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1.
J Neurol ; 268(12): 4448-4478, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1233263

ABSTRACT

BACKGROUND: The literature on neurological manifestations in COVID-19 patients has been rapidly increasing with the pandemic. However, data on CNS inflammatory disorders in COVID-19 are still evolving. We performed a literature review of CNS inflammatory disorders associated with coronavirus disease-2019 (COVID-19). METHODS: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords; "SARS-CoV-2 and neurological complication", "SARS-CoV-2 and CNS Complication" looking for reports of transverse myelitis, longitudinally extensive transverse myelitis, neuromyelitis optica, myelitis, Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD), Acute Disseminated Encephalomyelitis (ADEM), Acute Hemorrhagic Necrotizing Encephalitis/Acute Hemorrhagic Leukoencephalitis (AHNE/AHLE), Cytotoxic lesion of the Corpus Callosum/Mild Encephalopathy Reversible Splenium Lesion(CLOCC/MERS) and Optic neuritis published between December 01, 2019 and March 15, 2021. RESULTS: Our literature search revealed 43 patients meeting the diagnosis of myelitis, including Transverse Myelitis, ADEM, AHNE/AHLE or CLOCC/MERS and Optic neuritis. Acute myelitis was most commonly associated with non-severe COVID-19 and all reported cases of AHNE/AHLE had severe COVID-19 infection. Based on IDSA/ATS criteria of either requiring vasopressor for septic shock or mechanical ventilation, 49% (n = 18) patients were considered to have a severe COVID infection. There were 7 (n = 19%) fatalities. CONCLUSION: To our knowledge, this is among the first reviews that includes the clinical features, neuroimaging, CSF findings and outcomes in COVID-19-associated CNS inflammatory disorders. Our observational review study reveals that although rare, myelitis, ADEM, AHNE and CLOCC can be associated with COVID-19 infection. Further studies using MRI imaging and CSF analysis in early diagnosis and intervention of these disorders are warranted.


Subject(s)
COVID-19 , Central Nervous System Diseases/virology , Myelitis, Transverse , COVID-19/cerebrospinal fluid , COVID-19/diagnostic imaging , Central Nervous System Diseases/cerebrospinal fluid , Humans , Myelin-Oligodendrocyte Glycoprotein , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/virology , Neuroimaging , Observational Studies as Topic
2.
Case Rep Neurol Med ; 2021: 6658000, 2021.
Article in English | MEDLINE | ID: covidwho-1160967

ABSTRACT

There is increasing evidence that SARS-CoV-2 has neurotropic potential. We report on two paediatric patients who presented with encephalopathy during COVID-19 illness. Both patients had ADEM-like changes in their neuroimaging, negative SARS-CoV-2 RNA PCR in CSF, and paucity of PIMS-TS laboratory findings. However, the first patient was positive for serum MOG antibodies with normal CSF analysis, and the second had negative MOG antibodies but showed significant CSF lymphocytic pleocytosis. We concluded that the first case was a typical case of demyelination, which could have been triggered by different cofactors. In the second case, however, we postulated that the encephalopathic process was triggered by SARS-CoV-2, as no other cause was identified. With these two contrasting cases, we provide evidence that SARS-CoV-2-associated encephalitis can show ADEM-like changes, which can present during the postinfectious phase of COVID-19 illness. As ADEM is a relatively common type of postinfectious encephalitis in children, the distinguishing line between the two conditions of encephalitis and ADEM can be relatively fine. The development of more reliable diagnostic tools (e.g., anti-SARS-CoV-2 antibodies in CSF) might play an assisting role in the differentiation of these encephalopathic processes.

3.
Sci Rep ; 11(1): 7169, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1160544

ABSTRACT

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.


Subject(s)
Psychotic Disorders/cerebrospinal fluid , Adolescent , Adult , Age of Onset , Aged , Autoimmune Diseases of the Nervous System/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/psychology , Biomarkers/cerebrospinal fluid , COVID-19/psychology , Cerebrospinal Fluid Proteins/analysis , Child , Child, Preschool , Humans , Middle Aged , Psychotic Disorders/etiology , Psychotic Disorders/psychology , Retrospective Studies , Schizophrenia/cerebrospinal fluid , Young Adult
4.
Brain Behav Immun Health ; 13: 100238, 2021 May.
Article in English | MEDLINE | ID: covidwho-1116369

ABSTRACT

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) initially thought to be confined to the respiratory system only, is now known to be a multisystem disease. It is critical to be aware of and timely recognize neurological and neuroradiological manifestations affecting patients with COVID-19, to minimize morbidity and mortality of affected patients. METHODS: We performed a retrospective chart review of patients admitted to our Level 1 trauma and stroke center during the peak of the COVID-19 outbreak in New York from March 1st to May 30, 2020, with a positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) who presented mainly with neurological findings and had acute radiological brain changes on Computed Tomography (CT) scan. Patients with known chronic neurological disease processes were excluded from the study. We obtained and reviewed demographics, complete blood count, metabolic panel, D-dimer, inflammatory markers such as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), imaging, and patient's hospital course. We reviewed the current literature on neuroimaging, pathophysiology, and their clinical correlations on COVID-19. This case series study was approved by our institutional review board. RESULT: A total of 16 patients were selected for our case series. The most common neuroimaging features on CT, were territorial to multifocal ischemic infarcts, followed by a combination of ischemia and acute white matter encephalopathic changes, followed by temporal lobe predominant focal or more generalized encephalopathy with both confluent and non-confluent patterns, isolated cortical or more extensive intracranial hemorrhages and some combination of ischemia or hemorrhage and white matter changes. All our patients had severe acute respiratory distress syndrome (ARDS), most of them had elevated inflammatory markers, and D dimer. CONCLUSION: COVID-19 infection is a multi-organ disease, which can manifest as rapidly progressive neurological disease beyond the more common pulmonary presentation. Early recognition of various neurological findings and neuroimaging patterns in these patients will enable timely diagnosis and rapid treatment to reduce morbidity and mortality. Our retrospective study is limited due to small non-representative sample size, strict selection criteria likely underestimating the true extent of neurological manifestations of COVID-19, mono-modality imaging technique limited to predominantly CT scans and lack of CSF analysis in all except one patient. Multi-institutional, multi-modality, largescale studies are needed with radio-pathological correlation to better understand the complete spectrum of neurologic presentations in COVID-19 patients and study the causal relationship between SARS-CoV-2 and CNS disease process.

5.
Neuroradiology ; 63(5): 653-661, 2021 May.
Article in English | MEDLINE | ID: covidwho-1084384

ABSTRACT

PURPOSE: Acute hemorrhagic leukoencephalitis (AHLE) is a rare and severe form of acute disseminated encephalomyelitis (ADEM). Only a few reports of AHLE in coronavirus disease 2019 (COVID-19) patients have been described to date. We report a case of COVID-19-related AHLE along with a literature review describing salient clinical and imaging characteristics. METHODS: A literature search was performed on Medline (2020-present), PubMed, Cochrane Library, CINAHL, and Google scholar on 28 January 2021 for all articles published using MeSH terms "COVID-19" or "SARS-CoV-2" with "Acute hemorrhagic leukoencephalitis" or "Acute hemorrhagic encephalitis." Relevant case reports and case series describing clinical and imaging features of AHLE associated with SARS-CoV-2 infection were included, data compiled, and critically reviewed. RESULTS: Acute onset encephalopathy and rapidly deteriorating neurological status is the common clinical presentation in AHLE. CSF analysis reveals elevated proteins and lymphocytic pleocytosis. Typical neuroimaging features include multifocal, variable-sized, poorly defined cerebral white matter lesions with cortical sparing. Involvement of the brainstem, cerebellar peduncles, and deep grey matter can also occur, although rarely. Lesions are hyperintense on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images, hypointense on T1W images, and show microhemorrhages, variable diffusion restriction, and post-contrast enhancement. Extensive microhemorrhages, brainstem involvement, and gross hemorrhage often portend a poor prognosis. CONCLUSION: Heightened awareness about the clinical and imaging presentation of COVID-19-related AHLE can positively alter the outcome in a select few by enabling early diagnosis and aggressive management.


Subject(s)
COVID-19/complications , Leukoencephalitis, Acute Hemorrhagic/diagnostic imaging , Leukoencephalitis, Acute Hemorrhagic/virology , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Tomography, X-Ray Computed
6.
Int J Infect Dis ; 104: 390-397, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1014554

ABSTRACT

BACKGROUND: Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options. METHODS: We searched PubMed, Google Scholar, and Scopus databases using the keywords "SARS-CoV-2 in cerebrospinal fluid" and "SARS-CoV-2 and CNS Complications"" for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated. RESULTS: A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases. CONCLUSION: Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended.


Subject(s)
COVID-19/cerebrospinal fluid , Leukocytosis/cerebrospinal fluid , Nervous System Diseases/cerebrospinal fluid , SARS-CoV-2/physiology , COVID-19/complications , COVID-19/virology , Humans , Leukocytosis/etiology , Nervous System Diseases/etiology
7.
Case Rep Neurol ; 12(3): 359-364, 2020.
Article in English | MEDLINE | ID: covidwho-901496

ABSTRACT

COVID-19 has a broad spectrum of clinical presentations, including central nervous system manifestations that are not uncommon. The high pretest probability of COVID-19 in pandemic can lead to anchoring. We present a patient of COVID-19 pneumonia who presented with dyspnea and acute confusional state. His initial workup was suggestive of tuberculous meningoencephalitis with lymphocytic pleocytosis, high protein in CSF analysis, and suspicious MRI findings, which was later confirmed with a positive CSF culture. To the best of our knowledge, it is the first such case. Anchoring to the diagnosis of COVID-19 may deter clinicians from considering other concurrent diagnoses and a poor outcome consequently.

8.
J Neurol ; 268(8): 2671-2675, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-841658

ABSTRACT

OBJECTIVE: To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. METHODS: We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. RESULTS: Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed. CONCLUSIONS: Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.


Subject(s)
Brain Diseases , COVID-19 , Aged , Brain Diseases/drug therapy , Female , Humans , Immunoglobulins, Intravenous , Retrospective Studies , SARS-CoV-2
9.
J Neuroimmunol ; 349: 577400, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-792960

ABSTRACT

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Aphasia/etiology , Brain Diseases/virology , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Brain Diseases/drug therapy , Brain Diseases/immunology , COVID-19/immunology , Cytokine Release Syndrome/virology , Female , Humans , Middle Aged , SARS-CoV-2
10.
Neurol Sci ; 41(11): 3021-3022, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-739662

ABSTRACT

In December 2019, a new coronavirus infection was identified in China. Although the clinical presentation of COVID-19 is predominantly respiratory, more than 35%% of patients have neurological symptoms. We report an elderly female with asthenia, dry cough, anosmia, ageusia, fever, nausea, and a severe and persistent headache. She had confirmed COVID-19 using the nasal swab RT-PCR technique. Her cranial tomography was normal. The CSF analysis demonstrated a cell count of 21 cells/mm3 (80% lymphocytes and 20% monocytes), 34 mg/dl protein, and 79 mg/dl glucose. She improved after 4 days. Our report draws attention to the meningeal involvement of SARS-Cov-2.


Subject(s)
Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/complications , Headache/etiology , Leukocytosis/cerebrospinal fluid , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/complications , Aged , Betacoronavirus , COVID-19 , Female , Humans , Meningitis, Viral/virology , Pandemics , SARS-CoV-2
11.
Interdiscip Neurosurg ; 22: 100821, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-639099

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually causes fever, respiratory symptoms, malaise and myalgia. Recent observations suggested possible neurological complications of COVID-19, including the first report of suspected viral encephalitis. We report a case of a 29-year-old male with -on nasopharyngeal testing- confirmed SARS-CoV-2 infection with severe respiratory symptoms, followed by clinical and radiological signs of encephalitis. Magnetic resonance imaging (MRI) of the brain showed an asymmetric FLAIR-hyperintensity of the left medial temporal cortex associated with mild gyral expansion. Lumbar puncture was normal and PCR's for SARS-CoV-2 virus on CSF were negative. Clinicians treating SARS-CoV-2 infected patients should be aware of possible neurological complications, like encephalitis. The diagnosis of SARS-CoV-2 encephalitis is difficult as CSF analysis may be normal.

12.
Clin Neurophysiol Pract ; 5: 125-129, 2020.
Article in English | MEDLINE | ID: covidwho-592244

ABSTRACT

OBJECTIVES: We describe a patient suffering from Covid19-related acute respiratory distress syndrome (ARDS), highlighting the diagnostic role of the EEG in ICU. HISTORY: A Covid-19 patient undergoing mechanical ventilation due to related acute respiratory distress syndrome (ARDS), presented altered mental status in the ICU. Video-EEG revealed a focal monomorphic theta slowing in bilateral frontal-central regions. Concordant with the EEG localization, MRI showed abundant microbleeds located in bilateral white matter junction, various regions of corpus callosum and internal capsule, suggestive of Critical Illness-Associated Cerebral Microbleeds. CSF analysis excluded the presence of encephalitis, SARS-Cov2 RNA-PCR in CSF was negative. Clinical and biological picture was suggestive of cytokine release syndrome. CONCLUSION: This is the first reported case of Critical Illness-Associated Cerebral Microbleeds in the context of Covid-19. Knowledge of Covid-19 is still partial and acute neurological complications should be explored systematically. In our case, EEG helped to rule out non-convulsive status epilepticus, but revealed focal dysfunction, justifying further investigations.EEG plays a crucial role in these patients, allowing investigating the presence of focal or diffuse cerebral dysfunction. This is particularly helpful for Covid-19 patients in the ICU, where the neurological examination is challenging by the severity of the respiratory illness.

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