Balamuthia mandrillaris is a protist pathogen that can cause encephalitis with a mortality rate of more than 95%. Early diagnosis followed by aggressive treatment is a pre-requisite for successful prognosis. Current methods for identifying this organism rely on culture and microscopy, antibody-based methods using animals, or involve the use of molecular tools that are expensive. Here, we describe the isolation of antibody fragments that can be used for the unequivocal identification of B. mandrillaris. B. mandrillaris-specific antibody fragments were isolated from a bacteriophage antibody display library. Individual clones were studied by enzyme-linked immunosorbent assay, and immunofluorescence. Four antibody clones showed specific binding to B. mandrillaris. The usefulness of phage antibody display technology as a diagnostic tool for isolating antibody fragments against B. mandrillaris antigens and studying their biological role(s) is discussed further.
A pilot epidemiologic study of all cases of Reye and Reye-like syndromes was undertaken at 8 representative major hospitals in Peninsular Malaya from January 1st to December 31st 1986. The cases were classified as definitive Reye's syndrome, clinical Reye's syndrome and encephalo-hepatopathies. Less than 50% of cases reviewed fulfilled the National Center for Disease Control criteria for clinical Reye's syndrome. Causes of Reye-like syndromes/encephalo-hepatopathies included fulminant hepatitis, Japanese B encephalitis, dengue, septicaemia, and complex febrile fits. It was not possible to differentiate clinical Reye's syndrome from the other encephalo-hepatopathies by either the clinical features (except for jaundice) or biochemical parameters. Liver biopsy is necessary for a definitive diagnosis of Reye's syndrome in Malaysia, because of the high prevalence of Reye-like diseases. The mortality rate in the 2 groups of patients is similar. Ingestion of salicylates was not found to be significantly associated with Reye and Reye-like syndromes in this study.
We report a case of relapsing-remitting opsoclonus-myoclonus-ataxia syndrome (OMAS) in a patient with Hashimoto's encephalopathy, diagnosed after comprehensive evaluation. OMAS as a manifestation of Hashimoto's encephalopathy has been reported once previously. It is hoped that recognition of this entity and early initiation of immunotherapy will improve clinical outcomes for patients.
NMDAR encephalitis may be more common among non-Caucasians. A population-based study was conducted to estimate its incidence in Sabah, Malaysia, where the population consists predominantly of Austronesians (84%), and with a Chinese minority. Registries of NMDAR encephalitis at neurology referral centers were reviewed for case ascertainment. The annual incidence was 2.29/million (Austronesians: 2.56/million, Chinese: 1.31/million). Among pediatric population, the incidence was: Austronesians: 3.63/million, Chinese: 2.59/million. Our study demonstrated a higher incidence of NMDAR encephalitis among Austronesians than the predominantly Caucasian populations in Europe (0.5-0.9/million; pediatric: 0.7-1.5/million). Racial and genetic factors may contribute to risks of developing NMDAR encephalitis.
Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an immune mediated condition, which remains relatively unknown in Malaysia outside tertiary hospitals with neurology unit. It is often misdiagnosed as a psychiatric illness before definitive treatment is instituted. We report here an 18-year-old man who initially presented to the psychiatry unit before he was subsequently diagnosed as having anti-NMDAR encephalitis. To our knowledge, this is the first reported case of anti-NMDAR encephalitis in the east coast of Peninsular Malaysia.
Acute necrotising encephalopathy of childhood (ANEC) is an uncommon disease with characteristic clinical and imaging findings. We present two cases of ANEC secondary to Respiratory Syncytial Virus (RSV) and mycoplasma infections. An eight-month-old boy presented with features of gastroenteritis but soon developed multiple episodes of seizures. Blood and CSF cultures were negative but nasopharyngeal aspirate immunofluorescence was positive for RSV. A nine-year-old girl presented with abnormal behaviour following two days of prodromal symptoms. Her serological markers implicated mycoplasma (IgM titre 1: 640). CT brain of both patients showed bilateral symmetrical thalamic hypodensities, while MRI revealed more extensive white matter involvements.
Bickerstaff's brainstem encephalitis (BBE) is a rare immune-mediated disorder characterized by ophthalmoplegia, ataxia and disturbance of consciousness, which may overlap with Guillain-Barré syndrome (GBS) if there is additional limb weakness. We report a 7-month-old boy presented with ophthalmoplegia followed by a rapidly ascending paralysis of all four limbs and disturbance of consciousness. The initial impression was BBE with overlapping GBS. This was supported by sequential nerve conduction study (NCS) findings compatible with an acute inflammatory demyelinating polyneuropathy (AIDP). He received intravenous pulse methylprednisolone, intravenous immunoglobulin and plasmapharesis with complete clinical recovery after 6 weeks of illness and improved NCS findings from week 16. This is the first case of paediatric BBE with overlapping GBS with an AIDP subtype of GBS. It expands the clinical spectrum of this condition in children. Our case highlights the importance of sequential NCS in paediatric BBE with overlapping GBS for accurate electrophysiological diagnosis and prognosis particularly if the first NCS findings are not informative.
In the 1950s, Bickerstaff and Fisher independently described cases with a unique presentation of ophthalmoplegia and ataxia. The neurological features were typically preceded by an antecedent infection and the majority of patients made a spontaneous recovery. In the cases with Bickerstaff brainstem encephalitis, there was associated altered consciousness and in some, hyperreflexia, in support of a central pathology whereas in Fisher syndrome, patients were areflexic in keeping with a peripheral aetiology. However, both authors recognised certain similarities to Guillain-Barré syndrome such as the presence of peripheral neuropathy and cerebrospinal fluid albuminocytological dissociation. The discovery of immunoglobulin G anti-GQ1b antibodies in patients with Fisher syndrome and later in Bickerstaff brainstem encephalitis was crucial in providing the necessary evidence to conclude that both conditions were in fact part of the same spectrum of disease by virtue of their common clinical and immunological profiles. Following this, other neurological presentations that share anti-GQ1b antibodies emerged in the literature. These include acute ophthalmoparesis and acute ataxic neuropathy, which represent the less extensive spectrum of the disease whereas pharyngeal-cervical-brachial weakness and Fisher syndrome overlap with Guillain-Barré syndrome represent the more extensive end of the spectrum. The conditions can be referred to as the 'anti-GQ1b antibody syndrome'. In this review, we look back at the historical descriptions and describe how our understanding of Fisher syndrome and Bickerstaff brainstem encephalitis has evolved from their initial descriptions more than half a century ago.
The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.