Neurological disorders associated with COVID-19 in Sri Lanka.

BACKGROUND: Neurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka. METHODS: COVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 - May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations. RESULTS: One hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain-Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 - 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 - 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period. A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046). CONCLUSIONS: The spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.

Estimation of body weight using anthropometric parameters in Sri Lankan hospitalized adult patients.

Body weight is an important clinical parameter for accurate dosing of drugs with a narrow therapeutic window, However, it is difficult to measure the body weight of a patient if they cannot stand on a scale. There are several anthropometrics-based equations to estimate the body weight, but most of these are derived from white Caucasian populations and are not validated for South Asians. This study aimed to validate existing anthropometrics-based weight estimation equations and develop a new equation for the same purpose for Sri Lankan adults. This prospective study was conducted at the National Hospital of Sri Lanka over a 6-month period, split into a development and a validation phase. During the development phase, estimated body weight of patients by doctors and nurses and patients themselves were noted and compared against their actual body weight. In addition, 13 anthropometric measurements were taken, which were used to validate 12 anthropometrics-based equations to estimate body weight described in literature previously. Two new gender specific regression models to estimate the body weight in the local population was also derived and validated. A total of 502 (males = 249) and 217 (males = 108) patients were recruited for the development and validation phases respectively. Both doctors and patients had comparable accuracy in predicting body weight (p>0.05). All anthropometric based equations were significantly correlated with actual body weight (correlation coefficients: 0.741-0.869), and the new equations derived from the local data performed similarly to the best performing equation identified from the literature during validation phase. However, even the best of these equations could not outperform patient/physician estimates. When the patient weight cannot be measured, an estimate by the patient or the doctor may be the best substitute.

Case report long segment myelitis secondary to neuro melioidosis.

BACKGROUND: Neuro-melioidosis, comprising 4% of all cases of melioidosis carries a risk of high morbidity and mortality. We describe two Sri Lankan patients presenting with long segment myelitis secondary to melioidosis. CASE PRESENTATION: Case 1: 47-year-old male presented with right side hemiparesis which progressed rapidly to quadriparesis. Initial cerebro spinal fluid (CSF) analysis revealed protein 76 mg/dl and glucose 72 mg/dl but without a cellular reaction. MRI spine revealed long segment myelitis with contrast enhancement. The patient was treated with intravenous methyl prednisolone pulses (IV MPP) and plasma exchanges(PLEX) on suspicion of an immune mediated myelitis but without success. A repeat MRI revealed high signal changes in the brain stem and along the entire spinal cord with contrast enhancement. MRI brain after treatment with MPP/PLEX showed enhancing hyper intensities along the corticospinal tracts. The repeat CSF revealed protein 1187 mg/dl, glucose 78 mg/dl, lymphocytes 1600/mm3 and neutrophils 10,200/mm3. CSF culture has become positive for Burkholderia pseudomallei. Serum melioidosis antibody titre was 1: 320. He was started on IV meropenem with oral cotrimoxazole for 12 weeks followed by oral co trimoxazole. But he had poor clinical recovery. Case 2: 47-year-old female presented with bilateral lower limb weakness for 1-week duration. On examination, she had flaccid paraparesis with a sensory level at T11. Inflammatory markers were elevated. CSF analysis revealed protein 50 mg/dl with lymphocytes 172/mm3. MRI pan spine revealed a long segment myelitis. Serum melioidosis antibody titre was 1: 640. She was treated with IV meropenem for 8 weeks followed by oral co-trimoxazole with an excellent clinical and radiological response. CONCLUSION: Numerous neurological manifestations have been described with melioidosis, however long segment myelitis with a positive CSF culture is not yet reported. These cases signify the importance of considering melioidosis as a differential in patients with long segment myelitis especially in endemic areas.

Plasmapheresis for Extrapontine Myelinolysis: A Case Series and a Literature Review.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are syndromes of osmotic demyelination attributed to the rapid correction of hyponatraemia. Isolated EPM is a rare clinical entity which poses a significant diagnostic challenge especially in the absence of a rapid rise in sodium. Typical MRI findings aid in the diagnosis. Treatment for established osmotic demyelination syndrome (ODS) is nonstandardized and the prognosis is considered poor. Therefore, different strategies including plasmapheresis (TPE), immunoglobulins (IVIG), and steroids have been used. We present our findings from a series of successfully treated patients at a high-volume tertiary care center in Sri Lanka, with an appraisal of available literature. A total of 21 patients with established ODS are analyzed here, including 5 cases of EPM managed by the authors over a 2-year period. Thirteen (40.2%) patients were treated with plasmapheresis alone, 6 (28.5%) received dual therapy (TPE + IVIG or steroids) and 2 (9.5%) received triple therapy (TPE + IVIG + steroids). There was complete or near complete response in 18 (85.7%) and complete response in 10 (47.6%) patients. We conclude that although the management of CPM/EPM is largely symptomatic, patients may show a significant response to immunomodulatory therapy. The marked improvement in motor, cognitive, and functional domains supports an immune basis for osmotic demyelination. Plasmapheresis, in particular, leads to favorable outcomes in ODS which is supported by previously published case reports. We propose its utility as standard treatment.

Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress.

BACKGROUND: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. OBJECTIVES: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. DESIGN: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. RESULTS: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024. CONCLUSION: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

Outcomes of stroke patients undergoing thrombolysis in Sri Lanka; an observational prospective study from a low-middle income country.

BACKGROUND: Stroke related deaths are relatively higher in low- and middle-income countries where only a fraction of eligible patients undergo thrombolysis. There is also limited evidence on post-thrombolysis outcomes of patients from Asian countries in these income bands. METHODS: This is a single center prospective observational study of a patient cohort with acute ischaemic stroke, undergoing thrombolysis with alteplase (low and standard dose), over a 24-month period in 2019/2020. Modified Rankin scale (mRS) for dependency at 3 months (primary outcome), duration of hospital stay, incidence of symptomatic intracranial haemorrhages and all-cause mortality at 3 months (secondary outcomes) were recorded. Demographic, clinical and treatment related factors associated with these outcomes were explored. RESULTS: Eighty-nine patients (males - 61, 69%, mean age: 60 years ±12.18) were recruited. Time from symptom onset to reperfusion was 174 min ± 56.50. Fifty-one patients were independent according to mRS, 11 (12.4%) patients died, and 11 (12.5%) developed symptomatic intracranial haemorrhages by 3 months. Functional independence at 3 months was independently associated with National Institutes of Health Stroke Scale (NIHSS) on admission (p < 0.05). Thrombolysis with low dose alteplase did not lead to better or worse outcomes compared to standard dose. CONCLUSIONS: On admission NIHSS is predictive of functional independence at 3 months post-thrombolysis. Low dose alteplase may be as efficacious as standard dose alteplase with associated cost savings, but this needs to be confirmed by a prospective clinical trial for the Sri Lankan population.

Multiple sclerosis in Sri Lanka; epidemiology, demographic patterns and current trends.

Cases of Multiple sclerosis are being increasingly recognized in Sri Lanka and South Asia challenging the concept of MS being a disease of the West. Our study estimates a crude prevalence of 7.78 cases per 100,000 population in Sri Lanka. They carry a secure diagnosis satisfying the 2017 McDonalds criteria with sero-negativity for AQP4 and MOG antibodies. Demography and clinical presentations are similar to the western and regional nations. They show excellent visual and mobility outcomes over a long period of follow up. Further studies are necessary to evaluate a possible genetic predisposition contributing to the benign disease course.

Familial Multiple Sclerosis in a Mother and Son Pair: A Sri Lankan and a South Asian First.

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder involving the central nervous system (CNS). It is common amongst young females. Although the exact cause of MS is yet unknown, viral infections such as EBV, environmental factors, and autoimmune and genetic mechanisms involving HLA-DRB1 loci are implicated. Familial MS is reported from some geographic locations and ethnic groups but is thought to be rare in Asia. In this paper, we present both a Sri Lankan mother and her son, with clinically definite MS conforming to McDonald's 2017 clinical and MAGNIMS 2016 radiological criteria. Both had oligoclonal bands in their CSF (OCB-IEF) with no serum bands indicating intrathecal production and were negative for AQP4 and MOG IgG serology. Familial MS is more common among siblings, with sister-sister relationship having the highest rate. The lowest relation was amongst father-son and mother-son pairs. Amongst siblings, the risk of MS is between 3.5% and 4.7%. Inherited factors rather than common environmental exposure influence susceptibility in such cases. To the best of our knowledge, MS occurring in a mother-son pair has not been reported before either from Sri Lanka or South Asia.

Winging of Scapula due to a Sinister Etiology.

BACKGROUND: Scapular winging is a rare but disabling deformity, which is commonly caused by lesions of the long thoracic and spinal accessory nerves that innervate the serratus anterior and trapezius muscles, respectively. Across the literature, traumatic injury to the nerves account for the majority of cases. Less common, nontraumatic causes include viral illness, neuroinflammatory conditions, toxins, compressive lesions, and C7 radiculopathy. We present a case where an apical lung malignancy causes winging of scapula by infiltrating C5-C7 roots of brachial plexus, which has been reported only once in the literature. CASE: A 54-year-old male presented with recent onset painful difficulty in raising his right arm. He had no respiratory or constitutional symptoms. On examination, winging of scapula on the right side was noted with wasting and fasciculation involving the ipsilateral shoulder girdle. Proximal muscle power of the right upper limb was of 3/5 with preserved distal muscle power. No sensory loss was noted. A patch of bronchial breathing was found in the upper zone of the right lung with multiple hard cervical lymphadenopathies. Chest X-ray and contrast-enhanced computerized tomography-chest revealed a large tumor in the upper lobe of the right lung, which was confirmed to be a carcinoma of the lung. Electromyogram revealed large motor unit potentials and poor activation of right serratus anterior and internal scapulae muscles, while nerve conduction studies concluded the presence of a compressive lesion involving C5-C7 nerve roots of brachial plexus. Histology of a biopsy of the cervical lymph node confirmed metastasis from a poorly differentiated adenocarcinoma of the lung. The patient denied further investigation with MRI cervical spine. He was transferred to the cancer institute for further treatment. CONCLUSION: This case highlights the value of considering a compressive lung pathology with infiltration in the differential diagnosis, when evaluating winging of scapula.