While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.
Matched MeSH terms: Motor Neuron Disease/complications*; Motor Neuron Disease/genetics; Motor Neuron Disease/mortality; Motor Neuron Disease/epidemiology*
Neurological involvement associated with inflammatory bowel disease is well established though rarely reported in the literature. The coexistence of motor neurone disease with ulcerative colitis has never been previously documented. The case of a 53-year-old Indian male with distal ulcerative colitis who, two and a half years later, developed dysarthria, dysphagia, a wasted fasciculating tongue and palatal palsy characteristic of bulbar type motor neurone disease is described. Topical and oral steroids together with azathioprine and mesalazine suppositories controlled the bowel symptoms but did not improve the neurological deficit. Subsequently, the antiglutamate agent riluzole improved the mobility of his tongue. The close temporal relationship and relative infrequency of both these conditions in a Malaysian population along with the recognised association between ulcerative colitis and other neurological conditions deserve careful consideration as to whether a common denominator is involved. Documentation of coexistence of both disorders in a single patient is important in case similar associations are reported in future.
Matched MeSH terms: Motor Neuron Disease/complications*; Motor Neuron Disease/diagnosis*
Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis. Moreover, neuromuscular ultrasound experts including the group in this study have different views with regards to technical aspects, scanning protocols, and the parameters that should be assessed. Establishing standardized neuromuscular scanning protocols is essential for the development of the subspeciality to ensure uniform clinical and research practices. Therefore, we aimed to recommend consensus-based standardized scanning techniques and protocols for common neuromuscular disorders using the Delphi approach. A panel of 17 experts participated in the study, which consisted of three consecutive electronic surveys. The first survey included voting on six scanning protocols addressing the general scanning technique and five common categories of suspected neuromuscular disorders. The subsequent surveys focused on refining the protocols and voting on new steps, rephrased statements, or areas of non-agreement. A high degree of consensus was achieved on the general neuromuscular ultrasound scanning technique and the scanning protocols for focal mononeuropathies, brachial plexopathies, polyneuropathies, amyotophic lateral sclerosis, and muscle diseases. In this study, a group of neuromuscular ultrasound experts developed six consensus-based neuromuscular ultrasound scanning protocols that may serve as references for clinicians and researchers. The standardized protocols could also aid in achieving high-quality uniform neuromuscular ultrasound practices.
Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival.
Matched MeSH terms: Motor Neuron Disease/diagnosis*; Motor Neuron Disease/ethnology*; Motor Neuron Disease/mortality*; Motor Neuron Disease/epidemiology
We determined the clinical progression, disability and outcome of 11 Multifocal Motor Neuropathy (MMN) patients from Malaysia. Mean patient age was 46.8 (SD 13.3), with mean disease duration of 108.0 months (SD 80.2). All reported unilateral limb weakness at onset. At diagnosis, after mean 49.9 months (SD 73.5) delay, 7 (63.6%) had more than 2 limbs involvement. Nine (90%) of 10 patients received induction IVIg dose of 2.0 gm/kg responded, demonstrated improvement in MRCSS of > 2 points or mRS score of > 1 point. We observed 38.5% drop in IVIg dose to mean 1.12 gm/kg/month after 12 months of treatment, and a further 34.8% drop upon 24th month treatment to mean dose of 0.73 gm/kg/month. This was in parallel with initial improvement in MRCSS and mRS, observed among 88.9% and 77.8% of the patients, and later further improvement (33.3%) or stabilization (66.7%) of mRS score toward 2nd year. During the same period, 50% of patients reported deterioration in ONLS, 33.3% in grip strength and 16.7% in MMN-RODS. Beyond 36th month, average annual IVIg dose increased at 0.12 gm/kg/year (SD 0.09) or 11.2%, up to the 84th months. Despite that, progressive deterioration was observed in term of number of limbs involvement, definite motor conduction blocks on electrophysiology study, and both clinical as well as functional scores. Although IVIg dose reduction for maintenance treatment in MMN is recommended, careful clinical assessment is required to prevent under-treatment. Use of reliable and responsive modern outcome measures is important to quantify clinically relevant change to guide therapy.
Matched MeSH terms: Motor Neuron Disease/drug therapy*
To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barré syndrome subtypes and clinical features.
Matched MeSH terms: Motor Neuron Disease/immunology
Glutamate is the principal excitatory neurotransmitter in the central nervous system, and plays important roles in both physiological and pathological neuronal processes. Current understanding of the exact mechanisms involved in glutamate-induced neuronal excitotoxicity, in which excessive glutamate causes neuronal dysfunction and degeneration, whether acute or chronic, remain elusive. Conditions, due to acute insults such as ischaemia and traumatic brain injury, and chronic neurodegenerative disorders such as multiple sclerosis and motor neuron disease, suffer from the lack of translational neuroprotection in clinical setting to tackle glutamate excitotoxicity despite steady growth of animal studies that revealed complex cell death pathway interactions. In addition, glutamates are also released by non-neuronal cells including astrocytes and oligodendroglia. Thus, attempts to elucidate this complexity are closely related to our understanding of the glutamatergic circuitry in the brain. Neuronal cells develop a glutamatergic system at glutamatergic synapses that utilise glutamate as an intercellular signaling molecule to characterise the output, input, and termination of this signaling. As to signal input, various kinds of glutamate receptors have been identified and characterized. Na+-dependent glutamate transporters at the plasma membrane are responsible for the signal termination through sequestration of glutamate from the synaptic cleft. The signal output systems comprise vesicular storage and subsequent exocytosis of glutamate by using vesicular glutamate transporters. Similar to the mammalian brain, the regional differences of glutamatergic neurons and glutamate receptor neurons suggest many glutamatergic projections in the avian brain, as supported by recent evidence of glutamate-related genes distribution. Glutamatergic target areas are expected to show high activity of glutamate transporters that remove released glutamate from the synaptic clefts. This review summarises and compares glutamatergic circuits in the avian and mammalian brain, particularly in the olfactory pathway, the paffial organization of glutamatergic neurons and connection with the striatum, hippocampal-septal pathway, visual and auditory pathways, and granule cell-Purkinje cell pathway in the cerebellum. Comparative appreciation of these glutamatergic circuits, particularly with the localisation and/or expression of specific subtypes of glutamate transporters, would provide the morphological basis for physiological and pharmacological designs that supplement existing animal studies of the current proposed mechanisms that underlie glutamate-induced neuronal excitotoxicity.