National Neuroscience Institute Research Articles

Malin Regulates Wnt Signaling Pathway through Degradation of Dishevelled2

Using yeast-two hybrid screening followed by co-immunoprecipitation assay, we have found that the Lafora disease ubiquitin ligase malin interacts with dishevelled2, a key mediator of Wnt signaling pathway. Overexpression of malin enhances the degradation of dishevelled2 and inhibits Wnt signaling, which is evident from the down-regulation of β-catenin target genes and the decrease in β-catenin-mediated transcriptional activity. Partial knockdown of malin significantly increases the level of dishevelled2 and up-regulates Wnt signaling. Several malin mutants are found to be ineffective in degrading dishevelled2 and regulating the Wnt pathway. We have also found that malin enhances K48- and K63-linked ubiquitination of dishevelled2 that could lead to its degradation through both proteasome and autophagy. Altogether, our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease.

Selegiline use is associated with a slower progression in early Parkinson’s disease as evaluated by Hoehn and Yahr Stage transition times

This study was carried out to evaluate the association between selegiline use and Parkinson’s disease (PD) progression in a clinical sample by evaluating modified Hoehn and Yahr Stage (H&Y) stage transition times. Data were obtained from the movement disorder database of the National Neuroscience Institute in Singapore. Cox regression analysis was used to examine the association between baseline variables and H&Y stage transition times. In multi-variate Cox regression analysis, patients who were of younger age, shorter PD duration, lower Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores, on selegiline treatment (≥3 years) and not on COMT inhibitors were associated with longer transition times from stage 2–2.5. Patients who were treated with selegiline (≥3 years) and not on COMT inhibitors experienced longer transition times from stage 2.5–3. In conclusion, selegiline use for 3 years or more in early PD was associated with a slower progression of PD as evaluated by H&Y transition times.

Progression of Parkinson's disease as evaluated by Hoehn and Yahr stage transition times

This study was carried out to evaluate progression in Parkinson's disease (PD) by analyzing time taken to transit from one Hoehn and Yahr (H&Y) stage to the next stage and to investigate the variables that would be associated with H&Y transition times using a large PD database that contained prospectively collected information. Data were obtained from the movement disorder database of the National Neuroscience Institute in Singapore. Kaplan-Meier (KM) survival analysis was adopted to investigate the time taken to progress through various H&Y stages. Cox regression analysis was used to examine the association between the baseline variables at the entry point of each H&Y stage and the progression to the next stage. A total of 695 patients (mean age: 65.2, male: 57.3%) were studied. Using KM analysis, the median time taken to transit from H&Y stage 1 to 2, 2 to 2.5, 2.5 to 3 were 20, 62, and 25 months, respectively; whereas the median time taken to progress from stage 3 to 4 and 4 to 5 were 24 and 26 months, respectively. Cox regression analysis revealed that older age-at-diagnosis, longer PD duration, and higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at baseline were associated with a significantly faster progression through various H&Y stages. Gender and ethnicity were not associated with disease progression. In conclusion, H&Y transition time is a useful measure of disease progression in PD and may be utilized in clinical studies evaluating therapeutic interventions and prognostic factors in PD.

‘Diphasic’ levodopa-induced chorea in multiple system atrophy

International Journal of Clinical PracticeVolume 64, Issue 1 p. 126-128 ‘Diphasic’ levodopa-induced chorea in multiple system atrophy E. K. Tan, E. K. Tan Department of Neurology,Singapore General Hospital, SingHealth, National Neuroscience Institute, Department of Diagnostic Radiology,Search for more papers by this authorL. L. Chan, L. L. Chan Singapore General Hospital, SingaporeSearch for more papers by this author E. K. Tan, E. K. Tan Department of Neurology,Singapore General Hospital, SingHealth, National Neuroscience Institute, Department of Diagnostic Radiology,Search for more papers by this authorL. L. Chan, L. L. Chan Singapore General Hospital, SingaporeSearch for more papers by this author First published: 10 December 2009 https://doi.org/10.1111/j.1742-1241.2006.00889.xCitations: 2 Dr Eng King Tan MD, MRCP Senior Consultant Neurologist, Department of Neurology, Singapore General Hospital, Clinical Lecturer, National University of Singapore, Outram Road, Singapore 169608, SingaporeTel.: + 65 326 5003Fax: + 65 6220 3321Email: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume64, Issue1January 2010Pages 126-128 RelatedInformation

Hippocampal Volumes in First-Episode Psychosis

Hippocampal Volumes in First-Episode Psychosis

LRRK2 G2385R modulates age at onset in Parkinson's disease: A multi‐center pooled analysis

American Journal of Medical Genetics Part B: Neuropsychiatric GeneticsVolume 150B, Issue 7 p. 1022-1023 Letter to the Editor LRRK2 G2385R modulates age at onset in Parkinson's disease: A multi-center pooled analysis† E.K. Tan, E.K. Tan Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore Duke-NUS Graduate Medical School, Singapore, SingaporeSearch for more papers by this authorR. Peng, R. Peng Department of Neurology, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorY.R. Wu, Y.R. Wu Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorR.M. Wu, R.M. Wu Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, TaiwanSearch for more papers by this authorY.H. Wu-Chou, Y.H. Wu-Chou Human Molecular Genetics Laboratory, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorL.C. Tan, L.C. Tan Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, SingaporeSearch for more papers by this authorX.K. An, X.K. An Department of Neurology, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorC.M. Chen, C.M. Chen Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorS. Fook-Chong, S. Fook-Chong Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, SingaporeSearch for more papers by this authorC.S. Lu, Corresponding Author C.S. Lu c81214@adm.cgmh.org.tw Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan, No. 5, Fu-Shin Street, Kweishan, Taoyuan 33305, Taiwan.Search for more papers by this author E.K. Tan, E.K. Tan Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore Duke-NUS Graduate Medical School, Singapore, SingaporeSearch for more papers by this authorR. Peng, R. Peng Department of Neurology, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorY.R. Wu, Y.R. Wu Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorR.M. Wu, R.M. Wu Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, TaiwanSearch for more papers by this authorY.H. Wu-Chou, Y.H. Wu-Chou Human Molecular Genetics Laboratory, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorL.C. Tan, L.C. Tan Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, SingaporeSearch for more papers by this authorX.K. An, X.K. An Department of Neurology, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorC.M. Chen, C.M. Chen Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanSearch for more papers by this authorS. Fook-Chong, S. Fook-Chong Departments of Neurology and Clinical Research, Singapore General Hospital, National Neuroscience Institute, Singapore, SingaporeSearch for more papers by this authorC.S. Lu, Corresponding Author C.S. Lu c81214@adm.cgmh.org.tw Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan, No. 5, Fu-Shin Street, Kweishan, Taoyuan 33305, Taiwan.Search for more papers by this author First published: 16 January 2009 https://doi.org/10.1002/ajmg.b.30923Citations: 24 † How to Cite this Article: Tan EK, Peng R, Wu YR, Wu RM, Wu-Chou YH, Tan LC, An XK, Chen CM, Fook-Chong S Lu CS. 2009. LRRK2 G2385R Modulates Age at Onset in Parkinson's Disease: A Multi-Center Pooled Analysis. Am J Med Genet Part B 150B:1022–1023. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume150B, Issue75 October 2009Pages 1022-1023 RelatedInformation

Hippocampal Volumes in First-Episode Psychosis

Studies have shown that patients with schizophrenia have smaller hippocampi than healthy comparison subjects. There are, however, inconsistencies regarding the relationship between clinical characteristics and topographical differences in hippocampal volumetry. The authors investigated hippocampal volumes in minimally treated patients with first-episode schizophrenia spectrum disorders, relative to comparison subjects. Thirty-nine consecutive patients and 29 matched comparison subjects were scanned using 1.5 tesla MR system. Patients had significantly smaller right anterior, right, and anterior hippocampal volumes than comparison subjects. There was a gender by diagnosis effect: female patients showed significantly smaller anterior and right hippocampal volumes than female comparison subjects, an effect not seen in male patients. Our results suggest that smaller hippocampal volumes are present even in early stages of the illness.

Awake Craniotomy Under Local Anaesthesia and Monitored Conscious Sedation for Resection of Brain Tumours in Eloquent Cortex – Outcomes in 20 Patients

Resection or even biopsy of an intra-axial mass lesion in close relationship to eloquent cortex carries a major risk of neurological deficit. We review the safety and effectiveness of craniotomy under local anaesthesia and monitored conscious sedation for resection of mass lesions involving eloquent cortex. We performed a 3-year retrospective review of patients who underwent awake craniotomy under local anaesthesia at the National Neuroscience Institute, Singapore. All patients had tumours in close proximity to eloquent cortex, including speech areas in the dominant hemisphere as well as primary sensory and motor cortex in either hemisphere. Brain mapping was performed by direct cortical stimulation using the Ojemann stimulator to identify a safe corridor for surgical approach to the tumour. Intraoperative physiological monitoring was carried out by assessment of speech, motor and sensory functions during the process of surgical resection. All resections were evaluated and verified by postoperative imaging and reviewed by an independent assessor. Postoperative complications and neurological deficits, as well as extent of tumour resection, were evaluated. A total of 20 patients underwent stereotactic resection over a period of 3 years from July 2003 to August 2006. There were 7 male patients and 13 female patients, with a mean age of 39.8 years. The average length of stay was 5.5 days. There were no major anaesthetic complications and no perioperative deaths. Postoperative neurological deficits were seen in 6 patients (30%) and this was permanent in only 1 patient (5%). The degree of cytoreduction achieved was greater than 90% in 58% of patients and a further 21% had greater than 80% cytoreduction. Tumour surgery with conscious sedation in combination with frameless computer stereotactic guidance is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Uniting Chinese across Asia: the LRRK2 Gly2385Arg risk variant

European Journal of NeurologyVolume 15, Issue 3 p. 203-204 Uniting Chinese across Asia: the LRRK2 Gly2385Arg risk variant Correction(s) for this article ERRATUM Volume 15Issue 4European Journal of Neurology pages: 434-434 First Published online: March 18, 2008 E. K. Tan, E. K. Tan Department of Neurology, Singapore General Hospital, National Neuroscience Institute, SingaporeSearch for more papers by this authorA. H. Schapira, A. H. Schapira University Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK (e-mail: [email protected])Search for more papers by this author E. K. Tan, E. K. Tan Department of Neurology, Singapore General Hospital, National Neuroscience Institute, SingaporeSearch for more papers by this authorA. H. Schapira, A. H. Schapira University Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK (e-mail: [email protected])Search for more papers by this author First published: 14 February 2008 https://doi.org/10.1111/j.1468-1331.2007.02053.xCitations: 22Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume15, Issue3March 2008Pages 203-204 RelatedInformation

Idiopathic hypertrophic pachymeningitis causing seizures

European Journal of NeurologyVolume 15, Issue 2 p. e12-e13 Idiopathic hypertrophic pachymeningitis causing seizures K. Tan, K. Tan Department of Neurology, National Neuroscience Institute, SingaporeSearch for more papers by this authorS. A. Lim, S. A. Lim Department of Ophthalmology, Tan Tock Seng Hospital, SingaporeSearch for more papers by this authorA. Thomas, A. Thomas Consultant Pathologist, Parkway Laboratory Services, SingaporeSearch for more papers by this authorC. T. Lim, C. T. Lim Department of Neuroradiology, National Neuroscience Institute, SingaporeSearch for more papers by this authorS. Y. Wong, S. Y. Wong Consultant Infectious Disease Physician, Gleneagles Medical Centre, Singapore;Search for more papers by this authorC. B. Tan, C. B. Tan Consultant Neurologist, Gleneagles Medical Centre, SingaporeSearch for more papers by this author K. Tan, K. Tan Department of Neurology, National Neuroscience Institute, SingaporeSearch for more papers by this authorS. A. Lim, S. A. Lim Department of Ophthalmology, Tan Tock Seng Hospital, SingaporeSearch for more papers by this authorA. Thomas, A. Thomas Consultant Pathologist, Parkway Laboratory Services, SingaporeSearch for more papers by this authorC. T. Lim, C. T. Lim Department of Neuroradiology, National Neuroscience Institute, SingaporeSearch for more papers by this authorS. Y. Wong, S. Y. Wong Consultant Infectious Disease Physician, Gleneagles Medical Centre, Singapore;Search for more papers by this authorC. B. Tan, C. B. Tan Consultant Neurologist, Gleneagles Medical Centre, SingaporeSearch for more papers by this author First published: 21 January 2008 https://doi.org/10.1111/j.1468-1331.2007.02023.xCitations: 5 Dr C. C. Tchoyoson Lim, Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore (tel.: 65 6357 7021; fax: 65 6358 1259; e-mail: [email protected]). Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume15, Issue2February 2008Pages e12-e13 RelatedInformation

Pre-stroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from focal cerebral ischemia in rats

Background Inhibitory signals, i.e. neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the immune repair mechanisms of body. Objective To evaluate the effect of pre-stroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of focal cerebral ischemia. Design A completely randomized design, and controlled experiment. Setting Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. Materials Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in body mass from 180 to 250 g were provided by the Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGIs) a gift was provided by Dr. Xiao from the Department of Clinical Research, Singapore General Hospital, Singapore. Methods The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ▪ The involved rats were randomized into 3 groups: model group (group A), pcDNA3.1(+) group (group B) and pcDNA-NGIs group (group C), with 20 rats in each group. Left focal cerebral ischemia was permanently induced through middle cerebral artery occlusion with the assistance of an operating microscope. Successful middle cerebral artery occlusion was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week before middle cerebral artery occlusion for 6 weeks in group C. As control, pcDNA3.1 (+) was also administrated in the same way in group B and nothing was administrated in group A. ▪ The modified neurological severity score (mNSS), a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on 0–18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. ▪ The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine (BDA). Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains (30 μm) were reacted to BDA according to the manufacturer's instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system (Germany), and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. Main outcome measures ▪ The number of newly generated axons of corticorubral projection; ▪ The improvement of the sensorimotor deficit. Results All the involved 60 rats entered the final analysis. ▪ The number of newly generated axons of corticorubral projection of rats: Only ipsilateral axons of corticorubral projiction were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups A and B. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group C. Quantitative analysis showed that BDA-labelled axons in the denervated side of rats in group C were more than those in group B ( P < 0.05). ▪ The improvement of the sensorimotor deficit: At two weeks after middle cerebral artery occlusion, significant improvement in sensorimotor deficit was found in rats of group C. There was significant difference of improvement in sensorimotor deficit of rats between group C and group B or group A at eight and 10 weeks after middle cerebral artery occlusion ( P < 0.05). Conclusion Pre-stroke DNA immunization against NGIs led to increased sensorimotor recovery following focal cerebral ischemia and compensatory newly growth of axons from corticorubral projection.

Exploring the Relationship Between Panic Disorder and Parkinson's Disease

Back to table of contents Previous article Next article LETTERFull AccessExploring the Relationship Between Panic Disorder and Parkinson’s DiseaseEng-King Tan M.D., M.R.C.P.,Eng-King Tan M.D., M.R.C.P.Search for more papers by this author,Published Online:1 Jul 2007https://doi.org/10.1176/jnp.2007.19.3.343AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: I read with interest the recent report by Matsui et al. 1 in which the authors highlighted a patient who was diagnosed with Parkinson’s disease shortly after a panic attack. Though there is strong biological basis for the association of panic disorder with Parkinson’s disease, the case report raises a number of unanswered questions. Based on the presentation, one cannot exclude the possibility of chance occurrence of the two conditions. The onset of parkinsonian symptoms in their patient may be much earlier than the date when the patient first noticed them. It may be more convincing if longitudinal data were available where it can be shown that the two problems progressed in tandem. Furthermore, availability of detailed information on the patient’s premorbid personality and family history of psychiatric disorder would have been useful. I think the more interesting clinical question would be to determine the proportion of Parkinson’s disease patients who present with panic disorder before or at the time of diagnosis. To address that, I interviewed and examined 53 consecutive newly diagnosed Parkinson’s disease patients in our movement disorders clinic for evidence and history of panic disorder prior to the diagnosis. This was carried out as part of our routine clinical care, and I also received institutional ethics approval for evaluation of nonmotor symptoms in Parkinson’s disease. The patients’ mean age of onset was 62 (SD=11.5) years, with about 50% men and with the Hoehn and Yahr stage between 1 to 4. I found that none of our patients had history or evidence of panic disorder prior to Parkinson’s disease diagnosis. This suggests that panic disorder as a presentation prior to the onset of Parkinson’s disease symptoms was uncommon, at least in our population. Whether our finding reflects ethnicity-specific effects of phenotypic expression remains to be clarified. However, I agree that psychiatric nonmotor symptoms, such as anxiety, depression, and panic disorder, can be disabling in Parkinson’s disease patients, 2 , 3 and these are relatively less well studied than motor disability. Among anxiety disorders, it appears that generalized anxiety disorder, panic disorder and social phobias are most frequently encountered, and anxiety may develop before motor features. 3 To further our understanding of the pathophysiology of panic disorder in Parkinson’s disease, more prospective studies are needed to examine their cause-effect relationship and the temporal relationship of panic disorder with other psychiatric and cognitive disturbances. Department of Neurology, Singapore General Hospital, National Neuroscience Institute, SingaporeReferences1 . Matsui H, Udaka F, Oda M, et al: Parkinson’s disease following panic disorder. J Neuropsychiatry Clin Neurosci 2006;18:130Google Scholar2 . Witjas T, Kaphan E, Azulay JP, et al: Nonmotor fluctuations in parkinson’s disease: frequent and disabling. Neurology 2002; 59:408–413Google Scholar3 . Anxiety disorders in Parkinson’s disease. Adv Neurol 2005; 96:42–55Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 19Issue 3 Summer, 2007Pages 343-344 Metrics PDF download History Published online 1 July 2007 Published in print 1 July 2007

Clinical characteristics, neurophysiological grade and outcome of patients with carpal tunnel syndrome: A retrospective study

Background Carpal tunnel syndrome (CTS) is diagnosed mainly according to clinical symptoms, physical sign and neurodiagnostic laboratory examination. The therapeutic effect of conservative management and surgical operation in treating CTS need to be further observed and evaluated. Objective To analyze the clinical characteristics, neurophysiological grade and outcome in patients with CTS. Design Retrospective case-analysis. Setting Department of Neurology, First Affiliated Hospital, Medical College, Xi'an Jiaotong University. Participants Totally 161 patients with suspected CTS from National Neuroscience Institute of Singapore referred to the Neurodiagnostic Laboratory for the confirmatory testing between January and September 2002. The involved patients, 137 male and 24 female, were aged 21–85 years. Methods ▪ The condition of diabetes mellitus complicated by abnormal thyroid function was observed. ▪ The effect on predominant hand, and paraesthesia were observed. ▪ Neuroelectrophysiological studies were performed and the results were graded into mild, moderate and severe CTS according to the American Association of Electrodiagnostic Medicine (AAEM) criteria. ▪ Conservative management and surgical intervention were followed up 3 months later, and symptoms and physical sign basically disappeared, and function was basically recovered, which indicated that disease condition improved. Main Outcome Measures ▪ Condition of CTS complicated by metabolic disease; ▪ Effects on predominant hand and paraesthesia; ▪ Electrophysiological grading; ▪ Prognosis. Results Totally 161 patients participated in the final analysis. ▪ Condition of CTS complicated by metabolic disease: Among 161 patients, 17.4% (28/161) were documented to have diabetes mellitus and 7(4.3%) had hypothyroidism. ▪ Effects on predominant hand and paraesthesia: Dominant hand involvement was present in 134 patients (83.2%) and more than 75% had onset of symptoms in the dominant hand. Sensory symptoms like numbness and paresthesias were the predominant symptoms, accounting for 89.1% (134/161), this discomfort was felt in all 5 digits of the hand in 47.6%, and lateral three and half digits in 21.4%. The noctural symptoms were present in 30.4% (49/161) patients. ▪ Electrophysiological typing: The most frequent abnormality was that of the prolonged mid-palm median and ulnar latency difference in 146(54.7%) hands; 103(38.6%) hands had prolonged median motor distal latency. Absent response from thenar muscle was present in 35 (13.1%) hands. Nerve conduction study showed bilateral CTS in 105 (65.2%) patients and unilateral CTS in 56 (34.8%) patients. Sixteen patients with bilateral CTS had symptoms in one hand only. Overall, 36.8% had mild, 49.2 % had moderate and 13.9 % had severe CTS, with median duration of symptoms of 6, 9 and 14 months, respectively. ▪ Delay in diagnosis: 37(22.9%) patients delayed in diagnosis from 1–4 months, 16(43.2%) were misdiagnosed as cervical spondylosis; 6(16.2%) were ignored due to their condition by busy work; 15(40.5%) were unware of their symptoms. ▪ Prognosis: Follow up data was available for only 72.7% (117/161) patients. Conservative management was conducted in 73.5% (86/117). Clinical symptoms were resolved or improved in 65.1% (56/86) patients with 17 mild CTS, 29 moderate CTS, and 10 severe CTS. 26.5% (31/117) patients underwent surgery for CTS release, and clinical symptoms were improved in 12(38.7%) with moderate CTS and 2 (6.5%) with severe CTS at 3 months of follow up. Conclusion ▪ Sensory symptoms in CTS are more in severe and common in dominant hand. ▪ Conservative management showed resolution or improvement for mild and moderate CTS. Surgical intervention shows either resolution or improvement in clinical symptoms in moderate CTS. ▪ The common reasons for delay in diagnosis were due to misdiagnosis as cervical spondylosis and lack of awareness of the condition. ▪ Assessment on severity of CTS by electrophysiological grade is of important significance for determining therapeutic mean.

VOLUME VISUALIZATION FOR SURGICAL PLANNING SYSTEM

The 3D volume visualization is to overcome the difficulties of the 2D imaging by using computer technology. A volume visualization approach has been successfully implemented for Surgical Planning System in National Neuroscience Institute (NNI). The system allows surgeons to plan a surgical approach on a set of 2D image slices and process into volume models and visualise them in 3D rapidly and interactively on PC. In our implementation, we have applied it in neurosurgical planning. The surgeon can visualize objects of interest like tumor and surgical path, and verify that the surgical plan avoids the critical features and the planning of the surgical path can thus be optimal.

Poststroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from local cerebral ischemia in rats ○

Background Inhibitory signals, i.e. neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body's immune repair mechanisms. Objective To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia. Design Completely randomized grouping design, and controlled experiment. Setting Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. Materials Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGIs) a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore. Methods The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ▪The involved rats were randomized into 3 groups: pcDNA-NGIs group (group A), pcDNA3.1 (+) group (group B) and model group (group C), with 20 rats in each group. Left focal cerebral ischemia (FCI) was permanently induced through middle cerebral artery occlusion (MCAO) with the assistance of an operating microscope. Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 (+) was also administrated in the same way in group B and nothing was administrated in group C. ▪ The modified neurological severity score (mNSS), a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on a scale of 0–18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. ▪ The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains (30 μm) were reacted to BDA according to the manufacturer's instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system (Germany), and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. Main outcome measures ▪ The number of newly generated axons of corticorubral projection. ▪The improvement in sensorimotor deficit. Results All the involved 60 rats entered the stage of final analysis. ▪ The number of newly generated axons of corticorubral projection of rats: Only ipsilateral axons of CRP were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups B and C. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group A. Quantitative analysis showed that BDA-labeled axons in the denervated side of rats in group A were more than those in group B ( P < 0.05). ▪ Improvement in sensorimotor deficit of rats: At 2 weeks after immunization, significant improvement in sensorimotor deficit was found in rats of group A. There were significant differences of improvement in sensorimotor deficit of rats between group A and group B or group C at 12 and 14 weeks after immunization ( P < 0.05). Conclusion ▪ Poststroke DNA immunization against NGIs leads to increased sensorimotor recovery following FCI and compensatory newly growth of axons from corticorubral projection.

Hybrid Outcome Prediction Model for Severe Traumatic Brain Injury

Numerous studies addressing different methods of head injury prognostication have been published. Unfortunately, these studies often incorporate different head injury prognostication models and study populations, thus making direct comparison difficult, if not impossible. Furthermore, newer artificial intelligence tools such as machine learning methods have evolved in the field of data analysis, alongside more traditional methods of analysis. This study targets the development of a set of integrated prognostication model combining different classes of outcome and prognostic factors. Methodologies such as discriminant analysis, logistic regression, decision tree, Bayesian network, and neural network were employed in the study. Several prognostication models were developed using prospectively collected data from 513 severe closed head-injured patients admitted to the Neurocritical Unit at National Neuroscience Institute of Singapore, from April 1999 to February 2003. The correlation between prognostic factors at admission and outcome at 6 months following injury was studied. Overfitting error, which may falsely distinguish different outcomes, was compared graphically. Tenfold cross-validation technique, which reduces overfitting error, was used to validate outcome prediction accuracy. The overall prediction accuracy achieved ranged from 49.79% to 81.49%. Consistently high outcome prediction accuracy was seen with logistic regression and decision tree. Combining both logistic regression and decision tree models, a hybrid prediction model was then developed. This hybrid model would more accurately predict the 6-month post-severe head injury outcome using baseline admission parameters.

Medical Image Resource Center--making electronic teaching files from PACS.

A picture archive and communications system (PACS) is a rich source of images and data suitable for creating electronic teaching files (ETF). However, the potential for PACS to support nonclinical applications has not been fully realized: at present there is no mechanism for PACS to identify and store teaching files; neither is there a standardized method for sharing such teaching images. The Medical Image Resource Center (MIRC) is a new central image repository that defines standards for data exchange among different centers. We developed an ETF server that retrieves digital imaging and communication in medicine (DICOM) images from PACS, and enables users to create teaching files that conform to the new MIRC schema. We test-populated our ETF server with illustrative images from the clinical case load of the National Neuroscience Institute, Singapore. Together, PACS and MIRC have the potential to benefit radiology teaching and research.

Neurological Letter from Singapore

In December 2001, I was fortunate enough to be seconded from my position in University College, London, for a period of 2 years, to take up the post of Director...