Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients

Abstract Background Neurological manifestations are common in patients with COVID-19, but little is known about pathophysiological mechanisms. In this single-center study, we describe neurological manifestations of 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods 58 COVID-19 patients with neurologic manifestations and SARS-CoV-2 RT-PCR screening on CSF analysis were included. Clinical, laboratory, and brain MRI data were retrospectively collected and analyzed. Results Patients were mostly men (66%) with a median age of 62 years. Encephalopathy was frequent (81%), followed by a pyramidal dysfunction (16%), seizures (10%), and headaches (5%). Protein and albumin levels in CSF were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient suggesting impaired blood-brain barrier integrity. CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF. Regarding brain MRI, 20 (38%) patients presented leptomeningeal enhancement. Conclusions Brain MRI abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV 2 detection in CSF remained scanty.

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Cytokine Release Syndrome-Associated Encephalopathy in Patients with COVID-19

10.20944/preprints202006.0103.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Peggy Perrin ◽

Nicolas Collongues ◽

Seyyid Baloglu ◽

Dimitri Bedo ◽

Xavier Bassand ◽

...

Keyword(s):

Clinical Decision Making ◽

Clinical Laboratory ◽

Severe Disease ◽

Brain Mri ◽

Case Series ◽

Neurological Manifestations ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Mri Findings ◽

Depth Analysis

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

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Two neurologic facets of CTLA4-related haploinsufficiency

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000751 ◽

2020 ◽

Vol 7 (4) ◽

pp. e751

Author(s):

Xavier Ayrignac ◽

Radjiv Goulabchand ◽

Eric Jeziorski ◽

Patricia Rullier ◽

Clarissa Carra-Dallière ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Cytotoxic T Lymphocyte ◽

Wide Spectrum ◽

Brain Mri ◽

White Matter Hyperintensity ◽

Motor Deficit ◽

Neurologic Manifestations ◽

Combined Immunodeficiency ◽

Mri Findings ◽

Previous Diagnosis

ObjectiveTo describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (CTLA4) haploinsufficiency.MethodsThree patients from 2 families had neurologic manifestations in the context of CTLA4 haploinsufficiency. Their clinical and MRI findings are presented.ResultsA 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited CTLA4 haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig).ConclusionsThese cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4 haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.

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Brain MRI in SARS-CoV-2 pneumonia patients with newly developed neurological manifestations suggestive of brain involvement

Scientific Reports ◽

10.1038/s41598-021-00064-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Batil Alonazi ◽

Ahmed M. Farghaly ◽

Mohamed A. Mostafa ◽

Jehad A. Al-Watban ◽

Salah A. Zindani ◽

...

Keyword(s):

Imaging Modality ◽

Brain Mri ◽

Brain Lesion ◽

Brain Magnetic Resonance Imaging ◽

Neurological Manifestations ◽

Rt Pcr ◽

Significant Difference ◽

Brain Involvement ◽

Magnetic Resonance Imaging Mri ◽

The Impact

AbstractThe increased frequency of neurological manifestations, including central nervous system (CNS) manifestations, in patients with coronavirus disease 2019 (COVID-19) pandemic is consistent with the virus's neurotropic nature. In most patients, brain magnetic resonance imaging (MRI) is a sensitive imaging modality in the diagnosis of viral encephalitides in the brain. The purpose of this study was to determine the frequency of brain lesion patterns on brain MRI in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients who developed focal and non-focal neurological manifestations. In addition, it will compare the impact of the Glasgow Coma Scale (GCS) as an index of deteriorating cerebral function on positive brain MRIs in both neurological manifestations. This retrospective study included an examination of SARS-CoV-2 pneumonia patients with real-time reverse transcription polymerase chain reaction (RT-PCR) confirmation, admitted with clinicoradiologic evidence of COVID-19 pneumonia, and who were candidates for brain MRI due to neurological manifestations suggesting brain involvement. Brain imaging acquired on a 3.0 T MRI system (Skyra; Siemens, Erlangen, Germany) with a 20-channel receive head coil. Brain MRI revealed lesions in 38 (82.6%) of the total 46 patients for analysis and was negative in the remaining eight (17.4%) of all finally enclosed patients with RT-PCR confirmed SARS-CoV-2 pneumonia. Twenty-nine (63%) patients had focal neurological manifestations, while the remaining 17 (37%) patients had non-focal neurological manifestations. The patients had a highly significant difference (p = 0.0006) in GCS, but no significant difference (p = 0.4) in the number of comorbidities they had. Brain MRI is a feasible and important imaging modality in patients with SARS-CoV-2 pneumonia who develop neurological manifestations suggestive of brain involvement, particularly in patients with non-focal manifestations and a decline in GCS.

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Rapid detection of Listeria monocytogenes rhombencephalitis in an immunocompetent patient by multiplexed PCR

BMJ Case Reports ◽

10.1136/bcr-2018-225575 ◽

2018 ◽

pp. bcr-2018-225575 ◽

Cited By ~ 1

Author(s):

Rocco J Richards ◽

Matthew S Simon ◽

C Douglas Phillips ◽

Lindsay Lief ◽

Stephen G Jenkins ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Listeria Monocytogenes ◽

Cranial Nerve ◽

Rapid Detection ◽

Brain Mri ◽

Complete Recovery ◽

Immunocompetent Patient ◽

Brainstem Encephalitis ◽

Mri Findings ◽

Multiplexed Pcr

A 46-year-old previously healthy man presented with 1 week of headache, nausea, vomiting and dizziness. He was found to have cranial nerve deficits, his cerebrospinal fluid (CSF) demonstrated a lymphocytic pleocytosis and brain MRI suggested rhombencephalitis. Although Gram stains and cultures of his CSF did not identify a pathogen, Listeria monocytogenes DNA was detected by the FilmArray Meningitis/Encephalitis panel within 2 hours of performing a lumbar puncture. He was treated with ampicillin and gentamicin and had a near-complete recovery. This case highlights the importance of recognising L. monocytogenes infection as a cause of acute cranial nerve impairment with MRI findings suggestive of brainstem encephalitis. It also highlights the frequently atypical CSF profile and low yield of culture in L. monocytogenes rhombencephalitis and the value of multiplex PCR testing of CSF to rapidly identify this pathogen and permit targeted therapy.

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Retrospective Observational Study of Brain MRI Findings in Patients with Acute SARS-CoV-2 Infection and Neurologic Manifestations

Radiology ◽

10.1148/radiol.2020202422 ◽

2020 ◽

Vol 297 (3) ◽

pp. E313-E323 ◽

Cited By ~ 14

Author(s):

Lydia Chougar ◽

Natalia Shor ◽

Nicolas Weiss ◽

Damien Galanaud ◽

Delphine Leclercq ◽

...

Keyword(s):

Observational Study ◽

Brain Mri ◽

Retrospective Observational Study ◽

Neurologic Manifestations ◽

Mri Findings

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Serial MRI and CSF Analysis in a Dog Treated with Intrathecal Amphotericin B for Protothecosis

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-5701 ◽

2012 ◽

Vol 48 (2) ◽

pp. 125-131 ◽

Cited By ~ 6

Author(s):

Martin Young ◽

William Bush ◽

Melissa Sanchez ◽

Pat Gavin ◽

Mathew Williams

Keyword(s):

Cerebrospinal Fluid ◽

Amphotericin B ◽

Head Tilt ◽

Mri Findings ◽

Lipid Complex ◽

Fluid Analysis ◽

Csf Analysis ◽

Transient Improvement ◽

The Right ◽

The Brain

A 3 yr old female spayed English setter mixed-breed dog presented with diarrhea, weight loss, side stepping to the right, and a right head tilt. Rectal and cerebrospinal fluid cytology and culture confirmed a diagnosis of Prototheca zopfii. MRI of the brain showed inflammation of the brain and meninges, ventriculomegaly, and syringomyelia. Treatment with prednisone, itraconazole, and amphotericin B lipid complex administered intrathecally yielded transient improvement. Progressive brainstem signs were noted, and a repeat MRI and cerebrospinal fluid analysis documented persistent disease. This is the first description of the MRI findings and treatment with intrathecal amphoteracin B lipid complex for protothecosis of the central nervous system. Protothecosis should be considered in dogs with chronic diarrhea and compatible MRI findings.

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Neurologic and neuroimaging findings in patients with COVID-19

Neurology ◽

10.1212/wnl.0000000000010112 ◽

2020 ◽

Vol 95 (13) ◽

pp. e1868-e1882 ◽

Cited By ~ 27

Author(s):

Stéphane Kremer ◽

François Lersy ◽

Mathieu Anheim ◽

Hamid Merdji ◽

Maleka Schenck ◽

...

Keyword(s):

Ischemic Stroke ◽

Corticospinal Tract ◽

Brain Mri ◽

Clinical Signs ◽

Neurologic Manifestations ◽

Neurologic Manifestation ◽

Leptomeningeal Enhancement ◽

Wide Range ◽

Tract Involvement ◽

Abnormal Brain

ObjectiveTo describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.MethodsIn this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.ResultsThe cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20–92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009).ConclusionsPatients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.ClinicalTrials.gov identifierNCT04368390.

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Acute disseminated encephalomyelitis (ADEM) associated with COVID-19

BMJ Case Reports ◽

10.1136/bcr-2020-239597 ◽

2020 ◽

Vol 13 (12) ◽

pp. e239597

Author(s):

Lawrence Langley ◽

Claudia Zeicu ◽

Louise Whitton ◽

Mathilde Pauls

Keyword(s):

Cerebrospinal Fluid ◽

Critical Care ◽

Respiratory Failure ◽

Brain Mri ◽

Acute Disseminated Encephalomyelitis ◽

Neurological Deficits ◽

Oligoclonal Bands ◽

High Dose ◽

The Brain

A 53-year-old man admitted to the critical care secondary to respiratory failure due to COVID-19 developed agitation and global hypotonia. Brain MRI revealed bilateral hyperintense lesions throughout the brain and cerebrospinal fluid identified oligoclonal bands. Intravenous high-dose glucocorticoids were administered followed by an oral tapering dose and the patient clinically improved. Acute disseminated encephalomyelitis should be considered in patients with COVID-19 who present with altered mentation and polyfocal neurological deficits.

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AREA POSTREMA SYNDROME – A CHALLENGE FOR DIFFERENTIAL DIAGNOSIS BETWEEN MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISORDERS

Romanian Journal of Neurology ◽

10.37897/rjn.2017.4.4 ◽

2017 ◽

Vol 16 (4) ◽

pp. 154-157

Keyword(s):

Neuromyelitis Optica ◽

Area Postrema ◽

Brain Mri ◽

Clinical Findings ◽

The Body ◽

Oligoclonal Bands ◽

Neuromyelitis Optica Spectrum Disorders ◽

Peripheral Facial Palsy ◽

Csf Analysis ◽

Spectrum Disorders

Area postrema syndrome (APS) manifested with hiccups, nausea and vomiting is one of the core clinical findings in neuromyelitis optica spectrum disorders (NMOSD). We report the case of a 41-year-old woman, with no significant prior medical history, who presented with left upper limb paresthesias. The patient revealed two prior episodes, one 5 years ago, with paresthesias and mild paresis on the right side of the body and the other a few month ago, with right peripheral facial palsy, right facial anesthesia, headache, nausea and emesis. This led us to suspect area postrema syndrome and, possibly, NMOSD. Brain MRI did not show typical lesions for NMOSD, apart from a left periaqueductal lesion. Other potential diagnoses were excluded through laboratory workup. Serum anti-AQP4 antibody were negative, while CSF analysis was positive for oligoclonal bands. Based on clinical and paraclinical findings, a diagnosis of MS was made. This case illustrated that APS may also be present in MS and not only in NMOSD.

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COEXISTENCE OF MULTIPLE SCLEROSIS AND ALZHEIMER DISEASE: WHAT WE KNOW SO FAR?

10.5327/1980-5764.rpda107 ◽

2021 ◽

Author(s):

Igor Santiago ◽

Victor Elias ◽

Ivna Nóbrega ◽

Gabriela Martins ◽

José Artur D’Almeida ◽

...

Keyword(s):

Multiple Sclerosis ◽

Alzheimer Disease ◽

Brain Mri ◽

Poor Response ◽

Executive Dysfunction ◽

Oligoclonal Bands ◽

Retrospective Case ◽

Csf Analysis ◽

Age Related ◽

Pet Ct

Background: Multiple sclerosis (MS) and Alzheimer disease (AD) are neurodegenerative diseases with distinct pathophysiology but similar burdens. Early cognitive impairment in MS is unusual but, due to disease modifying therapies (DMT) advancements and bigger life expectancy, its coexistence with AD has become more common. Objective: To report a coexistence case of MS and AD. Methods: Retrospective case report and literature review. Results: 58-year-old patient presented with work issues, behavioral changes, gait disturbance and unbalance. It was disclosed an impairment of attention span, multitasking, executive dysfunction, and loss of memory for recent events. A PET/CT showed hypometabolism in frontal lobes and CSF analysis disclosed oligoclonal bands and increased TAU protein levels. The patient was initially treated with donepezil, with poor response. A later brain MRI showed typical demyelinating MS lesions. The patient was treated with Natalizumab due to high lesion load and functional impairment. Conclusion: As MS patients live longer, it’s important to recognize age-related comorbidities such as AD. In our patient a poor relapse perception contributed for a late MS diagnosis. The evaluation with PET/CT and increased TAU levels in CSF highly suggests a coexistence with AD. There are no peer-reviewed studies regarding coexisting MS and AD. Further research is necessary to better understand the clinical, demographic, and neuropathological features of the coexistence of both diseases.

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