Determination of Imaging Biomarkers to Decipher Disease Trajectories and Differential Diagnosis of Neurodegenerative Diseases (DIsease TreND).

BACKGROUND: Understanding disease progression of neurodegenerative diseases (NDs) is important for better prognosis and decisions on the appropriate course of treatment to slow down the disease progression. NEW METHOD: We present here an innovative machine learning framework capable of (1) indicating the trajectory of disease progression by identifying relevant imaging biomarkers and (2) automated disease diagnosis. Self-Organizing Maps (SOM) have been used for data dimensionality reduction and to reveal potentially useful disease-specific biomarkers, regions of interest (ROIs). These ROIs have been used for automated disease diagnosis using Least Square Support Vector Machines (LS-SVM) and to delineate disease progression. RESULTS: A multi-site, multi-scanner dataset containing 1316 MRIs was obtained from ADNI3 and PPMI. Identified biomarkers have been used to decipher (1) trajectory of disease progression and (2) identify clinically relevant ROIs. Furthermore, we have obtained a classification accuracy of 94.29 ±â€¯0.08% and 95.37 ±â€¯0.02% for distinguishing AD and PD from HC subjects respectively. COMPARISON WITH OTHER EXISTING METHODS: The goal of this study was fundamentally different from other machine learning based studies for automated disease diagnosis. We aimed to develop a method that has two-fold benefits (1) It can be used to understand pathology of neurodegenerative diseases and (2) It also achieves automated disease diagnosis. CONCLUSIONS: In the absence of established disease biomarkers, clinical diagnosis is heavily prone to misdiagnosis. Being clinically relevant and readily adaptable in the current clinical settings, the developed framework could be a stepping stone to make machine learning based Clinical Decision Support System (CDSS) for neurodegenerative disease diagnosis a reality.

Rapid Screening for Cognitive Impairment in Parkinson's Disease: A Pilot Study.

Aim. This study sought to establish the discriminant validity of a rapid cognitive screen, that is, the National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol, and compare its discriminant validity to the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) in detecting cognitive impairment (CI) in PD patients. Methods. One hundred and one PD patients were recruited from a movement disorders clinic in Singapore and they received the NINDS-CSN 5-minute protocol, MoCA, and MMSE. No cognitive impairment (NCI) was defined as Clinical Dementia Rating (CDR) = 0 and CI was defined as CDR ≥ 0.5. Results. Area under the receiver operating characteristic curve of NINDS-CSN 5-minute protocol was statistically equivalent to MoCA and larger than MMSE (0.86 versus 0.90, P = 0.07; 0.86 versus 0.76, P = 0.03). The sensitivity of NINDS-CSN 5-minute protocol (<9) was statistically equivalent to MoCA (<22) (0.77 versus 0.85, P = 0.13) and superior to MMSE (<24) (0.77 versus 0.52, P < 0.01) in detecting CI, while the specificity of NINDS-CSN 5-minute protocol (<9) was statistically equivalent to MoCA (<22) and MMSE (<24) (0.78 versus 0.88, P = 0.34). Conclusion. The NINDS-CSN 5-minute protocol is time expeditious while remaining statistically equivalent to MoCA and superior to MMSE and therefore is suitable for rapid cognitive screening of CI in PD patients.

Computer-based testing of the modified essay question: the Singapore experience.

BACKGROUND: The modified essay question (MEQ), featuring an evolving case scenario, tests a candidate's problem-solving and reasoning ability, rather than mere factual recall. Although it is traditionally conducted as a pen-and-paper examination, our university has run the MEQ using computer-based testing (CBT) since 2003. AIMS: We describe our experience with running the MEQ examination using the IVLE, or integrated virtual learning environment (https://ivle.nus.edu.sg), provide a blueprint for universities intending to conduct computer-based testing of the MEQ, and detail how our MEQ examination has evolved since its inception. METHODS: An MEQ committee, comprising specialists in key disciplines from the departments of Medicine and Paediatrics, was formed. We utilized the IVLE, developed for our university in 1998, as the online platform on which we ran the MEQ. We calculated the number of man-hours (academic and support staff) required to run the MEQ examination, using either a computer-based or pen-and-paper format. RESULTS: With the support of our university's information technology (IT) specialists, we have successfully run the MEQ examination online, twice a year, since 2003. Initially, we conducted the examination with short-answer questions only, but have since expanded the MEQ examination to include multiple-choice and extended matching questions. A total of 1268 man-hours was spent in preparing for, and running, the MEQ examination using CBT, compared to 236.5 man-hours to run it using a pen-and-paper format. Despite being more labour-intensive, our students and staff prefer CBT to the pen-and-paper format. CONCLUSIONS: The MEQ can be conducted using a computer-based testing scenario, which offers several advantages over a pen-and-paper format. We hope to increase the number of questions and incorporate audio and video files, featuring clinical vignettes, to the MEQ examination in the near future.

Abdominal pain from a thoracic epidural abscess.

Spinal epidural abscesses are difficult to diagnose and are associated with high morbidity and mortality. A 61-year-old Chinese woman fell and was admitted 5 days later with constant epigastric pain and constipation. Clinical examination was initially normal. Five days after admission, she developed urinary retention and mild lower limb weakness, progressing overnight to paraplegia. Clinical examination was consistent with a thoracic myelopathy. Neuroimaging showed a paracentral fluid collection compressing the thoracic cord at T8 level. Emergent neurosurgical intervention revealed an epidural abscess, which was drained. She responded to a 9-week course of antibiotics and recovered fully. Radicular pain from thoracic pathology can mimic intraabdominal pathology, and a high index of suspicion and prompt surgical intervention are essential to avoid the potentially devastating consequences of delayed recognition of epidural abscesses.

Dystonia gravidarum: a new entity?

We describe cervical dystonia occurring in a 31-year-old, previously well, primigravid, primiparous Chinese woman at 4 weeks' amenorrhea, which was ameliorated with low-dose clonazepam and disappeared completely by the end of the second trimester without recurring despite her being tapered off benzodiazepine therapy. Investigations were unremarkable for structural and biochemical causes of dystonia. Chorea, paraballismus, and restless legs syndrome are known to occur during pregnancy, attributable to high estrogen levels. Dystonia, on the other hand, has not been described to occur de novo in pregnancy. This association should be considered in women of reproductive age who present with cervical dystonia.

A blessing in disguise: resolution of tardive dyskinesia with development of cervical myelitis.

Tardive dyskinesia (TD), which is frequently seen in patients treated with dopamine receptor blocking agents, is difficult to manage. We report on a young Chinese man with bipolar disorder who developed TD after haloperidol treatment, involving the trunk, limbs, and orofacial area. TD persisted despite switching to atypical antipsychotic agents and treatment with valproate, benzodiazepines, and tetrabenazine. Resolution only occurred years later when he developed quadriplegia arising from infective myelitis of the cervical cord (C4-5). He had concomitant vertebral osteomyelitis, which was successfully treated with intravenous antibiotics. With intensive rehabilitation, he recovered the use of his limbs, but had no recurrence of TD. We attribute the resolution of orofacial dyskinesias with a cervical lesion to the interconnections between the orofacial area and cervical spine via the trigeminal nucleus (which has fibers descending as far caudally as C6), as well as to resetting of cortical maps.

Platysmal myoclonus in subclinical hyperthyroidism.

Hyperthyroidism is associated with various movement disorders, such as chorea and tremors. We report on a young Chinese woman with an unusual presentation of myoclonus, involving both platysmal muscles, in association with subclinical hyperthyroidism. The myoclonus was preceded by symptoms of hyperthyroidism, namely weight loss, menstrual disturbances, and heat intolerance. The movements abated with clonazepam and hyperthyroidism was treated with carbimazole. The myoclonus recurred briefly when she stopped taking clonazepam, but she has since remained well and euthyroid.

Post-traumatic paroxysmal exercise-induced dystonia: case report and review of the literature.

A young Chinese man sustained a back injury in a motorcycle accident in 2000 and had left lower limb weakness due to a lumbosacral plexopathy, diagnosed clinically and electromyographically. With rehabilitation, he recovered full function, but developed paroxysmal dystonia of the left leg only with prolonged exertion. He responded well to oral baclofen, relapsed when he stopped taking it, and remains well on low dose maintenance therapy. Dystonia occurring after trauma is well documented, but paroxysmal exercise-induced dystonia occurring after trauma has yet to be described. Paroxysmal exercise-induced dystonia responds variably to anticonvulsant therapy, but the literature does not report response to baclofen, especially in low doses.