticados con COVID-19 a quienes se les realizó un EEG. Resultados. El EEG mostró anormalidades en todos los casos, incluyendo un caso de muerte cerebral. El EEG supuso un cambio en el tratamiento clínico en cuatro de los pacientes (57%) y ayudó al clínico a informar a la familia. En los otros tres casos, se sospechó un origen tóxico-metabólico previo al EEG, por lo que no implicó un cambio en el tratamiento ya propuesto, aunque facilitó una orientación pronóstica. Se evidenciaron ondas lentas polimorfas en cinco casos. Actualmente, un paciente permanece hospitalizado y cuatro han fallecido. Conclusiones. El EEG fue de utilidad y facilitó la toma de decisiones en los pacientes con COVID-19 en los que se solicitó. Orientó al diagnóstico en casos en los que la tomografía computarizada no contribuyó y supuso un cambio en el tratamiento terapéutico en la mayoría de los pacientes. Los hallazgos más frecuentes fueron signos de encefalopatía y descargas epileptiformes.

Effects of the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) on the nervous system. What can we expect from SARS -CoV-2? / [Efectos de los coronavirus del síndrome respiratorio agudo grave (SARS-CoV) y del síndrome respiratorio del Medio Oriente (MERS-CoV) en el sistema nervioso. ¿Qué esperar del SARS-CoV-2?]

Coronaviruses cause respiratory and gastrointestinal disorders in animals and humans. The current SARS-CoV-2, the COVID-19 infectious agent, belongs to a subgroup called betacoronavirus including the SARS-CoV and MERS-CoV responsible for epidemics in 2002 and 2012, respectively. These viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ACE2) expressed in neurons and glial cells. Infections with SARS-CoV, MERS-CoV, and now SARS-CoV-2 also produce neurological signs such as acute cerebrovascular disease, impaired consciousness, and muscle injury, as well as dizziness, hypogeusia, hyposmia, hypoxia, neuralgia, and hypoxic encephalopathy. For this reason, close attention should be paid to the neurological manifestations of COVID-19 patients.

Los coronavirus son una familia de virus que se caracterizan por producir afectaciones respiratorias y gastrointestinales en animales y en seres humanos. El actual SARS-CoV-2, agente infeccioso de la COVID-19, pertenece a un subgrupo denominado betacoronavirus del que hacen parte el SARS-CoV y MERS-CoV, virus responsables de epidemias en el 2002 y el 2012, respectivamente. Estos virus también pueden infectar el sistema nervioso debido a su afinidad con la enzima convertidora de angiotensina humana 2 (ACE2), la cual se expresa en neuronas y células gliales. Se ha demostrado que las infecciones con SARS-CoV y MERS-CoV, y ahora también con el SARS-CoV-2, ocasionan condiciones neurológicas como la enfermedad cerebrovascular aguda, la conciencia alterada y las lesiones musculares, así como mareos, hipogeusia, hiposmia, hipoxia, neuralgia y encefalopatía hipóxica. Por ello debe prestarse mucha atención a las manifestaciones neurológicas de los pacientes de COVID-19.

Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 Infection: A Case Series.

OBJECTIVE: The purpose of this study was to report three patients COVID-19 infection with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM). METHODS: Patient data were obtained from medical records from the North Memorial Hospital, Robbinsdale, MN, USA. RESULTS: Three patients (two men and one woman, aged 38-63) presented with fatigue, cough, and fever leading to acute respiratory distress syndrome secondary to COVID-19 infection requiring ventilatory support. Two patients were unresponsive and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three patients were treated with intravenous corticosteroids and one improved markedly. The other two had minimal response to steroids and no further improvement after IVIG. CONCLUSION: Neurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune-mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment.

Postpartum consciousness disturbance: can covid-19 cause posterior reversible encephalopathy syndrome? / Alteración del nivel de conciencia puerperal: ¿puede el COVID-19 ser causa de síndrome de encefalopatía posterior reversible?

We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus. Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubation for decubitus intolerance. After extubation, she presented altered mental state that required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2. CT and CT-angiography were normal, spinal fluid tests were non-specific, and magnetic resonance imaging reported posterior reversible encephalopathy syndrome (PRES) (due to radiological features suggestive of white matter vasogenic edema affecting the parietal, temporal and occipital lobes, along with altered mental state) secondary to gestational hypertension. Eleven days after the cesarean section the patient began to develop hypertension that required treatment. PRES is associated with certain clinical (headache, altered mental state, visual disturbances and convulsions) and radiological (reversible changes in white substance mainly affecting the parietal, temporal, and occipital lobes) characteristics suggestive of vasogenic oedema In pregnant SARS-CoV-2 patients, the differential diagnosis of hypertension and altered mental state is often extremely complicated because complementary tests can be normal and there is no immediate sign of peripartum hypertension. SARS-CoV-2 genome sequencing in spinal fluid could have provided a definitive diagnosis, but the treatment would not have differed.

Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic.

INTRODUCTION: Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19. Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications. METHODS: This systematic review serves to summarize available information regarding the potential effects of different types of CoV on the nervous system and describes the range of clinical neurological complications that have been reported thus far in COVID-19. RESULTS: Two hundred and twenty-five studies on CoV infections associated neurological manifestations in human were reviewed. Of those, 208 articles were pertinent to COVID-19. The most common neurological complaints in COVID-19 were anosmia, ageusia, and headache, but more serious complications, such as stroke, impairment of consciousness, seizures, and encephalopathy, have also been reported. CONCLUSION: There are several similarities between neurological complications after SARS-CoV-1, MERS-CoV and COVID-19, however, the scope of the epidemics and number of patients are very different. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Accordingly, comprehensive knowledge of these complications will help health care providers to be attentive to these complications and diagnose and treat them timely.

Evolution and resolution of brain involvement associated with SARS- CoV2 infection: A close Clinical - Paraclinical follow up study of a case.

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.

Involvement of the Nervous System in SARS-CoV-2 Infection.

As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.