Amyotrophic lateral sclerosis and motor neuron syndromes in Asia.

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.

A guide to facilitate the early treatment of patients with idiopathic demyelinating disease (multiple sclerosis and neuromyelitis optica).

Definite diagnosis of inflammatory demyelinating disease (multiple sclerosis (MS) and neuromyelitis optica (NMO)) may require time, but early treatment offers the opportunity to maximize patient outcomes. The purpose of this report is to provide guidance to facilitate early treatment decisions for patients with inflammatory demyelinating disease, before definitive diagnosis. Neurology experts reviewed the existing literature and clinical evidence. A treatment decision pathway was developed, defining patients for whom first-line MS disease-modifying therapies (a) are unlikely to be effective, (b) may be effective but require careful monitoring and (c) are likely to provide benefit. This algorithm seeks to ensure that patients, particularly those in Asia, receive appropriate treatment early in inflammatory demyelinating disease.

Prevalence of spondyloarthritis in 504 Chinese patients with HLA-B27-associated acute anterior uveitis.

OBJECTIVES: To estimate the prevalence of spondyloarthritis (SpA) and the clinical features of human leucocyte antigen (HLA)-B27-associated acute anterior uveitis (HLA-B27 uveitis) in Chinese patients. METHODS: We conducted a retrospective cohort study using a structured chart review to record the complete ocular history, including the onset of uveitis, month of uveitis attack, specific eye involvement, the time of first attack, and rheumatic manifestations from 1987 to 2004. A total of 504 patients with HLA-B27 uveitis were consequently enrolled consecutively from the uveitis clinic of Taipei Veterans General Hospital. RESULTS: In total, 1719 attacks of uveitis in 504 patients were recorded. Females tended to have a higher frequency of attack than males, and those with a disease course of less than 5 years showed more uveitis recurrence. The same eye attacks were observed in 156 of 332 patients (47%), more than the expected percentage compared with attacks with random-eye occurrence (p < 0.001). A significantly higher number of uveitis attacks occurred in winter. SpA-related acute anterior uveitis (AAU) was found in 387 patients (76.8%). Ankylosing spondylitis (AS) occurred in 214 patients (42.5%), with a significantly higher prevalence in males than in females (p < 0.001). Undifferentiated SpA (USpA)-related AAU occurred in 150 patients (29.8%), with a significantly higher prevalence in females than in males (p < 0.001). Patients with SpA had an earlier onset of uveitis (p = 0.01) and a greater number (> or = 6) of attacks (p = 0.03). CONCLUSIONS: The prevalence of SpA was high in the Chinese population with HLA-B27-associated uveitis. The association with SpA indicated an earlier age of uveitis onset and a greater likelihood of having a higher number of uveitis attacks.

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 Poser's 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.

Sequence of a gene encoding a putative primary sigma factor from Borrelia burgdorferi strain B31.

Utilizing a polymerase chain reaction-based approach, the gene (rpoD) encoding the primary sigma factor from Borrelia burgdorferi strain B31 was cloned and sequenced. Nucleotide sequence analysis revealed an open reading frame (ORF) of 1632 bp (543 amino acids (aa), 63.7 kDa). Comparison with Escherichia coli sigma 70 and Bacillus subtilis sigma 43 showed a high degree of similarity in the aa sequences, especially for the regions that are known to be required for promoter recognition and core binding.

Interferon-gamma inhibition suppresses experimental allergic neuritis: modulation of major histocompatibility complex expression of Schwann cells in vitro.

This study examines the modulation of major histocompatibility complex (MHC) expression on Lewis rat Schwann cells (Scs) cultured in the presence of dorsal root ganglion neurons (DRG). MHC class I and II molecules were induced on Scs using recombinant murine interferon-gamma (IFN-gamma), lymph node cells (LNC), removed at day 9 from Lewis rats with experimental allergic neuritis (EAN) and syngeneic T-cell line cells responsive to P2 basic protein. EAN LNC induced MHC class I on Scs but only IFN-gamma or P2-responsive T-cells induced MHC class II. Control LNC from animals injected with Freund's adjuvant alone or naive spleen cells did not induce MHC class II. P2 T-cells clustered in aggregates to the Scs. Similar studies were performed with inhibitors of IFN-gamma; hydrocortisone, cyclosporin A, dibutyryl cyclic AMP, methyl-xanthine and prostaglandin E2. Each agent produced a dose-dependent inhibition of MHC expression and prevented clustering of P2-responsive T-cells to Scs.

Sequence diversity of a gene encoding a putative primary sigma factor among Borrelia burgdorferi sensu lato strains.

Twenty-six strains of Borrelia burgdorferi sensu lato were subjected to polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis for assessing the sequence divergence of rpoD gene encoding the primary sigma factor. Four and five RFLP patterns were observed from two fragments of rpoD gene. Sequence analysis of a subgenic fragment covering region 1 through 4 from 13 strains of Borrelia burgdorferi s. 1. revealed that 21 of 450 deduced amino acid residues were diverged. These results indicate that the sequence heterogeneity of rpoD is present in different strains of Borrelia burgdorferi s. 1., and agreed well with the current classification of genospecies.

Lack of cervical paraspinal muscle involvement in juvenile distal spinal muscular atrophy: an electromyographic study on 15 cases.

Electromyography (EMG) of the lower cervical paraspinal muscles was performed in 15 young Chinese males with distal spinal muscular atrophy of the upper extremities. The lack of fibrillation and positive sharp waves in all patients, both in early or active and chronic or steady stages, did not correlate with the EMG status in the affected upper extremity on the same side. This finding is in striking contrast with that in amyotrophic lateral sclerosis.

Molecular epidemiological studies on foot-and-mouth disease type O Taiwan viruses from the 1997 epidemic.

Sequence diversity was assessed of the complete VP1 gene directly amplified from 49 clinical specimens during an explosive foot-and-mouth disease (FMD) outbreak in Taiwan. Type O Taiwan FMD viruses are genetically highly homogenous, as seen by the minute divergence of 0.2-0.9% revealed in 20 variants. The O/HCP-0314/TW/97 and O/TCP-022/TW/97 viral variants dominated FMD outbreaks and were prevalent in most affected pig-raising areas. Comparison of deduced amino acid sequences around the main neutralizable antigenic sites on the VP1 polypeptide showed no significant antigenic variation. However, the O/CHP-158/TW/97 variant had an alternative critical residue at position 43 in antigenic site 3, which may be due to selective pressure in the field. Two vaccine production strains (O1/Manisa/Turkey/69 and O1/Campos/Brazil/71) probably provide partial heterologous protection of swine against O Taiwan viruses. The type O Taiwan variants clustered in sublineage A1 of four main lineages in the phylogenetic tree. The O/Hong Kong/9/94 and O/1685/Moscow/Russia/95 viruses in sublineage A2 are closely related to the O Taiwan variants. The causative agent for the 1997 epidemic presumably originated from a single common source of type O FMD viruses prevalent in neighboring areas.

Evaluation of cervical radiculopathy by cervical root stimulation.

For precise evaluation of cervical radiculopathy, cervical root stimulation (CRS), conventional electromyographic (EMG) studies, nerve conduction velocity (NCV) studies and F responses were done in 32 patients with clinical symptoms and signs of cervical radiculopathy. While performing CRS, a monopolar needle was inserted into the paraspinal muscles, and the compound muscle action potentials (CMAPs) in the biceps, triceps and abductor digiti minimi muscles were recorded. Conventional EMG was abnormal in 18 (56.2%), whereas CRS was abnormal in 25 (78.1%). Among the 25 patients with positive CRS tests, 13 received surgical decompression for cervical root compression caused either by a cervical disc or by foramen narrowing due to spondylosis. Only 10 out of 13 (76.9%) had abnormal conventional EMG findings. CRS provides a sensitive method for making a direct evaluation of proximal root conduction and is a good aid for pre-surgical evaluation of cervical radiculopathy.

Elevated plasma high-mobility group box 1 protein is a potential marker for neuromyelitis optica.

High-mobility group box 1 protein (HMGB1) has cytokine activities and mediates systemic inflammation as well as immune responses. The aim of this study was to determine if plasma HMGB1 level can be used as a marker for neuromyelitis optica (NMO) and to differentiate NMO from multiple sclerosis (MS). We measured plasma levels of HMGB1, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin 17 (IL-17) in 29 patients with NMO and 20 patients with MS at enrollment and at 2years follow-up (at the time of definitive diagnosis) by enzyme-linked immunosorbent assay. Plasma HMGB1 level was significantly greater in the NMO group compared to the MS group (P<0.001). Plasma levels of TNF-α, IFN-γ, and IL-17 were significantly greater in the NMO group compared to the MS group, and HMGB1 level was positively correlated with TNF-α, IFN-γ, and IL-17 levels. Univariate logistic regression analysis showed a significant association of HMGB1 level, and IFN-γ level with NMO diagnosis. Although this study included a limited sample size, we attempted to determine an optimized cutoff point for HMGB1 (≥2 ng/ml), which provided 89.7% sensitivity and 95.0% specificity for the diagnosis of NMO. These results indicate that plasma HMGB1 level might serve as a surrogate marker for NMO disease activity and aid in the differentiation of NMO from MS at the early disease stage.

Magnetically enhanced high-specificity virus detection using bio-activated magnetic nanoparticles with antibodies as labeling markers.

This study describes magnetically driven suppression of cross-reactions among molecules. First, the magnetic nanoparticles are coated with bio-probes and dispersed in liquid. The bio-probes can then bind with homologous or heterologous bio-targets. When alternating-current (ac) magnetic fields are applied, magnetic nanoparticles rotate driven by ac magnetic fields. Thus, the bio-targets bound on the surface of magnetic nanoparticles experience a centrifugal force. The centrifugal force can be manipulated by adjusting the angular frequency of the rotating magnetic nanoparticles. The angular frequency is determined by the applied ac magnetic field frequency. Since the binding force for good binding is much higher than that of poor binding, frequency manipulation is needed for the centrifugal force to be higher than the poor-binding force but lower than the good-binding force. Therefore, poor binding which contributes to cross reactions between molecules can be suppressed efficiently by control of the ac magnetic field frequency.

Mitochondrial disease with encephalopathy or limb girdle myopathy: a report of five cases.

Over the past 13 years at VGH-Taipei, five cases were morphologically defined as having mitochondrial disease and clinically presented with syndromes other than chronic progressive external ophthalmoplegia. There were two cases presenting with dementia, extensive and symmetrical intracerebral calcification but no clinical and other laboratory evidence of skeletal muscle affection; one case with MERRF syndrome; one case with congenital myopathy and cardiomyopathy; and one case with prednisolone-responsive and polymyositis-like myopathy. The following comments are made: 1. The inexplicably lower incidence of encephalopathy group might result from inadequate alertness of clinicians. 2. The clinical classification might have some clinical convenience, but, identification of defects at the DAN level and determination of the phenotypic expression with clinical, morphologic and biochemical methods are fundamental for future rational diagnosis and classification of mitochondrial diseases.

Muscle biopsy in juvenile distal spinal muscular atrophy.

The myopathological changes in properly selected muscles can allow evaluation of the definite distribution of neuronogenic denervation which can probably not be found by clinical examination or EMG study of inadequate muscle sampling. We performed muscle biopsies in 13 Chinese patients with chronic juvenile monomelic motor neuron disease involving the distal part of the upper extremities. According to our findings and the literature review, the neurogenic changes selectively affected the muscles innervated by C7, 8 and T1 spinal nerves while sparing others. Consequently, the term 'juvenile lower cervical spinal muscular atrophy' is suggested.

Miller fisher syndrome: a hospital-based retrospective study.

Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barré syndrome (GBS). However, some investigators believed that the syndrome could be explained by a central origin. To obtain more information about MFS for comparison with GBS, we conducted a retrospective study by analyzing the clinical data of MFS patients admitted to our hospital over a period of 11 years. The calibrated male/female ratio was 1.65. A seasonal clustering in winter was noted. The percentage of MFS among GBS was especially high (18%, 11/60) in Taiwan when compared with other series. Involvement of limb muscle strength, autonomic function and cranial nerves, except ocular motor nerves, was rarely found in our patients. When MFS is accompanied by limb weakness, it might represent a transitional form between MFS and GBS. Bulbar palsy and dysautonomia might predict a relatively poor prognosis. To obtain more reliable information, lumbar puncture should be done 1 week after disease onset, and electrophysiological tests should be done serially in every MFS patient. Eighty percent (80%, 4/5) of our patients were positive for IgG anti-GQ(1b) antibody activity. In our study, there is more evidence indicating that MFS is a peripheral nervous system disorder; however, no definite conclusion could be made as to whether MFS is exclusively a peripheral or central nervous system disorder. We think MFS is an immune-mediated clinical entity which mainly involves the peripheral nervous system with rare involvement of other parts of the central nervous system.

Clinical and electrophysiological correlation in chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin therapy: a case report.

The clinical effect of high-dose intravenous immunoglobulin (IVIg) is reported as correlated with electrophysiological study in a 15-year-old boy with chronic inflammatory demyelinating polyneuropathy (CIDP). Within three months the patient developed from progressive paraparesis to complete quadriplegia with relative preservative of sensory and bulbar functions. High dose IVIg with 0.4 gm/kg per day was given for five consecutive days, and recovery occurred during the first week, particularly in both the lower limbs. Maximal benefit was achieved by another course of IVIg treatment. The effect maintained for six weeks, but muscle power deteriorated rapidly one week later. Muscle power improved again after another two courses of IVIg infusion. Serial nerve conduction velocity studies showed an improvement in the distal latencies and the amplitudes of compound muscle action potentials (CMAPs) which were not, however, well correlated with the clinical improvement. No improvement in nerve conduction velocities was ever noted.

Myoclonus associated with hyperthyroidism and thymoma: a case report.

Movement disorders associated with hyperthyroidism or thymoma are extremely rare. A 52-year-old woman had developed myoclonus since June, 1989. Hyperthyroidism and thymoma were diagnosed 1 month and 9 months later. Myoclonus improved after thyroid treatment and thymectomy. If the association was not only a coincident phenomenon, autoimmunity should be considered in this previously unrecognized association.

Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia.

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12, 800, normal 55-60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.

Tree-based linkage and association analyses of asthma.

Tree-based linkage analyses and association studies are introduced and applied for two data sets on asthma from Genetic Analysis Workshop 12. Consistent and strong evidence of linkage and association to markers on chromosomes 1 and 11 is revealed. Linkage to chromosome 16 in one data set and association with D6S276 in the other data set are also detected.

Ictal speech manifestations in temporal lobe epilepsy: a video-EEG study.

To evaluate ictal speech manifestations in complex partial seizures (C PS), we reviewed videotapes of 68 consecutive patients who underwent anterior temporal lobectomy (ATL) for treatment of intractable epilepsy in Taiwan. In all, 261 CPS were collected from their video-EEG (VEEG) recordings. Cerebral speech dominance was determined by intracarotid injection of sodium amobarbital (Wada test) in all cases. Ictal speech manifestations, classified as verbalization or vocalization, occurred in 32 patients (47.1%) with 96 seizures (36.8%). Ictal verbalization occurred in 10 patients (14.7%). Ictal vocalization was observed in 28 patients (41.2%); including 6 patients who also had ictal verbalization. Thirty-six patients (52.9%) had no seizure with ictal speech manifestations. Ictal verbalization had significant lateralization value: 90% of patients with this manifestation had seizure focus in the nondominant temporal lobe (p = 0.049). Seizures of patients with ictal vocalization were not more likely to arise from either temporal lobe. We also observed bilingual patients who exclusively spoke in their mother tongue (Taiwanese) rather than the acquired language (Mandarin) in 72.2% of seizures with verbalization. This finding is significant and contrary to a commonly held notion that the acquired language is used in seizures associated with speech behaviors.