Cheng-Yin Tan

Nipah virus infection, an emerging paramyxoviral zoonosis

Abstract.The Nipah virus outbreak represented one of several bat-derived paramyxoviruses that has emerged during the last decade to cause severe human and animal disease. The pathogenesis of Nipah infection is associated with its ability to infect blood vessels and extravascular parenchyma in many organs, particularly in the central nervous system. The clinical manifestations of acute Nipah infection range from fever and mild headache to a severe acute encephalitic syndrome in which there is a high mortality. Much remains to be understood about this new disease, including its intriguing ability to cause relapsing encephalitis in some survivors. This review provides an overview of the Nipah outbreak, focussing on what is presently known about it as an infectious disease, including the clinical aspects, pathology and pathogenesis.

Myopathic dropped head syndrome: a syndrome of mixed aetiology.

We report two patients with myopathic dropped head syndrome, a rare and interesting neuromuscular syndrome characterised by a predominant weakness of the neck extensor muscles. The first patient, a middle aged Chinese man, presented with progressive weakness of neck extension but his clinical course later stabilised despite a lack of response to corticosteroids. Muscle biopsy revealed a necrotising myopathy with no evidence of inflammation. This patient supports the existence of an idiopathic restricted non-inflammatory myopathy, a so called isolated neck extensor myopathy syndrome which is recognised to pursue a less progressive, more benign course. Our second patient had histopathological evidence for polymyositis; there was a favourable response to steroids. Our cases underscore the fact that there may be a spectrum of pathological processes associated with the myopathic dropped head syndrome ranging from non-inflammatory muscle necrosis to a full blown inflammatory myositis.

Clinical and pathological manifestations of human henipavirus infection.

The clinicopathological features of human Nipah virus and Hendra virus infections appear to be similar. The clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. The pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. Viral inclusions, antigens, nucleocapsids and RNA are readily demonstrated in blood vessel wall and numerous types of parenchymal cells. Relapsing henipavirus encephalitis is a rare complication reported in less than 10% of survivors of the acute infection and appears to be distinct from the acute encephalitic syndrome. Pathological evidence suggests viral recrudescence confined to the central nervous system as the cause.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features

We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy.

Delayed facial palsy in Miller Fisher syndrome.

Miller Fisher syndrome is characterised by the triad of ophthalmoplegia, ataxia and areflexia. However, facial palsy can occur during the course of the illness although development of facial palsy when other cardinal signs of Miller Fisher syndrome have reached nadir or improving, is unusual. This delayed appearance of facial palsy can be easily overlooked by the treating clinician. Here, we report four patients with Miller Fisher syndrome and delayed-onset facial palsy. We discuss the possible underlying reasons behind the delay in facial palsy.

Nerve ultrasound can distinguish chronic inflammatory demyelinating polyneuropathy from demyelinating diabetic sensorimotor polyneuropathy

Diabetic patients with poor glycaemic control can demonstrate demyelinating distal sensorimotor polyneuropathy (D-DSP) on electrophysiology. Distinguishing D-DSP from chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging. In this study, we investigated the role of nerve ultrasound in differentiating the two neuropathies. Nerve ultrasound findings of D-DSP patients (fulfilling the electrophysiological but not clinical criteria for CIDP) were compared with non-diabetic CIDP patients (fulfilling both criteria). We studied 108 and 95 nerves from 9 D-DSP and 10 CIDP patients respectively. CIDP patients had significantly larger cross-sectional areas of the median nerve at the mid-arm (17.0 ± 12.5 vs 8.7 ± 2.6; p = 0.005), ulnar nerve at the wrist (7.3 ± 3.1 vs 4.1 ± 1.0; p = 0.001), mid forearm (8.8 ± 5.3 vs 5.5 ± 1.5; p = 0.002) and mid-arm (14.5 ± 14.1 vs 7.5 ± 1.9; p = 0.013), and radial nerve at mid forearm (4.1 ± 2.4 vs 1.2 ± 0.4; p < 0.001). In comparison to D-DSP, CIDP patients had markedly larger nerves at the proximal and non-entrapment sites of the upper limbs, suggesting that nerve ultrasound is useful in differentiating the two neuropathies.

Prevalence and associations of neuropathic pain in a cohort of multi-ethnic Asian low back pain patients

The prevalence of neuropathic low back pain differs in different ethnic populations. The aims of the study are to determine its frequency and associations in a multi-ethnic cohort of Asian low back pain patients. This was a cross-sectional study of low back patients seen at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Neuropathic low back pain patients were identified using the painDETECT questionnaire and compared with non-neuropathic (unclear or nociceptive) low back pain patients, in terms of socio-demographic and clinical factors, pain severity (numerical pain rating scale, NPRS), disability (Roland Morris Disability Questionnaire, RMDQ), as well as anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Of 210 patients, 26 (12.4%) have neuropathic low back pain. Neuropathic pain is associated with non-Chinese ethnicity, higher body mass index and pain radiation below the knee. Patients with neuropathic pain have significantly higher NPRS and RMDQ scores, and there are more subjects with anxiety on HADS. However, there are no differences between the groups in age, gender, pain duration or underlying diagnosis of low back pain. The prevalence of neuropathic low back pain in a multi-ethnic Malaysian cohort is lower than previously reported in other populations with possible differences between ethnic groups. It is associated with greater pain severity, disability and anxiety.

Clinical Characteristics, Pain, and Quality of Life Experiences of Trigeminal Neuralgia in a Multi-Ethnic Asian Cohort

AIMS To describe the clinical characteristics of trigeminal neuralgia (TN) in a multi-ethnic Malaysian population and to relate them to standardized measures of pain severity, anxiety, depression, and quality of life (QoL). METHODS Patients fulfilling the International Headache Society (IHS) criteria for TN were prospectively interviewed for their demographic and clinical data. Pain intensity was rated with a visual analog scale (VAS), anxiety and depression were determined by the Hospital Anxiety and Depression Scale (HADS), and QoL was assessed by the Short-Form 36 (SF-36) questionnaire. Chi-square, Mann-Whitney U, and Spearman correlation tests were used to test for differences considering a significance level of P < .05. RESULTS Of the 75 included patients, 52 (69.3%) were women with a mean ± standard deviation (SD) onset age of 52.0 ± 12.7 years, and 57.3% were Chinese, 24.0% Malay, and 18.7% Indian. Pain was more common on the right side (69.3%) and in the maxillary and mandibular divisions. VAS scores for pain at its worst were higher in anxious/borderline anxious patients compared to non-anxious patients (89.5 ± 15.9 vs 80.9 ± 17.2, respectively; P < .05), and VAS scores for pain at its least were higher in depressed/borderline depressed subjects compared to non-depressed subjects (38.4 ± 25.8 vs 23.0 ± 19.2, respectively; P < .05). Chinese patients had lower VAS scores for pain at its least compared to Indian patients (19.7 ± 16.1 vs 39.9 ± 24.7; P < .01). TN patients scored lower in all eight domains of the SF-36 compared to the general population. Indian patients had lower scores in role limitations due to physical health (8.9 ± 23.2 vs 49.4 ± 43.8; P < .01) and social function (56.3 ± 13.6 vs 76.5 ± 23.6; P < .01) than Chinese patients, and Malay patients had lower mental health scores compared to Chinese patients (59.1 ± 19.5 vs 73.0 ± 21.0; P < .01). CONCLUSION Clinical characteristics of TN patients were similar to those of other populations. There were differences in pain ratings and QoL between TN patients of different ethnicities, as well as between those with anxiety and depression.

G.P.78

Human muscle sarcocystosis is usually asymptomatic but can present monosymptomatically as focal muscle pain and/or swelling or rarely, with acute systemic symptoms in an outbreak. We describe features of acute myositis seen in an outbreak of Sarcocystis nesbitii infection in Malaysia in 2012. Infected patients presented acutely with fever and generalised myalgia, which in some included the face and jaw muscles. In about half the patients, myalgia was moderate to severe. There were 17 patients in whom myositis could be confirmed either by the presence of painful muscle swelling or hyperintensity on MRI STIR sequences suggesting muscle inflammation. Muscle swelling and inflammation on MRI were multifocal rather than diffuse and there was predominant involvement of the facial and masticatory muscles suggesting a possible predilection of the sarcocysts for these muscles. Muscle biopsy confirmed the diagnosis by demonstrating the presence of intracellular sarcocysts which was confirmed to be S. nesbitii by molecular methods. Inflammatory changes did not surround the infected muscle fibres but were seen focally with necrosis elsewhere within the muscle. Tissue eosinophilia was not prominent. Laboratory investigations revealed elevated serum creatine kinase and eosinophil count only in a third and half of the patients respectively. Even without specific treatment, muscle pain and swelling gradually subsided over a period of weeks to months. In summary, acute S. nesbitii myositis presented with fever and multifocal muscle pain and swelling. The multifocal nature of muscle inflammation was confirmed on MRI. The intracellular location of the sarcocysts does not elicit a direct immune response but sarcocysts may secrete chemical antigens that result in inflammation elsewhere.