Heng Thay Chong

Nipah Virus Infection: Pathology and Pathogenesis of an Emerging Paramyxoviral Zoonosis

In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.

Relapsed and late-onset Nipah encephalitis.

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow‐up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late‐onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late‐onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late‐onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single‐photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late‐onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.

Nipah encephalitis outbreak in Malaysia, clinical features in patients from Seremban.

BACKGROUND An outbreak of viral encephalitis occurred among pig industry workers in Malaysia in September 1998 to April 1999. The encephalitis was attributed to a new paramyxovirus, Nipah virus. This is a description of the clinical features of 103 patients treated in the Seremban Hospital with characterization of the prognostic factors. METHODS Clinical case records and laboratory investigations were reviewed. The case definition was: patients from the outbreak area, direct contact or in close proximity with pigs, clinical or CSF features of encephalitis. RESULTS The mean age was 38 years, 89% were male, 58% were ethnic Chinese, 78% were pig farm owners or hired workers. The mean incubation period was 10 days. The patients typically presented with nonspecific systemic symptoms of fever, headache, myalgia and sore throat. Seizures and focal neurological signs were seen in 16% and 5% respectively. In the more severe cases, this was followed by drowsiness and deteriorating consciousness requiring ventilation in 61%. Autonomic disturbances and myoclonic jerks were common features. The mortality was high at 41%. Systolic hypertension, tachycardia and high fever were associated with poor outcome. On the other hand, 40% recovered fully. As for the other 19%, the residual neurological signs were mostly mild. CONCLUSION Nipah virus caused an encephalitis illness with short incubation period and high mortality. The prognosis for the survivors was good.

Serological Evidence of Possible Human Infection with Tioman virus, a Newly Described Paramyxovirus of Bat Origin

Tioman virus, a relatively new paramyxovirus, was isolated from fruit bats (Pteropus species) on Tioman Island, Malaysia, in 2001. The objective of this study was to determine the prevalence of antibodies to T. virus in island inhabitants, by use of comparative ELISA and serum neutralization assays. Of the 169 human sera analyzed, 5 (approximately 3.0%) were positive for T. virus, by comparative ELISA. Of these 5 sera, 3 (1.8% of the total) had neutralizing antibodies against T. virus, suggesting previous infection of this study population by this virus or a similar virus.

Magnetic Resonance Imaging of Asians with Multiple Sclerosis was similar to that of the West.

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Posers criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

The past, present and future of imaging in multiple sclerosis

Despite technological advances in imaging, multiple sclerosis (MS) remains a clinical diagnosis that is supported, but not replaced, by laboratory or imaging findings. However, imaging is essential in the current diagnostic criteria of MS, for prediction of the likelihood of MS for patients with clinically isolated syndromes, correlation with lesion pathology and assessment of treatment outcome. This article gives an overview of imaging in MS with particular emphasis on the role of MRI in various diagnostic imaging criteria. Novel imaging for MS using 3 Tesla field strengths, magnetization transfer imaging, diffusion tensor imaging, magnetic resonance spectroscopy and cell-specific contrast will be reviewed.

Proposed modifications to the McDonald criteria for use in Asia

In the latest revision to McDonald diagnostic criteria for multiple sclerosis (MS), the authors commented that the Asian neurological community will determine whether the Criteria can be generalized to their population and how modifications to the Criteria will make them more appropriate in the Asian population [1]. In 2006, a group of leading Asian neurologists with an interest in MS proposed some modifications to the McDonald criteria for Asians with MS (see Table 1) [2]. The proposal was based on MS as an idiopathic inflammatory demyelinating disease disseminated in time and place. For the spinal magnetic resonance imaging (MRI), instead of stating that the lesion should be under two vertebral segments in length, our proposal was to place no restriction on the length of the spinal cord lesion [1–3]. This is because long spinal cord lesions are frequently seen in Asian with classical as well as optic-spinal MS. For example, in a retrospective joint Asian MRI study of MS patients who fulfilled Poser criteria, it was found that in 86 patients, spinal cord lesions had a mean length of 3.5 + 3.3 vertebral segments. Forty-seven percent of the cord lesions were longer than two vertebral segments in length, 29% in patients with classical MS, and 52% in those with optic-spinal MS [4]. For spinal cord swelling, the McDonald criteria stated that there should be no swelling of the cord and that the lesion should occupy only part of the cross section of the cord. In the same joint Asian MRI study, cord swelling was seen in 23% of the lesions, 13% in classical MS, and 29% in opticspinal MS; complete cross sectional involvement was also seen in 23% of the lesions, 7% in classical MS, and 33% in optic-spinal MS [4,5]. We thus propose that spinal cord swelling and complete crosssectional cord involvement should not exclude the diagnosis of MS in Asians. The McDonald criteria require nine T2hyperintense MRI brain lesions or one gadoliniumenhancing lesion as one of the criteria of dissemination in space. In the revised McDonald criteria, an enhancing spinal cord lesion is considered equivalent to an enhancing brain lesion [1,3]. In the joint Asian study, the McDonald criteria and its revised version had a sensitivity of only 49% and 52% among 66 Asians with MS [1,3,5]. The low sensitivity is partly due to fewer brain lesions in Asians with MS [4]. To improve the sensitivity of brain MRI in diagnosing MS in Asians, the proposed modification to the McDonald criteria was to accept four or more T2-hyperintense lesions in patients under the age of 60 years as being sufficient. The proposal was based on the joint Asian MRI study, where 69% of 101 patients had four or more T2-hyperintense brain lesions, 84% in 51 classical MS, and 52% in 50 optic-spinal MS [4]. Swanton, et al. [6] recently proposed more than one lesion in two or more typical sites (juxtacortical, periventricular, posterior fossa, and spinal cord) as criteria for dissemination in space. As 72% of the patients in the joint Asian MRI study would fulfill the Swanton Criteria (unpublished data), it would also be an acceptable alternative. The McDonald criteria [3] require that the lymphocyte pleocytosis in cerebrospinal fluid (CSF) should be less than 50/mm3. There have been a number of studies reporting that a significant proportion of Asian MS patients have a CSF lymphocytic pleocytosis of more than 50/mm3 [7]. Although CSF pleocytosis of more than 50/mm3 might suggest other diagnoses by itself, this should not unequivocally exclude the diagnosis of MS in

Use of permeability surface area-product to differentiate intracranial tumours from abscess.

Background and Purpose Clinical and radiological findings of intracranial abscesses may mimic the findings of brain tumours and vice versa. However, the discrimination is of great clinical importance in planning treatment and in following prognosis and response to therapy. This study evaluates the Computed Tomography (CT) perfusion parameters, especially the permeability index, with the aim of evaluating the usefulness of dynamic CT perfusion imaging as an alternative tool to differentiate necrotic brain tumours and intracerebral abscesses. Materials and Methods A total of 21 patients underwent perfusion CT study and were divided into 2 groups: Group 1, patients with necrotic brain tumours (n=13); and Group 2, patients with cerebral abscesses (n=8). The mean perfusion parameters were obtained from the enhancing part of the lesion. The relative ratios were then calculated by using the results from mirrored regions within the contralateral hemisphere as reference. Results The results of this study showed that there was significant difference in the relative permeability surface values between necrotic brain tumours and cerebral abscesses (p=0.005). By applying the ROC curve, a value of 25.1 for rPS was found to be the best estimate to distinguish necrotic brain tumours from cerebral abscesses with a specificity of 88 % and sensitivity of 70 %. Conclusion CT perfusion, especially permeability surface, may allow for better differentiation of cerebral abscesses from brain tumours, making it a strong additional imaging modality in the early diagnosis of these two entities.