Permanent Visual Impairment due to Delayed Diagnosis of Shunt Malfunction in Case of Lack of Typical Features of Increased Intracranial Pressure and Unchanged Ventricular Size.

OBJECTIVE: We present the clinical features, imaging, and management of 5 cases of visual impairment as the primary manifestation ventriculoperitoneal (V-P) shunt malfunction. METHODS: We retrospectively reviewed the medical records of 126 patients of V-P shunt malfunction in Shanghai Children's Medical Center between 2015 and 2020. Medical records including all hospital admissions were reviewed and follow-up data were collected. RESULTS: Five children (3.97%) had visual impairment as the primary manifestation of V-P shunt malfunction, with a mild or no headache. Four broken distal shunt catheters and one proximal catheter blockage were confirmed intraoperatively and cured by surgery. None of the patients had a definite improvement in ophthalmic examinations after 4-52 months of follow-up. CONCLUSION: Visual impairment as the primary manifestation of V-P shunt malfunction was uncommon and could be easily missed or misdiagnosed as the only problem for lack of typical features of increased intracranial pressure and unchanged ventricular size. Earlier definitive diagnosis and surgical intervention could prevent a further development of the visual loss caused by V-P shunt malfunction.

Surgical Treatment of Congenital Dermal Sinus: An Experience of 56 Cases.

OBJECTIVE: This study aims to assess the impact of early diagnosis and surgery on children with congenital dermal sinus, investigate the relationship between MRI findings and extent of surgical exploration, and summarize our clinical experience with the surgical management in cases with central nervous system (CNS) infection. METHODS: The skin features, preoperative MRI images, intraoperative findings, postoperative pathological characteristics, and prognoses of 56 children with congenital dermal sinus were analyzed retrospectively. RESULTS: All the children had a pinpoint ostium in the skin, and 52 out of the 56 children (92.9%) had intraspinal dermoid cysts or epidermoid cysts. Before surgery, MRI did not show intraspinal lesions in 13 children, and surgery revealed intradural lesions in 9 of these children (69.2%). Among 46 children without CNS infection, 16 children had neurological impairment before surgery. After surgery, recovery was complete in 36 children, partial in 9 children, and absent in 3 children. All children with CNS infection had neurological impairment before surgery. After surgery, the condition improved in 8 children and exacerbated in 2 children. Children without CNS infection had statistically significantly better prognosis than children with CNS infection (p = 0.03). CONCLUSION: A pinpoint ostium in the dorsal midline is the characteristic feature of congenital dermal sinus. In cases without intraspinal lesions on MRI, the spinal canal should be explored intraoperatively to ensure complete removal of the lesion and prevent recurrences. In cases without CNS infection, early diagnosis and timely surgery are beneficial to the recovery of nerve function.

Bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap technique for nonsyndromic unilateral coronal synostosis.

Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.

High-yield ectoine production in engineered Corynebacterium glutamicum by fine metabolic regulation via plug-in repressor library.

Ectoine is a high-value protective and stabilizing agent with different applications in biopharmaceuticals, biotechnology, and fine chemicals. Here, efficient production of ectoine in Corynebacterium glutamicum was achieved by combination of metabolic engineering and plug-in repressor library strategy. First, the ectBAC cluster from Pseudomonas stutzeri was introduced into strain K02, and the titer of the obtained strain was 2.12 g/L. Metabolic engineering was then performed for further optimization, including removal of competing pathways (pck and ldh knockout), deletion of glycolysis repressor (sugR knockout), and enhancement of precursor supply (overexpression of Ecasd and CglysCS301Y). Next, two repressor libraries were designed for targeted flux control to improve ectoine production. Finally, strain CB5L6 produced 45.52 g/L ectoine and had the highest yield in C. glutamicum. For the first time, plug-in repressor library was employed to engineer C. glutamicum for metabolites production, which will provide a guideline for the construction of microbial cell factories.

Subthalamic deep brain stimulation for refractory Gilles de la Tourette's syndrome: clinical outcome and functional connectivity.

BACKGROUND: Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette's syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated. METHODS: Ten patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive-compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset. RESULTS: The overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices. CONCLUSIONS: STN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.

Preventive surgery for asymptomatic spinal lipomas in children.

AIM: To explore the clinical effect and significance of preventive surgery of asymptomatic spinal lipo-mas in children. MATERIAL AND METHODS: We retrospective analysis of clinical data of 168 cases with asymptomatic spinal lipoma from April 2001 to June 2019 in our hospital. The patients were aged from 1.5 months to 15 years (the average age was 7 months), and there were no neurological symptoms such as pain, incontinence, and / or bilateral lower limb dysfunction before surgery. The surgical proce-dure included: completely removed the lipomas in subcutaneous and extramedullary tissues of the spinal cord, subtotal resection of intraspinal fat, cutting and separating the spinal cord including the medullary cones from the dura sac to release the tethered cord. RESULTS: For the 168 children with spinal lipomas included in the study, complete resection was undertaken for the dorsal spinal lipomas , subtotal resection was taken for the transitional and chaotic spinal lipomas .Subcutaneous effusion caused by cerebrospinal fluid leakage occurred in 5 cases after surgery, which was cured after multiple puncture and aspiration. Six patients developed mild in-continence immediately after the operation, 5 of whom completely returned to normal within 1 month, and 1 had no relief of symptoms.159 of the 168 patients were followed up for 3 to 19 years (the median follow-up time was 76 months). Long-term postoperative symptoms occurred in 13 patients (7.7%), including 12 cases of spinal cord retethering and 1 case of lipoma enlargement. CONCLUSION: Preventive surgery can reduce the incidence of neurological dysfunction in children with asymp-tomatic spinal lipomas in the future.

Pallidal stimulation as treatment for camptocormia in Parkinson's disease.

Camptocormia is a common and often debilitating postural deformity in Parkinson's disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.

Subthalamic Stimulation for Camptocormia in Parkinson's Disease: Association of Volume of Tissue Activated and Structural Connectivity with Clinical Effectiveness.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been reported to be effective for camptocormia in Parkinson's disease (PD). However, the association between clinical effectiveness and the stimulated volumes or structural connectivity remains unexplored. OBJECTIVE: To investigate the effectiveness of STN-DBS for treating camptocormia in PD and its association with volumes of tissue activated (VTA) and structural connectivity. METHODS: We reviewed video recordings of patients who had undergone STN-DBS. The total and upper camptocormia (TCC and UCC) angles were measured to quantify changes in camptocormia. The Movement Disorders Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) was used to assess motor symptoms. Pre- and postoperative brain images were collected for modeling volume of VTA and structural connectivity using Lead-DBS software. RESULTS: Participants included 36 patients with PD (8 with TCC-camptocormia and 2 with UCC-camptocormia) treated with bilateral STN-DBS. After surgery, patients showed a significant improvement in postural alignment at follow-up (mean follow-up duration: 6.0±2.2 months). In the entire sample, higher structural connectivity to the right supplementary motor area (SMA) and right lateral premotor cortex along the dorsal plane (PMd) was associated with larger postsurgical improvements in axial signs and TCC angles after stimulation was turned on. In patients diagnosed with camptocormia, larger improvement in camptocormia angles after STN-DBS was associated with a larger VTA overlap with STN (R = 0.75, p = 0.032). CONCLUSION: This study suggests that both VTA overlap with STN and structural connectivity to cortical motor regions are associated with the effectiveness of STN-DBS for managing camptocormia in PD.

Factors That Affect Chinese Parents' Willingness to Donate Children's Biospecimens in Pediatric Research.

Objective: To examine the factors that may influence Chinese parent's willingness to donate their children's biospecimens for use in pediatric research. Study Design: Parents or caregivers of the patients in the neurosurgery ward, oncological surgery ward, and internal medical wards at Shanghai Children's Medical Center were recruited during the period of March 1, 2016 to July 8, 2018. The questionnaire included the willingness to provide consent for donating their children's clinical biospecimens, their attitudes toward and motivations for donating their children's clinical biospecimens, opinions of contributing specimens, and an ethical consideration for their children's future willingness to donate biospecimens. Participants' demographic data and children's basic information were collected. Results: The majority of the participants agreed to donate the patients' biospecimens for research. Parents with pronounced religious beliefs, less education, who had only one child, child with a more severe disease, and living in an urban district were associated with negative attitudes toward biospecimen donation, but none of other parents' sociodemographic characteristics and some of the children's basic characteristics disclosed significant differences in donation attitudes. In five different types of biospecimens, parents were more reluctant to donate specific blood biospecimens. Physical pain and privacy protection were of most concern to parents when it came to donating their child's biospecimens. It was widely believed in parents that reconsent would be necessary for the 18-year-old adolescent. Conclusions: Our findings explored the factors that were of greatest worry to parents related to parents' willingness to donate their child's biospecimens in China. We recommend greater patient explanation to enhance the participant's engagement in the biospecimen donation, and the adolescent's attitude toward biospecimen donation needs further consideration.

[Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases].

OBJECTIVE: This study aimed to evaluate the effort of applying frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater in the treatment of sagittal synostosis. METHODS: From April 2008 to June 2013, sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. The CT images showed that both sides of the parietal bone of artificial sagittal groove gradually merged postoperative 1 year, and skull almost completely normal healing after operation 2 or 3 years, without deformity recurrence within 5 years. Among them all, 61 children's intelligence is normal and 2 children's lagged behind normal level, no further improvement. RESULTS: Patients were followed up 1 - 5 years (an average of 43 months). Skull growth was excellent in all patients, the anteroposterior diameter was shortened by 14.6 mm averagely, the transverse diameter was increased by 12.3 mm averagely, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. CONCLUSIONS: The application of frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater can be used in the treatment of sagittal synostosis. Surgery without removing bone flaps is less traumatic and results in no massive bleeding. It can effectively relieve brain compression and promotes transversal expansion of the brain during surgery and subsequent normal brain development.

Prevention of infection by antibiotic-impregnated shunts after pediatric hydrocephalus treatment: A single center, retrospective study in China.

OBJECTIVE: To investigate infection prevention by antibiotic-impregnated shunts (AIS) relative to conventional ones after pediatric hydrocephalus treatment. METHODS: This single center, retrospective analysis comprised 807 consecutive pediatric cases of hydrocephalus shunting performed by the same neurosurgeon between January 2001 and February 2013. Conventional and AIS catheters were used in 303 and 504 cases, respectively. Study outcomes were infection rates at 6 months (primary), and at 1 month and between 1 and 6 months (secondary). An infant (<1year) subgroup was also analyzed. RESULTS: The AIS relative to the conventional catheter group had significantly lower infection rates at 6 months (1.98% [10/504] vs. 5.95% [18/303], two-tailed p=0.0046; central nervous system: 60% and 55.56%; abdominal: 20% and 27.77%; wound: 20% and 16.67%, respectively) and 1 month (0.19% [1/504] vs. 2.65% [8/303], p=0.0023, respectively), but statistically similar rates between 1 and 6 months (1.79% [9/504] vs. 3.30% [10/303], p=0.2296, respectively). In the infant subgroup, AIS application was also associated with reduction in shunt infection (1.49% [7/470] vs. 3.76% [10/266], p=0.0489, respectively). CONCLUSION: AIS as compared to conventional catheter use appears to lower infection risk at 6 months, mainly during the first month, after hydrocephalus therapy in children.

Pathological changes and surgical treatment of lipomas of the conus medullaris.

OBJECTIVE: To describe the pathological changes of lipomas of the conus medullaris and the appropriate surgical treatment for removing such lipomas for optimal reconstruction of the normal spinal cord anatomy. METHODS: Data were collected on 73 patients, aged 1.5 months to 18 years, who underwent surgical removal of a lipoma of the conus medullaris at Shanghai Children's Medical Center from January 2005 to December 2008. Neurological symptoms included pain, urine and stool incontinence, and bilateral lower limb dysfunction. The surgical procedures consisted of excision of subcutaneous and intradural extramedullary lipoma, partial excision of intramedullary lipoma, detachment of the spinal cord from the dural membrane, relief of tethered spinal cord, and excision of the affected filum terminale. RESULTS: The main pathological changes in patients with lipoma of the conus medullaris were ventral deviation of the spinal cord caused by compression from a dorsal lipoma, traction on the spinal cord from attachment of intradural lipoma and subcutaneous lipoma, increased tight fit between the spinal cord and the dural membrane on both sides, and degeneration of the filum terminale. A total of 67 patients were followed up for 6 months to 4 years. Improvement after surgery varied among the symptomatic patients. A total of 5 patients had transient deterioration of symptoms after surgery. All asymptomatic patients remained asymptomatic. CONCLUSION: Only through thorough understanding of the pathology of the lipoma of the conus medullaris, we could optimally excise the lipoma, untether the spinal cord, reconstruct the normal anatomy of the spinal cord, and rehabilitate neurological function.