Brain computed tomography reading of stroke patients by resident doctors from different medical specialities: An eye-tracking study.

BACKGROUND: Using the eye-tracking technique, our work aimed to examine whether difference in clinical background may affect the training outcome of resident doctors' interpretation skills and reading behaviour related to brain computed tomography (CT). METHODS: Twelve resident doctors in the neurology, radiology, and emergency departments were recruited. Each participant had to read CT images of the brain for two cases. We evaluated each participant's accuracy of lesion identification. We also used the eye-tracking technique to assess reading behaviour. We recorded dwell times, fixation counts, run counts, and first-run dwell times of target lesions to evaluate visual attention. Transition entropy was applied to assess the temporal relations and spatial dynamics of systematic image reading. RESULTS: The eye-tracking results showed that the image reading sequence examined by transition entropy was comparable among resident doctors from different medical specialties (p = 0.82). However, the dwell time of the target lesions was shorter for the resident doctors from the neurology department (4828.63 ms, p = 0.01) than for those from the resident doctors from the radiology (6275.88 ms) and emergency (5305.00 ms) departments. The eye-tracking results in individual areas of interest only showed differences in the eye-tracking performance of the first-run dwell time (p = 0.05) in the anterior cerebral falx. DISCUSSION: Our findings demonstrate that resident doctors from different medical specialties may achieve similar imaging reading patterns for brain CT. This may mitigate queries regarding the influence of different backgrounds on training outcomes.

Cortical excitability in patients with REM sleep behavior disorder with abnormal TRODAT-1 SPECT scan: an insight into prodromal Parkinson's disease.

Introduction: REM Sleep Behavior Disorder (RBD) has been highlighted to identify a patient with prodromal Parkinson's disease (PD). Although many studies focus on biomarkers to predict an RBD patient's evolution from prodromal PD to clinical PD, the neurophysiological perturbation of cortical excitability has not yet been well elucidated. Moreover, no study describes the difference between RBD with and without abnormal TRODAT-1 SPECT. Methods: By measuring the amplitude of motor evoked potentials (MEP), the cortical excitability changes after transcranial magnetic stimulation (TMS) were evaluated in 14 patients with RBD and eight healthy controls (HC). Seven of the 14 patients with RBD showed abnormal TRODAT-1 (TRA-RBD), and seven were normal (TRN-RBD). The tested parameters of cortical excitability include resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral silence period (CSP), and input-output recruitment curve. Results: The RMT and AMT showed no difference among the three studied groups. There was only SICI at inter-stimuli-interval 3 ms revealing group differences. The TRA-RBD demonstrated significant differences to HC in these aspects: decreased SICI, increased ICF, shortening of CSP, and augmented MEP amplitude at 100% RMT. Moreover, the TRA-RBD had a smaller MEP facilitation ratio at 50% and 100% of maximal voluntary contraction when compared to TRN-RBD. The TRN-RBD did not present any difference to HC. Conclusion: We showed that TRA-RBD shared similar cortical excitability changes with clinical PD. These findings would provide further insight into the concept that RBD is the highly prevalent entity in prodromal PD.

Oral presentation assessment and image reading behaviour on brain computed tomography reading in novice clinical learners: an eye-tracking study.

BACKGROUND: To study whether oral presentation (OP) assessment could reflect the novice learners' interpretation skills and reading behaviour on brain computed tomography (CT) reading. METHODS: Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students' reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. RESULTS: The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p < 0.001] improved after instruction. Both the scores of systematic OP ratings [0 vs.1 in both cases, p < 0.001] and eye-tracking studies (Case 1: 3.42 ± 0.62 and 3.67 ± 0.37 in TE, p = 0.001; Case 2: 3.42 ± 0.76 and 3.75 ± 0.37 in TE, p = 0.002) showed that the image reading behaviour changed before and after instruction. The results of linear mixed models suggested a significant interaction between instruction and area of interests for case 1 (p < 0.001) and case 2 (p = 0.004). Visual attention to the target lesions in the case 1 assessed by dwell time were 506.50 ± 509.06 and 374.38 ± 464.68 milliseconds before and after instruction (p = 0.02). However, the dwell times in the case 2, the fixation counts and the frequencies of accurate lesion diagnoses in both cases did not change after instruction. CONCLUSION: Our results showed OP performance may change concurrently with the medical students' reading behaviour on brain CT after a structured instruction.

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study.

BACKGROUND: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. METHODS: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. RESULTS: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. CONCLUSIONS: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

The severity progression of non-motor symptoms in Parkinson's disease: a 6-year longitudinal study in Taiwanese patients.

Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson's disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4-6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

Nonmotor symptoms of 820 Taiwanese patients with Parkinson's disease: an exploratory-comparative study.

INTRODUCTION: Nonmotor symptoms (NMSs) severely affect the daily quality of life of patients with Parkinson's disease (PD). Although many studies have documented the clinical characteristics of NMSs in PD patients, some issues remain unaddressed. The severity and gender distribution of NMSs in Asian and the Western patients differ. The correlations between clinical characteristics and NMS manifestations remain unclear. We studied these relationships in a large cohort of Taiwanese PD patients. METHODS: Patients with PD were recruited from the outpatient clinic of a tertiary medical center and evaluated with standardized assessment protocols, including the NonMotor Symptoms Scale (NMSS), Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, Mini-Mental Status Examination, and Montreal Cognitive Assessment. RESULTS: Among 820 patients enrolled, 41.8% were female. The prevalence of the NMSs was 96.5%, with attention/memory (79.51%) being the most frequently involved domain. The mean severity score on the NMSS was 36.48 ± 34.30. Male patients reported higher NMS prevalence and severity than female patients, mostly in the gastrointestinal tract and urinary domains. We found that the severity of NMSs was correlated with disease duration, UPDRS Part III score, and H&Y stage. CONCLUSION: Although they exhibited similar NMS prevalence, Taiwanese PD patients reported less intense NMSs compared with those reported by Western patients. Furthermore, the NMS items our patients emphasized and gender discrepancies were distinct from those in Western studies.

Sleep disturbances in Taiwanese patients with Parkinson's disease.

INTRODUCTION: Sleep disturbance is a common nonmotor symptom of Parkinson's disease (PD) and strongly affects patients' quality of life. The relationship between excessive daytime sleepiness (EDS) and nighttime problems remains uncertain. Arguments persist regarding the risk factors for sleep disturbance among patients with PD. Furthermore, the prevalence of EDS appears to be lower in Asian countries. Herein, we conducted the study to describe the characteristics of sleep problems in a sample of Taiwanese PD patients and delineate the difference with reported sleep disturbances in Caucasian PD patients from the literature. METHODS: Patients with PD were recruited from the outpatient clinic of a tertiary medical center and were evaluated using standardized assessment protocols, including the Parkinson's Disease Sleep Scale (PDSS), the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 39-Item Parkinson's Disease Questionnaire (PDQ-39). RESULTS: A total of 225 patients with PD were recruited. The mean age of patients with PD was 65.7 years old and the mean disease duration was 8.18 years. Among the patients, 53.8% were defined as poor sleepers (PSQI > 5) and 26.3% had EDS. Seventy-one percent of the poor sleepers used hypnotic medications. The poor sleepers were worse in the scores of Unified Parkinson's Disease Rating Scale (UPDRS), PDSS, and the PDQ-39, and received higher levodopa daily dosage. A PDSS score of <126 indicate that a patient with PD was a poor sleeper. EDS was positively correlated with advanced Hoehn and Yahr stages and use of dopamine agonists but not with levodopa daily dosage and levodopa equivalent daily dosage. CONCLUSIONS: Taiwanese patients with PD had a lower prevalence of EDS compared with the literatures reported in Caucasian patients. We identify and suggest that PDSS total score, rather than subcategory items, should be used to predict poor sleep among patients with PD.

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder.

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations.

Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is the second common neurodegenerative disease. Identification of biomarkers for early diagnosis and prediction of disease progression is important. The present comparative proteomic study of serum samples using two-dimensional fluorescence differential gel electrophoresis followed by ELISA confirmation demonstrated that protein expression of Rab35 was increased in PD patients compared with matched control subjects and other parkinsonian disorders, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). The serum level of Rab35 was significantly correlated with the age at onset of PD. The median age of onset in patients with higher Rab35 serum level was 5 years younger than those with lower Rab35 serum level. There was a positive correlation between the Rab35 level and disease duration of PD. Moreover, the protein expression of Rab35 was increased in the substantia nigra but not in the striatum of mouse models of PD, including MPTP-treated mice, rotenone-treated mice, (R1441C) LRRK2 or (G2019S) LRRK2 transgenic mice. Furthermore, overexpression of Rab35 increased the aggregation and secretion of mutant A53T α-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild-type or A53T α-synuclein in SH-SY5Y cells deteriorated cell death. Our results suggest that Rab35 is potentially useful in the differential diagnosis of parkinsonian disorders and is implicated in the pathogenesis of PD.

Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: a replication study in a Taiwanese cohort.

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative diseases and usually refers to a complex disorder with multiple genetic and environmental factors influencing disease risk. We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population. METHODS: 17 Single Nucleotide Polymorphisms (SNPs) markers located within SNCA gene as well as the 16 SNP markers within LRRK2 gene were chosen for genotyping and evaluated their haplotype structure in a cohort of sporadic PD patients and control individuals. RESULTS: This study showed that two SNPs near the promoter region (rs2301134 and rs2301135) of SNCA gene gave the greatest evidence for an association with PD (p ≤ 0.01) and a haplotype block with two SNPs in the 3' UTR (rs356221 and rs11931074) revealed another evidence of association (p ≤ 0.02). For the LRRK2 gene, only R1628P variants of total 16 SNPs giving a marginal significant association with PD across the whole gene (p = 0.0058) and no haplotype block was constructed. Many genetic variants (A419V, I1122V, R1441C, R1441G, R1441H, Y1699C, M1869V, M1869T, I2012T, G2019S, and I2020T) from previous reports were not detected in our cohort. CONCLUSIONS: We have replicated a population-based PD association study in a collection of 626 cases and 473 control subjects and confirm that genetic variants of both SNCA and LRRK2 genes are associated with susceptibility to sporadic PD but in a different distribution.

Visual selection and the human frontal eye fields: effects of frontal transcranial magnetic stimulation on partial report analyzed by Bundesen's theory of visual attention.

While the frontal eye fields (FEF) are traditionally associated with eye movements, recent work indicates possible roles in controlling selective visual processing. We applied 10 Hz bursts of transcranial magnetic stimulation (TMS) over left or right human FEF while subjects performed a partial-report task that allowed quantitative estimates of top-down control and other parameters affecting visual performance. Participants selectively reported digits in a relevant color (targets) but not those in an irrelevant color (nontargets) from a brief masked display. A target could appear alone or together with an accompanying item (nontarget or target) in the same or opposite hemifield. Targets were normally identified better when presented with a nontarget than with another target, indicating prioritization of task-relevant targets and thus top-down control. We found this usual pattern of results without TMS, and also with TMS over left FEF. However, during right FEF TMS, the detrimental impact of accompanying distractors increased. Formal analysis in terms of Bundesen's (1990) theory of visual attention confirmed that right FEF TMS diminished the top-down control parameter for both hemifields, indicating an FEF role in top-down selection even for targets defined by the nonspatial property of color. Direct comparison with our previous findings for parietal TMS (Hung et al., 2005) confirmed the distinct role of FEF in top-down control, plus right-hemisphere predominance for this in humans.

Asymmetric involvement in sporadic creutzfeldt-jakob disease: clinical, brain imaging, and electroencephalographic studies.

OBJECTIVE: To ascertain the characteristics of patients with sporadic Creutzfeldt-Jakob disease (CJD) and to determine the findings of electroencephalography (EEG) and brain magnetic resonance imaging (MRI). METHODS: We pooled patients at a hospital from 2000 to 2008, and classified them according to WHO diagnostic criteria as having probable or possible CJD. We retrospectively analyzed their clinical manifestations, brain MRI, and EEG findings to evaluate correlations among them. RESULTS: In this study, 12 probable and 4 possible CJD patients were identified. Ten patients with probable CJD had asymmetric manifestations with hemiparesis, focal myoclonus, dystonia or apraxia; 9 had clinical manifestations mimicking the corticobasal syndrome. In contrast, neurological examinations did not show asymmetric signs in 4 patients with possible CJD. EEG showed a typical periodic sharp wave complex (PSWC) in 12 patients with probable CJD; most of them had bright signal intensity on diffusion-weighted imaging of the cortex and/or basal ganglia. There was a high tendency for asymmetric clinical manifestations that correlated with the presentation of PSWC and cortical lesions observed on the brain MRI scan. CONCLUSIONS: Our study indicates that asymmetric extrapyramidal symptoms/signs, in clinical features with characteristic abnormalities on MRI and EEG findings, might contribute to early diagnosis of sporadic CJD.

The effect of continuous theta burst stimulation over premotor cortex on circuits in primary motor cortex and spinal cord.

OBJECTIVE: To understand the effect of continuous theta burst stimulation (cTBS) given to the premotor area, we studied the circuits within the primary motor cortex and spinal cord after cTBS over the dorsal premotor area (PMd). METHODS: Three sets of parameters, including corticospinal excitability, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) and forearm reciprocal inhibition (RI) were tested. RESULTS: Paralleling the effects of cTBS applied directly to the primary motor cortex, cTBS over the left PMd suppressed corticospinal excitability as measured by the change in the size of MEPs evoked by single pulse TMS over primary motor cortex. Premotor cTBS appeared to have a longer lasting, but no more powerful effect on corticospinal excitability than motor cTBS, however, unlike motor cTBS it had no effect on SICI or ICF. Finally, although premotor cTBS had no effect on spinal H-reflexes, it did reduce the third phase of RI between forearm extensor and flexor muscles. CONCLUSIONS: Premotor cTBS is a quick and useful way of modulating excitability in cortical and possibly subcortical motor circuits. SIGNIFICANCE: Premotor cTBS can be used as an alternative to regular rTMS to evaluate cortical function, motor behaviours and the response to disease therapy.

Agenesis of the corpus callosum in Turner's syndrome: report of a case and review of the literature.

Turner's syndrome (TS) is a genetic disorder caused by loss of entire or a substantial part of the X-chromosome, but association with central nervous system (CNS) abnormalities is rarely reported. A 32-year-old female with TS was found to have agenesis of the corpus callosum (ACC) and various clinical features including coarctation of aorta, hypertelorism, small jaw, short and webbed neck, cubitus valgus, and absence of the uterus. Karyotype analysis revealed X monosomy cell line (45, X). There have been only three other cases of TS associated with ACC. High prenatal lethality of TS fetuses with congenital CNS malformations may decrease the incidence of this association. Neuropsychological studies showed a normal intelligence neither prominent learning disability nor discrepancy between verbal and non-verbal items.

Visual selection and posterior parietal cortex: effects of repetitive transcranial magnetic stimulation on partial report analyzed by Bundesen's theory of visual attention.

Posterior parietal cortex (PPC) may contribute to visual selection by exerting top-down influences on visual processing. To seek direct evidence for this, we used 10 Hz repetitive transcranial magnetic stimulation (rTMS) over right or left PPC in nine healthy volunteers during a partial (selective) report task that allows quantitative assessment of top-down control and other parameters. Participants reported digits in a relevant color ("targets") but not those in an irrelevant color ("nontargets") from a brief masked display, in which a target could appear alone or together with an accompanying item (nontarget or target) in the same or opposite hemifield. Generally, a given target is identified better when presented with a nontarget than with another target, indicating top-down selection of task-relevant targets; this applied here with no rTMS or left PPC rTMS. However, rTMS over the right PPC changed the performance pattern. A left target no longer impeded report of a right target more strongly than did a left nontarget, whereas the greater impact of a right target than a right nontarget in disrupting report of a left target was increased. Formal analysis in terms of Bundesen's (1990) theory of visual attention indicated that right PPC rTMS diminished top-down control for the left hemifield while enhancing this for the right hemifield, particularly for bilateral two-item displays. These findings indicate a role for right PPC in top-down spatial selection, which applies even when the target is defined by a nonspatial property (here color).