PostScript J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-323839 on 13 July 2020. Downloaded from LETTER fornices. The images were consistent with infection with COVID-19. SARS-CoV -2 limbic encephalitis. PCR was positive in a nasopharyngeal Cerebrospinal fluid (CSF) examination swab. SARS-CoV -2 IgG was negative.3 CSF A case of limbic encephalitis showed white cell count 3/mm3, red blood was subsequently tested for SARS CoV-2 at associated with asymptomatic cells 11/mm3, protein 1.0 g/L (0.15–0.45) National Reference Laboratory in Colin- and glucose 3.5 mmol/L (2.2–3.9). CSF dale, where the RNA- dependent RNA- COVID-19 infection PCR was negative for streptococci, menin- polymerase (RdRp) gene is the target, and gococcus, haemophilus, listeria, Esche- at University College London Hospitals Since the emergence of the severe acute richia coli, herpes simplex virus (HSV) (UCLH), where the Nucleocapsid gene is respiratory syndrome coronavirus 2 1 and 2, human herpesvirus 6 (HHV6), the target. Both were negative. (SARS- CoV-2), millions have been diag- enteroviruses, parechovirus, cytomegalo- She was treated with ceftriaxone, nosed with COVID-19. The major clinical virus (CMV), Varicella zoster virus (VZV) aciclovir and levetiracetam. After the MRI manifestations of SARS-CoV -2 infection are and Cryptococcus. Oligoclonal bands and CSF results, ceftriaxone and aciclovir pulmonary, however reports of COVID-19- were negative in CSF and serum. CSF IgG were stopped, pabrinex and pulsed intra- associated central nervous system compli- index was normal (0.48). venous methylprednisolone (1 g/day for cations emerged.1 2 We report a case of Neuroimmunology tests were negative 3 days) were started. After steroid treat- encephalitis in a pulmonologically asymp- in serum and CSF for LGi1 and Caspr 2, ment, GCS improved rapidly from 6/15 to tomatic patient with COVID-19. NMDA receptor antibodies, anti- Hu, anti- 14/15 (E4/V4/M6). She was disoriented to A 66- year-old female presented in mid- Yo, anti- Ri, anti- Ma-1, anti- Ma-2, anti- CV2 time and place and amnestic. She had mild March 2020, with a few hours history of (CRMP-5), anti- Amphiphysin, anti- Zic-4, word- finding difficulties. Cranial nerve confusion. She was completely well until anti- Sox 1, anti- Tr, anti-GAD, anti- examination was normal. There was no the day of admission. There was no medical, Aquaporin 4, anti-MOG and anti-DPPX. limb weakness, ataxia, pyramidal or extra- infectious or behavioural prodrome. There ANA and ANCA were negative. HIV and pyramidal signs or gait abnormalities. Plan- was no alcohol or nutritional history. She treponemal serology testing was negative. tars were flexor. She also received a course had travelled to Spain, the USA and Mexico A CT of chest, abdomen and pelvis of intravenous immunoglobulin and made in the 3 months prior, but had been home showed multiple small peripheral foci of a steady improvement. Addenbrooke’s for 19 days. She suddenly complained that ground- glass opacification in the lungs, Cognitive Examination (ACE III) scores her head ‘felt funny’. She carried on normal suggestive of bilateral atypical pulmonary were 61/100 at baseline with subscores of tasks but, within an hour, became confused, amnestic and was unaware of why social distancing measures were being observed. copyright. On admission, her temperature was 37.9°C. Other observations were normal. She was lymphopaenic at 0.4×109/L (0.8– 3.1). Full blood count was otherwise normal. C- reactive protein (CRP) was 14.5 mg/L (0–5). Routine blood tests, including renal function, liver function and clotting, were normal. A brain CT was unremarkable. Six hours after admission, she had a single, spontaneously resolving, generalised tonic- http://jnnp.bmj.com/ clonic seizure. Her postictal Glasgow Coma Scale (GCS) was 6/15 (E1/V1/M4). This remained unchanged for 48 hours. Post- ictal neurological examination showed equal, reactive pupils, no response to visual menace, no vestibulo-ocular reflex, normal tone bilaterally, symmetrical brisk reflexes on September 25, 2021 by guest. Protected and extensor plantars. She remained febrile (37.9°C) for 48 hours. Oxygen saturation dropped to 93% on air only once during her 4- week admission. She never developed breathlessness, cough or tachypnoea. An MRI of the brain on day 2 showed non- enhancing, symmetrical T2 and FLAIR (fluid- attenuated inversion recovery) hyperintensities in mesial temporal lobes and medial thalami and to a lesser extent upper pons, as well as scattered subcortical Figure 1 MRI brain. Corresponding Axial T2 (top row), Axial Diffusion weighted (middle row) and white matter hyperintensities (figure 1). Axial FLAIR (bottom row) images demonstrate T2 hyperintense signal abnormalities in the limbic lobes, There were no microhaemorrhages on bilateral medial thalami and frontal white matter. The limbic and thalamic lesions show punctate and T2* imaging. Diffusion scans showed small, discrete foci of high signal on DWI, without demonstrable restriction on ADC maps (not shown). punctate bright signal on the B1000 map Similar lesions were also present in the pons but less conspicuous in signal and number (not shown). in the medial temporal lobes, thalami and There were no microhaemorrhages or abnormal lesional or meningeal enhancement. J Neurol Neurosurg Psychiatry November 2020 Vol 91 No 11 1229 PostScript J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-323839 on 13 July 2020. Downloaded from 13/18 for attention, 12/26 for memory, is not possible. It may be that the pres- All authors critically reviewed the manuscript for 3/14 for fluency, 21/26 for language and ence of the virus in CSF is transitory, or intellectual content and edited the article. 12/16 for visuospatial skills. Ten weeks after that the pathogenesis is a SARS-CoV -2- Funding MPL is supported by the National Institute symptom onset, ACE III score was 88/100 induced immune response. IgG antibodies for Health Research, University College London with only memory (22/26) and verbal to SARS- CoV-23 were negative, suggesting Hospitals Biomedical Research Centre fluency (7/14) incompletely recovered. She that the COVID-19 infection was likely Competing interests None declared. remains on 20 mg prednisolone. concomitant with the CNS presentation Patient consent for publication Next of kin and that the CNS presentation was para- consent obtained. infectious, not postinfectious. The pres- Provenance and peer review Not commissioned; DISCUSSION ence of intrathecal antibodies could give externally peer reviewed. Neurological manifestations of COVID-19 support to the hypothesis of direct inva- This article is made freely available for use in appear more common in patients with sion of the CNS. We were not able to test accordance with BMJ’s website terms and conditions 2 for intrathecal antibodies in the CSF, as for the duration of the covid-19 pandemic or until severe respiratory disease. However, our otherwise determined by BMJ. You may use, download patient had minimal respiratory involve- the assay had not been validated at the and print the article for any lawful, non- commercial ment. No common COVID-19 symptoms time of our patient’s admission; however, purpose (including text and data mining) provided that developed, despite immunosuppressive we hypothesise that the intrathecal anti- all copyright notices and trade marks are retained. treatment. This case illustrates the fact bodies would have been negative because © Author(s) (or their employer(s)) 2020. No commercial that neurological manifestations associ- the CSF was collected 48 hours after re- use. See rights and permissions. Published by BMJ. ated with COVID-19 infection are not a symptom onset. Larger case series would reflection of critical illness, and makes a help clarify whether the neurological associations reported to date are simply case for actively looking for evidence of To cite Zambreanu L, Lightbody S, Bhandari M, et al. J COVID-19 infection in patients presenting coincidental given the prevalence of Neurol Neurosurg Psychiatry 2020;91:1229–1230. COVID-19 infection, or whether there with neurological illness. Received 12 May 2020 The brain imaging appearances here are are particular phenotypes and correla- Revised 22 June 2020 strikingly similar to those described by tions specific to SARS- CoV-2. Our case Accepted 29 June 2020 Poyiadji et al4 in the location of the signal suggests that neurological manifestations Published Online First 13 July 2020 abnormality, but there was no haemor- can be the initial symptom of COVID-19 J Neurol Neurosurg Psychiatry 2020;91:1229–1230. rhagic change. Acute necrotising encepha- and that COVID-19 infection should be doi:10.1136/jnnp-2020-323839 considered in patients presenting with lopathy was considered in the differential, ORCID iDs limbic encephalitis. given the thalamic and subtle pontine Laura Zambreanu http:// orcid. org/ 0000- 0002- 0257- copyright. changes. There was no previous or family 8362 Laura Zambreanu ,1,2 Sophie Lightbody,3 Michael P Lunn http:// orcid. org/ 0000- 0003- 3174- 6027 history of similar episodes to suggest 3 4 infection- induced acute encephalopathy. Mohit Bhandari, Chandrashekar Hoskote, Hala Kandil,5 Catherine F Houlihan,6,7 We felt that the patient’s age, the lack of Michael P Lunn 8,9 REFERENCES 1 Helms J, Kremer S, Merdji H, et al. Neurologic features infectious prodrome, the cognitive neuro- 1 logical deficit without motor features and MRC Centre for Neuromuscular Diseases, University