Cognitive sequelae after recovery from an initial COVID-19 disease are present in a subset of affected individuals, coalescing around several important issues such as effects of age, COVID-19 disease severity, comorbidities, and other factors. Some neuropsychological symptoms appear more common among certain patient populations. Comorbidities may complicate neuropsychological assessment as well. Hence, we need a guideline-based evaluation to guide neuropsychological rehabilitation. Drawing from the recent revision of the German National Guideline for the Long- and Post-COVID Syndrome and current advances in international guidance on neuropsychological assessment, this article provides practical and scientifically informed recommendations for the neuropsychological assessment of individuals recovering from coronavirus-related diseases.

It is well established that neurological and non-neurological autoimmune disorders can be triggered by viral infections. It remains unclear whether SARS-CoV-2 infection induces similar conditions and whether they show a distinctive phenotype. We retrospectively identified patients with acute inflammatory CNS conditions referred to our laboratory for antibody testing during the pandemic (March 1 to August 31, 2020). We screened SARS-COV-2 IgA/IgG in all sera by ELISA and confirmed the positivity with additional assays. Clinical and paraclinical data of SARS-COV-2-IgG seropositive patients were compared to those of seronegative cases matched for clinical phenotype, geographical zone, and timeframe. SARS-CoV-2-IgG positivity was detected in 16/339 (4%) sera, with paired CSF positivity in 3/16. 5 of these patients had atypical demyelinating disorders and 11 autoimmune encephalitis syndromes. 9/16 patients had a previous history of SARS-CoV-2 infection and 6 of them were symptomatic. In comparison with 32 consecutive seronegative controls, SARS-CoV-2-IgG-positive patients were older, frequently presented with encephalopathy, had lower rates of CSF pleocytosis and other neurological autoantibodies, and were less likely to receive immunotherapy. When SARS-CoV-2 seropositive versus seronegative cases with demyelinating disorders were compared no differences were seen. Whereas seropositive encephalitis patients less commonly showed increased CSF cells and protein, our data suggest that an antecedent symptomatic or asymptomatic SARS-CoV-2 infection can be detected in patients with autoimmune neurological conditions. These cases are rare, usually do not have specific neuroglial antibodies.

Purpose of review COVID-19 and systemic critical illness are both associated with neurological complications. We provide an update on the diagnosis and critical care management of adult patients with neurological complications of COVID-19. Recent findings Large prospective multicentre studies conducted in the adult population over the last 18 months improved current knowledge on severe neurological complications of COVID-19. In COVID-19 patients presenting with neurological symptoms, a multimodal diagnostic workup (including CSF analysis, brain MRI, and EEG) may identify different syndromes associated with distinct trajectories and outcomes. Acute encephalopathy, which represents the most common neurological presentation of COVID-19, is associated with hypoxemia, toxic/metabolic derangements, and systemic inflammation. Other less frequent complications include cerebrovascular events, acute inflammatory syndromes, and seizures, which may be linked to more complex pathophysiological processes. Neuroimaging findings include infarction, haemorrhagic stroke, encephalitis, microhaemorrhages and leukoencephalopathy. In the absence of structural brain injury, prolonged unconsciousness is usually fully reversible, warranting a cautious approach for prognostication. Advanced quantitative MRI may provide useful insights into the extent and pathophysiology of the consequences of COVID-19 infection including atrophy and functional imaging changes in the chronic phase. Summary Our review highlights the importance of a multimodal approach for the accurate diagnosis and management of complications of COVID-19, both at the acute phase and in the long-term.

A 58-year-old man was admitted to the hospital with acute neurological manifestations of encephalitis 15 days after a previous upper respiratory COVID-19 illness. On presentation, he was confused with altered mental status, aggressive behavior, and a Glasgow coma scale score of 10/15. Laboratory investigation, brain computed tomography (CT), and brain magnetic resonance imaging (MRI) were unremarkable with normal results. Although the cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative, we found increased concentrations of positive immunoglobulin (Ig) A and IgG antibodies in CSF, suggesting acute central nervous system (CNS) infection and indirect confirmation of virus neuroinvasion. There was no evidence of humoral auto-reactivity, and we rejected the hypothesis of autoimmune encephalitis with known autoantibodies. On the fifth day of hospitalization, myoclonic jerks emerged as a new neurological sign until the added levetiracetam led to total remission. The patient achieved full recovery after antiviral and corticosteroid therapy implementation of 10 days in the hospital. This case report emphasizes the importance of the presence of CSF IgA and IgG antibodies to diagnose encephalitis in COVID-19 patients as an indirect confirmation of CNS infection.

In light of the rising evidence of the association between viral and bacterial infections and neurodegeneration, we aimed at revisiting the infectious hypothesis of Alzheimer’s disease and analyzing the possible implications of COVID-19 neurological sequelae in long-term neurodegeneration. We wondered how SARS-CoV-2 could be related to the amyloid-β cascade and how it could lead to the pathological hallmarks of the disease. We also predict a paradigm change in clinical medicine, which now has a great opportunity to conduct prospective surveillance of cognitive sequelae and progression to dementia in people who suffered severe infections together with other risk factors for Alzheimer’s disease.

Rationale: Acute encephalopathy is a severe neurological complication of coronavirus disease 2019 (COVID-19). Most cases of acute encephalopathy associated with COVID-19 occur within several weeks of COVID-19 onset. We describe a case series of 6 patients who developed delayed encephalopathy (DE) after COVID-19. Patient concerns and diagnoses: We evaluated patients who recovered from COVID-19 and showed acute disturbance of consciousness or focal neurological deficits without recurrence of pneumonitis. Six patients, 2 females and 4 males, with ages ranging from 65 to 83 years were included. Durations of hospitalization due to COVID-19 were between 25 and 44 days. The severity of COVID-19 was moderate in 5 and severe in 1 patient. Patients were rehospitalized for acute disturbance of consciousness concomitant with postural tremor and, abnormal behavior, hemiplegia, aphasia, or apraxia between 34 and 67 days after the onset of COVID-19. Chest computed tomography showed no exacerbation of pneumonitis. Brain magnetic resonance imaging showed no specific findings except in 1 patient with an acute lacunar infarction. Electroencephalogram demonstrated diffuse slowing in all patients. Repeat electroencephalogram after recovery from encephalopathy demonstrated normal in all patients. One of the 6 patients had cerebrospinal fluid (CSF) pleocytosis. CSF protein levels were elevated in all patients, ranging from 51 to 115 mg/dL. CSF interleukin-6 levels ranged from 2.9 to 10.9 pg/mL. The immunoglobulin index was 0.39 to 0.44. Qlim(alb) < QAlb indicating dysfunction of the blood–brain barrier was observed in all patients. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction of CSF was negative in all patients. Neuronal autoantibodies were absent in serum and CSF. Interventions and outcomes: Immunotherapy including steroid pulses was administered to 3 patients; however, symptoms of encephalopathy resolved within several days in all patients, regardless of treatment with immunotherapy, and their consciousness levels were recovered fully. Notably, postural tremor remained for 2 weeks to 7 months. Lessons: In our patients, DE after COVID-19 was characterized by symptoms of acute encephalopathy accompanied with tremor in the absence of worsening pneumonitis after the fourth week of COVID-19 onset. Our findings indicate blood–brain barrier dysfunction may contribute to the pathogenesis of DE after COVID-19.

This systematic review focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients that had detected SARS-CoV-2 virus in cerebrospinal fluid (CSF). A systematic literature search was carried out in PubMed, Embase, Scopus, Web of Science, Medrxiv, and Biorxiv databases from inception to 19 December 2021. Case reports or case series involving patients with proved SARS-CoV-2 presence in CSF by polymerize chain reaction were included. Our search strategy produced 23 articles documenting a total of 23 patients with positive SARS-CoV-2 in the CSF. Fever (55%) was the most common symptom, followed by headaches (41%), cough (32%), and vomiting/nausea (32%). The majority of the cases included was encephalitis (57%), 8 of which were confirmed by magnetic resonance imaging. The second most prevalent presentation was meningitis. The cerebral spinal fluid analysis found disparities in protein levels and normal glucose levels in most cases. This study demonstrates that SARS-CoV-2 can enter the nervous system via various routes and cause CNS infection symptoms. SARS-CoV-2 has been shown to infect the CNS even when no respiratory symptoms are present and nasopharyngeal swabs are negative. As a result, SARS-CoV-2 should be considered as a possible cause of CNS infection and tested for in the CSF.

Since the discovery of the coronavirus disease 2019 outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ failure, while the co-existence of these two culprits can accelerate the rate of disease progression and magnify the severity of the disease. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidneys, brain, eyes, gastrointestinal system, and bones, and sub-sequent manifestation of multi-system organ failure.

Most commonly, COVID-19 presents as a respiratory disease, but a growing body of clinical evidence shows that neurological symptoms and complications contribute significantly to the clinical spectrum of the disease, especially in patients with severe disease. The public health impact of the long-term (or even life-long) consequences of the disease may be much greater than the acute manifestations of SARS-CoV-2 infection. As the pandemic has evolved, the number of neurological manifestations as part of the clinical spectrum of the disease has increased. The diverse neurological manifestations of COVID-19 range from mild symptoms (myalgia, headache, fatigue, dizziness, anosmia, ageusia) to more severe manifestations such as encephalopathy, encephalitis, acute and chronic polyneuropathy. Neurological symptoms and complications of COVID-19 do not necessarily require direct infection of structures in the peripheral or central nervous system, but may occur secondary to a severe systemic reaction to SARS-CoV-2 infection outside the nervous system. The neurotoxicity of SARS-CoV-2 infection may be secondary to immune-mediated pathogenesis and coagulation dysfunction. To substantiate the therapeutic choice, it is necessary to study the pathophysiological processes and clinical trials.

Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A variety of viruses have been described with a potential of inducing or contributing to the occurrence of parkinsonism and Parkinson’s disease (PD), although the relationship between the two remains a matter of debate originating with the description of encephalitis lethargica in the aftermath of the Spanish flu in 1918. While some viral infections have been linked to an increased risk for the development of PD, others seem to have a causal link with the occurrence of parkinsonism. Here, we review the currently available evidence on viral-induced parkinsonism with a focus on potential pathophysiological mechanisms and clinical features. We also review the evidence on viral infections as a risk factor for developing PD and the link between SARS-CoV-2 and parkinsonism, which might have important implications for future research and treatments.

The coronavirus can infect the upper respiratory tract, sinuses, and nose, and its severity manifests in its respiratory symptoms and neurological and psychological consequences. The majority of people who have COVID-19 present with moderate flu-like illness, and patients who are elderly with comorbid conditions, such as hypertension and diabetes, are more prone to experience severe illness and death. However, in the ongoing COVID-19 pandemic, neurological consequences have become a substantial source of morbidity and mortality. COVID-19 poses a global hazard to the nervous system because of its widespread dispersion and multiple pathogenic pathways. This review offers a critical assessment of the acute and long-term neurological effects of the COVID-19 virus. Some neurological problems include headache, dizziness, myalgia/fatigue, meningitis, ischemic/hemorrhagic stroke, and myelitis. Other people who have contracted COVID-19 also exhibit neurological features such as loss of taste and smell, reduced consciousness, and Guillain-Barré syndrome. This study seeks to help neurologists comprehend the wide range of neurologic aspects of COVID-19, as understanding neurological symptoms may help with the management and enhance the patient's outcomes.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly infects the respiratory system, several investigations have shown the involvement of the central nervous system (CNS) along the course of the illness, with encephalitis being one of the symptoms. The objective of this systematic review was to evaluate the characteristics (clinical, neuro-radiological aspects, and laboratory features) and outcomes of encephalitis in COVID-19 patients. PubMed, Scopus, and Google Scholar databases were searched from 1 December 2019 until 21 July 2022 to identify case reports and case series published on COVID-19 associated with encephalitis. The quality of the included studies was assessed by the Joanna Briggs Institute critical appraisal checklists. This systematic review included 79 studies, including 91 COVID-19 patients (52.7% male) experiencing encephalitis, where 85.6% were adults (49.3 ± 20.2 years), and 14.4% were children (11.2 ± 7.6 years). RT-PCR was used to confirm 92.2% of the COVID-19 patients. Encephalitis-related symptoms were present in 78.0% of COVID-19 patients at the time of diagnosis. In these encephalitis patients, seizure (29.5%), confusion (23.2%), headache (20.5%), disorientation (15.2%), and altered mental status (11.6%) were the most frequently reported neurologic manifestations. Looking at the MRI, EEG, and CSF findings, 77.6%, 75.5%, and 64.1% of the patients represented abnormal results. SARS-CoV-2-associated or -mediated encephalitis were the most common type observed (59.3%), followed by autoimmune encephalitis (18.7%). Among the included patients, 66.7% were discharged (37.8% improved and 28.9% fully recovered), whereas 20.0% of the reported COVID-19-positive encephalitis patients died. Based on the quality assessment, 87.4% of the studies were of high quality. Although in COVID-19, encephalitis is not a typical phenomenon, SARS-CoV-2 seems like a neuropathogen affecting the brain even when there are no signs of respiratory illness, causing a high rate of disability and fatality.

Background and objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection commonly leads to neurologic manifestations. In the present review, we aimed to investigate potential neuroimaging markers of early diagnosis and prognosis of neurologic manifestations in COVID-19. Methods: Our study was registered in the Prospective Register of Systematic Reviews (PROSPERO) under the protocol CDR42021265443. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we selected 51 studies for whole-manuscript analysis. Results: Magnetic resonance imaging (MRI) was the most common imaging method. The pattern, sites of lesion, signs, and symptoms of neurologic injury varied. Such manifestations possibly resulted from a direct viral infection or, most likely, from indirect mechanisms including coagulation disturbances, hypoxemia, and immunological responses. Conclusion: The heterogeneity of the studies precludes any generalization of the findings. Brain MRI is the most informative imaging exam. Population studies including the entire spectrum of COVID-19 are missing. There is still a need for future population studies evaluating neurologic manifestations of all COVID-19 severities acutely and chronically.

According to best current estimates, approximately 10% of those infected with SARS-CoV-2-virus experience long-term clinical and nonspecific neurological symptoms that may last for several weeks or months. This is currently referred to as “Long-COVID” or “Post-COVID-Syndrome”. Based on current knowledge, the most common long-term symptoms of COVID-19 disease include fatigue and poor concentration, but particularly also headache and musculoskeletal pain. However, given the novelty of COVID-19, only a few studies have systematically evaluated the central nervous alterations in the pain processing structures of our brain. Those first insights are yet important in order to offer patients adequate therapeutic options. Based on a systematic review of the literature, we will therefore provide an overview of the central nervous alterations in the brain described in the context of SARS-CoV-2 infection, focusing on findings with brain imaging.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Samim M, et al. J Clin Neurol. 2022 Nov;18(6):692-710. https://doi.org/10.3988/jcn.2022.18.6.692

The COVID-19 pandemic has profoundly changed hospital activities, including nuclear medicine (NM) practice. This review aimed to determine and describe the impact of COVID-19 on NM in Europe and critically discuss actions and strategies applied to face the pandemic. A literature search for relevant articles was performed on PubMed, covering COVID-19 studies published up until January 21, 2021. The findings were summarized according to general and specific activities within the NM departments. The pandemic strongly challenged NM departments: a reduction in the workforce has been experienced in almost every center in Europe due to personnel diagnosed with COVID-19 and other reasons related to the coronavirus. NM departments introduced procedures to limit COVID-19 transmission, including environmental and personal hygiene, social distancing, rescheduling of non–high-priority procedures, the correct use of personal protective equipment, and prompt identification of suspect COVID-19 cases. A proportion of the departments experienced a delay in radiopharmaceuticals supply or technical assistance during the pandemic. Furthermore, the pandemic resulted in a significant reduction of diagnostic and therapeutic NM procedures, as well as a reduced level of care for patients affected by diseases other than COVID-19, such as cancer or acute cardiovascular disease. Telemedicine services have been set up to maintain medical assistance for patients. COVID-19 pandemic has reshaped human work resources, patient's diagnostic and therapeutic management, operative models, radiopharmaceutical supplies, teaching, training and research of NM departments. Limits of availability of resources emerged. Nonetheless, we have to provide continuity in care, especially for fragile patients, maintaining infection control measures. Challenges that have been faced should reshape our vision and get us prepared for the future.

The autoantibody profile associated with known autoimmune diseases in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that adults with COVID-19 had a moderate prevalence of autoantibodies against the lung antigen KCNRG, and SLE-associated Smith autoantigen. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin(IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoringin vivodecay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Together these findings demonstrate that administration of high-dose IVIG is responsible for the detection of several autoantibodies in MIS-C and KD. Further studies are needed to investigate autoantibody production in MIS-C patients, independently from IVIG administration.

We reviewed the literature to describe outcomes associated with abnormal neuroimaging findings among adult COVID-19 patients. We performed a systematic literature review using PubMed and Embase databases. We included all studies reporting abnormal neuroimaging findings among hospitalized patients with confirmed COVID-19 and outcomes. Data elements including patient demographics, neuroimaging findings, acuity of neurological symptoms and/or imaging findings relative to COVID-19 onset (acute, subacute, chronic), and patient outcomes were recorded and summarized. After review of 775 unique articles, a total of 39 studies comprising 884 COVID-19 patients ≥ 18 years of age with abnormal neuroimaging findings and reported outcomes were included in our analysis. Ischemic stroke was the most common neuroimaging finding reported (49.3%, 436/884) among patients with mortality outcomes data. Patients with intracranial hemorrhage (ICH) had the highest all-cause mortality (49.7%, 71/143), followed by patients with imaging features consistent with leukoencephalopathy (38.5%, 5/13), and ischemic stroke (30%, 131/436). There was no mortality reported among COVID-19 patients with acute disseminated encephalomyelitis without necrosis (0%, 0/8) and leptomeningeal enhancement alone (0%, 0/12). Stroke was a common acute or subacute neuroimaging finding, while leukoencephalopathy was a common chronic finding. Among hospitalized COVID-19 patients with abnormal neuroimaging findings, those with ICH had the highest all-cause mortality; however, high mortality rates were also seen among COVID-19 patients with ischemic stroke in the acute/subacute period and leukoencephalopathy in the chronic period. Specific abnormal neuroimaging findings may portend differential mortality outcomes, providing a potential prognostic marker for hospitalized COVID-19 patients.

На сьогодні пандемія COVID‑19 триває вже близько двох років. Хоча знання фахівців значно покращились у питаннях профілактики та лікування важких форм захворювання, патогенез та лікування синдрому пост-COVID‑19 залишаються актуальними питаннями в медичній та науковій спільнотах. Актуальність проблеми полягає в значному поширенні цього стану серед перехворілих, зниженні якості життя пацієнтів, нестачі знань про частоту, механізми перебігу та причини віддалених наслідків, нечітких уявленнях стосовно підходів до діагностики та лікування, а також відсутності нормативних документів щодо ведення таких пацієнтів. У серпні 2020 року британськими дослідниками вперше було запропоновано термін пост-COVID‑19. Наявні дані свідчать про значні відмінності в епідеміологічних оцінках поширеності синдрому пост-COVID‑19 через відмінності в методах відбору, періодах спостереження та розмірах вибірок. Частота синдрому пост-COVID‑19 оцінюється в 10-35%, тоді як для госпіталізованих пацієнтів вона може досягати й 85%. Втомлюваність є найпоширенішим симптомом, про який повідомляється в 17,5-72,0% випадків після перенесеного COVID‑19, потім услід за задишкою, частота якої становить 10-40%, виникають психічні проблеми, біль у грудях, нюхова і смакова дисфункція, що зустрічаються відповідно до 26, 22 та 11% реконвалесцентів. Більше однієї третини пацієнтів із синдромом пост-COVID‑19 мають вже наявні супутні захворювання, найчастіше зустрічаються гіпертонія та цукровий діабет. Опубліковані на сьогодні дані свідчать про те, що більшість пацієнтів із синдромом пост-COVID‑19 мають хороший прогноз без подальших ускладнень та летальних наслідків. Більшість досліджень досі зосереджувалися на симптомах, пов’язаних із синдромом пост-COVID‑19, а не на дисфункції органів. В огляді представлено аналіз досліджень щодо визначення синдрому пост-COVID‑19, вивчення впливу перенесеної інфекції на різні системи органів та надано основні потенційні механізми розвитку ускладнень. Особлива увага приділена наслідкам перенесеного COVID‑19 з боку ендокринних органів. Запропоновані рекомендації щодо обстеження і ведення пацієнтів із синдромом пост-COVID‑19.

Neurologic involvement is well-recognized in coronavirus disease (COVID-19). This article reviews the neuroimaging manifestations of COVID-19 on CT and MRI, presenting cases from the New York City metropolitan region encountered by the authors during the first surge of the pandemic. The most common neuroimaging manifestations are acute infarcts with large clot burden and intracranial hemorrhage, including microhemorrhages. However, a wide range of additional imaging patterns occur, including leukoencephalopathy, global hypoxic injury, acute demyelinating encephalomyelitis, cytotoxic lesions of the corpus callosum, olfactory bulb involvement, cranial nerve enhancement, and Guillain Barré syndrome. The described central nervous system abnormalities largely represent secondary involvement from immune activation that leads to a prothrombotic state and cytokine storm; evidence for direct neuroinvasion is scant. Comorbidities such as hypertension, complications of prolonged illness and hospitalization, as well as associated supportive treatments, also contribute to the central nervous system involvement in COVID-19. Routine, long-term, neurologic follow-up may be warranted, given emerging evidence of long-term microstructural and functional changes on brain imaging, after COVID-19 recovery.

Objective: Coronavirus disease (COVID-19) vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication observed within 2 weeks of adenovirus-vectored vaccination. Case Report: A 52-year-old male patient, with a family history of autoimmune diseases, presented with a new onset of worsening headache with nausea and vomiting post-vaccination. The patient was diagnosed with VITT based on laboratory findings demonstrating thrombocytopenia, elevated D-dimer, and dural sinus thrombosis identified on neuroimaging. The patient was successfully treated with high-dose immunoglobulin, steroids, and non-heparin anticoagulants, without any neurologic sequelae. Finally, a confirmatory test with anti-platelet factor 4 antibody was strongly positive. Conclusion: Physicians should be vigilant when treating patients presenting with new-onset thunderclap headache, progressive worsening headache, and awakening headache accompanied by nausea or vomiting after vaccination, even if no definite clinical neurological deficits are identified. Emergency laboratory test results for demonstrating elevated D-dimer levels, decreased platelet count, and neuroimaging correlation are integral for diagnosis and must be the standard protocol. Treatment with non-heparin anticoagulants, high-dose intravenous immunoglobulin, and steroids that halt or slow the immune-mediated prothrombotic process should be initiated immediately. Considering the high mortality rate of VITT, treatment should be initiated prior to confirmatory test results.

Minor neurological symptoms such as anosmia are relatively common manifestations of coronavirus disease 2019 (COVID-19). However, severe affection of the central nervous system (CNS) occurs in a minority of cases and its treatment and pathophysiology is not yet well understood. It has been described that encephalitis due to COVID-19 may be caused by the proinflammatory state due to the cytokine storm or direct invasion of the virus in the CNS. Here we present a case of a 66-year-old man with bipolar disorder and moderate respiratory COVID-19 symptoms who presented to the emergency department with a decreased level of consciousness. Brain computerized tomography (CT) showed no acute pathology. A thorough investigation of other possible causes of CNS affection was negative. The patient was treated with pulse therapy with methylprednisolone and presented a significant improvement of his neurological condition, being discharged with a complete neurological recovery five days after the start of the treatment. This case illustrates the importance of a high index of suspicion in diagnosing severe CNS impairment in mild respiratory COVID-19 cases. Also, this case corroborates with previous reports of glucocorticoid response in CNS impairment associated with COVID-19, although more robust studies are required to confirm this relation.

Background and Purpose: A variety of neurological manifestations have been attributed to COVID-19, but there is currently limited evidence regarding risk factors and outcomes for delirium in critically ill patients with COVID-19. The purpose of this study was to identify delirium in a large cohort of ICU patients with COVID-19, and to identify associated features and clinical outcomes at the time of hospital discharge. Methods: This is an observational cohort study of 213 consecutive patients admitted to an ICU for COVID-19 respiratory illness. Delirium was diagnosed by trained abstractors using the CHART-DEL instrument. The associations between key clinical features, sedation and delirium were examined, as were the impacts of delirium on clinical outcomes. Results: Delirium was identified in 57.3% of subjects. Delirious patients were more likely to receive mechanical ventilation, had lower P: F ratios, higher rates of renal replacement therapy and ECMO, and were more likely to receive enteral benzodiazepines. Only mechanical ventilation remained a significant predictor of delirium in a logistic regression model. Mortality was not significantly different, but delirious patients experienced greater mechanical ventilation duration, ICU/hospital lengths of stay, worse functional outcomes at discharge, and were less likely to be discharged home. Conclusions: Delirium is common in critically ill patients with COVID-19 and appears to be associated with greater disease severity. When present, delirium is associated with worse functional status at discharge, but not increased mortality. Additional studies are necessary to determine the generalizability of these results and the impact of delirium on longer-term cognitive and functional outcomes.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain–Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood–brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severely impacted the Italian healthcare system, underscoring a dramatic shortage of specialized doctors in many disciplines. The situation affected the activity of the residents in neurology, who were also offered the possibility of being formally hired before their training completion. Aims: (1) To showcase examples of clinical and research activity of residents in neurology during the COVID-19 pandemic in Italy and (2) to illustrate the point of view of Italian residents in neurology about the possibility of being hired before the completion of their residency program. Results: Real-life reports from several areas in Lombardia—one of the Italian regions more affected by COVID-19—show that residents in neurology gave an outstanding demonstration of generosity, collaboration, reliability, and adaptation to the changing environment, while continuing their clinical training and research activities. A very small minority of the residents participated in the dedicated selections for being hired before completion of their training program. The large majority of them prioritized their training over the option of earlier employment. Conclusions: Italian residents in neurology generously contributed to the healthcare management of the COVID-19 pandemic in many ways, while remaining determined to pursue their training. Neurology is a rapidly evolving clinical field due to continuous diagnostic and therapeutic progress. Stakeholders need to listen to the strong message conveyed by our residents in neurology and endeavor to provide them with the most adequate training, to ensure high quality of care and excellence in research in the future.

Acute disseminated encephalomyelitis (ADEM) has been reported after coronavirus disease 2019 (COVID-19). In this review, we systematically included worldwide reported cases on this association. We included 30 case reports (pediatric and adults) and explored epidemiological and clinical evidence. We described time to diagnosis, clinical, imaging, and laboratory features, response to treatment regimens, and differences regarding severity. Also, an original case report was presented. Neurologists must be alert to the occurrence of multifocal neurological symptoms with or without encephalopathy in patients recovered from COVID-19. Timely MRI studies should be performed to establish the diagnosis and to consider early corticosteroid-based treatment.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to various neurological manifestations. There is an urgent need for a summary of neuroimaging findings to accelerate diagnosis and treatment plans. We reviewed prospective and retrospective studies to classify neurological abnormalities observed in patients with the SARS-CoV-2 infection. Methods: The relevant studies published in Scopus, PubMed and Clarivate Analytics databases were analysed. The search was performed for full-text articles published from 23 January 2020 to 23 February 2021. Results: In 23 studies the number of patients with SARS-CoV-2 infection was 20,850 and the number of patients with neurological manifestations was 1996 (9.5%). The total number of patients with neuroradiological abnormalities was 602 (2.8%). SARS-CoV-2 has led to various neuroimaging abnormalities which can be categorised by neuroanatomical localisation of lesions and their main probable underlying pathogenesis. Cranial nerve and spinal root abnormalities were cranial neuritis and polyradiculitis. Parenchymal abnormalities fell into four groups of: (a) thrombosis disorders, namely ischaemic stroke and sinus venous thrombosis; (b) endothelial dysfunction and damage disorders manifested as various types of intracranial haemorrhage and posterior reversible encephalopathy syndrome; (c) hypoxia/hypoperfusion disorders of leukoencephalopathy and watershed infarction; and (d) inflammatory disorders encompassing demyelinating disorders, encephalitis, vasculitis-like disorders, vasculopathy and cytotoxic lesions of the corpus callosum. Leptomeninges disorders included meningitis. Ischaemic stroke was the most frequent abnormality in these studies. Conclusion: The review study suggests that an anatomical approach to the classification of heterogeneous neuroimaging findings in patients with SARS-CoV-2 and neurological manifestations would lend itself well for use by practitioners in diagnosis and treatment planning.

Background Prevalence and etiology of unconsciousness are uncertain in hospitalized patients with coronavirus disease 2019 (COVID-19). We tested the hypothesis that increased inflammation in COVID-19 precedes coma, independent of medications, hypotension, and hypoxia. Methods We retrospectively assessed 3203 hospitalized patients with COVID-19 from March 2 through July 30, 2020, in New York City with the Glasgow Coma Scale and systemic inflammatory response syndrome (SIRS) scores. We applied hazard ratio (HR) modeling and mediation analysis to determine the risk of SIRS score elevation to precede coma, accounting for confounders. Results We obtained behavioral assessments in 3203 of 10,797 patients admitted to the hospital who tested positive for SARS-CoV-2. Of those patients, 1054 (32.9%) were comatose, which first developed on median hospital day 2 (interquartile range [IQR] 1–9). During their hospital stay, 1538 (48%) had a SIRS score of 2 or above at least once, and the median maximum SIRS score was 2 (IQR 1–2). A fivefold increased risk of coma (HR 5.05, 95% confidence interval 4.27–5.98) was seen for each day that patients with COVID-19 had elevated SIRS scores, independent of medication effects, hypotension, and hypoxia. The overall mortality in this population was 13.8% (n = 441). Coma was associated with death (odds ratio 7.77, 95% confidence interval 6.29–9.65) and increased length of stay (13 days [IQR 11.9–14.1] vs. 11 [IQR 9.6–12.4]), accounting for demographics. Conclusions Disorders of consciousness are common in hospitalized patients with severe COVID-19 and are associated with increased mortality and length of hospitalization. The underlying etiology of disorders of consciousness in this population is uncertain but, in addition to medication effects, may in part be linked to systemic inflammation.

Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare, and often of uncertain significance. In this review, we provide an overview of the neurological impact that occur in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19.

We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID‐19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS‐CoV‐2) polymerase chain reaction (PCR). We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement. In 117 publications, we identified 193 patients with COVID‐19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS‐CoV‐2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS‐CoV‐2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024). The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID‐19 is associated with increased likelihood of a positive CSF SARS‐CoV‐2 PCR. However, a positive CSF SARS‐CoV‐2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.