Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

Sleep apnea patients with epiglottic collapse elevate their larynx more with swallowing; videofluoroscopic swallowing study of 80 patients.

OBJECTIVE: The epiglottis plays an integral role in the swallowing mechanism and is also implicated as an obstruction site in obstructive sleep apnea (OSA). The underlying causes of epiglottic collapse during sleep remain unclear. This study aimed to investigate the cognitive functions using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the neurophysiological and anatomical factors using videofluoroscopic swallowing studies (VFSS). We compared patients with OSA exhibiting epiglottic collapse to those without, assessing differences in anatomical or neurophysiological characteristics. METHODS: The study included 12 patients with epiglottic collapse (Epi-group) and 68 without (non-Epi group), all undergoing overnight polysomnography (PSG), drug-induced sleep endoscopy (DISE), LOTCA, and VFSS. Oral transit time (OTT), pharyngeal delay time (PDT), and pharyngeal transit time (PTT) were considered as neurophysiological traits, and laryngeal elevation length (LE) as anatomical trait, and were measured across various test diets (10 ml of liquid, soft, or solid). RESULTS: The study comprised 80 individuals, 57 men and 23 women, with no significant age, sex, body mass index or PSG parameters between groups, or DISE findings, with the exception of epiglottic collapse. Swallowing metrics from VFSS were normal, with no differences in OTT, PDT, PTT, or LOTCA scores. Notably, patients with epiglottic collapse showed a greater laryngeal elevation when swallowing soft and solid foods (p = 0.025 and p = 0.048, respectively). CONCLUSIONS: Patients with epiglottic collapse do not exhibit neurophysiological or cognitive impairments when compared to non-Epi group. However, the Epi-group displayed a significantly increased laryngeal elevation length. This suggests that anatomical factors may have a more substantial role in the development of epiglottic collapse than neurophysiological factors.

Predictors of Burden for First-Ever Stroke Survivor's Long-Term Caregivers: A Study of KOSCO.

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

Intrathecal Baclofen Injection Efficacy for Spasticity Management in Patients With Stroke: A Meta-Analysis.

Although intrathecal baclofen injections have been used for spasticity management regarding stroke, spinal cord injury, and central nervous system diseases, their relative efficacy is controversial. This systematic review scoured 3 multinational electronic databases (Cochrane Library, MEDLINE, and Embase) to isolate relevant studies. We analyzed non-randomized studies and randomized control trials (RCTs) with direct comparisons against other spasticity management interventions for adult stroke patients. Risk of Bias (RoB) and the Risk of Bias Assessment tool for Non-randomized Studies evaluations were implemented with Cochrane's RoB tool. Meta-analysis was performed with Revman 5.4, and evidence validity was assessed with the Grading of Recommendations, Assessment, Development, and Evaluations method. Lastly, the intrathecal baclofen injection meta-analysis included 2 RCTs and 7 non-RCTs for assessing spasticity and 4 non-RCTs to measure gait velocity. Based on this data, intrathecal baclofen injection significantly impacted spasticity and gait speed. Thus, intrathecal baclofen injection can potentially treat severe spasticity unresponsive to conventional spasticity therapy. Furthermore, clinicians must consider individual patient characteristics and conditions when contemplating intrathecal baclofen injection for spasticity intervention.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Overground Gait Training With a Wearable Robot in Children With Cerebral Palsy: A Randomized Clinical Trial.

Importance: Cerebral palsy (CP) is the most common developmental motor disorder in children. Robot-assisted gait training (RAGT) using a wearable robot can provide intensive overground walking experience. Objective: To investigate the effectiveness of overground RAGT in children with CP using an untethered, torque-assisted, wearable exoskeletal robot. Design, Setting, and Participants: This multicenter, single-blind randomized clinical trial was conducted from September 1, 2021, to March 31, 2023, at 5 rehabilitation institutions in Korea. Ninety children with CP in Gross Motor Function Classification System levels II to IV were randomized. Intervention: The RAGT group underwent 18 sessions of RAGT during 6 weeks, whereas the control group received standard physical therapy for the same number of sessions during the same period. Main Outcome and Measures: The primary outcome measure was the Gross Motor Function Measure 88 (GMFM-88) score. Secondary outcome measures were the GMFM-66, Pediatric Balance Scale, selective control assessment of the lower extremity, Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), 6-minute walking test scores (distance and oxygen consumption), muscle and fat mass via bioelectrical impedance analysis, and gait parameters measured via 3-dimensional analysis. All assessments were performed for all patients at baseline, at the end of the 6-week intervention, and after the 4-week follow-up. Results: Of the 90 children (mean [SD] age, 9.51 [2.48] years; 49 [54.4%] male and 41 [45.6%] female) in the study, 78 (86.7%) completed the intervention, with 37 participants (mean [SD] age, 9.57 [2.38] years; 19 [51.4%] male) and 41 participants (mean [SD] age, 9.32 [2.37] years; 26 [63.4%] male) randomly assigned to the RAGT and control groups, respectively. Changes in the RAGT group significantly exceeded changes in the control group in GMFM-88 total (mean difference, 2.64; 95% CI, 0.50-4.78), GMFM-E (mean difference, 2.70; 95% CI, 0.08-5.33), GMFM-66 (mean difference, 1.31; 95% CI, 0.01-2.60), and PEDI-CAT responsibility domain scores (mean difference, 2.52; 95% CI, 0.42-4.63), indicating independence in daily living at postintervention assessment. At the 4-week follow-up, the RAGT group showed significantly greater improvements in balance control (mean difference, 1.48; 95% CI, 0.03-2.94) and Gait Deviation Index (mean difference, 6.48; 95% CI, 2.77-10.19) compared with the control group. Conclusions and Relevance: In this randomized clinical trial, overground RAGT using a wearable robot significantly improved gross motor function and gait pattern. This new torque-assisted wearable exoskeletal robot, based on assist-as-needed control, may complement standard rehabilitation by providing adequate assistance and therapeutic support to children with CP. Trial Registration: CRIS Identifier: KCT0006273.

The Effect of Repetitive Transcranial Magnetic Stimulation on Cognition in Diffuse Axonal Injury in a Rat Model.

Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague-Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI.

Long-Term Functional Outcome in Patients With Isolated Thalamic Stroke: The KOSCO Study.

BACKGROUND: Information on the long-term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. METHODS AND RESULTS: Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (P<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability. CONCLUSIONS: Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long-term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.

Association between Height and Functional Outcomes of Patients 6 Months after a Stroke: A Multicenter Prospective Observational Cohort Study.

Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.