Para-infectious aseptic meningo-encephalitis following SARS-CoV-2 infection: two case reports

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

Neurological involvement associated with COVID-19 infection in children

Acute transverse myelitis after BNT162b2 vaccination against COVID-19: Report of a fatal case and review of the literature

To assess the relation of a distinctive pattern of short tau inversion recovery muscle hyperintensity with inflammatory cerebrospinal fluid result in dogs. All dogs that had a short tau inversion recovery sequence performed in addition to other magnetic resonance sequences of the cervical spine and concurrent cerebrospinal fluid evaluation during the study period were included. All magnetic resonance studies were anonymised and reviewed by a board certified radiologist and board certified neurologist. A board certified pathologist examined the cerebrospinal fluid and the results were reviewed. Forty-nine cases fulfilled the inclusion criteria. Repeatable patterns of short tau inversion recovery hyperintensity were identified in 20 dogs. The clinical diagnosis in all these 20 cases was of meningoencephalomyelitis of unknown origin. This diagnosis was confirmed by inflammatory cerebrospinal fluid changes in 18 and suspected from clinical presentation and response to therapy in the remaining 2. In this study, the short tau inversion recovery changes identified were restricted to cases with inflammatory spinal cord disease. The short tau inversion recovery change had a sensitivity of 78%, and a specificity of 92% in predicting inflammatory cerebrospinal fluid, suggesting that short tau inversion recovery sequences are a useful addition to the investigation of suspected inflammatory spinal cord disease.

Sarcoidosis and obsessive-compulsive symptoms

Ramsay Hunt syndrome is defined as herpes zoster oticus associated with an acute peripheral facial nerve paresis and quite often with other cranial nerve lesions. The combination of motor, sensory and autonomic involvement leads to a variety of neurological damage patterns, i. e. facial muscle paresis, hearing and balance disorders, sensory problems and disturbances of taste as well as lacrimal and nasal secretion. Additional variability of the clinical picture of Ramsay Hunt syndrome is produced by varying patterns of skin involvement explained by individual anastomoses between cranial and cervical nerves. Knowledge of these findings and an early diagnosis of Ramsay Hunt syndrome are important as prognosis of cranial nerve damage depends on the time at which acyclovir-corticosteroid therapy is started.

BackgroundThe SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany.MethodsBetween March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS).ResultsMajor clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR.ConclusionsIn line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.

ObjectivesIn this study, we aimed to determine the frequency of neurological signs, symptoms, and complications in coronavirus disease 2019 (COVID-19) patients. We also sought to explore the general characteristics of stroke patients in particular.MethodsA retrospective cohort study was conducted among COVID-19 patients who were hospitalized between April-September 2020 at the Al-Noor Specialist Hospital in Makkah city, Saudi Arabia. The study included patients who were aged ≥18 years and presented with or were reported to have any neurological manifestations and/or complications secondary to COVID-19 infection.ResultsA total of 79 patients were included. The mean age of the cohort was 63.6 years, with a significant male predominance (67.1%). The most commonly reported neurological signs and symptoms were altered level of consciousness (45.9%), dizziness (11.5%), and focal neurological deficit (10.4%). Acute ischemic stroke was seen in 18 patients. Most of them were males (66.7%). Most strokes were in the right middle cerebral artery territory (MCA) (50.0%). Diabetic patients were four times more at risk to develop stroke [odds ratio (OR)=3.76; 95% confidence interval (CI): 1.1-29.9]. Patients with respiratory failure were 21 times more likely to have a stroke (OR=21.3; 95% CI: 2.2-54.6). Patients with acute respiratory distress syndrome recorded a three-fold increased risk for developing stroke (OR=2.96; 95% CI: 1.25-37.3). Critically ill patients had double the risk of stroke (OR=1.8; 95% CI: 1.1-6.9). Other neurological complications were hemorrhagic stroke (3.3%), subacute/chronic infarction (23.3%), meningitis (10%), and brain mass lesion (3.3%).ConclusionsNeurological symptoms and complications are not uncommon among COVID-19 patients. Most of these patients had poor outcomes. Acute ischemic stroke was the most common finding on neuroimaging.

BackgroundCOVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients.Case presentationWe describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion.ConclusionOur findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

Patients with spinal canal pathology, including spinal stenosis and lumbar disk disease, are often not considered candidates for neuraxial blockade because of the risk of exacerbating preexisting neurologic deficits or developing new neurologic dysfunction. In contrast, a history of spine surgery is thought to increase the likelihood of difficult or unsuccessful block. In this retrospective study we investigated the risk of neurologic complications and block efficacy in patients with preexisting spinal canal pathology, with or without a history of spine surgery, after neuraxial anesthesia. During the 15-year study period, all patients with a history of spinal stenosis or lumbar radiculopathy undergoing a neuraxial technique were studied. Patient demographics, preoperative neurologic diagnoses and neurologic findings at the time of surgery/neuraxial block, details of the neuraxial block including technique (spinal vs. epidural, single injection vs. continuous), injectate, technical complications (paresthesia elicitation, bloody needle/catheter placement, inability to advance catheter, accidental dural puncture), and block success were noted. New or progressive neurologic deficits were identified. All patients were followed until resolution or last date of evaluation. There were 937 patients included, 207 (22%) of whom had undergone spinal surgery. A history of spinal stenosis was present in 187 (20%), lumbar radiculopathy in 570 (61%), and peripheral neuropathy in 210 (22%) patients; 180 patients (19%) had multiple neurologic diagnoses. A majority of patients had active but stable neurologic symptoms at the time of surgery. Overall block success was 97.2%. A history of spine surgery did not affect the success rate or frequency of technical complications. Ten (1.1%; 95% confidence interval [CI] 0.5%-2.0%) patients experienced new deficits or worsening of existing symptoms. Three (1.4%) complications occurred in patients with a history of spinal surgery, and the remaining 7 (1.0%) in patients without prior surgical decompression or stabilization (P = NS). Although an orthopedic procedure was not a risk factor, in 5 of the 6 patients in which the surgery was a unilateral lower extremity procedure, the postoperative deficit involved the operative side. Likewise, in both patients undergoing bilateral orthopedic procedures who developed bilateral deficits, the outcome was worse on the previously affected side. A surgical cause was presumed to be the primary etiology in 4 (40%) of 10 patients. The primary etiology of the remaining 6 (60%) complications was judged to be nonsurgical (including anesthetic-related factors). The presence of a preoperative diagnosis of compressive radiculopathy (P = 0.0495) or multiple neurologic diagnoses (P = 0.005) increased the risk of neurologic complications postoperatively. We conclude that patients with preexisting spinal canal pathology have a higher incidence of neurologic complications after neuraxial blockade (1.1%; 95% CI 0.5%-2.0%) than that previously reported for patients without such underlying pathology. However, in the absence of a control group of surgical patients with similar anatomic pathology undergoing general anesthesia, we cannot determine whether the higher incidence of neurologic injury is secondary to the surgical procedure, the anesthetic technique, the natural history of spinal pathology, or a combination of factors and the relative contributions of each.

BackgroundHelminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common among populations with high tuberculosis prevalence. Our aim was to determine whether S. stercoralis coinfection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM).MethodsFrom June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817 and NCT03100786), underwent pretreatment S. stercoralis testing by serology, stool microscopy, and/or stool polymerase chain reaction. Comparisons of pretreatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical end points were performed in groups with or without active S. stercoralis infection.ResultsOverall, 9.4% participants (63 of 668) tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pretreatment CSF neutrophil counts (median [interquartile range], 3/μL [0–25/μL] vs 14 /μL [1–83/μL]; P = .04), and with reduced CSF interferon ɣ, interleukin 2, and tumor necrosis factor α concentrations (11.4 vs 56.0 pg/mL [P = .01], 33.1 vs 54.5 pg/mL [P = .03], and 4.5 vs 11.9 pg/mL [P = .02], respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in participants with active S. stercoralis infection compared with uninfected participants (3.8% [1 of 26] vs 30.0% [33 of 110], respectively; P = .01).ConclusionsS. stercoralis coinfection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes.

A method is presented to help explain the genesis of cerebrospinal fluid (CSF) pressure changes associated with a variety of alterations within the craniospinal system. Translation of the x-axis is used to convert the usual plot of CSF pressure vs. change in CSF volume (CSF P/ΔV curve) to a plot of CSF pressure vs. total CSF volume (the CSF P/V curve). This translation permits analysis of craniospinal pressure/volume dynamics in terms of the factors that change CSF equilibrium pressure (Peq) or CSF equilibrium volume (Veq) or that alter the shape of the CSF P/V curve. Changes in Peq are produced only by changes in the net CSF flow/pressure relationship. The shape of the CSF P/V curve changes only in response to alterations in mechanical properties of craniospinal tissues. Veq is altered either by changes in the CSF net flow/pressure curve or by variation in mechanical properties of the tissues around the CSF space. Only CSF volume changes alter CSF pressure by movement of a point along a single P/V curve. Volume changes in all other craniospinal compartments alter CSF pressure by changing Peq, by changing Veq, or by changing the shape of the CSF P/V curve. Depending on how tissue mechanical properties are changed, on how other mechanical factors in the craniospinal axis are altered, and on how the net CSF flow/pressure function has been changed, a perturbation of the craniospinal system may selectively alter Peq, Veq, or the shape of the CSF P/V curve. After a perturbation of the craniospinal system, total CSF volume is related to a new CSF P/V curve to generate a new level of CSF pressure. If changes in the net CSF flow/pressure curve or in tissues around the CSF space occur slowly, CSF pressure and volume may not be significantly different from Peq and Veq, whereas if these changes occur rapidly CSF pressure and volume may be markedly different from Peq and Veq. (Neurosurgery, 6: 453-462, 1980)

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive degenerative demyelinating disease that results from infection with JC virus. PML usually occurs in an immunocompromised individual, putatively attributable to reactivation of a latent JC virus. In childhood PML has been reported in individuals with acquired immunodeficiency syndrome (AIDS),1–3 Wiskott–Aldrich syndrome,4 and inherited immunodeficiencies.5,,6We report here a 15-year-old boy with generalized morphea, a form of limited cutaneous sclerodema, and secondary amyloidosis who developed PML. The rapid onset of his neurologic manifestations and the initial neuroimaging studies suggested acute disseminated encephalomyelitis (ADEM), and a brain biopsy was needed for the diagnosis of PML. A 15-year-old boy with scleroderma and amyloidosis was admitted for progressive ataxia, dysarthria, and weakness. His medical history was notable for generalized morphea confirmed by a skin biopsy at 3 years of age. He had severe cutaneous involvement and finger and toe contractures attributable to skin and soft tissue involvement. He was treated with prednisone andD-penicillamine for several years. All autoantibodies were negative, and immunologic work-up revealed normal complement and immunoglobulin levels but a low absolute T-cell count of 533 cells/μL. There was no evidence of active arthritis or recurrent infections. Two years before admission, he was diagnosed with secondary amyloidosis with serum amyloid A protein by liver biopsy. A concomitant skin biopsy showed no evidence of amyloid deposition and continued to be consistent with morphea. Proteinuria was noted. Prednisone was stopped, and chlorambucil (4 mg per day) was started. He responded well to the chlorambucil over the next several months with significant regression of amyloidosis-related clinical findings and marked dermatologic improvement. He was maintained on chlorambucil only. However, 2 months before admission the dosage had to be decreased from 4 mg to 3 mg daily because of leukopenia with a white …

Several case studies have reported on neurological complications caused by a primary Epstein-Barr virus (EBV) infection. We aimed to investigate the viral loads and the clinical and inflammatory characteristics of this disease entity. We evaluated all 84 cases in which the EBV polymerase chain reaction test (PCR) was requested on cerebrospinal fluid (CSF) for the period 2003-2008. Fourteen patients with proven neuroborreliosis served as the control group. Nine patients were diagnosed with a primary EBV infection and neurological symptoms (median age 36 y; 4 male). Viral DNA copies in CSF were detected by PCR in 7 of 9 patients. The presenting symptoms were meningeal signs, epileptic insults, polyradiculomyelitis, polyradiculitis, and/or sudden cognitive disorders. All EBV cases had a pleocytosis with significantly increased mononuclear leukocytes as compared to the neuroborreliosis group (median 99% interquartile range (96-100%) versus 90% (86-97%). In cases with a primary EBV infection, viral loads ranged from 43 to 3202 copies/ml in CSF and from 61 to 15,595 copies/ml in serum. Seventy-eight percent of the cases had a positive PCR on CSF. This study provides criteria for diagnosing neurological disease during primary EBV infection. Primary EBV infections in immune competent persons can cause a broad range of neurological symptoms, with lymphocytic and monocytic inflammation both in blood and CSF.

In The Lancet Microbe's August issue, Grégory Destras and colleagues1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar reported on a retrospective RT-PCR screening of all cerebrospinal fluid (CSF) samples received by the virology laboratory of a single university hospital during the COVID-19 epidemic in France (between Feb 1 and May 11, 2020). Of the CSF samples from the 23 patients with confirmed COVID-19, only two were slightly positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most likely as a result of contamination by blood. Other studies have reported negative CSF findings in patients with COVID-19, specifically examining samples from patients with confirmed disease and neurological complications, as opposed to the systematic screening operated by Destras and colleagues.1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar Neumann and colleagues2Neumann B Schmidbauer ML Dimitriadis K et al.Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms.J Neurol Sci. 2020; 418117090Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar analysed samples collected from 30 patients in six German centres between March and June, 2020. Bellon and colleagues3Bellon M Schweblin C Lambeng N et al.Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients.Clin Infect Dis. 2020; (published online Aug 8.)https://doi.org/10.1093/cid/ciaa1165Crossref Scopus (16) Google Scholar examined 31 patients. Espíndola and colleagues4Espíndola OM Siqueira M Soares CN et al.Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.Int J Infect Dis. 2020; 96: 567-569Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar described eight patients and reviewed literature reports on 30 additional cases. All of these studies showed that SARS-CoV-2 is not detectable in the CSF of patients with COVID-19 and neurological manifestations. The importance of these results, and the reason why researchers at different laboratories are focusing on the same line of research, should be found in the question of how the virus can damage the nervous system. Is it a direct or indirect mechanism? The results from the studies mentioned here point toward an indirect mechanism.1Destras G Bal A Escuret V et al.Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.Lancet Microbe. 2020; 1: e149Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 2Neumann B Schmidbauer ML Dimitriadis K et al.Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms.J Neurol Sci. 2020; 418117090Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 3Bellon M Schweblin C Lambeng N et al.Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients.Clin Infect Dis. 2020; (published online Aug 8.)https://doi.org/10.1093/cid/ciaa1165Crossref Scopus (16) Google Scholar, 4Espíndola OM Siqueira M Soares CN et al.Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.Int J Infect Dis. 2020; 96: 567-569Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar Further results5Franke C Ferse C Kreye J et al.High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms.medRxiv. 2020; (published online July 6.) (preprint)https://doi.org/10.1101/2020.07.01.20143214Google Scholar support an indirect mechanism, showing a high prevalence of autoantibodies, mainly against unknown autoantigens in the brain, in CSF from patients with COVID-19 and neurological complications. It appears, therefore, that neurological manifestations of COVID-19 are not caused by direct cytopathic effects but indirect immune-mediated mechanisms targeting various unknown elements of the nervous system. Testing the immune reactivity of the CSF of patients with COVID-19 and neurological manifestations against candidate targets for autoimmunity might be the next step to elucidate the mechanisms of damage to the nervous system by SARS-CoV-2. I declare no competing interests. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemicSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged since December, 2019, and spread worldwide, causing the COVID-19 pandemic. Despite COVID-19 being a respiratory tract infection, the pathophysiology in both adults and children is incompletely understood. Neurological signs and symptoms—from headache to meningitis—have been reported in hospitalised patients.1,2 SARS-CoV-2 can enter and replicate in neuronal cells in vitro,3 but the association between neurological manifestations and presence of SARS-CoV-2 in cerebrospinal fluid (CSF) has only been tested in a few cases, with one patient testing positive for SARS-CoV-2 in a case report4 and seven of seven patients testing negative in a case series. Full-Text PDF Open Access