Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome.

PURPOSE: The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. METHODS: Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. RESULTS: There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p < 0.001). CONCLUSION: The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Platelet abnormalities in patients with Parkinson's disease undergoing preoperative evaluation for deep brain stimulation.

Normal hemostatic function is important for reduction of the risk of intracranial hemorrhage during stereotactic neurosurgery including deep brain stimulation (DBS) surgery. This study investigates the hemostatic function in patients with Parkinson's disease (PD) undergoing preoperative evaluation for DBS, with emphasis on the number and function of platelets. In 107 PD patients, only one had abnormal activated partial prothrombin time and normal prothrombin time. Among the other 106 patients, six (5.7%) had only thrombocytopenia, seven (6.6%) only prolonged bleeding time (BT), and 14 (13.2%) only prolonged closure time (CT) of platelet function analyzer 100 (PFA-100). Totally, 34 of the 106 patients (32.1%) had at least one of three kinds of platelet abnormalities. No factor was found to be associated with the occurrence of platelet abnormalities except that abnormal platelet group and prolonged BT subgroup had more patients using selegiline and lower UPDRS-III motor subscore with medication off than normal platelet group (p < 0.05). The use of selegiline was significantly correlated with prolonged BT (p = 0.0041) and platelet abnormality (p = 0.0197). Therefore, it is important to have detailed evaluation of the hemostatic function for PD patients undergoing preoperative evaluation for DBS, especially the platelet number and function.

Long-Term Outcomes of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series.

BACKGROUND: Among dystonia patients receiving globus pallidus internus (GPi) deep brain stimulation (DBS), long-term outcomes remain to be established. To report the long-term outcomes of GPi DBS in a patient cohort with idiopathic and acquired dystonia. METHODS: In this long-term follow-up cohort, there were 4 patients with idiopathic dystonia and 2 patients with acquired dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale was used to evaluate 6 consecutive patients preoperatively and at 6 months, 12 months, and the last follow-up. The relationship between etiology and clinical improvement was analyzed. Stimulation parameters were evaluated for similarities and differences among these patients. RESULTS: The mean follow-up of our cohort was 65.3 months (median 40.5 months). The average improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (mean ± SEM) were 56% ± 7.6, 67% ± 6.8 and 66% ± 9.7 at 6 months, 12 months, and the last follow-up, respectively. There was greater improvement during the long-term follow-up in the 4 patients with idiopathic dystonia than in the 2 patients with acquired dystonia. The 2 most ventral electrodes (contact 0 and 1) were activated in all 11 leads in this cohort. The average stimulation intensity, pulse width and frequency were 2.0 ± 0.24 mA, 252 ± 43 µs, and 99 ± 6.0 Hz, respectively. CONCLUSIONS: Isolated dystonia, either monogenic or idiopathic, usually responds better to GPi DBS than to acquired dystonia. Selection of patients by dystonia etiology, accurate placement of DBS leads in GPi targets, and proper stimulation programming are crucial to achieve better long-term outcomes.

Long-term outcomes of moyamoya disease following indirect revascularization in middle adulthood: A prospective, quantitative study.

BACKGROUND/PURPOSE: Our previous study demonstrated that indirect revascularization is effective in the treatment of adult moyamoya patients. This prospective study aims to evaluate the long-term effectiveness of indirect revascularization in moyamoya patients in middle adulthood. METHODS: From January 2013 to June 2019, moyamoya patients more than 40 years of age underwent indirect revascularizations were studied. The hypoperfusion area of brains was revascularized. The cerebral angiography and time-to-peak (TTP) scoring (ranged 0-14) of the magnetic resonance perfusion study were used to evaluate the revascularization effect. RESULTS: During the study period, 50 consecutive adult moyamoya patients underwent indirect revascularization. Seventeen patients (27 cerebral hemispheres) more than 40 years of age were included. The mean age was 47.9 ± 6.4 years, and 13 patients were female. The pre-operative Suzuki stages were I, II, III, IV, V, and VI in 1, 1, 9, 13, 0, and 3 hemispheres, respectively. After a mean follow-up period of 52.5 ± 20.6 months, all patients had improvement or stabilization of their clinical conditions. Available post-operative angiography demonstrated Matsushima grading A in 18 of 20 hemispheres. The mean TTP score of all 27 hemispheres improved from 5.0 ± 3.3 pre-operatively to 12.0 ± 2.1 after surgery (p < 0.001). The post-operative mean TTP score of the 7 hemispheres without angiographic follow-up was 10.4 ± 1.8. One patient had persistent mild motor weakness after 56-month follow-up. Transient complications with full recovery occurred in 3 patients. CONCLUSION: Indirect revascularization is a safe method with satisfactory long-term results in moyamoya patient in middle adulthood.

Contemporary management of pediatric spinal tumors: a single institute's experience in Taiwan in the modern era.

INTRODUCTION: Pediatric spinal tumors are unique pathologies treated by pediatric neurosurgeons. Special attention is required for the preservation of neural function and bony alignment. We reported our experience in the management of these challenging lesions. METHODS: A total of 75 pediatric patients with spinal tumors treated at the National Taiwan University Hospital from 1998 to 2018 were identified retrospectively. Clinical data, radiographic image, and pathological report were reviewed for analysis. RESULTS: There were 37 females and 38 males. The median age was 9 years. Thirty-eight tumors (50.6%) were extradural, 20 (26.7%) intradural extramedullary, and 17 (22.6%) intramedullary. The most common pathologies were glioma, ependymoma, and neuroblastoma. The rate of total and subtotal resection was 45.3% and 21.3%. Thirty-four patients (45.3%) required post-operative adjuvant therapy. Eight patients (10.6%) with spinal deformity had simultaneous tumor excision and spinal fusion surgery. Additional six (8%) patients had subsequent spinal fixation and fusion for deformity after primary tumor operation. Eighty-four percent of patients were ambulatory 3 years after operation. For patients with intradural extramedullary and intramedullary tumors, worse survival outcome was associated with tumor derived from CSF seeding and cranial involvement of spinal tumor, while poorer functional outcome was correlated with cranial involvement and adjuvant therapy with chemotherapy or radiotherapy. CONCLUSIONS: Pediatric spinal tumor surgery carries low surgical morbidity and mortality under current standard of neurosurgical practice. Post-operative adjuvant therapy is required for nearly half of the cases. Spinal deformity requires special attention and sometimes surgical correction. Contemporary management of pediatric spinal tumors enables effective ablation of the lesion and delivers favorable outcome for the majority of patients.

The role of sacral laminoplasty in the management of spina bifida and sacral cystic lesions: case series.

OBJECTIVE: Although laminae are not viewed as essential structures for spinal integrity, in the sacrum the anatomical weakness and gravity makes it a vulnerable area for CSF accumulation and expansion. The congenital or postoperative defects of sacral laminae, such as in patients with spina bifida, make this area more susceptible to forming progressive dural ectasia, pseudomeningocele, or expansile arachnoid cyst (Tarlov cyst). In addition, adhesions between the dura and surrounding soft tissue after laminectomy can cause some local symptoms, which are difficult to relieve. The authors propose that sacral laminoplasty with titanium mesh can provide a rigid support and barrier to resolve these sacral lesions and local symptoms. METHODS: From January 2016 to December 2017, patients with progressive CSF-containing lesions in the sacral area and defective sacral laminae were included in the study. After repair of the lesion, the authors performed sacral laminoplasty with titanium mesh in each patient. Subsequently, the soft tissue and skin were closed primarily. RESULTS: A total of 6 patients were included. Four patients with repaired myelomeningocele had progressive dural ectasia. One patient with lipomyelomeningocele previously underwent detethering surgery and developed postoperative pseudomeningocele. One patient had a symptomatic Tarlov cyst. Four of these 6 cases presented with low-back pain and local tenderness. During follow-up, ranging from 13 to 37 months, all 6 patients experienced no recurrence of dural ectasia or pseudomeningocele and were free from local symptoms. CONCLUSIONS: Sacral laminoplasty with titanium mesh is a safe and effective procedure for treating progressive sacral dural ectasia and refractory pseudomeningocele, preventing CSF leakage as well as relieving local symptoms that may occur years after previous surgery for spina bifida.

Using a burr hole valve prevents proximal shunt failure in infants and toddlers.

OBJECTIVE: Proximal malfunction is the most common cause of ventriculoperitoneal (VP) shunt failure in young children. In this study, the authors sought to determine factors that affect the migration rate of ventricular catheters in hydrocephalic children who undergo shunt implantation in the first 3 years of life. METHODS: The authors reviewed the medical records and imaging studies of newly diagnosed and treated hydrocephalic children who were younger than 3 years. Patients who received VP shunt insertion through the parieto-occipital route were not included. In total, 78 patients were found who underwent VP shunt insertion between December 2006 and April 2017. Eighteen patients were excluded due to mortality, short follow-up period (< 1 year), and lack of imaging follow-up. The age, sex, etiology of hydrocephalus, initial length of ventricular catheter, valve type (burr hole vs non-burr hole), time to ventricular catheter migration, subsequent revision surgery, and follow-up period were analyzed. The diagnosis of a migrated ventricular catheter was made when serial imaging follow-up showed progressive withdrawal of the catheter tip from the ventricle, with the catheter shorter than 4 mm inside the ventricle, or progressive deviation of the ventricular catheter toward the midline or anterior ventricular wall. RESULTS: Sixty patients were enrolled. The mean age was 5.1 months (range 1-30 months). The mean follow-up period was 50.9 months (range 13-91 months). Eight patients had ventricular catheter migration, and in 7 of these 8 patients a non-burr hole valve was used. In the nonmigration group, a non-burr hole valve was used in only 6 of the 52 patients. Six of the 8 patients with catheter migration needed second surgeries, which included removal of the shunt due to disconnection in 1 patient. The remaining 2 patients with shunt migration were followed for 91 and 46 months, respectively, without clinical and imaging changes. The authors found that patient age at catheter insertion, ventricular catheter length, and the use of a burr hole valve were protective factors against migration. After ventricular catheter length and patient age at catheter insertion were treated as confounding variables and adjusted with multivariable Weibull proportional hazards regression, the use of a burr hole valve shunt remained a protective factor. CONCLUSIONS: The use of burr hole valves is a protective factor against ventricular catheter migration when the shunt is inserted via a frontal route. The authors suggest the use of a burr hole valve along with a frontal entry point in hydrocephalic children younger than 3 years to maintain long-term shunt function.

Improving Indirect Revascularization for Effective Treatment of Adult Moyamoya Disease: A Prospective Clinical, Cerebral Angiographic, and Perfusion Study.

BACKGROUND: Indirect revascularization is simple and safe, but it is not commonly used in adult moyamoya disease owing to its unreliable effect. This prospective study aimed to evaluate the effectiveness of indirect revascularization in treating adult moyamoya disease after refinement of the surgical technique and perioperative care. METHODS: Adult patients who underwent indirect revascularization as the primary treatment for moyamoya disease between November 2013 and January 2017 were studied. The indirect revascularization procedures included encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis in the temporal region and encephalo-pericranio-synangiosis in other hypoperfusion areas. The preoperative and postoperative clinical conditions, cerebral angiography findings, and time-to-peak prolongation areas on magnetic resonance perfusion studies were assessed to evaluate the revascularization effect. Refinements of the surgical technique included the selection of surgical area based on perfusion imaging, craniotomy size, and number of affected hemispheres, along with the inclusion of a dural flap in every procedure. RESULTS: Nineteen patients (17 females and 2 males), and a total of 31 cerebral hemispheres, were included. The mean patient age was 32.7 ± 11.4 years. After a mean follow-up of 38.6 ± 11.5 months, all patients showed clinical improvement or stabilization. Available postoperative angiography demonstrated Matsushima grade A or B in 19 of 21 hemispheres. The mean time-to-peak prolongation index of all 31 hemispheres improved from 24.09 ± 9.83% preoperatively to 12.82 ± 6.75% at 3-6 months after surgery (P < 0.001). The complication rate was 12.9%, and all complications were transient. CONCLUSIONS: With refinements of surgical techniques and perioperative care, indirect revascularization is more reliable and can be a viable alternative treatment for adult moyamoya disease. In our cohort, outcomes were satisfactory, with mean 38.6-month follow-up.