Massive Brain Swelling Following Reduction Cranioplasty for Secondary Turricephaly.

ABSTRACT: Cranioplasty is commonly performed to treat craniosynostosis. A rare postsurgical complication is massive brain swelling with elevated intracranial pressure. This commonly presents with mydriasis, coma, and seizures; radiologic findings include cerebral edema, parenchymal hemorrhages, and ischemic changes.The authors describe a 9-year-old boy who developed massive brain swelling following reduction cranioplasty for secondary turricephaly. His history included surgical repair of metopic-craniosynostosis at age 5.5 months, by means of an anterior cranial-vault reconstruction with fronto-orbital advancement. After presenting to our clinic with a significant turricephalic skull deformity, he underwent cranial reduction cranioplasty. On postoperative day 1, mild neurological signs associated to increased intracranial pressure were noticed. As they worsened and massive brain swelling was identified, he was treated pharmacologically. On postoperative day 13, the patient was operated for decompression.A literature review yielded 4 articles related to massive brain swelling for post-traumatic craniectomies. None described elevated intracranial pressure or massive brain swelling following cranial reduction for secondary craniosynostosis. The main dilemma regarding our patient was the necessity and timing of a second operation.The literature did not reveal relevant recommendations regarding treatment timing nor preventative measures.The authors recommend presurgical neuro-ophthalmological and imaging evaluation, for comparisons and management during the immediate and short-term follow-ups. The authors suggest that for a patient presenting with signs and symptoms of cerebral edema or high intracranial pressure following reduction-cranioplasty, pharmacological treatment should be initiated promptly, and careful drainage and eventual surgical-treatment should be considered if no improvement is shown in the subsequent days.

Postoperative hydrocephalus management may cause delays in adjuvant treatment following paediatric posterior fossa tumour resection: a multicentre retrospective observational study.

INTRODUCTION: Hydrocephalus persists in 10-40% of children with posterior fossa tumours (PFT). A delay in commencement of adjuvant therapy (AT) can negatively influence survival. The objective of this study was to determine whether postoperative cerebrospinal fluid (CSF) diversion procedures caused potentially preventable delays in AT. METHODS: A retrospective study of children diagnosed with PFT requiring AT from 2004 to 2018 from two large centres was conducted. Data on histology, timing of ventriculo-peritoneal shunt (VPS) insertion, and AT was collected. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) score was calculated. The primary outcome was delay in AT beyond 40 days post-resection. Progression-free and overall survival were assessed. RESULTS: Out of 196 primary PFT resections, 144 fitted the inclusion criteria. Mean age was 6.57 ± 4.62. Histology was medulloblastoma (104), ependymoma (27), and others (13). Forty patients had a VPS inserted; 17 of these experienced a delay in AT. A total of 104 patients were not shunted; 15 of these had delayed AT (p = 0.0007). Patients who had a VPS insertion had longer intervals from surgery to commencement of AT (34.5 vs 30.8, p = 0.05). There was no significant difference in mCPPRH score between those who had a VPS (4.03) and those who did not (3.61; p = 0.252). Multivariable linear regression modelling did not show a significant effect of VPS or mCPPRH on progression-free survival or OS. CONCLUSION: CSF diversion procedures may cause a preventable delay in the initiation of adjuvant therapy. Early post-operative VP shunt insertion, rather than a 'wait and see policy' should be considered in order to reduce this delay.

Hyperlactatemia in children following brain tumor resection: prevalence, associated factors, and clinical significance.

PURPOSE: Hyperlactatemia is associated with worse outcome among critically ill patients. The prevalence of hyperlactatemia in children following craniotomy for intracranial tumor resection is unknown. This study was designed to assess the prevalence, associated factors, and significance of postoperative hyperlactatemia in this context. METHODS: A retrospective study was conducted at an intensive care unit of a tertiary, pediatric medical center. Children younger than 18 years admitted following craniotomy for brain tumor resection between October 2004 and November 2019 were included. RESULTS: Overall, 222 elective craniotomies performed in 178 patients were analyzed. The mean age ± SD was 8.5 ± 5.5 years. All but two patients survived to discharge. All were hemodynamically stable. Early hyperlactatemia, defined as at least one blood lactate level ≥ 2.0 mmol/L during the first 24 h into admission, presented following 74% of the craniotomies; lactate normalized within a mean ± SD of 11 ± 6.1 h. The fluid balance per body weight at 12 h and 24 h into the intensive care unit admission was similar in children with and without hyperlactatemia [7.0 ± 17.6 vs 3.5 ± 16.4 ml/kg, p = 0.23 and 4.0 ± 27.2 vs 4.6 ± 29.4 ml/kg, p = 0.96; respectively]. Hyperlactatemia was associated with higher maximal blood glucose, older age, and a pathological diagnosis of glioma. Intensive care unit length of stay was similar following craniotomies with and without hyperlactatemia (p = 0.57). CONCLUSIONS: Hyperlactatemia was common in children following craniotomy for brain tumor resection. It was not associated with hemodynamic impairment or with a longer length of stay.

Suturectomies Assisted by Cranial Orthosis Remodeling for the Treatment of Craniosynostosis Can Be Performed Without an Endoscope.

BACKGROUND: Minimally-invasive endoscopic strip-craniectomy (or suturectomy) for the repair of craniosynostosis combined with postoperative cranial orthotic molding has been widely adopted in the past 2 decades, proving itself as a safe and effective procedure. Over time the authors transitioned from performing an endoscopic strip-craniectomy, to performing the same surgery without the endoscope. The authors here describe our technique and compare its results to those published in the literature for endoscopic suturectomies. METHODS: A retrospective chart review was performed for patients with nonsyndromic craniosynostosis who underwent minimally-invasive nonendoscopic suturectomy between 2019 and 2020 at our institution. RESULTS: Thirteen patients (11 males; 2 females) were operated including 5 Metopic, 5 Sagittal, 2 coronal, and 1 lambdoid craniosynostosis. The average age at surgery was 4.35 months. The average length of surgery was 71 minutes. Averaged intraoperative estimated blood loss was 31.54 mL. Eleven patients received a blood transfusion (most before performing the skin incision) with a mean amount of 94.62 mL of blood transfused during surgery. The mean hemoglobin at discharge was 10.38 mg/dL. There was only 1 intraoperative mild complication. The mean intrahospital length of stay was 1.77 days with no postoperative complications noted. All patients initiated remodeling orthotic treatment following surgery. Long-term follow-up scans were available for 8 patients (5 metopic, 2 sagittal, and 1 lambdoid) with an average follow-up of 9 months. In all cases, there was a significant improvement in the skull width at the synostosis location as well as in the skull proportions and symmetry. The above outcomes are similar to those published in the literature for endoscope-assisted strip-craniectomies. CONCLUSIONS: Suturectomies assisted with cranial orthosis remodeling for the treatment of all types of nonsyndromic craniosynostosis can be performed without an endoscope while maintaining minimal-invasiveness, good surgical results, and low complication rates.

External lumbar drainage in progressive pediatric idiopathic intracranial hypertension.

OBJECTIVE: Pediatric idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure despite normal cerebrospinal fluid and neuroimaging findings. Initial management is typically medical; however, nearly 10% of children will eventually require surgery for persistent headache and/or vision loss. External lumbar drainage, which is a considerably safer treatment option, has not been adequately analyzed in children with medically refractory IIH. METHODS: The authors conducted a single-institution retrospective analysis of children with medically refractory IIH who had undergone external lumbar drain (ELD) placement because of worsening papilledema, reflected as increased retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) testing. The main outcome measures were effects of external lumbar drainage on papilledema resolution, symptoms, and vision. RESULTS: The authors analyzed the medical records of 13 children with IIH (11 girls, mean age 15.0 ± 2.3 years) whose mean CSF opening pressure was 45.5 ± 6.8 cm H2O. In all children, the average global RNFL thickness in both eyes significantly increased at ELD placement (right eye 371.8 ± 150.2 µm, left eye 400.3 ± 96.9 µm) compared with presentation thickness (right eye 301.6 ± 110.40 µm, left eye 350.2 ± 107.7 µm) despite acetazolamide medical therapy (20-30 mg/kg/day), leading to ELD placement after 9.5 ± 6.9 days (range 3-29 days). After ELD insertion, there was headache resolution, gradual and continuous improvement in optic disc thickness, and preservation of good vision. CONCLUSIONS: ELD placement in children with medically refractory IIH who demonstrated worsening papilledema with increased RNFL thickening on OCT testing typically results in symptom relief and disc edema resolution with good visual outcome, often preventing the need for additional definitive surgeries that carry greater failure and morbidity risks.

The "Three on a Stick" Incision-A Curvilinear Solution for the Occipital and Suboccipital Region.

BACKGROUND: Different conditions of the posterior fossa such as Chiari malformations, tumors, and arachnoid cysts require surgery through a suboccipital approach, for which a typical midline vertical linear incision is used. Curvilinear incisions have been carried in all other scalp regions other than the sub region for better cosmetic outcomes; a vertical curvilinear incision in the occipital and suboccipital region has not been reported. OBJECTIVE: To evaluate the cosmetic value and safety of the "3 on a stick" vertical suboccipital curvilinear incision. METHODS: We compared curvilinear to linear incisions, considering the scar's width, color, how conspicuous, and how well the scar could be covered by hair naturally. RESULTS: Between 2010 and 2016, 68 children with Chiari I malformation were surgically intervened. The curvilinear incision was performed in 56 (82.4%) while a linear incision in 12 (17.6%) children. There were only 2 (2.9%) wound related complications (superficial dehiscences) in the curvilinear group and 1 additional dehiscence in a linear incision case. There were no neural or vascular complications. Scars were very similar among the 2 groups; both were equally conspicuous but curvilinear ones seemed to get covered better by hair. CONCLUSION: The "3 on a stick" curvilinear incision of the suboccipital region is safe and allows for better hair coverage of the scar. It can be used for multiple conditions requiring a midline suboccipital or even occipital approach, such as Chiari malformations, tumors, and cysts.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

Surgical Management of Giant Retrocerebellar Arachnoid Cysts with a Cystoventricular Stent After Long-Term, Independent, and Simultaneous Intracystic and Intraventricular Pressure Monitoring.

BACKGROUND: Outcomes of surgical treated patients with giant retrocerebellar arachnoid cysts with the available typically preferred techniques frequently are unsatisfactory. OBJECTIVES: We hypothesized that a pressure gradient may exist between the cyst and the ventricular system that may be responsible for the posterior fossa-related symptoms and headaches, and, if so, that connecting both cavities by means of a shunt catheter (i.e., cystoventricular stent), the pressure differences would equilibrate and the symptoms resolve. To prove our hypothesis, we decided to simultaneously monitor the intracyst pressure and the intraventricular pressure. METHODS: This was a retrospective chart review analysis of 5 consecutive patients with giant retrocerebellar arachnoid cysts treated between 2014 and 2016. RESULTS: Four patients underwent 3 days of continuous intracranial pressure monitoring, and 1 patient was monitored in the surgical suit. Cyst and ventricular pressures tended to be within normal accepted values in all patients, and a pressure gradient was noticed only in the 2 patients with previous cyst surgeries. All patients were treated with a cystoventricular stent, and overall, had long-term sustained good outcomes, with resolution of symptoms in 3 and significant improvement in 2. CONCLUSIONS: Patients with symptomatic large retrocerebellar arachnoid cysts do not seem to have increased intracranial pressure, and regardless of the presence or absence of a pressure gradient between the cyst and the ventricles, a cystoventricular stent seems to be effective and the best first surgical option to offer.

The Acetazolamide Challenge: A Tool for Surgical Decision Making and Predicting Surgical Outcome in Patients with Arachnoid Cysts.

Background and Study Aims Arachnoid cysts (ACs) are benign congenital malformations of the arachnoid that may present with either localizing or nonspecific symptoms. ACs with mass effect are detected frequently in asymptomatic patients. Conversely, symptomatic patients may present without imaging signs of a focal mass effect that emphasizes the difficulty of relying on imaging as the sole criteria in surgical selection. We hypothesize that symptomatic AC may be related to the elevated fluid pressure within the cyst on surrounding structures. Thus reducing the amount of fluid in the cyst or surrounding cerebrospinal fluid (CSF) by using acetazolamide (AZM), a carbonic anhydrase inhibitor known to reduce CSF production, might mimic surgical decompression and therefore could serve as a decision-making tool in patients with ACs. Methods and Patients A total of 103 patients with radiographically proven ACs were initially identified. Twenty (19.4%) were symptomatic and underwent a trial of oral AZM. Data were collected meeting inclusion/exclusion criteria for this cohort study and analyzed retrospectively/prospectively. Results Overall, 17 patients were able to tolerate the AZM and had at least some subjective improvement in their symptoms during the AZM challenge and underwent surgical therapy. Surgery was beneficial in 16 patients (94.1%). Following surgery, symptoms resolved in 13 patients (76.5%) and improved in 3 (17.6%). Conclusion The AZM challenge may support the clinical decision to recommend surgery in those patients whose symptoms improve during AZM therapy.

Pediatric Primary Diffuse Leptomeningeal Primitive Neuroectodermal Tumor: A Case Report and Literature Review.

BACKGROUND: Primary diffuse leptomeningeal primitive neuroectodermal tumor (PDL PNET) is extremely rare, with only 19 cases reported in the literature to date. We present a case of a child with rapidly progressive PDL PNET and a literature review. A 10-year-old boy presented with mood lability, hallucinations, generalized pain, enuresis, and headaches. Initial investigation failed to produce a diagnosis. The symptoms progressed to seizure, back pain, and papilledema. Imaging showed acute hydrocephalus and mild diffuse leptomeningeal enhancement without an identifiable primary lesion. METHODS: The hydrocephalus was managed with a ventriculostomy - later replaced by a ventriculoperitoneal shunt after ruling out infection. A dura mater biopsy obtained prior to shunt insertion was unrevealing. Repeat MRI at the 2-month follow-up showed severe interval progression of the leptomeningeal enhancement with thick lumbar spinal subdural enhancing areas. A biopsy from the inflamed arachnoid at the L3-L4 level unveiled a leptomeningeal PNET diagnosis. RESULTS: Despite adjuvant therapy with chemoradiation, the disease progressed, and the patient died 22 months after the initial presentation. Nineteen other cases of PDL PNET have been reported in the literature and were analyzed. CONCLUSION: Primary leptomeningeal PNET is an extremely rare disease. Optimal treatment is not well established, and the prognosis is very poor.

Tectal Lesions in Children: A Long-Term Follow-Up Volumetric Tumor Growth Analysis in Surgical and Nonsurgical Cases.

BACKGROUND/AIMS: Different tectal masses have been described; most are low-grade gliomas. Only 20-30% of all lesions grow, as shown on follow-up MRIs, requiring surgical resection at some point. The aim of this study is to describe the experience of a single institution managing pediatric patients with tectal lesions. METHODS: We retrospectively studied and analyzed 40 children with tectal lesions managed from 1990 to 2006; the mean age at diagnosis was 9.4 years. A volumetric classification was used to analyze tumor growth trends. More than 1 year of imaging follow-up was available for 23 patients. RESULTS AND CONCLUSION: Medium- and large-volume-size lesions were associated with the need for surgery. About half of the nonsurgical lesions grew at least 50% over a period of 4.5 years and did not require surgical resection.

Conus Medullaris Level in Vertebral Columns With Lumbosacral Transitional Vertebra.

BACKGROUND: The estimated prevalence of lumbar or sacral transitional vertebrae (LSTV) in the population is 4% to 30%. Few small patient series have studied the normal level of the conus medullaris (CM) in individuals with LSTV. OBJECTIVE: To determine, by using a large cohort of patients, whether individuals of all ages with LSTV have different CM positions in the spinal canal in comparison with the rest of the population with normal vertebral columns. METHODS: We performed an institutional retrospective analysis of spinal magnetic resonance images on individuals with LSTV of all ages, sexes, and pathologies during a 10-year period. Fifty-seven percent of patients (n = 467) had a lumbarized vertebra and 43% had sacralized vertebra (n = 355). Mean age at the time of the study was 55 ± 19 years (range 1-97 years). Fifty-two percent were male and 48% were female. Sixty percent of subjects with a sacralized vertebra were female, and 54.5% of those with a lumbarized vertebra were male (P = .001). RESULTS: The CM in individuals with a lumbarized vertebra was seen to be lower at L1-2 to L2s, than un those with a sacralized vertebra where most conuses were at T12-L1 to L1s (P ≤ 0.001). The CM level was similarly distributed among sexes and ages. CONCLUSION: In our series, the CM level, when lumbarization occurred, was lower, with a mean level at L1-L2, whereas a more superior mean level at T12-L1 was seen when sacralization occurred. CM level was not influenced by sex, age, or pathology other than tethered cords.

Intracranial Injuries from Dog Bites in Children.

BACKGROUND/AIMS: Infants are especially at risk for intracranial injuries from dog bites due to their small stature and thin skull. Only 21 case reports have been published in the literature. We aim to add knowledge and treatment recommendations based on a more substantial sample. METHODS: Ten pediatric patients with a penetrating skull injury as a result of a dog bite, treated at our institution between 1992 and 2010, were identified and analyzed descriptively. A literature review of the 21 case reports was also conducted. RESULTS AND CONCLUSION: Early diagnosis and treatment can prevent complications from hemorrhage or infections. Based on our results, we recommend obtaining a head CT for all victims sustaining injuries to the head, early use of broad spectrum antibiotics, debridement and irrigation of tissue, and follow-up to identify late infectious complications.

Long-term outcome of extratemporal resection in posttraumatic epilepsy.

OBJECT: Posttraumatic epilepsy (PTE) is a common cause of medically intractable epilepsy. While much of PTE is extratemporal, little is known about factors associated with good outcomes in extratemporal resections in medically intractable PTE. The authors investigated and characterized the long-term outcome and patient factors associated with outcome in this population. METHODS: A single-institution retrospective query of all epilepsy surgeries at Regional Epilepsy Center at the University of Washington was performed for a 17-year time span with search terms indicative of trauma or brain injury. The query was limited to adult patients who underwent an extratemporal resection (with or without temporal lobectomy), in whom no other cause of epilepsy could be identified, and for whom minimum 1-year follow-up data were available. Surgical outcomes (in terms of seizure reduction) and clinical data were analyzed and compared. RESULTS: Twenty-one patients met inclusion and exclusion criteria. In long-term follow-up 6 patients (28%) were seizure-free and an additional 6 (28%) had a good outcome of 2 or fewer seizures per year. Another 5 patients (24%) experienced a reduction in seizures, while only 4 (19%) did not attain significant benefit. The presence of focal encephalomalacia on imaging was associated with good or excellent outcomes in 83%. In 8 patients with the combination of encephalomalacia and invasive intracranial EEG, 5 (62.5%) were found to be seizure free. Normal MRI examinations preoperatively were associated with worse outcomes, particularly when combined with multifocal or poorly localized EEG findings. Two patients suffered complications but none were life threatening or disabling. CONCLUSIONS: Many patients with extratemporal PTE can achieve good to excellent seizure control with epilepsy surgery. The risks of complications are acceptably low. Patients with focal encephalomalacia on MRI generally do well. Excellent outcomes can be achieved when extratemporal resection is guided by intracranial EEG electrodes defining the extent of resection.

Failure to treat obstructive hydrocephalus with endoscopic third ventriculostomy in a patient with neurodegenerative Langerhans cell histiocytosis.

The second most frequent central nervous system involvement pattern in Langerhans cell histiocytosis (LCH) is a rare condition documented in a number of reports called "neurodegenerative LCH" (ND-LCH). Magnetic resonance images confirming the presence of the disease usually demonstrate striking symmetric bilateral hyperintensities predominantly in the cerebellum, basal ganglia, pons, and/or cerebral white matter. The authors here describe for the first time in the literature a patient with ND-LCH and concomitant hydrocephalus initially treated using endoscopic third ventriculostomy (ETV). This 9-year-old boy, who had undergone chemotherapy for skin and lung LCH without central nervous system involvement at the age of 10 months, presented with acute ataxia, headaches, and paraparesis and a 1-year history of gradually increasing clumsiness. Magnetic resonance images showed obstructive hydrocephalus at the level of the aqueduct of Sylvius and signs of ND-LCH. After registering high intracranial pressure (ICP) spikes with an intraparenchymal pressure monitor, an ETV was performed. A second ETV was required months later because of ostomy occlusion, and finally a ventriculoperitoneal shunt was placed because of ostomy reocclusion. Endoscopic third ventriculostomy was initially considered the treatment of choice to divert cerebrospinal fluid without leaving a ventriculoperitoneal shunt and to obtain biopsy specimens from the periinfundibular recess area. The third ventriculostomy occluded twice, and an endoscopic aqueduct fenestration was unsuccessful. The authors hypothesized that an inflammatory process related to late ND disease was responsible for the occlusions. Biopsy specimens from the infundibular recess and fornix column did not show histopathogical abnormalities. Increased ICP symptoms resolved with cerebrospinal fluid diversion. This case is the first instance of ND-LCH with hydrocephalus reported in the literature to date. Shunt placement rather than ETV seems to be the favorable choice in relieving elevated ICP.

Brain computed tomography angiographic scans as the sole diagnostic examination for excluding aneurysms in patients with perimesencephalic subarachnoid hemorrhage.

OBJECTIVE: In an era in which new computed tomographic scanners approach 100% sensitivity for finding intracranial aneurysms in patients with a perimesencephalic subarachnoid hemorrhage (SAH) pattern, digital subtraction angiography (DSA) is still considered the gold standard. Our purpose was to investigate whether or not computed tomography angiographic (CTA) scanning can be used as the sole diagnostic tool in this setting, and thus replace DSA. METHODS: Two hundred fifty patients with atraumatic SAH presented to our institute between November 2001 and November 2005. We performed a retrospective search for those patients who had a negative brain CTA scan for aneurysms. Of these, those with a computed tomographic scan showing perimesencephalic SAH at admission were selected, and only those who had DSA performed were included. RESULTS: We found 30 patients with negative brain CTA scans that matched the perimesencephalic SAH pattern and had DSA performed. The mean time for performing a brain CTA scan was 3.8 +/- 4.4 days, and for DSA 11 +/- 12 days, after the initiation of symptomatology. The interval between CTA and DSA was 5.9 +/- 15 days. There were two patients in whom CTA was considered negative but still suspicious for having an aneurysm; DSA was negative for both. CONCLUSION: Brain CTA scanning alone is a good and conclusive diagnostic tool to rule out aneurysms in patients presenting with the classic perimesencephalic SAH pattern and thus can replace DSA and its corresponding risks. The latter can be reserved for those patients in whom CTA is doubtful.

Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop.

Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies.