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Clinical report
Encephalitis as a neurological manifestation of COVID-19
Encefalitis como manifestación neurológica del COVID-19
Herminia Lozano Gómez
Corresponding author
fiex_hermi1990@hotmail.com

Corresponding author.
, Ana Pascual Bielsa, Paula Abansés Moreno, María Pilar Luque Gómez, Almudena Matute Guerrero, Juan José Araiz Burdio
Servicio de Medicina Intensiva, Hospital Clínico Universitario Lozano Blesa, Zargoza, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Around mid-December 2019&#44; the first cases of pneumonia and respiratory distress were reported in Wuhan&#44; China&#44; as a result of infection by a new coronavirus &#40;SARS-CoV-2&#41;&#44; which in the following months was to become the largest epidemic in recent years in living memory&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Coronaviruses are common and widely distributed&#44; causing upper respiratory tract infections in most cases&#46; The clinical manifestations are similar to the flu&#44; and the most common symptoms are fever &#40;90&#37;&#41;&#44; cough and myalgias &#40;50&#37;&#41; and headache &#40;10&#37;&#41;&#46; Some more specific symptoms of SARS-CoV-2 infection are anosmia and ageusia&#44; which have been considered early symptoms and affect 60&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The development of bilateral pneumonia&#44; respiratory superinfections or respiratory distress syndrome are the most common complications&#59; however&#44; other extrapulmonary involvement&#44; such as cardiomyopathy or encephalitis&#44; has also been reported&#44; although less frequently&#46; Besides&#44; they entail a complicated diagnosis and a poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We report the case of two patients with SARS-CoV-2 infection whose main involvement was neurological&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Case 1</span><p id="par0025" class="elsevierStylePara elsevierViewall">52-year-old male&#44; a native of the Dominican Republic&#44; resident in Spain for eight years&#44; and with no medical history of interest&#46; The patient came to the emergency department reporting a 4-day history of fever and headache and neurological symptoms consisting of gait disturbances and dysarthria of sudden onset&#44; just 2&#160;h before&#46; Physical examination showed a body temperature of 36&#160;&#176;<span class="elsevierStyleSmallCaps">C</span>&#44; baseline oxygen saturation of 95&#37;&#44; Glasgow 15&#44; bradypsychia and dysarthric speech&#44; with no other obvious neurological focus&#46; Laboratory tests showed a C-reactive protein concentration of 40&#46;5&#160;mg&#47;L &#40;normal range 0&#46;1&#8211;5&#160;mg&#47;L&#41;&#44; white blood cells 6&#46;6&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;L &#40;76&#46;3&#37; neutrophils and 7&#46;42&#37; lymphocytes&#41;&#46; A brain computed tomography &#40;CT&#41; scan was performed&#44; which showed no abnormalities&#46; The rapid test for influenza A and B viruses and respiratory syncytial virus was negative&#44; as was the <span class="elsevierStyleItalic">legionella</span> and pneumococcus urine antigen test&#46; SARS-Cov-2 disease was confirmed after polymerase chain reaction &#40;PCR&#41; analysis of nasopharyngeal swab and was admitted to the infectious disease unit pending study completion&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Three hours after admission&#44; he presented with a generalized tonic-clonic seizure&#44; with sustained post-critical clouding of consciousness&#44; for which he was admitted to the Intensive Care Unit &#40;ICU&#41; and required orotracheal intubation and mechanical ventilation&#46; A lumbar puncture was performed to obtain cerebrospinal fluid &#40;CSF&#41;&#44; which was clear in appearance and whose biochemistry and microbiology were completely normal&#46; Given the suspicion of neurological involvement by SARS-CoV-2&#44; its isolation in the CSF was requested&#44; which was negative&#46; Antibiotic treatment with levetiracetam and antibiotic treatment with ceftriaxone were initiated&#46; In addition&#44; antiviral treatment with lopinavir&#47;ritonavir and hydroxychloroquine and &#174;-interferon was started and discontinued early&#44; according to the hospital protocol in place at the time&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">24&#160;h after admission to the ICU he developed bilateral mydriasis&#46; The new brain CT scan showed predominantly right-sided cortico-subcortical hypodense areas in the sulci of the frontal convexity&#44; probably of ischaemic origin&#44; and signs of diffuse cerebral oedema &#40;fig&#46; 1&#41;&#46; An intracranial cerebral pressure &#40;ICP&#41; sensor showed intracranial hypertension &#40;60&#160;mmHg&#41; and treatment was started with thiopental perfusion &#40;2&#160;g&#47;12&#160;h&#41;&#44; corticosteroid pulses &#40;methylprednisolone 1&#160;g&#47;24&#160;h&#41; and plasmapheresis sessions for seven days&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A new CT scan of the brain showed multiple hyperdense lesions&#44; compatible with autoimmune disseminated leukoencephalopathy&#46; Given the normalization of ICP figures&#44; the barbiturate coma therapy was discontinued&#46; The electroencephalogram &#40;EEG&#41; was suggestive of poor prognostic criteria and transcranial Doppler data were compatible with brain death&#46; After the consensus of the multidisciplinary medical team with the family&#44; life support treatment was limited&#44; resulting in the death of the patient&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Case 2</span><p id="par0045" class="elsevierStylePara elsevierViewall">A 70-year-old man with a history of cardiovascular risk factors &#40;hypertension&#44; DM&#44; dyslipidaemia&#44; and former smoker&#41;&#44; moderate alcohol consumption&#44; stage IIIA chronic renal failure&#44; atrial fibrillation &#40;chronically anticoagulated with acenocoumarol&#41;&#44; COPD&#44; and apnoea-hypoventilation syndrome&#44; night CPAP carrier&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The patient had been diagnosed with SARS-CoV-2 infection during the epidemiological study after contact with a positive case&#46; He came to the emergency department three days later with deterioration of general condition&#44; instability and difficulty standing upright&#46; During the clinical examination&#44; oxygen saturation was 96&#37;&#44; with no work of breathing&#44; and cardiopulmonary auscultation did not reveal pathological sounds except for an irregular heart rhythm&#44; previously known&#46; Brain CT without acute findings&#46; He was admitted to the hospital ward for study and treatment with ceftriaxone&#44; azithromycin&#44; and methylprednisolone at doses of 20&#160;mg&#47;24&#160;h IV&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">He was assessed by the Neurology Department on several occasions&#44; whose clinical assessment was an episode of delirium or abstinence from alcohol consumption&#46; CT and brain CT angiography were repeated&#44; showing no abnormalities&#46; There was a progressive neurological worsening of the patient&#44; with the onset of a Cheyne-Stokes respiratory pattern and desaturation up to 88&#37;&#46; A pulmonary CT angiography was performed&#44; which showed small-vessel pulmonary embolisms&#44; for which the dose of subcutaneous enoxaparin was increased to 80&#160;mg&#47;12&#160;h&#44; the patient was intubated and transferred to the Intensive Care Unit&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A lumbar puncture was performed&#44; and CSF was obtained&#44; with clear fluid and normal pressure&#46; Empirical treatment with acyclovir&#44; ceftriaxone&#44; and ampicillin was initiated and corticosteroid treatment was maintained&#46; Biochemistry&#44; microbiology&#44; and PCR for SARS-CoV-2 in CSF were negative&#46; The EEG showed a non-convulsive status epilepticus that resolved with the start of treatment with levetiracetam&#44; with the following EEGs showing slowed activity&#44; but without signs of status epilepticus&#46; Magnetic resonance imaging &#40;MRI&#41; showed signs of small vessel encephalopathy which did not justify the clinical condition&#46; In coordination with the neurology department&#44; 1&#160;g of intravenous methylprednisolone bolus was administered over 72&#160;h&#44; with no improvement&#46; The patient remained in hospital for several weeks and was transferred to the long-stay unit where he died&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Since the beginning of the pandemic&#44; extensive data on the main manifestations of COVID-19 have been published&#46; Among all of them&#44; neurological involvement seems to be uncommon&#44; although with very varied manifestations and different pathophysiology&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The most common neurological manifestations are usually mild&#44; such as headache&#44; anosmia&#44; and ageusia&#46; However&#44; there are other manifestations with greater clinical significance and&#44; above all&#44; greater morbidity and mortality&#44; including cerebral ischaemic processes&#44; encephalitis&#44; alterations in the level of consciousness or memory and polyneuropathies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Encephalitis is defined as the occurrence of an acute and sustained encephalopathy lasting more than 24&#160;h &#40;including lethargy&#44; irritability&#44; or behavioural changes&#41; and evidence of brain inflammation&#44; manifested by fever&#44; vomiting&#44; seizures&#44; EEG abnormalities and&#47;or compatible CT or MRI&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The most common aetiology is viral&#44; specifically secondary to the herpes simplex virus&#46; Nevertheless&#44; other viruses such as varicella zoster virus &#40;VZV&#41;&#44; Epstein Barr virus &#40;EBV&#41; or cytomegalovirus &#40;CMV&#41; have also been isolated from CSF&#44; but less frequently&#46; The emergence of SARS-CoV-2 over the past year has led to the occurrence of new cases of encephalitis due to this cause&#59; however&#44; the diagnosis is based on clinical and&#47;or neuroimaging findings&#44; as this virus has only been isolated in CSF in a very specific manner and with extremely limited means&#44; such as reverse transcription PCR&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5&#44;6</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Although the new coronavirus is not&#44; a priori&#44; a neurotropic virus&#44; but rather its primary target is the nasopharyngeal epithelium&#44; the pathophysiology by which neurological involvement occurs is not entirely clear&#44; and there could be several mechanisms involved&#46; Firstly&#44; transient virus spread to the CSF with extremely low titres is contemplated&#44; which makes virus isolation difficult&#46; Another option&#44; which according to experts is the most plausible&#44; is immune-mediated encephalitis&#58; SARS-CoV-2 would produce an immune response and an activation of the cytokine cascade &#40;complement&#44; Il-6&#44; IL-10&#44; TNF&#44; coagulation&#44; etc&#46;&#41; leading to the brain oedema and swelling responsible for the clinical condition&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4&#44;5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Acute necrotising encephalopathy &#40;ANE&#41; is a rare neurological complication caused by cytokine storm and damage to the blood-brain barrier&#44; reported after severe viral infections&#46; It presents with necrotic lesions with perilesional enhancement on brain CT&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In any case&#44; life support and treatment of intracranial hypertension are paramount&#46; Given the existing hyperinflammatory state&#44; the use of intravenous immunoglobulins and corticosteroids&#44; or even plasmapheresis&#44; could promote viral clearance and be useful&#46; Cyclophosphamide or rituximab are treatments with significant side effects&#44; which is why they have not been used to date&#46; No treatment has shown proven efficacy&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;8</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Due to the increasing incidence of COVID-19&#44; its neurological manifestations are becoming more and more common&#46; There is&#44; therefore&#44; an urgent need to understand and diagnose neurological syndromes as early as possible in order to optimise treatment&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interests</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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            0 => "Encefalitis"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In the context of the global COVID-19 pandemic&#44; the different clinical manifestations of this infection pose a challenge for healthcare professionals&#46; Respiratory involvement&#44; the main symptom of SARS-CoV-2 infection&#44; means that other manifestations&#44; such as neurological&#44; take a back seat&#44; with the consequent delay in diagnosis and treatment&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">All COVID-19 patients admitted with neurological symptoms or diagnosed with encephalitis since March 2020 in a tertiary hospital in Zaragoza&#44; Spain&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Two patients with COVID-19 infection confirmed by nasopharyngeal PCR and whose clinical picture consisted of neurological alterations compatible with encephalitis&#46; Cerebrospinal fluid &#40;CSF&#41; microbiology was negative for bacteria and viruses&#44; including SARS-CoV-2 but&#44; given the clinical suspicion of encephalitis due to the latter&#44; antiviral treatment with immunoglobulins and plasmapheresis was started early&#46; Despite this&#44; the evolution was not satisfactory&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">COVID-19 encephalitis is a recently described clinical entity&#44; whose pathophysiology is still unknown and no treatment with clinical evidence is available to date&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">En el contexto de la pandemia mundial por COVID-19&#44; las distintas manifestaciones cl&#237;nicas de esta infecci&#243;n suponen un reto para los profesionales sanitarios&#46; La afectaci&#243;n respiratoria&#44; s&#237;ntoma principal de la infecci&#243;n por SARS-CoV-2&#44; hace que otras manifestaciones&#44; como las neurol&#243;gicas&#44; pasen a un segundo plano&#44; con el consecuente retraso en el diagn&#243;stico y tratamiento&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Todo paciente COVID-19 que ha ingresado con sintomatolog&#237;a neurol&#243;gica o diagnosticado de encefalitis desde Marzo de 2020 en un hospital de tercer nivel en Zaragoza&#44; Espa&#241;a&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Dos pacientes con infecci&#243;n COVID-19 confirmada por PCR nasofar&#237;ngea y cuyo cuadro cl&#237;nico consist&#237;a en alteraciones neurol&#243;gicas compatibles con encefalitis&#46; La microbiolog&#237;a del l&#237;quido cefalorraqu&#237;deo &#40;LCR&#41; fue negativa para bacterias y virus&#44; incluido el SARS-CoV-2 pero&#44; ante la sospecha cl&#237;nica de encefalitis por este &#250;ltimo&#44; se instaur&#243; tratamiento antiviral&#44; con inmunoglobulinas y plasmaf&#233;resis de forma precoz&#46; A pesar de ello la evoluci&#243;n no fue satisfactoria&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La encefalitis por COVID-19 es una entidad cl&#237;nica descrita recientemente&#44; cuya fisiopatolog&#237;a a&#250;n se desconoce y no se dispone&#44; hasta la fecha&#44; de un tratamiento con evidencia cl&#237;nica&#46;</p></span>"
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        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0110" class="elsevierStylePara elsevierViewall">To the Intensive Medicine Department of the Lozano Blesa Zaragoza University Clinical Hospital&#46;</p>"
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Article information
ISSN: 23870206
Original language: English
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2024 April 12 0 12
2024 March 7 0 7
2024 February 7 1 8
2024 January 26 0 26
2023 December 23 0 23
2023 November 24 1 25
2023 October 16 5 21
2023 September 12 0 12
2023 August 12 1 13
2023 July 11 0 11
2023 June 28 3 31
2023 May 19 0 19
2023 April 9 0 9
2023 March 5 2 7
2023 February 5 0 5
2023 January 7 0 7
2022 December 13 0 13
2022 November 4 0 4
2022 October 2 0 2
2022 September 3 0 3
2022 August 3 0 3
2022 July 3 0 3
2022 June 1 0 1
2022 May 3 0 3
2022 April 3 0 3
2022 March 3 0 3
2022 February 2 0 2
2022 January 1 0 1
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos