Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes.

OBJECTIVE: To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. METHODS: In this nationwide program, 669,797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. RESULTS: After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid α-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 ± 1.3 months, the same age as normal children. CONCLUSIONS: ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes.

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study.

OBJECTIVE: To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). DESIGN: A sham-controlled, double-blind parallel study design. SETTING: A tertiary hospital. PARTICIPANTS: People with stroke (N=72) who presented with unilateral hemiplegia. INTERVENTIONS: Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP-) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. MAIN OUTCOME MEASURES: Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. RESULTS: MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P<.001), followed by group B (MEP-, MRC>1; 5.2±2.2 score change) and group C (MEP-, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. CONCLUSIONS: The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines.

A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment.

The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m(2)). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes.

Intraoperative brain mapping to identify corticospinal projections during resective epilepsy surgery in children with congenital hemiparesis.

PURPOSE: The purpose of the study is to determine corticospinal organization using intraoperative neurophysiologic monitoring (IONM) during resective epilepsy surgery for patients with congenital hemiparesis and intractable epilepsy. METHODS: Ten patients, aged 3-17, with intractable epilepsy underwent resective surgery. Transcranial stimulation (TCS) was achieved using a pair of cork screws at Cz and C3/C4, respectively. A 1 × 4 stimulating electrode strip was placed on the presumed motor cortex of the affected hemisphere for direct cortical stimulation (DCS) after craniotomy. Multipulse TCS and DCS train stimulation was delivered, with simultaneous recordings from bilateral abductor pollicis brevis and abductor halluces, to determine the corticospinal projection pattern of the paretic limbs. RESULTS: The above mapping techniques revealed ipsilateral corticospinal projections from the contralesional hemisphere to target muscles in the paretic limbs in three patients, projections from both hemispheres to target muscles in three, and preserved crossed projections from the affected hemisphere in four. Nine patients were seizure free after surgery. Five had unchanged postoperative functional status, and three showed minimally improved use of the paretic hand. Two developed new motor deficits after surgery, which may have been due to a premotor syndrome in one patient, since it completely resolved within 2 weeks. The other experienced increased weakness of the paretic lower limb because a small part of the eloquent cortex was removed for better seizure control. CONCLUSIONS: Using IONM to define the corticospinal projection pattern is a valuable technique that can potentially replace preoperative fMRI and transcranial magnetic stimulation in resective epilepsy surgery, particularly for younger patients.

Health-related quality of life in children and adolescents with spinal dysraphism: results from a Taiwanese sample.

PURPOSE: This study was designed to investigate health-related quality of life (HRQL) in children and adolescents with spinal dysraphism and to determine the differences between the myelomeningocele (MMC) and lipomyelomeningocele (LMMC) groups. METHODS: Thirty-two patients (mean age, 13.2 years) with MMC and 28 patients (mean age, 11.3 years) with LMMC participated in this study. HRQL was measured using the Child Health Questionnaire-Parent Form 50 (CHQ-PF50). The CHQ-PF50 scores for the study participants were compared with those of a reference sample of healthy Taiwanese children. Outcomes for children with MMC were compared with those for children with LMMC. We also explored the relationships of the lesion level and associated medical problems with HRQL in these subjects. RESULTS: Patients with MMC had significantly lower scores on the physical and psychosocial aspects of CHQ-PF50 than did healthy children. Patients with LMMC had lower scores on some domains but had comparable psychosocial summary scores. Significant differences were noted between the MMC and LMMC groups for all subscales and both summary scores. Children with a higher lesion level had poor physical health (r = -0.52, P < 0.001) but not poor psychosocial health. The number of associated medical problems, indicating their severity, was related to both physical (r = -0.77, P < 0.001) and psychosocial health (r = -0.57, P < 0.001). CONCLUSIONS: Children and adolescents with MMC have reduced HRQL compared with those with LMMC. Children and adolescents with more associated medical problems have the greatest risk of diminished physical and psychosocial well-being.

Ultrasound-guided refilling of an intrathecal baclofen pump--a case report.

INTRODUCTION: Refilling intrathecal baclofen (ITB) pumps can be difficult because many patients gain excessive weight after implantation due to their reduced expenditure of energy on muscle spasticity. METHODS: We report a case of a 12-year-old girl with spastic quadriplegia who gained 20 lbs after pump implantation. It was necessary to identify the access port of her pump by ultrasonography during drug refilling so as to avoid multiple needle punctures. RESULTS: The access port of the pump was readily visible by ultrasonography and stood out from other parts of the pump. CONCLUSION: Localisation of the access ports of ITB pumps by ultrasonography proved to be a feasible and easy technique for refilling the drug reservoir in patients with excessive weight gain and abundant subcutaneous fat after ITB therapy.

Methylmalonic acidemia/propionic acidemia - the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups.

BACKGROUND: Most patients with isolated methylmalonic acidemia (MMA) /propionic acidemia (PA) presenting during the neonatal period with acute metabolic distress are at risk for death and significant neurodevelopmental disability. The nationwide newborn screening for MMA/PA has been in place in Taiwan from January, 2000 and data was collected until December, 2016. RESULTS: During the study period, 3,155,263 newborns were screened. The overall incidence of MMA mutase type cases was 1/121,356 (n = 26), 1 cobalamin B was detected and that for PA cases (n = 4) was 1/788,816. The time of referral is 8.8 days for MMA patients, and 7.5 days for PA patients. The MMA mutase type patients have higher AST, ALT, and NH3 values as well as a lower pH value (p < 0.05). The mean age for liver transplantation (LT) is 402 days (range from 0.6-6.7 yr) with 16 out of 20 cases (80.0%) using living donors. The mean admission length shortened from 90.6 days/year (pre-LT) to 5.3 days/year (at 3rd year post-LT) (p < 0.0005). Similarly, the tube feeding ratio decreased from 67.8 to 0.50% (p < 0.00005). The anxiety level of the caregiver was reduced from 33.4 to 27.2 after LT (p = 0.001) and the DQ/IQ performance of the patients was improved after LT from 50 to 60.1 (p = 0.07). CONCLUSION: MMA/PA patients with LT do survive and have reduced admission time, reduced tube feeding and the caregiver is less anxious.

EMG changes during graded isometric exercise in pianists: comparison with non-musicians.

BACKGROUND: Long-term piano training might induce some biochemical and structural adaptations in the intrinsic muscles of the hand or change the motor strategy of the nervous system. The main purpose of this study was to analyze whether the intrinsic muscles of the hands of pianists and sedentary controls differ in electromyographic characteristics at different strengths. METHODS: Fifteen college piano students and 15 sedentary controls were asked to sit on an examination bench and perform first dorsal interosseous muscle contractions for 1 minute. The motor unit potentials were recorded during various percentages of maximal voluntary muscle contraction (MVC) by automatic decomposition electromyography. RESULTS: The pianists demonstrated a significantly higher firing rate, shorter duration, and higher amplitude of motor unit potentials during minimal muscle contractions than the sedentary controls. But when comparing all the parameters at other degrees of contractions, the pianists were found to have significantly higher firing rate only at 25% and 50% of MVC, and higher amplitude at maximal contraction than the control group. The amplitude at maximal control contraction was higher in pianists than in controls. CONCLUSION: These results imply that high-frequency and highly efficient muscle fibers are recruited in pianists when minimal muscle contractions are performed, which also indicate that by using smaller motor units, pianists may delicately control their fine motor performance.

Longitudinal changes in health-related quality of life in preschool children with cerebral palsy of different levels of motor severity.

BACKGROUND: When setting goals for cerebral palsy (CP) interventions, health-related quality of life (HRQoL) is an important outcome. AIMS: To compare longitudinal changes in HRQoL in children with CP of different levels of motor severity. METHODS AND PROCEDURES: Seventy-three children with CP were collected and classified into three groups based on Gross Motor Function Classification System (GMFCS) levels. HRQoL was assessed by parent's proxy of the TNO-AZL Preschool Quality of Life (TAPQOL) at baseline and 6 months later. OUTCOMES AND RESULTS: Children with GMFCS level V had a lower total TAPQOL score and scores in all domains than those with level I-IV (p<0.01), except for the non-motor subdomain of physical functioning at follow-up. With regards to longitudinal changes, the children with GMFCS level V had greater improvements in physical (p=0.016) and cognitive functioning (p=0.042), but greater deterioration in emotional functioning (p=0.008) than those with levels I-II at 6 months of follow-up. CONCLUSIONS AND IMPLICATIONS: Motor severity was associated with TAPQOL scores in all domains and changes in some domains in children with CP. Clinicians should early identify children at risk of a poor HRQoL and plan timely treatment strategies to enhance the HRQoL of children with CP.

Effects of action observation therapy and mirror therapy after stroke on rehabilitation outcomes and neural mechanisms by MEG: study protocol for a randomized controlled trial.

BACKGROUND: Loss of upper-extremity motor function is one of the most debilitating deficits following stroke. Two promising treatment approaches, action observation therapy (AOT) and mirror therapy (MT), aim to enhance motor learning and promote neural reorganization in patients through different afferent inputs and patterns of visual feedback. Both approaches involve different patterns of motor observation, imitation, and execution but share some similar neural bases of the mirror neuron system. AOT and MT used in stroke rehabilitation may confer differential benefits and neural activities that remain to be determined. This clinical trial aims to investigate and compare treatment effects and neural activity changes of AOT and MT with those of the control intervention in patients with subacute stroke. METHODS/DESIGN: An estimated total of 90 patients with subacute stroke will be recruited for this study. All participants will be randomly assigned to receive AOT, MT, or control intervention for a 3-week training period (15 sessions). Outcome measurements will be taken at baseline, immediately after treatment, and at the 3-month follow-up. For the magnetoencephalography (MEG) study, we anticipate that we will recruit 12 to 15 patients per group. The primary outcome will be the Fugl-Meyer Assessment score. Secondary outcomes will include the modified Rankin Scale, the Box and Block Test, the ABILHAND questionnaire, the Questionnaire Upon Mental Imagery, the Functional Independence Measure, activity monitors, the Stroke Impact Scale version 3.0, and MEG signals. DISCUSSION: This clinical trial will provide scientific evidence of treatment effects on motor, functional outcomes, and neural activity mechanisms after AOT and MT in patients with subacute stroke. Further application and use of AOT and MT may include telerehabilitation or home-based rehabilitation through web-based or video teaching. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02871700 . Registered on 1 August 2016.

Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes.

BACKGROUND: Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date. METHODS: Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness. Clinical, laboratory, and neuroimaging data were analyzed. RESULTS: Fourteen newborns were diagnosed with GA-1 (incidence: 1/106,474). C5DC concentration was clearly increased after carnitine loading in the affected newborns, but not in false-positive newborns (p = 0.004), indicating that this test is useful as an adjuvant diagnostic method. Eleven patients followed in our hospital were enrolled, namely nine NBS patients and two patients diagnosed clinically. IVS10-2A>C was the most common mutation. Two novel mutations (T36fs and N291K) were identified. Pendular nystagmus was found in two pediatric GA-1 patients. The corresponding pathology was optic atrophy in one patient, but remained undetermined in the other patient. The frequency of encephalopathic crisis decreased substantially following NBS. Among patients diagnosed by NBS, cognitive functioning was better among patients with good compliance than patients with poor compliance (p = 0.03). Abnormalities were detected by brain MRI including diffusion-weighted imaging and apparent diffusion coefficient maps; these affected various brain regions at different stages of the disease. Basal ganglion injuries occurred after an encephalopathic crisis. White matter disease was prevalent among older patients, either with or without an encephalopathic crisis. CONCLUSION: Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome.

Complex regional pain syndrome after transradial cardiac catheterization.

Complex regional pain syndrome (CRPS) is a disease with unclear pathophysiology. The condition is characterized by pain, soft tissue change, vasomotor change, and even psychosocial disturbance. It may affect the upper more than the lower extremities, and the distal more than the proximal. The trigger factors include carpal tunnel release, Dupuytren's repair, tendon release procedures, knee surgery, crush injury, ankle arthrodesis, amputation, and hip arthroplasty. Rarely, it has been associated with stroke, mastectomy, pregnancy, and osteogenesis imperfecta. Herein, we present a rare case of a patient who was diagnosed with CRPS after transradial cardiac catheterization. CRPS was first diagnosed due to hand swelling, allodynia, paresthesia, and the limited range of motion of interphalangeal, metacarpophalangeal, and wrist joints, with the preceding factor of transradial cardiac catheterization, and was then confirmed by a three-phase bone scan. After intensive physical therapy with hydrotherapy, manual soft tissue release, and occupational therapy for the hand function, there was much improvement in range of motion and hand function. There was no allodynia or painful sensation in the follow-up. After training, the functional status of this patient was adequate for daily activity.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

Effect of pillow size preference on extensor digitorum communis muscle strength and electromyographic activity during maximal contraction in healthy individuals: a pilot study.

BACKGROUND: Cervical pillow height is an important factor that affects the perception of pillow comfort. However, few studies have addressed methods for predicting a patient's preferred cervical pillow size. We studied the effect of pillow size preference on the strength and electromyographic (EMG) signals of the upper extremity muscle. If the response of the upper extremity muscle is affected by pillow size preference, this would aid in devising an alternate strategy for selecting the optimal pillow size. METHODS: Twenty-nine healthy individuals (mean age: 28.6 years, range: 24-55 years) participated in this study. The participants performed isometric maximal finger extension in the supine position with their heads supported on four different size preferences of cervical pillow (the most comfortable, next most comfortable, worst, and next worst). Maximal contraction force and peak-to-peak EMG amplitude of the extensor digitorum communis (EDC) during contraction were measured. One-way repeated-measures analysis of variance was used to evaluate the effect of pillow size preference. We also explored the relationship between anthropometric parameters and the individual's cervical pillow height preference. RESULTS: The two most comfortable pillows were associated with significantly larger maximal EDC force than the two worst pillows. However, no significant differences in EMG were observed between pillows. No statistically significant correlation was found between anthropometric parameters and pillow height preference. CONCLUSION: The results suggest that anatomical body measurements are not good predictors of optimal pillow height. As EDC muscle strength is affected by pillow height preference, maximal EDC muscle strength may be a useful complement for selecting the optimal pillow size.

Pediatric aquatic therapy on motor function and enjoyment in children diagnosed with cerebral palsy of various motor severities.

This study investigates the effects of pediatric aquatic therapy on motor function, enjoyment, activities of daily living, and health-related quality of life for children with spastic cerebral palsy of various motor severities. Children with spastic cerebral palsy were assigned to a pediatric aquatic therapy group (n = 11; mean age = 85.0 ± 33.1 months; male : female = 4 : 7) or a control group (n = 13; mean age = 87.6 ± 34.0 months; male : female = 9 : 4). The statistic results indicate that the pediatric aquatic therapy group had greater average 66-item Gross Motor Function Measure following intervention than the control group (η(2) = 0.308, P = .007), even for children with Gross Motor Function Classification System level IV (5.0 vs 1.3). The pediatric aquatic therapy group had higher Physical Activity Enjoyment Scale scores than the control group at post-treatment (P = .015). These findings demonstrate that pediatric aquatic therapy can be an effective and alternative therapy for children with cerebral palsy even with poor Gross Motor Function Classification System level.

Localization of the cricothyroid muscle under ultrasound guidance for vagal nerve mapping.

During surgical removal of tumors of the skull base or cerebellopontine angle with brainstem compression, the vagus nerve is at a high risk for injury that can result in permanent or transient swallowing and speech dysfunction. Intramuscular recording of cricothyroid muscle can be used for vagal nerve mapping during intraoperative neurophysiologic monitoring so as to prevent the above complications. However, it is a small muscle that lies beneath the strap muscles over the anterior neck and is not easily accessible by a blind approach. Here, we present a case in which cricothyroid muscle was identified for precise electrode placement under ultrasound guidance during preparation for intraoperative monitoring. We concluded that localization of the cricothyroid muscle by ultrasonography proved to be a feasible and easy technique, and the compound muscle action potential recorded by this approach is clearly recognizable during intraoperative vagal nerve mapping.