Quality of life after selective dorsal rhizotomy: an assessment of family-reported outcomes using the CPQoL questionnaire.

BACKGROUND: Selective dorsal rhizotomy (SDR) is widely accepted as an effective procedure for management of lower limb spasticity in children with cerebral palsy. However, effects of the procedure on quality of life are not widely reported and less so using a structured and validated quality of life tool such as Cerebral Palsy Quality of Life Questionnaire (CPQoL). Here, we present complete data for CPQoL outcomes for SDR patients operated in a single institution at 2 years follow-up. METHODS: Patients were operated over a 5-year period by the same surgeon using the same technique in a single institution. CPQoL questionnaires were completed by patients and families pre-operatively and at 6 months, 1 year and 2 years post-operatively. Data was collected prospectively. RESULTS: A total of 78 patients (58 male, 20 female), age range 2.6-13.8 years (median 6.33) were included whom underwent SDR between October 2012-November 2017. All had complete follow-up up to 2 years post-procedure (most recent November 2019). Four patients were excluded due to incomplete follow-up data. Statistically significant improvement was seen across five out of seven CPQoL domains and this was sustained to 2 years post-SDR. CONCLUSIONS: We demonstrate using a validated Quality of Life Tool that SDR has a beneficial effect on the quality of life for patients with cerebral palsy at this length of follow-up.

Chiari I malformation and altered cerebrospinal fluid dynamics-the highs and the lows.

PURPOSE: This paper reviews the altered cerebrospinal fluid dynamics that can be associated with paediatric Chiari I malformation and we present our own institutional experience. METHODS: We conducted a thorough review of the literature and retrospectively analyzed all cases of operatively managed paediatric Chiari 1 malformation at our institution between February 2006 and February 2019. RESULTS: Acquired Chiari malformation (ACM) can radiologically mimic Chiari I and has been associated with both intracranial hypotension (either secondary to lumboperitoneal shunting or spontaneous CSF hypotension) and idiopathic intracranial hypertension (IIH). At our institution, 61 paediatric cases (range, 2-15 years) underwent foramen magnum decompression (FMD) for Chiari I malformation. Whilst 80% (50/61) of cases underwent FMD with no preceding or post-operative problems of CSF dynamics, 8% (5/61) of cases had hydrocephalus at initial presentation requiring CSF diversion followed by FMD for persistent Chiari, and 10% (6/61) developed hydrocephalus following FMD and required long-term CSF diversion. CONCLUSIONS: In paediatric ACM, the management of intracranial hypotension involves thorough radiological assessment and inclusion/adjustment of a valve in the case of lumboperitoneal shunting or epidural blood patch or interventional techniques in the case of spontaneous CSF leak. Thereby, unwarranted posterior fossa decompression surgery is avoided. In the case of IIH and Chiari I malformation, children who have recurrent symptoms despite adequate posterior fossa decompression surgery (failed Chiari), there is a strong role for intracranial pressure monitoring as raised intracranial pressure may indicate long-term CSF diversion.

Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines.

PURPOSE: Hydrocephalus (HC) has a multifactorial and complex picture of pathophysiology due to aetiology, age at and duration since onset. We have previously identified distinctions in markers of cell death associated with different aetiologies. Here, we examined cerebrospinal fluid (CSF) from human HC neonates for cytokines to identify further distinguishing features of different aetiologies. METHODS: CSF was collected during routine lumbar puncture or ventricular tap from neonates with hydrocephalus, or with no neurological condition (normal controls). Total protein, Fas receptor, Fas ligand, stem cell factor (SCF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured and compared between 8 unaffected and 28 HC neonatal CSF samples. RESULTS: Total protein was significantly (P < 0.05) raised in late-onset hydrocephalus (LOH). Fas receptor was raised (P < 0.05) in post-haemorrhagic hydrocephalus (PHH) and spina bifida with hydrocephalus (SB/HC), but no difference in Fas ligand was found. SCF was raised (P < 0.05) in SB/HC. HGF was found in all HC and was increased (P < 0.01) in PHH. Increased VEGF was found in PHH (P < 0.01) and SB/HC (P < 0.05). Variable levels of IL-6, TNF-α and IGF-1 were found in all HC groups compared with none in normal. CONCLUSIONS: LOH was unusual with significantly raised total protein indicating an inflammatory state. Increased Fas receptor, VEGF, IGF-1 and HGF suggest anti-apoptotic and repair mechanism activation. By contrast, elevated TNF-α and IL-6 indicate inflammatory processes in these neonatal brains. Taken with our previous study, these data indicate that different pathophysiology, inflammation and repair are occurring in HC of different aetiologies and that additional treatment strategies may benefit these infants in addition to fluid diversion.

Prognostic value of leukocytosis in pediatric traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess leukocytosis and its prognostic value in pediatric isolated traumatic brain injury (TBI). METHODS: Two hundred one children with isolated TBI admitted to the authors' institution between June 2006 and June 2018 were prospectively followed and their data retrospectively analyzed. Initial blood leukocyte count (i.e., white cell count [WCC]), Glasgow Coma Scale (GCS) score, CT scans, duration of hospital stay, and Pediatric Cerebral Performance Category Scale (PCPCS) scores were analyzed. RESULTS: The mean age was 4.2 years (range 0.2-16 years). Seventy-four, 70, and 57 patients had severe (GCS score 3-8), moderate (GCS score 9-13), and mild (GCS score 14-15) TBI, respectively, with associated WCC of 20, 15.9, and 10.7 × 109/L and neutrophil counts of 15.6, 11.3, and 6.1 × 109/L, respectively (p < 0.01). Higher WCC and neutrophil counts were demonstrated in patients with increased intracranial mass effect on CT, longer hospital stay, and worse 6-month PCPCS score (p < 0.05). Multivariate regression revealed a cutoff leukocyte count of 16.1 × 109/L, neutrophil count of 11.9 × 109/L, and neutrophil-to-lymphocyte ratio (NLR) of 5.2, above which length of hospital stay and PCPCS scores were less favorable. Furthermore, NLR was the second most important independent risk factor for a poor outcome (after GCS score). The IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) adult TBI prediction model applied to this pediatric cohort demonstrated increased accuracy when WCC was incorporated as a risk factor. CONCLUSIONS: In the largest and first prospective study of isolated pediatric head injury to date, the authors have demonstrated that WCC > 16.1 × 109/L, neutrophil count > 11.9 × 109/L and NLR > 5.2 each have predictive value for lengthy hospital stay and poor PCPCS scores, and NLR is an independent risk factor for poor outcome. Incorporating the initial leukocyte count into TBI prediction models may improve prognostication.

Surgical resection of cavernous angioma located within eloquent brain areas: International survey of the practical management among 19 specialized centers.

PURPOSE: The practical management of cavernous angioma located within eloquent brain area before, during and after surgical resection is poorly documented. We assessed the practical pre-operative, intra-operative, and post-operative management of cavernous angioma located within eloquent brain area. METHOD: An online survey composed of 61 items was sent to 26 centers to establish a multicenter international retrospective cohort of adult patients who underwent a surgical resection as the first-line treatment of a supratentorial cavernous angioma located within or close to eloquent brain area. RESULTS: 272 patients from 19 centers (mean 13.6 ± 16.7 per center) from eight countries were included. The pre-operative management varied significantly between centers and countries regarding the pre-operative functional assessment, the pre-operative epileptological assessment, the first given antiepileptic drug, and the time to surgery. The intra-operative environment varied significantly between centers and countries regarding the use of imaging systems, the use of functional mapping with direct electrostimulations, the extent of resection of the hemosiderin rim, the realization of a post-operative functional assessment, and the time to post-operative functional assessment. The present survey found a post-operative improvement, as compared to pre-operative evaluations, of the functional status, the ability to work, and the seizure control. CONCLUSIONS: We observed a variety of practice between centers and countries regarding the management of cavernous angioma located within eloquent regions. Multicentric prospective studies are required to solve relevant questions regarding the management of cavernous angioma-related seizures, the timing of surgery, and the optimal extent of hemosiderin rim resection.

Predictors of Epileptic Seizures and Ability to Work in Supratentorial Cavernous Angioma Located Within Eloquent Brain Areas.

BACKGROUND: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area. OBJECTIVE: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery. METHODS: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas. RESULTS: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P = .013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P = .042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P < .001) is an independent predictor of inability to work at the time of surgery. History of epileptic seizures at the time of surgery (OR, 7.61; 95% CI, 1.67-85.42; P = .003) and partial resection of the CA and/or of the hemosiderin rim (OR, 12.02; 95% CI, 3.01-48.13; P < .001) are independent predictors of uncontrolled seizures postoperatively. Inability to work at the time of surgery (OR, 19.54; 95% CI, 1.90-425.48; P = .050), Karnofsky Performance Status ≤ 70 (OR, 51.20; 95% CI, 1.20-2175.37; P = .039), uncontrolled seizures postoperatively (OR, 105.33; 95% CI, 4.32-2566.27; P = .004), and worsening of cognitive functions postoperatively (OR, 13.71; 95% CI, 1.06-176.66; P = .045) are independent predictors of inability to work postoperatively. CONCLUSION: The functional-based resection using intraoperative functional brain mapping allows safe resection of CA and the peripheral hemosiderin rim located within or close to eloquent brain areas.

Factors associated with 30-day ventriculoperitoneal shunt failure in pediatric and adult patients.

OBJECTIVE The aim of this study was to provide a comprehensive benchmark of 30-day ventriculoperitoneal (VP) shunt failure rates for a single institution over a 5-year study period for both adult and pediatric patients, to compare this with the results in previously published literature, and to establish factors associated with shunt failure. METHODS A retrospective database search was undertaken to identify all VP shunt operations performed in a single, regional neurosurgical unit during a 5-year period. Data were collected regarding patient age, sex, origin of hydrocephalus, and whether the shunt was a primary or secondary shunt. Operative notes were used to ascertain the type of valve inserted, which components of the shunt were adjusted/replaced (in revision cases), level of seniority of the most senior surgeon who participated in the operation, and number of surgeons involved in the operation. Where appropriate and where available, postoperative imaging was assessed for grade of shunt placement, using a recognized grading system. Univariate and multivariate models were used to establish factors associated with early (30-day) shunt failure. RESULTS Six hundred eighty-three VP shunt operations were performed, of which 321 were pediatric and 362 were adult. The median duration of postoperative follow-up for nonfailed shunts (excluding deaths) was 1263 days (range 525-2226 days). The pediatric 30-day shunt failure rates in the authors' institution were 8.8% for primary shunts and 23.4% for revisions. In adults, the 30-day shunt failure rates are 17.7% for primary shunts and 25.6% for revisions. In pediatric procedures, the number of surgeons involved in the operating theater was significantly associated with shunt failure rate. In adults, the origin of hydrocephalus was a statistically significant variable. Primary shunts lasted longer than revision shunts, irrespective of patient age. CONCLUSIONS A benchmark of 30-day failures is presented and is consistent with current national databases and previously published data by other groups. The number of surgeons involved in shunt operations and the origin of the patient's hydrocephalus should be described in future studies and should be controlled for in any prospective work. The choice of shunt valve was not a significant predictor of shunt failure. Most previous studies on shunts have concentrated on primary shunts, but the high rate of early shunt failure in revision cases (in both adults and children) is perhaps where future research efforts should be concentrated.

Low-Grade Glioma with Foci of Early Transformation Does Not Necessarily Require Adjuvant Therapy After Radical Surgical Resection.

BACKGROUND: Low-grade glioma (LGG) is a slow-growing tumor often found in young adults with minimal or no symptoms. As opposed to true low-grade lesions such as dysembryoplastic neuroepithelial tumors, they are associated with continuous growth and inevitable malignant transformation. METHODS: Case series of patients who have had en bloc resection of LGG with foci of anaplasia found embedded within the tumor specimen and not at margins. Patients were offered and agreed to a conservative approach avoiding adjuvant therapy. RESULTS: In the current case series, we describe a small subset of LGG that have shown foci of high-grade glioma but have shown behavior and growth tendencies similar to LGG after radical surgical resection. No patient to date has shown recurrent disease requiring adjuvant therapy. CONCLUSIONS: This case series supports the use of early aggressive surgical treatment of grade II gliomas that are premalignant. It acts as proof of concept that after radical resection, the presence of small foci of transformation embedded within grade II tumor may be treated with close radiologic surveillance rather than immediate adjuvant therapy.

Does patient ethnicity affect site of craniosynostosis?

OBJECT: There are no published papers examining the role of ethnicity on suture involvement in nonsyndromic craniosynostosis. The authors sought to examine whether there is a significant difference in the epidemiological pattern of suture(s) affected between different ethnic groups attending a regional craniofacial clinic with a diagnosis of nonsyndromic craniosynostosis. METHODS: A 5-year retrospective case-notes analysis of all cases involving patients attending a regional craniofacial clinic was undertaken. Cases were coded for the patients' declared ethnicity, suture(s) affected by synostosis, and the decision whether to have surgical correction of synostosis. The chi-square test was used to determine whether there were any differences in site of suture affected between ethnic groups. RESULTS: A total of 312 cases were identified. Of these 312 cases, ethnicity data were available for 296 cases (95%). The patient population was dominated by 2 ethnic groups: white patients (222 cases) and Asian patients (56 cases). There were both more cases of complex synostosis and fewer cases of sagittal synostosis than expected in the Asian patient cohort (χ(2) = 9.217, p = 0.027). CONCLUSIONS: There is a statistically significant difference in the prevalence of the various sutures affected within the nonsyndromic craniosynostosis patient cohort when Asian patients are compared with white patients. The data from this study also suggest that nonsyndromic craniosynostosis is more prevalent in the Asian community than in the white community, although there may be inaccuracies in the estimates of the background population data. A larger-scale, multinational analysis is needed to further evaluate the relationship between ethnicity and nonsyndromic craniosynostosis.

Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss.

BACKGROUND: In hydrocephalus an imbalance between production and absorption of cerebrospinal fluid (CSF) results in fluid accumulation, compression and stretching of the brain parenchyma. In addition, changes in CSF composition have a profound influence on the development and function of the brain and together, these can result in severe life-long neurological deficits. Brain damage or degenerative conditions can result in release of proteins expressed predominantly in neurons, astroglia, or oligodendroglia into the brain interstitial fluid, CSF and blood. Determination of such products in the CSF might be of value in diagnosing cause, aetiology and/or assessing the severity of the neurological damage in patients with hydrocephalus. We therefore analysed CSF from human neonates with hydrocephalus for these proteins to provide an insight into the pathophysiology associated with different aetiologies. METHODS: CSF was collected during routine lumbar puncture or ventricular tap. Samples were categorized according to age of onset of hydrocephalus and presumed cause (fetal-onset, late-onset, post-haemorrhagic or spina bifida with hydrocephalus). Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), vimentin and 2' , 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were analysed through Western blotting of hydrocephalic CSF samples (n = 17) and compared with data from CSF of normal infants without neurological deficits (n = 8). RESULTS: GFAP was significantly raised only in CSF from post-haemorrhagic hydrocephalus while MBP was significantly raised in post-haemorrhagic and in spina bifida with hydrocephalus infants. Vimentin protein was only detected in some CSF samples from infants with late-onset hydrocephalus but not from other conditions. Surprisingly, CNPase was found in all neonatal CSF samples, including normal and hydrocephalic groups, although it was reduced in infants with late onset hydrocephalus compared with normal and other hydrocephalic groups. CONCLUSIONS: Apart from CNPase, which is an enzyme, the markers investigated are intracellular intermediate filaments and would be present in CSF only if the cells are compromised and the proteins released. Raised GFAP observed in post-haemorrhagic hydrocephalus must reflect damage to astrocytes and ependyma. Raised MBP in post-haemorrhagic and spina bifida with hydrocephalus indicates damage to oligodendrocytes and myelin. Vimentin protein detected in some of the late-onset hydrocephalic samples indicates damage to glial and other progenitors and suggests this condition affects periventricular regions. The presence of CNPase in all CSF samples was unexpected and indicates a possible novel role for this enzyme in brain development/myelination. Less CNPase in some cases of late-onset hydrocephalus could therefore indicate changes in myelination in these infants. This study demonstrates differential glial damage and loss in the developing human neonatal hydrocephalic brain associated with different aetiologies.

Forniceal glioma in children. Clinical article.

OBJECT: Five to ten percent of pediatric brain tumors are located in the ventricles. Among them, forniceal lesions are rare and their management has not often been described. The aim of this study was to review the clinical, radiological, and histopathological features as well as the feasibility of surgical excision and the outcomes in these patients. METHODS: From a retrospective analysis of 250 cases of supratentorial pediatric glioma, the records of 8 children presenting with forniceal lesions were selected and reviewed. RESULTS: The median age of patients in the cohort was 13.5 years. Presenting features included intracranial hypertension (7 cases), hypothalamic dysfunction (2), and memory dysfunction (3). Complete resection was possible in only 1 case, where the lesion was mainly exophytic; the remaining patients had either a partial resection or biopsy. On histological review, the tumors were confirmed as pilocytic astrocytoma (4 lesions), WHO Grade II astrocytoma (3), and ganglioglioma (1). Postoperatively, working and retrograde memory was normal for all patients, but the authors found a mild alteration in verbal episodic memory in 5 patients. Despite fatigability for 5 patients, academic achievement was normal for all but 2, both of whom had preoperative school difficulties. Additional treatment was required for 5 patients for tumor progression, with a median interval of 19 months from surgery. At a median follow-up duration of 4.9 years, all patients had stable disease. CONCLUSIONS: In this series, forniceal gliomas were found to be low-grade gliomas. They are surgically challenging, and only exophytic lesions may be cured surgically. Due to the high rate of progression of residual disease, adjuvant therapy is recommended for infiltrative tumors, and it yielded excellent results.