- Late-Onset Langerhans Cell Histiocytosis with Cerebellar Ataxia as an Initial Symptom. [Journal Article]
- CRCase Rep Neurol 2016 Sep-Dec; 8(3):218-223
- Late-onset progressive cerebellar ataxia is a diagnostic challenge because of a poor correlation between genotype and phenotype, and a broad range of secondary causes that extend beyond the neurologi...
Late-onset progressive cerebellar ataxia is a diagnostic challenge because of a poor correlation between genotype and phenotype, and a broad range of secondary causes that extend beyond the neurological field. We report the case of a 45-year-old woman admitted after 2 years of slowly progressing cerebellar ataxia, dysarthria, and emotional instability. Notably, she was diagnosed with diabetes insipidus at the age of 35. As 'idiopathic cerebellar ataxia' was suspected, diagnostic tests, including genetic testing as well as serum and cerebrospinal fluid analyses, and brain magnetic resonance imaging (MRI) were performed. All results were normal except those of MRI, performed 9 months prior to admission, which showed multiple dot-like white matter lesions with unclear cause. On a repeated brain MRI, a new lesion presenting as a 1.5-cm-sized highly enhancing mass attached to the right frontal skull was found. A sharply marginated lytic skull defect was also evident on skull X-ray, which corresponded to the lesion mass. Given these new radiological findings, a systemic review of the patient's medical history for rare secondary causes of cerebellar ataxia was performed, with particular attention to her past 'diabetes insipidus'. The mass, lytic lesion of the skull, white matter lesion, diabetes insipidus, and cerebellar ataxia all suggested a final diagnosis of Langerhans cell histiocytosis (LCH), which was confirmed histopathologically. This is a rare case of late-onset LCH with an unusual initial symptom which underlines the importance of carefully reviewing the patient's medical history and broadening the search for etiologies beyond the nervous system.
- Translational Research for Pediatric Lower Urinary Tract Dysfunction. [Review]
- INInt Neurourol J 2016; 20(Suppl 2):S105-111
- This review provides a comprehensive view of translational research aimed at elucidating the pathophysiology of pediatric lower urinary tract dysfunction (LUTD). A web search was conducted according ...
This review provides a comprehensive view of translational research aimed at elucidating the pathophysiology of pediatric lower urinary tract dysfunction (LUTD). A web search was conducted according to combinations of keywords, and the significance of each article was defined by the author. The dramatic evolution of the mass analysis method of genomes, transcripts, and proteins has enabled a comprehensive analysis of molecular events underlying diseases, and these methodologies have also been applied to pediatric LUTD. In genetic analyses of syndromes underlying daytime incontinence, urofacial (Ochoa) syndrome may be creating a prototype of a new research approach. Nocturnal enuresis has long been studied genetically, and several candidate loci have been reported. However, the pursuit for enuresis genes has been abandoned partly because genetic association and enuresis phenotype (bladder or renal type) could not be linked. Enuresis associated with diabetes insipidus has provided new insights into the etiology of the diseases. A chronobiological approach may shed new light on this area. Posterior urethral valves and neurogenic bladders have attracted the interest of pediatric urologists to the smooth muscle biology of the bladder. Bladder exstrophy and cloacal anomalies are rare but major anomalies caused by defective urorectal development and have recently been studied from a genetic standpoint. Translational studies for pediatric LUTD may be extended to adult bladder disease, or to application of precision medicine for diseased children.
- Bartter's and Gitelman's syndrome. [Journal Article]
- COCurr Opin Pediatr 2016 Nov 30
- CONCLUSIONS: As long as gene therapy is not available, the overall therapeutic management follows the clinical presentation, which leads to the underlying pathophysiology of renal salt wasting. Thus, when dealing with Bartter's syndrome and Gitelman's syndrome, the correct physiologic and pharmacologic characterization appears to be essential for a sound diagnostic and therapeutic patient management.
- Postoperative outcome of body core temperature rhythm and sleep-wake cycle in third ventricle craniopharyngiomas. [Journal Article]
- NFNeurosurg Focus 2016; 41(6):E12
- OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indicati...
OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indications for the endoscopic endonasal approach (EEA) to be used for these tumors as well. The aim of this study was to assess the outcome of sleep-wake cycle and body core temperature (BCT), both depending on hypothalamic control, in patients affected by craniopharyngiomas involving the third ventricle that were surgically treated via an EEA. METHODS All consecutive adult patients with craniopharyngiomas that were treated at one center via an EEA between 2014 and 2016 were prospectively included. Each patient underwent neuroradiological, endocrinological, and ophthalmological evaluation; 24-hour monitoring of the BCT rhythm; and the sleep-wake cycle before surgery and at follow-up of at least 6 months. RESULTS Ten patients were included in the study (male/female ratio 4:6, mean age 48.6 years, SD 15.9 years). Gross-total resection was achieved in 8 cases. Preoperative BCT rhythm was pathological in 6 patients. After surgery, these disturbances resolved in 2 cases, improved in another 3, and remained the same in 1 patient; also, 1 case of de novo onset was observed. Before surgery the sleep-wake cycle was pathological in 8 cases, and it was restored in 4 patients at follow-up. After surgery the number of patients reporting diurnal naps increased from 7 to 9. CONCLUSIONS The outcome of the sleep-wake cycle and BCT analyzed after EEA in this study is promising. Despite the short duration of the authors' experience, they consider these results encouraging; additional series are needed to confirm the preliminary findings.
- Outcomes in transcranial microsurgery versus extended endoscopic endonasal approach for primary resection of adult craniopharyngiomas. [Journal Article]
- NFNeurosurg Focus 2016; 41(6):E6
- OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors h...
OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors has become more widely accepted, yet there remains controversy over which approach leads to better outcomes. The purpose of this study is to determine whether differences in outcomes were identified between TCM and extended endoscopic endonasal approaches (EEEAs) in adult patients undergoing primary resection of suprasellar craniopharyngiomas at a single institution. METHODS A retrospective review of all patients who underwent resection of their histopathologically confirmed craniopharyngiomas at the authors' institution between 2005 and 2015 was performed. Pediatric patients, revision cases, and patients with tumors greater than 2 standard deviations above the mean volume were excluded. The patients were divided into 2 groups: those undergoing primary TCM and those undergoing a primary EEEA. Preoperative patient demographics, presenting symptoms, and preoperative tumor volumes were determined. Extent of resection, tumor histological subtype, postoperative complications, and additional outcome data were obtained. Statistical significance between variables was determined utilizing Student t-tests, chi-square tests, and Fisher exact tests when applicable. RESULTS After exclusions, 21 patients satisfied the aforementioned inclusion criteria; 12 underwent TCM for resection while 9 benefitted from the EEEA. There were no significant differences in patient demographics, presenting symptoms, tumor subtype, or preoperative tumor volumes; no tumors had significant lateral or prechiasmatic extension. The extent of resection was similar between these 2 groups, as was the necessity for additional surgery or adjuvant therapy. CSF leakage was encountered only in the EEEA group (2 patients). Importantly, the rate of postoperative visual improvement was significantly higher in the EEEA group than in the TCM group (88.9% vs 25.0%; p = 0.0075). Postoperative visual deterioration only occurred in the TCM group (3 patients). Recurrence was uncommon, with similar rates between the groups. Other complication rates, overall complication risk, and additional outcome measures were similar between these groups as well. CONCLUSIONS Based on this study, most outcome variables appear to be similar between TCM and EEEA routes for similarly sized tumors in adults. The multidisciplinary EEEA to craniopharyngioma resection represents a safe and compelling alternative to TCM. The authors' data demonstrate that postoperative visual improvement is statistically more likely in the EEEA despite the increased risk of CSF leakage. These results add to the growing evidence that the EEEA may be considered the approach of choice for resection of select confined primary craniopharyngiomas without significant lateral extension in centers with experienced surgeons. Further prospective, multiinstitutional collaboration is needed to power studies capable of fully evaluating indications and appropriate approaches for craniopharyngiomas.
- The learning curve in endoscopic endonasal resection of craniopharyngiomas. [Journal Article]
- NFNeurosurg Focus 2016; 41(6):E9
- OBJECTIVE There is a paucity of literature regarding the learning curve associated with performing endoscopic endonasal cranial base surgery. The purpose of this study was to determine to what extent...
OBJECTIVE There is a paucity of literature regarding the learning curve associated with performing endoscopic endonasal cranial base surgery. The purpose of this study was to determine to what extent a learning curve might exist for endoscopic endonasal resection in cases of craniopharyngiomas. METHODS A retrospective review was performed for all endoscopic endonasal craniopharyngioma resections performed at Thomas Jefferson University from 2005 to 2015. To assess for a learning curve effect, patients were divided into an early cohort (2005-2009, n = 20) and a late cohort (2010-2015, n = 23). Preoperative demographics, clinical presentation, imaging characteristics, extent of resection, complications, tumor control, and visual and endocrine outcomes were obtained. Categorical variables and continuous variables were compared using a 2-sided Fisher's exact test and t-test, respectively. RESULTS Only the index operation performed at the authors' institution was included. There were no statistically significant differences between early and late cohorts in terms of patient age, sex, presenting symptoms, history of surgical or radiation treatment, tumor size or consistency, hypothalamic involvement, or histological subtype. The rate of gross-total resection (GTR) increased over time from 20% to 65% (p = 0.005), and the rate of subtotal resection decreased over time from 40% to 13% (p = 0.078). Major neurological complications, including new hydrocephalus, meningitis, carotid artery injury, or stroke, occurred in 6 patients (15%) (8 complications) in the early cohort compared with only 1 (4%) in the late cohort (p = 0.037). CSF leak decreased from 40% to 4% (p = 0.007). Discharge to home increased from 64% to 95% (p = 0.024). Visual improvement was high in both cohorts (88% [early cohort] and 81% [late cohort]). Rate of postoperative panhypopituitarism and permanent diabetes insipidus both increased from 50% to 91% (p = 0.005) and 32% to 78% (p = 0.004), which correlated with a significant increase in intentional stalk sacrifice in the late cohort (from 0% to 70%, p < 0.001). CONCLUSIONS High rates of near- or total resection and visual improvement can be achieved using an endoscopic endonasal approach for craniopharyngiomas. However, the authors did find evidence for a learning curve. After 20 cases, they found a significant decrease in major neurological complications and significant increases in the rates of GTR rate and discharge to home. Although there was a large decrease in the rate of postoperative CSF leak over time, this was largely attributable to the inclusion of very early cases prior to the routine use of vascularized nasoseptal flaps. There was a significant increase in new panhypopituitarism and diabetes insipidus, which is attributable to increase rates of intentional stalk sacrifice.
- Risk factors associated with the surgical management of craniopharyngiomas in pediatric patients: analysis of 1961 patients from a national registry database. [Journal Article]
- NFNeurosurg Focus 2016; 41(6):E8
- OBJECTIVE Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available followi...
OBJECTIVE Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available following the resection of craniopharyngiomas in the pediatric population remain limited. The authors sought to identify potential risk factors associated with outcomes following surgical management of pediatric craniopharyngiomas. METHODS The Nationwide Inpatient Sample database and Kids' Inpatient Database were analyzed to include admissions for pediatric patients (≤ 18 years) who underwent a transcranial or transsphenoidal craniotomy for resection of a craniopharyngioma. Patient-level factors, including age, race, comorbidities, and insurance type, as well as hospital factors were collected. Outcomes analyzed included mortality rate, endocrine and nonendocrine complications, hospital charges, and length of stay. A multivariate model controlling for variables analyzed was constructed to examine significant independent risk factors. RESULTS Between 2000 and 2011, 1961 pediatric patients were identified who underwent a transcranial (71.2%) or a transsphenoidal (28.8%) craniotomy for resection of a craniopharyngioma. A major predilection for age was observed with the selection of a transcranial (23.4% in < 7-year-olds, 28.1% in 7- to 12-year-olds, and 19.7% in 13- to 18-year-olds) versus transphenoidal (2.9% in < 7-year-olds, 7.4% in 7- to 12-year-olds, and 18.4% in 13- to 18-year-olds) approach. No significant outcomes were associated with a particular surgical approach, except that 7- to 12-year-old patients had a higher risk of nonendocrine complications (relative risk [RR] 2.42, 95% CI 1.04-5.65, p = 0.04) with the transsphenoidal approach when compared with 13- to 18-year-old patients. The overall inpatient mortality rate was 0.5% and the most common postoperative complication was diabetes insipidus (64.2%). There were no independent factors associated with inpatient mortality rates and no significant differences in outcomes among groups based on sex and race. The average length of stay was 11.8 days, and the mean hospital charge was $116,5 22. Hospitals with medium and large bed capacity were protective against nonendocrine complications (RR 0.53, 95% CI 0.3-0.93, p = 0.03 [medium]; RR 0.45, 95% CI 0.25-0.8, p < 0.01 [large]) and total complications (RR 0.73, 95% CI 0.55-0.97, p = 0.03 [medium]; RR 0.68, 95% CI 0.51-0.9, p < 0.01 [large]) when compared with hospitals with small bed capacity (< 200 beds). Patients admitted to rural hospitals had an increased risk for nonendocrine complications (RR 2.56, 95% CI 1.11-5.9, p = 0.03). The presence of one or more medical comorbidities increased the risk of higher total complications (RR 1.38, 95% CI 1.14-1.68), p < 0.01 [1 comorbidity]; RR 2.37, 95% CI 1.98-2.84, p < 0.01 [≥ 2 comorbidities]) and higher total hospital charges (RR 2.9, 95% CI 1.08-7.81, p = 0.04 [1 comorbidity]; RR 9.1, 95% CI 3.74-22.12, p < 0.01 [≥ 2 comorbidities]). CONCLUSIONS This analysis identified patient age, comorbidities, insurance type, hospital bed capacity, and rural or nonteaching hospital status as independent risk factors for postoperative complications and/or increased hospital charges in pediatric patients with craniopharyngioma. Transsphenoidal surgery in younger patients with craniopharyngioma was a risk factor for nonendocrine complications.
- Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway. [Journal Article]
- NCNat Commun 2016 Nov 28; 7:13636
- Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin typ...
Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway. Wnt5a successfully increases the apical membrane localization of AQP2 and urine osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP level and PKA activity. The importance of calcineurin is further confirmed with its activator, arachidonic acid, which shows vasopressin-like effects underlining that calcineurin activators may be potential therapeutic targets for heritable NDI.
- [Langerhans cell histiocytosis and Erdheim-Chester disease, a continuity?] [Journal Article]
- RMRev Med Interne 2016 Nov 23
- CONCLUSIONS: The literature review finds forty observations linking the two diseases that may suggest a pathophysiological link, especially with the hematopoietic myeloid stem cell CD34+. The term inflammatory myeloid neoplasm was advanced.
New Search Next
- Endoscopic endonasal management of rare sellar lesions: clinical and surgical experience on 78 cases and review of the literature. [Journal Article]
- WNWorld Neurosurg 2016 Nov 22
- CONCLUSIONS: Endoscopic endonasal approaches offer some specific benefits in the treatment of these patients.