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Pediatric Neurology Jun 2024Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes...
Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial.
BACKGROUND
Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia.
METHODS
This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years.
RESULTS
Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (-4.5 ± 2.9 vs -3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events.
CONCLUSION
A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.
PubMed: 38945037
DOI: 10.1016/j.pediatrneurol.2024.06.004 -
Archives of Physical Medicine and... Jun 2024To retrospectively evaluate the comparative effect of two wheelchair seating systems, Custom-Contoured Wheelchair Seating (CCS) and Modular Wheelchair Seating (MWS), on...
Effect of wheelchair seating systems on scoliosis progression for children with neurological and neuromuscular disorders: a retrospective study of Custom-Contoured Wheelchair Seating and Modular Wheelchair Seating.
OBJECTIVES
To retrospectively evaluate the comparative effect of two wheelchair seating systems, Custom-Contoured Wheelchair Seating (CCS) and Modular Wheelchair Seating (MWS), on scoliosis progression in children with neuromuscular and neurological disorders and to determine any predictors for scoliosis progression.
DESIGN
Longitudinal, retrospective cohort study SETTING: National Health Service regional posture and mobility service PARTICIPANTS: Non-ambulant paediatric wheelchair users with neuromuscular and neurological disorders (N = 75; 36 male, 39 female; mean age at seating intervention, 10.50 ± 3.97 years) issued CCS and MWS by the South Wales Posture and Mobility Service from 2012 to 2022.
INTERVENTIONS
Two specialized wheelchair seating systems, CCS and MWS.
MAIN OUTCOME MEASURES
A generalized least squares (GLS) model was used to estimate the effect of seat type on Cobb angle over time.
RESULTS
Of the 75 participants enrolled, 51% had cerebral palsy. Fifty were issued CCS and 25 were issued MWS. Baseline Cobb angle was 32.9±18.9° for the MWS group and 48.0±31.0° for the CCS group. The GLS model demonstrated that time since seating intervention (χ = 122, p < .0001), seating type (χ = 52.5, p < .0001), and baseline scoliosis severity (χ = 41.6, p < .0001) were predictive of scoliosis progression. Condition was not a strong predictor (χ = 9.96, p = .0069), and sex (χ = 5.67, p = .13) and age at intervention (χ = 4.47, p = .35) were not predictive. Estimated contrasts of medical condition with seat type over time demonstrated smaller differences between MWS and CCS over time. Predicted scoliosis velocity was found to attenuate with use of CCS over time compared to MWS, although, scoliosis deteriorated regardless of intervention.
CONCLUSIONS
Our findings showed paediatric wheelchair users with neurological and neuromuscular disorders prescribed CCS showed greater mitigation of scoliosis progression over time compared to those issued MWS.
PubMed: 38944100
DOI: 10.1016/j.apmr.2024.06.007 -
International Journal of Surgery Case... May 2024Primary intracranial neuroendocrine tumors (NETs) are exceedingly rare, often posing diagnostic challenges, particularly in non-secreting variants. These tumors may...
INTRODUCTION AND IMPORTANCE
Primary intracranial neuroendocrine tumors (NETs) are exceedingly rare, often posing diagnostic challenges, particularly in non-secreting variants. These tumors may initially present with nonspecific symptoms, leading to delayed diagnosis and potential neurological complications.
CASE REPORT
We present the case of a 33-year-old male admitted with a one-year history of progressively worsening headache accompanied by acute left ptosis and diplopia. Initial examination revealed left eye ptosis and hypotropia, indicative of third and fourth cranial nerve paralysis. Cavoscopy revealed a mild anterior wall bulge of the sphenoid with normal mucosa. MRI imaging unveiled an expansive clival process extending towards the sellar region and left cavernous sinus, completely occupying the sphenoid sinus and exerting mass effect on the pituitary stalk. Hormonal assays were within reference ranges, ruling out a hormonally-active tumor. Endoscopic endonasal surgery for biopsy revealed a low-grade neuroendocrine tumor positive for cytokeratin AE1/AE2, chromogranin A, synaptophysin, and beta-catenin, with a Ki-67-labeling index <2 %. Somatostatin receptor scintigraphy confirmed intense hyper fixation of the tracer in the sphenoidal tumor, supporting its neuroendocrine origin. The patient declined surgical intervention after informed consent, opting for C1 somatostatin analogs prior to radiotherapy. One-year follow-up demonstrated symptom stability with no tumor progression.
CLINICAL DISCUSSION
To this day, no consensus among reports concerning the optimal management of these cases. Imaging assessment is crucial to validate the primary nature of the tumor and to exclude any distant localization. Various therapeutic modalities, such as surgery, radiotherapy, and somatostatin analogs, should be considered based on the specific characteristics and extent of the tumor.
CONCLUSION
Our case is a clear reminder that neuroendocrine tumors should be considered as a differential diagnosis for skull base neoplasms.
PubMed: 38943936
DOI: 10.1016/j.ijscr.2024.109750 -
Journal of Clinical Neuroscience :... Jun 2024Aneurysms of the posterior cerebral circulation constitute a burdensome condition with high mortality and morbidity. In the modern era, there has been a trend toward...
When microsurgery becomes the only lifesaving resource: An institutional experience treating patients from low-income backgrounds affected by posterior circulation brain aneurysms.
BACKGROUND AND OBJECTIVE
Aneurysms of the posterior cerebral circulation constitute a burdensome condition with high mortality and morbidity. In the modern era, there has been a trend toward favoring an endovascular approach over microsurgery for aneurysm cases. Nevertheless, this transition has yet to be mirrored in low-to-middle-income countries where endovascular therapy may not be widely available. Herein, we aim to illustrate our experience treating these challenging conditions in patients from low-income backgrounds and discuss the relevance of the clinical setting in the treatment decision.
METHODS
The authors conducted a retrospective review of the health records of patients who received microsurgical treatment for aneurysms in the posterior circulation, including the basilar artery (BA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) in an institution providing treatment to people of low-income backgrounds. Epidemiological data, microsurgical technique, and neurological function were retrieved and analyzed.
RESULTS
Surgical clipping was employed for 12 patients (75% female) harboring 15 aneurysms (87% in the posterior circulation and 62% ruptured at presentation). Aneurysms were predominately located in the BA (69%), followed by the PCA (15%) and PICA (15%). Among neurological complications, 25% of patients developed oculomotor nerve palsy. The mortality rate was 17% owing to complications such as cerebral vasospasm, infarction, and severe intracranial hypertension. At the 6-month follow-up, 90% of patients had a good clinical outcome (modified Rankin scale scores of 0-2).
CONCLUSION
The present case series illustrates the manifest role of microsurgical techniques for posterior circulation aneurysms, particularly in a scenario where endovascular techniques are not easily accessible. Importantly, this clinical setting pressure could exhort trainees to strive for microsurgical mastery and gain a competitive advantage.
PubMed: 38943907
DOI: 10.1016/j.jocn.2024.06.014 -
Gait & Posture Jun 2024Many children with cerebral palsy (CP) show impairments in trunk posture control, one crucial factor contributing to impairments in gait and arm manipulation.
BACKGROUND
Many children with cerebral palsy (CP) show impairments in trunk posture control, one crucial factor contributing to impairments in gait and arm manipulation.
RESEARCH QUESTION
The goal of this study was to test the feasibility of the cable-driven hippotherapy system on improving trunk posture control and walking function in children with CP.
METHOD
Ten children were recruited in this study with average age 6.4 ± 3.0 years old, and were randomly assigned to the robotic group and the conventional balance training group. A custom designed cable-driven robotic hippotherapy system was used to deliver controlled pelvis perturbations while children were sitting astride. Participants from both groups underwent intensive robotic hippotherapy training or conventional balance training, depending on their group assignment, for 6 weeks (3 time/week). Outcome measures were assessed pre and post 6 weeks of robotic or conventional balance training, and 8 weeks after the end of training (follow-up test). The primary outcome measure was trunk control, which was measured using the Trunk Control Measurement Scale (TCMS). In addition, the Gross Motor Function Measure (GMFM-66), self-selected overground walking speed, and 6-minute walking distance were also assessed.
RESULTS
The change in TCMS score from baseline to the post intervention was significantly greater for the robotic group than that for the conventional group (i.e., 6 ± 3 vs. -1 ± 5, p = 0.048, Mann-Whitney test). GMFM scores, self-selected overground walking speed, and 6-minute walking distance showed no significant improvement after robotic hippotherapy and after conventional balance training (p > 0.05).
SIGNIFICANCE
Results from this study indicated that it was feasible to improve trunk posture control in children with CP using a cable-driven robotic hippotherapy system. Knowledge obtained from this study may provide an insight for the development of new perturbation-based intervention approaches for improving trunk posture control in children with CP.
PubMed: 38943825
DOI: 10.1016/j.gaitpost.2024.06.020 -
Pediatric Research Jun 2024Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the...
BACKGROUND
Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the myelinating cells of the central nervous system. Clemastine was previously shown to induce oligodendrocyte differentiation and myelination in mouse models of PWMI at a dose of 10 mg/kg/day. The minimum effective dose (MED) of clemastine is unknown. Identification of the MED is essential for maximizing safety and efficacy in neonatal clinical trials. We hypothesized that the MED in neonatal mice is lower than 10 mg/kg/day.
METHODS
Mouse pups were exposed to normoxia or hypoxia (10% FiO2) from postnatal day 3 (P3) through P10. Vehicle or clemastine at one of four doses (0.5, 2, 7.5 or 10 mg/kg/day) was given to hypoxia-exposed pups. Myelination was assessed at age P14 and 10 weeks to determine the MED. Clemastine pharmacokinetics were evaluated at steady-state on day 8 of treatment.
RESULTS
Clemastine rescued hypoxia-induced hypomyelination with a MED of 7.5 mg/kg/day. Pharmacokinetic analysis of the MED revealed C 44.0 ng/mL, t 4.6 h, and AUC 280.1 ng*hr/mL.
CONCLUSIONS
Based on these results, myelination-promoting exposures should be achievable with oral doses of clemastine in neonates with PWMI.
IMPACT
Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates. Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment. The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials. We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.
PubMed: 38942888
DOI: 10.1038/s41390-024-03326-w -
Heart, Lung & Circulation Jun 2024Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors,...
BACKGROUND
Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes.
METHOD
Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients.
RESULTS
A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36).
CONCLUSIONS
The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.
PubMed: 38942623
DOI: 10.1016/j.hlc.2024.04.167 -
BMJ Paediatrics Open Jun 2024Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic...
BACKGROUND
Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic medical conditions in Japan and explore factors leading to increased use of these devices.
METHODS
This retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Children receiving HHD aged ≤18 years between April 2011 and March 2019 were included. Children newly administered HHD between 2011 and 2013 were followed up for 5 years, and logistic regression analysis was performed to assess the relationship between increased HHD use and each selected risk factor (comorbidity or types of HHD). The models were adjusted for age category at home device introduction, sex and region.
RESULTS
Overall, 52 375 children receiving HHD were identified. The number (proportion) of children receiving HHD increased during the study period (11 556 [0.05%] in 2010 and 25 593 [0.13%] in 2018). The most commonly administered HHD was oxygen (51.0% in 2018). Among the 12 205 children receiving HHD followed up for 5 years, 70.4% and 68.3% who used oxygen or continuous positive airway pressure, respectively, were released from the devices, while only 25.8% who used mechanical ventilation were released from the device. The following diagnosis/comorbidities were associated with increased HHD use: other neurological diseases (OR): 2.85, 95% CI): 2.54-3.19), cerebral palsy (OR: 2.16, 95% CI: 1.87 to 2.49), congenital malformations of the nervous system (OR: 1.70, 95% CI: 1.34 to 2.13) and low birth weight (OR: 1.68, 95% CI: 1.41 to 2.00).
CONCLUSIONS
This study provides nationwide population-based empirical data to clarify the detailed information regarding children receiving HHD in Japan. This information could assist healthcare professionals in improving the quality of life of these children and their families and help health policymakers consider measures.
Topics: Humans; Japan; Retrospective Studies; Female; Male; Child; Home Care Services; Child, Preschool; Infant; Adolescent; Chronic Disease; Infant, Newborn
PubMed: 38942589
DOI: 10.1136/bmjpo-2024-002685 -
Experimental Neurology Jun 2024Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective...
Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective therapeutic strategies to ameliorate these chronic learning and memory impairments after TBI are limited. Two pharmacological targets for enhancing cognition are nicotinic acetylcholine receptors (nAChRs) and GABA receptors (GABARs), both of which regulate hippocampal network activity to form declarative memories. A promising compound, 522-054, both allosterically enhances α7 nAChRs and inhibits α5 subunit-containing GABARs. Administration of 522-054 enhances long-term potentiation (LTP) and cognitive functioning in non-injured animals. In this study, we assessed the effects of 522-054 on hippocampal synaptic plasticity and learning and memory deficits in the chronic post-TBI recovery period. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 12 wk after injury, we assessed basal synaptic transmission and LTP at the Schaffer collateral-CA1 synapse of the hippocampus. Bath application of 522-054 to hippocampal slices reduced deficits in basal synaptic transmission and recovered TBI-induced impairments in LTP. Moreover, treatment of animals with 522-054 at 12 wk post-TBI improved cue and contextual fear memory and water maze acquisition and retention without a measurable effect on cortical or hippocampal atrophy. These results suggest that dual allosteric modulation of α7 nAChR and α5 GABAR signaling may be a potential therapy for treating cognitive deficits during chronic recovery from TBI.
PubMed: 38942266
DOI: 10.1016/j.expneurol.2024.114879 -
Journal of Clinical Neuroscience :... Jun 2024Patients with spinal meningioma may present preoperatively with paralysis and sensory deficits. However, there is a paucity of detailed evaluations and a lack of...
BACKGROUND
Patients with spinal meningioma may present preoperatively with paralysis and sensory deficits. However, there is a paucity of detailed evaluations and a lack of consensus regarding imaging findings that are predictive of neurological symptoms in patients with spinal meningioma.
METHODS
Herein, a total of 55 patients who underwent surgical resection of spinal meningiomas in eight hospitals between 2011 and 2021 were enrolled. Patient characteristics, degree of muscle weakness, sensory disturbances, and the presence of bowel/bladder dysfunction (BBD) before surgical treatment were evaluated using medical records. Patients with American Spinal Injury Impairment Scale grades A-C and the presence of BBD were classified into the paralysis (+) group. Patients with sensory disturbances were assigned to the sensory disturbance (+) group. Based on magnetic resonance (MR) and computed tomography images, the tumor location was classified according to the spinal level and its attachment to the dura mater. To evaluate tumor size, the tumor occupation ratio (OR) was calculated using the area and distance measurement method in horizontal MR images, and the maximum length and area of the tumor in the sagittal plane were measured.
RESULTS
Of all patients, 85 % were women. The mean age of patients at surgery was 69.7 years. Twenty-eight (51 %) and 41 (75 %) patients were classified into the paralysis (+) and sensory disturbance (+) groups, respectively. The average tumor length and area in the sagittal plane were 19.6 mm and 203 mm, respectively; OR-area and diameters were 70.3 % and 72.3 %, respectively. In univariate analyses, tumor length and area in the sagittal plane were significant risk factors for paralysis. OR-diameter, symptom duration, and a low MIB-1 index correlated with sensory disturbances. Multivariate logistic regression analysis demonstrated that the area and length of the tumor in the sagittal plane were significantly correlated with paralysis, whereas the OR-diameter and symptom duration significantly correlated with sensory disturbances. The cut-off values for the area and length of the tumor in the sagittal plane to predict paralysis were 243 mm and 20.1 mm, respectively.
CONCLUSIONS
Preoperative paralysis in patients with spinal meningiomas was significantly associated with sagittal tumor size than with high tumor occupancy in the horizontal plane. Sensory disturbances were associated with high occupancy in the horizontal plane. Patients with spinal meningiomas > 20 mm in length or 243 mm in area in the sagittal plane are at risk of developing paralysis and could be considered for surgery even in the absence of paralysis.
PubMed: 38941916
DOI: 10.1016/j.jocn.2024.06.021