Unusual neurological manifestations in children during the COVID-19 pandemic

Objective: To present paediatric cases of unusual neuroinflammatory conditions encountered during the COVID-19 pandemic in Trinidad & Tobago. Methods: Retrospective study design. Inpatient paediatric patients (aged 0-16 years) hospitalized for neurological complaints from June 2020 - August 2021 at EWMSC. Outcome measures were age at presentation, sex, ethnicity, diagnosis, radiological findings, blood/CSF findings, COVID-19 PCR and antibodies testing, treatment, outcomes and other systems involved. Results: Twenty (20) patients (aged 4-months-old to 15-years-old) had documented neurological involvement. 50% had a diagnosis of ADEM/ADS/AHNE;45% had a diagnosis of either CNS vasculitis (n=3), autoimmune encephalitis (n=3) or GBS (n=3);5% had a diagnosis of acute COVID-19 encephalitis. 70% were of African descent. The youngest age group (0-4 years) (n=11) constituted more males (82%) whereas the eldest age group (10-15 years) (n=3) were all females. Neuroimaging findings were corpus callosal lesions;deep white matter T2 hyperintensities;cerebellar involvement;area postrema and brainstem/C-spine involvement;microhaemorrhages and necrotizing/haemorrhagic lesions (peripheral/central). 70% of patients were either SARS-CoV-2 PCR or COVID-19 antibodies positive. Other systems were involved in 40% to 62.5% (n=5) had cardiac involvement (myocarditis, coronary arteries dilatation, valve regurgitation) and 37.5% (n=3) had pancreatic involvement (autoimmune pancreatitis, type 1 diabetes mellitus). Treatment modalities for CNS manifestations (n=17) were clinically based - 24% (n=4) 3rd line treatment, 29% (n=5) 2nd line treatment, 41% (n=7) 1st line treatment and 6% (n=1) requiring no treatment. All 3 patients with a diagnosis of GBS responded appropriately to IVIG. Developmental outcomes were worst in patients with a diagnosis of autoimmune encephalitis. Conclusion: We have had an explosion of neuro-inflammatory cases since the COVID-19 pandemic began. The range of neuroradiological diagnoses and other systemic involvement (including criteria for PIMS) are interesting, alluding to a neuroinflammatory mechanism. Effects on long-term sequelae and developmental outcomes are concerning in some cases, however, still unknown at this stage.

Recurrent cerebral venous sinus thromboses (CVST's) and livedo reticularis rash-a case of Sneddon syndrome

Background Sneddon syndrome is a rare, progressive small and medium-vessel vasculopathy characterized by the clinical occurrence of livedo racemosa and ischaemic cerebrovascular events. Objectives We present the clinical course and management of this rare condition. Methods An 18-year-old female of East Indian descent presented with the following: CNS involvement: Recurrent Cerebral Venous Sinus Thromboses + Cognitive impairment - Skin: Livedo reticularis rash - Eyes: Bilateral optic nerves atrophy - CVS: Mild to moderate LAD dilation (16/12/2020) - MS: Polyarticular arthritis She first presented at 8-years-old with new-onset squint, ataxia and fever and was treated as culture-negative meningitis (CSF white cells 1238 neutrophils, CSF protein 110mg/ dL). At 16-years-old, she presented with expressive aphasia, headache, fever, left earache and was treated as acute mastoiditis. Regarding the recurrent presentations of CVST's there was involvement of left transverse sinus (untreated 2 years ago), then over a 1-month period despite anticoagulation, right transverse sinus with extension into the right sigmoid sinus and left straight and posterior superior sagittal sinus. She presented with headache, vomiting and new-onset seizures (GTCS) prior to these presentations. An extension of this clot after being non-compliant with low-molecular weight heparin for 1 week resulted in a venous infarct with surrounding oedema. She presented with progressive right-sided weakness and expressive aphasia and within 24 hours, encephalopathic with decerebrate posturing in subclinical status epilepticus. She was managed in PICU for refractory status epilepticus and raised intracranial pressure. There is also a family history of early stroke (maternal cousin with CVST at 8yo on long-term anticoagulation). Results Her inflammatory markers continued to increase despite antibiotic coverage at meningitic doses and she was treated for a CNS vasculitis/Catastrophic Antiphospholipid syndrome with IV anticoagulation (UFH), high-dose steroids then IVIG. Her neurological state gradually improved (coma -> vegetative state -> minimally conscious -> conscious). This was followed by Rituximab therapy 375 mg/m2 weekly x4. Her neurological function gradually improved as she was able to verbally communicate and developed anti-gravity movement of the right side. Hypertension and fever also settled, and inflammatory markers steadily decreased post treatment. Investigations: ANA, dsDNA, ENA negative pANCA borderline positive but MPO, PR3 Antibodies negative Anticardiolipin antibodies negative (on warfarin) Infectious screen (HIV, Hepatitis, COVID-19 serology, Mantoux test, CSF Acid-fast bacilli) - negative CSF cell count - 33 white cells (neutrophils), protein 183mg/dL Skin biopsy report (26/11/2020) - Neutrophils, lymphocytes of leucocytoclasis seen in vessels of dermis. Thrombosis of fibrinoid necrosis of vessel walls and extravasated red blood cells also seen - Obstructive vasculopathy for clinical correlation;Possible Sneddon syndrome/Antiphospholipid syndrome Conclusions There are few case reports describing the clinical course and treatment of this rare syndrome. In our case, treatment for Catastrophic Antiphospholipid syndrome (steroids, IVIG, rituximab and anticoagulation) was beneficial in improving the clinical outcome.

Seronegative NMOSD-a post SARS-COV-2 neurological complication associated with paediatric multisystem inflammatory syndrome (PIMS)?

Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. There are limited cases describing the development of NMOSD post SARSCOV- 2. Objectives We present a case of seronegative NMOSD meeting the diagnostic criteria with coronary artery involvement and the probable association of Paediatric Multisystem Inflammatory Syndrome (PIMS)/SARS-COV-2. Methods A 13-year-old female of Chinese descent met the diagnostic criteria for sero-negative NMOSD: . Optic neuritis (presented initially with decreased vision right eye, progressed to complete blindness involving both eyes;optic discs swelling bilaterally) + enhancing focus in left parieto-occipital region . Area postrema syndrome (intractable vomiting) + enhancing lesion in the left aspect of the dorsal medulla . Acute brainstem syndrome (autonomic dysfunction, respiratory distress with new-onset squint) + enhancing foci in medulla . Symptomatic cerebral syndrome (left arm weakness, headache, behaviour change) + several enhancing foci within the cerebral hemisphere and sulcal thickening/oedema enhancement in the right fronto-temporal lobe She presented initially with headache and behaviour change x8 days;weakness left arm x6 days;loss of vision right eye x6 days;facial numbness x6 days;vomiting x2 days but no preceding viral illness/vaccine. She was initially managed as ADEM/ADS with steroids (imaging at this time revealed cerebral lesions). However, a protracted illness persisted with intractable nausea/vomiting, and development of new symptoms (squint, autonomic dysfunction, respiratory distress). Repeat imaging showed new involvement of the dorsal and ventral medulla. IVIG and rituximab treatment were then commenced. Results CSF pleocytosis (22 white cells) and elevated protein concentration (131mg/dL) were present. Anti-MOG and Aquaporin-4 antibodies testing post steroids were negative. ESR increased to 82 mm/hr and ANA titre was mildly elevated during her illness. ENA, dsDNA titres normal. COVID-19 IgM antibody level rose to 0.921. Infectious screen negative (Hepatitis studies, HIV, HSV, ASOT). Neoplastic workup negative (Antineuronal antibodies, CEA, CA-125, AFP, Blood film). MRI pelvis was normal. Anticardiolipin and lupus anticoagulant antibodies negative. Interestingly, ECHO done post steroids, IVIG and during rituximab treatment showed moderately dilated left middle coronary artery and severely dilated left anterior descending artery. Her neurological function has improved post IVIG and rituximab. Conclusions Due to the evidence of inflammation and neurological and cardiac dysfunction, we question whether this could be a post SARS-COV-2 related presentation of PIMS. This is our 3rd case in Trinidad & Tobago linking coronary artery and neurological involvement in the same patients possibly in relation to SARS-COV-2. The other cases: 1) 20-month-old with corpus callosal lesions and right coronary artery ectasia post-treatment 2) 2-year 7-months-old with long segment of cord enlargement with heterogenous appearance from C1 to C6 and dilated coronary arteries/mild mitral regurgitation/pericardial effusion.

P292 Online HIV/STI-Clinical Training for Eleven Pacific Island Countries Provided by the UNDP Multi-Country Western Pacific Integrated HIV/TB Programme

BackgroundThe Pacific Islands have a low HIV prevalence, but high rates of STI’s and large high-risk populations. The UNDP Programme supports 11 Pacific Island Countries (PICs). In-country clinical training are provided as well as HIV/TB diagnostics, treatments, and specialist HIV clinical advice. In 2020, in-country support was not possible because of the COVID19 pandemic.ApproachAfter discussion with UNDP partners and PICs HIV/STI-healthcare workers, we presented the following online education:Monthly webinars. Eight one-hour webinars on Zoom, each repeated 4 hours later as the PICs span 7 time-zones. These case-based educational webinars covered HIV/STI clinical care related topics. Guest speakers were invited for specialist topics.In-country HIV/STI-online education workshops run over one-day for nine PICs and over half-day for Niue and Tuvalu, the two smallest PICs. The workshops ran in late 2020 to build on the webinar knowledge and were tailored to in-country needs. Training was mainly case based, co-facilitated by a worker from the Fijian HIV-positive peoples NGO, FJN+, with guest speakers invited for specialist topics.OutcomesMonthly webinars: 323 individual attendances for the 8 webinars. 114 evaluations were returned;95% found the HIV webinars very helpful and 92% would recommend them to other clinical staff. As poor internet was a problem, the presentation slides and the recorded webinars were sent to the PIC attendees.In-country online HIV/STI-education workshops: 241 participants across the PICs. A planning meeting was conducted with each PIC. The average scores in questionnaires pre– and post-training doubled from 40% to 80%. Participants found the case-based training useful and requested follow-up training.Innovation/SignificanceThis is first time in the HIV/STI clinical support to the Pacific has been provided on-line and despite internet challenges, it is an economical and efficient way to provide ongoing HIV/STI clinical education in this remote setting.

Management of a unique case of acute disseminated encephalomyelitis (ADEM) in a lowresource setting

Clinical findings: NC, a 20-month-old male presented in July 2020 with new-onset focal motor seizures, drowsiness and developmental regression. There was a preceding history of fever, vomiting and diarrhoea about 1 to 2 weeks prior to presenting. On examination, he was noted to have erythema nodosum over his shins, unable to fix and follow even to light stimulus, no head nor trunk control with generalized increased tone, hyperreflexia and upgoing plantar responses bilaterally. Investigations: Blood investigations: lymphopenia, mild increase in ESR 16mm/hr, transaminases elevated, CK elevated. CSF investigations: CSF protein 143mg/dL, glucose 88mg/dL, CSF cell count 28 white cells, 17 red cells. EEG: background slowing right > left. MRI brain (initial): transient lesions along corpus callosum, petechial haemorrhages within superior aspect of cerebellar vermis Treatment: He was treated with 5 days IV methylprednisolone 30mg/kg/day followed by oral prednisolone. He was treated as a protracted ADEM illness with IVIG (2g/kg over 2 days) when he clinically deteriorated. Steroids were slowly tapered over 8 weeks. Progress: 2 weeks post IVIG-speech and language milestones improved to baseline, started cruising. 6 weeks post IVIG-able to walk independently however, not able to climb/run. Follow-up investigations: 2 months post admission: 2019-CoV IgM Antibodies (blood): 1.123 (range 0-1). Of note, we have had a total of 4 patients managed for ADEM within the past 3 months. 3 presented with preceding viral GE symptoms. Most recently the other was initially managed for Kawasaki disease and is also COVID 19 IgM positive. We are awaiting COVID-19 antibody testing for these patients to determine whether they are linked. Unfortunately, in our resource-limited setting, PCR testing was initially only performed on patients with a travel history and respiratory symptoms.