Review of Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords "SARS-CoV-2" and "neurological illness" for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals' brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients' CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Treatment of Long-Haul COVID Patients With Off-Label Acyclovir.

The SARS-CoV-2 virus (COVID-19) became a global pandemic in March 2020. This novel, highly infectious virus caused millions of infections and deaths around the world. Currently, there are few medications that are available for the treatment of COVID-19. Those affected are most commonly given supportive care, with some experiencing symptoms for months. We report a series of four cases depicting the successful use of acyclovir in the treatment of the virus SARS-CoV-2 in patients with long-haul symptoms, especially those in the realm of encephalopathy and neurological problems. Treatment with acyclovir in these patients resolved their symptoms and lowered their IgG and IgM titers, supporting the use of acyclovir as a safe and effective treatment for COVID-19 neurologic symptoms. We suggest the use of the antiviral medication, acyclovir, as a treatment for patients with long-term symptoms and unusual presentations of the virus, such as encephalopathy or coagulopathy.

Living and dying well with dementia

Many people with intellectual disability, particularly those with Down syndrome, are at increased risk for Alzheimer's disease. Recent findings suggest that while onset may be at an earlier age and more rapid in early dementia stages, there is often a long late stage where decisions about end-of-life care and dying well must be supported. For the individual and caregivers, later stages of dementia can be complicated by lack of understanding and preparedness by both generic palliative care and intellectual disability services. The COVID-19 pandemic has posed significant challenges for staff and family, and many have struggled with moral distress as they feel forced to act in a manner contrary to their own care beliefs. Three case studies with reflective questions about caring for people with Down syndrome and dementia are offered, one from the COVID-19 period. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The effect of COVID-19 on patients with preexisting autoimmune diseases

In December 2019, a new Coronavirus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), appeared in China, spreading rapidly around the globe and becoming a pandemic. SARS-CoV-2 is the cause of a serious life-threatening disease known as COVID-19. The risk of SARS-CoV-2 infection in patients with preexisting systemic autoimmune diseases (AID) appears to be slightly higher than in the general population, but the clinical course does not appear to be different. However, we must bear in mind that the use of corticosteroids, immunomodulatory drugs, and biological therapy in patients with AID can modulate the risk of hospitalization and death. The alterations in the innate and adaptive immune response found in patients with cytokine storm due to COVID-19 are the reasons for the high morbidity and mortality. Thus, clinicians should early identify the symptoms and closely monitor patients with risk factors for developing these complications and the interactions with other systems such as the immune-neuro-endocrine system. © 2023 Elsevier Inc. All rights reserved.

Imaging and neuropathological findings in patients with Post COVID-19 Neurological Syndrome-A review.

Post COVID-19 syndrome is determined as signs and symptoms that appear during or after an infection consistent with SARS-CoV-2 disease, persist for more than 12 weeks and are not explained by an alternative diagnosis. This review presents the neuropathological findings and imaging findings in Post COVID-19 Neurological Syndrome: the focal point is on the manifestations of involvement evident on brain and spine imaging.

Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: A preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)

Objectives: To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID. Design: Single-centre observational study. Participants: Adult patients experiencing unexplained long-lasting neurological symptoms after mild COVID. Of the 58 consecutive patients referred in our centre, 50 were included. Intervention: Patients were contacted for a standardised psychometric evaluation by phone, followed by a self- survey. Main outcome: Positive diagnosis of SSD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). Results: Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self- survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%). Conclusion: A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Cranial Nerve Impairment Associated With COVID-19 Infections: A Systematic Review.

The COVID-19 pandemic has created huge economic and healthcare burdens. In most cases, the virus affects the lungs and causes respiratory symptoms. Additionally, its impact on the cranial nerves remains unclear. We thus aimed to investigate cranial nerve dysfunction in patients with COVID-19 infection.  We conducted a systematic literature search of relevant and eligible literature in five databases: PubMed, Web of Science, Medline, EBSCO, and Google Scholar.  Our sample included 21 case reports, one case series with 29 patients, and one analytical study with 135 cases. Participant ages ranged from 23 months to 72 years (mean age of 47.5 ± 19.02). The mean time from respiratory symptoms to the onset of neurological signs was (9.6 ± 7.4) days, and the mean recovery time was (16.3 ± 15.3) days.  Cranial nerve impairment associated with COVID-19 infection has affected a large population, from infants to the elderly. Facial and abducent nerves were the most commonly affected cranial nerves with reported good prognosis or complete recovery within a few days to weeks. Olfactory dysfunctions were widely detected among COVID-19 patients.

Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.

Rehabilitation in Post COVID-19 Neurological Syndrome

Aim: Was a study of the role of neuroprotection therapy in rehabilitation possible neurological manifestations of post-COVID-19 syndrome and its effect on productivity in post-COVID-19 patients. Materials and Methods: All patients underwent neuropsychological testing immediately after the COVID-19 treatment and after the administration of neuroprotection therapy. Results:.ll patients voiced complaints typical of asthenic syndrome. Upon the neuroprotection, a verified (P<0,01) increase in well-being, activity and mood in both the Test groups was observed. Significantly, in the Test group 1 showed verified (P<0,01) increase in all indicators after the neuroprotection course, compared with the Test group 2 upon the implementation of a rehabilitation program only. Upon the neuroprotection and comprehensive rehabilitation program, both the test groups and the control group proved a decrease in the signs of asthenic syndrome, with Test groups 1 and 2 displayed verified effect (.<0,01). Both, upon neuroprotection and upon the four-week rehabilitation program, the following verified positive changes in the level of severity of asthenic syndrome were observed. Conclusions: Early administration of neuroprotection able maliorating neurological manifestations of post-COVID-19 syndrome, reducing recovery time and enhansing productivity in post-COVID-19 patients.

COVID-19 atypical Parsonage-Turner syndrome: a case report.

BACKGROUND: Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection. CASE PRESENTATION: We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection. CONCLUSIONS: We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised.

COVID-19-Associated Encephalopathy-Case Series and Clinical Considerations.

Neurological manifestations of the SARS-CoV-2 infection are present in up to 80% of the affected patients. While the majority of them is benign, in certain patients, viral replication in the central nervous system results in a severe disruption in cognitive function as well as basic life functions. In this case series, the authors present a detailed description of the three SARS-CoV-2 infection cases, which were all complicated by severe encephalopathy. Consecutive neurological status changes were described for each patient with detailed imaging and clinical sequelae. In the discussion, the authors highlight similarities in the course of the disease in presented patients, as well as common features in test results. An effective causal treatment could not be introduced in any of the patients, nor could the progression of the central nervous system (CNS) damage be stopped. The authors hope that the experiences they gathered will help to accelerate the diagnostic and therapeutic process in other patients with COVID-19-associated encephalopathy and result in introducing an effective treatment.

Long-term neuropsychiatric consequences of SARS-COV infections

While the COVID-19 pandemic continues to spread globally, with relistic hope that will be solved with adequate vacination, more and more evidences are collected about the presence of psychiatric and neurological manifestations and symptoms associated with this diseas. Neurological manifestations, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of centra nervous system symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. The review of the so far published papers shows that although more and more papers are reporting neurological and psyhiatric manifestations associated with COVID-19, many items remain unclear. The long-term psychological implications of this infectious diseases should not be ignored. In this paper, we aim to present a some of psychological consequences and neurological disorders associated with the SARS-CoV-2 infection, and to emphasize the need a global action that requires close coordination and open-data sharing between hospitals, academic and public health institutions and the fast establishment of harmonised research priorities to face a cut and long-term the neurological and psychological consequences (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Long-term effect of SARS-CoV-2 infection: Post-Covid-19 neurological syndrome / Efecto a largo plazo de la infección por SARS-CoV-2: Síndrome neurológico post-Covid-19

RESUMEN La pandemia de la COVID-19 ha provocado aproximadamente 182 millones de casos y cerca de cuatro millones de muertes en todo el mundo, comprometiendo con mayor frecuencia a personas de 25 y 64 años de edad. Esta infección afecta principalmente al sistema respiratorio, pero otros órganos y sistemas pueden verse afectados a corto plazo como el neurológico. Una gran población de pacientes ha logrado superar la infección por el SARS-CoV-2, sin embargo, han comenzado a reportarse una serie de manifestaciones clínicas tardías, básicamente neuropsiquiátricas, dentro de ellas se ha referido a la ansiedad, depresión, deterioro del sueño, dolor muscular, mareos, cefaleas, fatiga, anosmia, entre otros; a este conjunto de manifestaciones tardías se le ha denominado síndrome neurológico post-Covid-19 y requiere por un lado, la atención de la comunidad médica para investigar las manifestaciones tardías o secuelas de esta enfermedad y por otro lado, una vigilancia médica ante la consulta de pacientes con estas manifestaciones.

ABSTRACT The COVID-19 pandemic has caused approximately 182 million cases and nearly four million deaths worldwide, most frequently involving people between 25 and 64 years of age. This infection primarily affects the respiratory system, but other organs and systems can be affected in the short term, such as the neurological system. A large population of patients has managed to overcome the SARS-CoV-2 infection, however, a serie of late clinical manifestations have begun to be reported, basically neuropsychiatric, including anxiety, depression, disorder of sleep, muscle pain, dizziness, headaches, fatigue, anosmia, among others; this set of late manifestations has been called post-Covid-19 neurological syndrome and requires, on the one hand, the attention of the medical community to investigate the late manifestations or sequel of this disease and, on the other hand, medical vigilance when consulting patients with these manifestations.

Acute COVID-19 Cerebellitis: A Rare Neurological Manifestation of COVID-19 Infection.

The COVID-19 virus is well known to cause respiratory tract infections but several non-respiratory presentations and post-infectious complications have been well reported since its origin. With this case report, we present a rare manifestation of COVID-19 infection that presented as acute cerebellitis. This is a case of a 63-year-old Caucasian male patient who presented with altered mental status and ataxia. He was diagnosed with COVID-19 infection about five days prior to presenting to the hospital. Neurological exam was consistent with cerebellar symptoms like broad bases gait, truncal ataxia and subsequent imaging revealed white matter degeneration and edema of the cerebellar hemispheres. The symptoms completely resolved following treatment of ongoing COVID-19 infection with corticosteroids and intravenous remdesivir. With this case report, we intend to discuss the available literature regarding the clinical manifestations, management, and prognosis of COVID-19-induced cerebellitis.

Post-COVID 19 Neurological Syndrome: a fresh challenge in neurological management.

Not applicable.

The importance of thinking about Guillain-Barré syndrome during the COVID-19 pandemic: a case with pure dysautonomic presentation.

Guillain-Barré syndrome (GBS) is a peripheral nervous system disease caused by an immune-mediated inflammatory mechanism, usually triggered by a previous infectious process or vaccine; its typical presentation is a rapid and progressive bilateral limb hyposthenia, associated with sensory deficits and reduction or absence of osteotendinous reflexes. However, also autonomic nervous system can be involved with heart rate fluctuations, blood pressure instability, pupillary dysfunction, and urinary retention. Since the beginning of COVID-19 pandemic, GBS has been reported among neurological complications of SARS-CoV-2 infection, although etiopathological mechanisms still have to be clearly defined. We report the case of a 79-year-old man with multiple comorbidities, including diabetes, who was affected by SARS-CoV-2 interstitial pneumonia and developed dysautonomic symptoms after 10 days of hospitalization. A neurological evaluation was performed, and GBS was considered as a possible cause of the clinical manifestations. This hypothesis was confirmed by electrophysiological study and further supported, ex-juvantibus, by the satisfactory response to immunoglobulin treatment. In our opinion, this case of pure dysautonomic presentation of GBS in a SARS-CoV-2 positive patient is relevant because it suggests to consider GBS upon SARS-CoV-2 infection even if the symptoms have uncommon characteristics (e.g., pure vegetative manifestations) and if there are confounding factors which could lead to a misdiagnosis (e.g., old age, SARS-CoV-2 infection consequences and diabetes).

COVID-19: Impact of diagnosis threat and suggestibility on subjective cognitive complaints.

A subset of recovered COVID-19 patients report persistent neurological symptoms. These include non-specific symptoms (e.g., headaches and fatigue) which were found to be affected by psychological processes in other disorders (e.g., post-concussion syndrome, PCS, after mild traumatic brain injury). The current study assessed the impact of diagnosis threat (i.e., information regarding the long-term neurological impact of COVID-19) and suggestibility on endorsed symptoms of both recovered patients and healthy controls. Method: Recovered patients (n = 90) and healthy controls (n = 210) described their cognitive functioning after being randomly assigned to: (a) Experimental group: These participants read an article that explored long-term neurological symptoms among COVID-19 survivors. (b) Control group: These participants read an article providing general information regarding the disease. Results: Recovered patients, but not healthy controls, endorsed more symptoms in the experimental condition compared to the control condition. Moreover, suggestibility was correlated with endorsement of symptoms. Conclusions: Post COVID-19 neurological symptoms may, at least partially, be affected by non-neurological factors such as diagnosis threat. Information regarding long-term effects of COVID-19 may skew reported symptoms with highly suggestible individuals particularly susceptible to these effects. Further research, however, is needed to validate and elaborate upon these initial findings.

Pacientes con COVID-19 recuperados informan síntomas neurológicos persistentes (e.g., dolor de cabeza y fatiga) que se vieron afectados por procesos psicológicos en otros trastornos (e.g., Síndrome postconmoción cerebral después de una lesión cerebral traumática leve). Se evaluó el impacto de la amenaza del diagnóstico (i.e., información sobre el impacto neurológico a largo plazo del COVID-19) y la sugestión sobre los síntomas respaldados tanto de pacientes recuperados como de controles sanos. Método: Pacientes recuperados (n = 90) y controles sanos (n = 210) informaron sobre su funcionamiento cognitivo después de haber sido asignados al azar a: (a) condición que exploró los síntomas neurológicos a largo plazo entre los sobrevivientes de COVID-19; (b) condición de control que proporciona información general sobre la enfermedad. Resultados: Pacientes recuperados, pero no los controles sanos, aprobaron más síntomas en la condición experimental que en la control. La sugestión se asoció con una mayor aprobación de síntomas. Conclusiones: Los síntomas neurológicos posteriores al COVID-19 pueden verse afectados, al menos parcialmente, por factores no neurológicos como la amenaza del diagnóstico. La información sobre los efectos a largo plazo de COVID-19 puede sesgar los síntomas informados en individuos altamente sugestionables. Se necesitan más investigaciones para validar y desarrollar estos hallazgos iniciales.