Abstract
Introduction
Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare immune-mediated neurological disorder that can be triggered by occult malignancy, such as neuroblastoma or small cell lung carcinoma (paraneoplastic), and various infections including scrub typhus, influenza, varicella, HHV-6, HIV, enteroviruses, EBV, CMV, Coxsackie virus and West Nile Virus (para-infectious). 1 Although Dengue fever is a common mosquito-borne illness in tropical regions, its neurological complications are infrequent.1,2 Among these, OMAS is particularly rare, with only a few reported cases following Dengue infection.
Case report
A 7-month old male infant with previously normal developmental milestones presented with a 3-day history of high-grade fever and erythematous macular rash. Initial physical and neurological examinations were normal. Laboratory investigations revealed haemoconcentration (Hb 152 g/L, haematocrit 47), thrombocytopenia (98 × 109/L), leukopenia (2.3 × 109/L) and NS1 antigen positivity for Dengue. Screening for other tropical infections including malaria, enteric fever and rickettsial infections was negative. The baby was managed with oral paracetamol and hydration, becoming afebrile after two days. However, from the sixth day, he exhibited increasing irritability, restlessness, decreased sleep and involuntary eye and arm movements. Neurological examination revealed bilateral, chaotic, multi-directional saccadic eye movements (opsoclonus), tremulousness, myoclonic jerks, hypotonia of the limbs and ataxia, with the infant unable to sit unsupported or grasp objects due to tremors.
Further evaluations ruled out macrocytic anaemia, vitamin B12 deficiency, neurometabolic diseases and malignancy such as neuroblastoma. An MRI brain scan, cerebro-spinal fluid (CSF) examination, and CT scans of thorax and abdomen, and urinary VMA, were normal. The CSF was acellular with a normal value of glucose (34 mmol/L, corresponding blood glucose of 51.6 mmol/L), protein (220 mg/L) and lactate (0.8 mmol/L).
Owing to the presence of opsoclonus (key clinical distinguishing feature), OMAS was favoured over post-infectious ataxia. Other infections, such as influenza, varicella, HHV-6, HIV, enteroviruses, EBV and CMV, were excluded. The infant was started on low-dose clonazepam for irritability and sleep disturbance and received methylprednisolone pulse therapy (20 mg/kg/day for five days) followed by oral prednisolone. We intended to start injections of ACTH, but these were unaffordable. Hence, we continued with oral corticosteroids. After one week of such, he showed significant improvement in ataxia, opsoclonus and irritability. By the end of two weeks, he was able to sit transiently with support. At baseline, Mitchell-Pike OMS rating scale score was 12, which was reduced to 5 at the end of two weeks. Follow-up at two months post-illness revealed a completely normal neurological examination. As he had responded favourably to corticosteroids, no other immunomodulatory treatment was commenced.
Discussion
Reported neurological manifestations of Dengue include encephalitis/encephalopathy, myelitis, Guillain-Barré syndrome, Miller Fisher syndrome, Bickerstaff encephalitis, brachial neuritis and optic neuritis. 3 A review of existing literature identified ten cases of OMAS following Dengue infection (ages 10–45 years) (Table 1).3–10 Our patient is younger than all previous reported cases. While most previously reported had symptom onset between days 4 and 11 after fever onset, few had atypical features such as CSF pleocytosis, leptomeningeal enhancement on neuroimaging, signs of meningeal irritation, signs of raised intracranial pressure and focal slowing in EEG. But all recovered completely within a few weeks, with or without immunotherapy.
Clinical description of reported cases of OMAS associated with Dengue fever in published literature.
The pathogenesis of neurological complications following Dengue probably involves one of the following mechanisms: post-infectious immune-mediated CNS or PNS injury, antibody-dependent enhancement, systemic complications or direct neurotropism. 3 In our case, immune-mediated injury seems the most probable cause, as OMAS symptoms began shortly after Dengue symptoms, with no CSF pleocytosis, elevated proteins or neuroimaging abnormalities. While the primary treatment for OMAS associated with malignancy such as neuroblastoma involves tumour removal and ACTH therapy, additional immunotherapy, including IVIg, rituximab or cyclophosphamide, are also commonly used. Previous studies 11,12 have favoured ACTH over corticosteroids, probably because ACTH acts both through endogenous corticosteroid production and through direct melanocortin receptor-mediated immunomodulation. However, in resource-limited settings, the affordability of ACTH remains a major challenge. Moreover, most previously reported Dengue-triggered OMAS cases showed improvement even without ACTH. In para-infectious cases, symptoms often subside over a few weeks with only symptomatic management and appropriate treatment of the underlying infection.
Footnotes
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.