Publications by authors named "Kurtis I Auguste"

60 Publications

somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case.

J Neurosurg Case Lessons 2022 Jun 6;3(23):CASE2247. Epub 2022 Jun 6.

Departments of Ophthalmology.

Background: In the past decade, next-generation sequencing has spurred significant progress in the understanding of cytogenetic alterations that occur in meningiomas. Eighty percent of adult meningiomas harbor pathogenic somatic variants involving , , , , , or Somatic variants in associated with meningiomas usually localize to the gene's WD40 domains but are mutually exclusive to germline mutations, which cause a distinctive autosomal dominant syndrome.

Observations: This case involved a 15-year-old girl with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis, and syndromic features, including craniosynostosis, brain anomalies, syndactyly, brachydactyly, epicanthus, and patent ductus arteriosus. Genetic testing of the meningioma specimen 7 years after biopsy showed a pathogenic p.R641C variant within the WD40 domain of the gene. Additional testing of unaffected tissues identified the same variant at lower allele frequencies, consistent with postzygotic somatic mosaicism.

Lessons: The authors report postzygotic somatic mosaicism for a p.R641C variant in the gene in a patient with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis and a constellation of systemic findings previously recognized in patients with germline mutations of this gene. This is the first report of optic nerve sheath meningioma in a patient with mutation in the gene.
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http://dx.doi.org/10.3171/CASE2247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204931PMC
June 2022

The Hybrid Operative Suite with Intraoperative Biplane Rotational Angiography in Pediatric Cerebrovascular Neurosurgery: Utility and Lessons Learned.

Pediatr Neurosurg 2022 4;57(4):245-259. Epub 2022 May 4.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Introduction: The benefits of performing open and endovascular procedures in a hybrid neuroangiography surgical suite include confirmation of treatment results and reduction in number of procedures, leading to improved efficiency of care. Combined procedural suites are infrequently used in pediatric facilities due to technical and logistical limitations. We report the safety, utility, and lessons learned from a single-institution experience using a hybrid suite equipped with biplane rotational digital subtraction angiography and pan-surgical capabilities.

Methods: We conducted a retrospective review of consecutive cases performed at our institution that utilized the hybrid neuroangiography surgical suite from February 2020 to August 2021. Demographics, surgical metrics, and imaging results were collected from the electronic medical record. Outcomes, interventions, and nuances for optimizing preoperative/intraoperative setup and postoperative care were presented.

Results: Eighteen procedures were performed in 17 patients (mean age 13.4 years, range 6-19). Cases included 14 arteriovenous malformations (AVM; 85.7% ruptured), one dural arteriovenous fistula, one mycotic aneurysm, and one hemangioblastoma. The average operative time was 416 min (range 321-745). There were no intraoperative or postoperative complications. All patients were alive at follow-up (range 0.1-14.7 months). Five patients had anticipated postoperative deficits arising from their hemorrhage, and 12 returned to baseline neurological status. Four illustrative cases demonstrating specific, unique applications of the hybrid angiography suite are presented.

Conclusion: The hybrid neuroangiography surgical suite is a safe option for pediatric cerebrovascular pathologies requiring combined surgical and endovascular intervention. Hybrid cases can be completed within the same anesthesia session and reduce the need for return to the operating room for resection or surveillance angiography. High-quality intraoperative angiography enables diagnostic confirmation under a single procedure, mitigating risk of morbidity and accelerating recovery. Effective multidisciplinary planning enables preoperative angiograms to be completed to inform the operative plan immediately prior to definitive resection.
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http://dx.doi.org/10.1159/000524875DOI Listing
August 2022

Repetitive transcranial magnetic stimulation (rTMS) as therapy in an infant with epilepsia partialis continua.

Epilepsy Behav Rep 2022 28;18:100511. Epub 2021 Nov 28.

University of California, San Francisco, Department of Neurosurgery, 400 Parnassus Ave 8 Floor, San Francisco, CA 94143, United States.

We present a case of a 10-month-old girl undergoing repetitive TMS (rTMS) for the treatment of drug-resistant epilepsy. A 10-month-old girl, later diagnosed with pathogenic POLG1 mutations, presented to our institution with chronic progressive EPC (epilepsia partialis continua) manifesting as a frequent, left-sided, synchronous continuous jerking of the arms and legs. The seizures were drug-resistant to multiple antiseizure medications and epilepsy surgery, responding only to continuous anesthesia. rTMS therapy was attempted to interrupt seizures. rTMS therapy, using an activating protocol to introduce a temporary lesion effect, was used to interrupt persistent, ongoing seizures. rTMS can be safely used to abort seizures in patients as young as 10 months old.
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http://dx.doi.org/10.1016/j.ebr.2021.100511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850736PMC
November 2021

Superior Long-term Appearance of Strip Craniectomy Compared with Cranial Vault Reconstruction in Metopic Craniosynostosis.

Plast Reconstr Surg Glob Open 2022 Feb 9;10(2):e4097. Epub 2022 Feb 9.

Division of Plastic and Reconstructive Surgery, Department of Surgery, UCSF Craniofacial Center, University of California San Francisco, San Francisco, Calif.

Background: Strip craniectomy with orthotic helmet therapy (SCOT) is an increasingly supported treatment for metopic craniosynostosis, although the long-term efficacy of deformity correction remains poorly defined. We compared the longterm outcomes of SCOT versus open cranial vault reconstruction (OCVR).

Methods: Patients who underwent OCVR or SCOT for isolated metopic synostosis with at least 3 years of follow-up were identified at our institution. Anthropometric measurements were used to assess baseline severity and postoperative skull morphology. Independent laypersons and craniofacial surgeons rated the appearance of each patient's 3D photographs, compared to normal controls.

Results: Thirty-five patients were included (15 SCOT and 20 OCVR), with similar follow-up between groups (SCOT 7.9 ± 3.2 years, OCVR 9.2 ± 4.1 years). Baseline severity and postoperative anthropometric measurements were equivalent. Independent adolescent raters reported that the forehead, eye, and overall appearance of SCOT patients was better than OCVR patients ( < 0.05, all comparisons). Craniofacial surgeons assigned Whitaker class I to a greater proportion of SCOT patients with moderate-to-severe synostosis (72.2 ± 5.6%) compared with OCVR patients with the same severity (33.3 ± 9.2%, = 0.02). Parents of children who underwent SCOT reported equivalent satisfaction with the results of surgery (100% versus 95%, > 0.99), and were no more likely to report bullying (7% versus 15%, = 0.82).

Conclusions: SCOT was associated with superior long-term appearance and perioperative outcomes compared with OCVR. These findings suggest that SCOT should be the treatment of choice for patients with a timely diagnosis of metopic craniosynostosis.
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http://dx.doi.org/10.1097/GOX.0000000000004097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830858PMC
February 2022

Navigated transcranial magnetic stimulation mapping of the motor cortex for preoperative diagnostics in pediatric epilepsy.

J Neurosurg Pediatr 2021 Jun 25:1-8. Epub 2021 Jun 25.

3Department of Neurosurgery, University of California, San Francisco, California.

Objective: Navigated transcranial magnetic stimulation (nTMS) is a noninvasive technique often used for localization of the functional motor cortex via induction of motor evoked potentials (MEPs) in neurosurgical patients. There has, however, been no published record of its application in pediatric epilepsy surgery. In this study, the authors aimed to investigate the feasibility of nTMS-based motor mapping in the preoperative diagnostic workup within a population of children with medically refractory epilepsy.

Methods: A single-institution database was screened for preoperative nTMS motor mappings obtained in pediatric patients (aged 0 to 18 years, 2012 to present) with medically refractory epilepsy. Patient clinical data, demographic information, and mapping results were extracted and used in statistical analyses.

Results: Sixteen patients met the inclusion criteria, 15 of whom underwent resection. The median age was 9 years (range 0-17 years). No adverse effects were recorded during mapping. Specifically, no epileptic seizures were provoked via nTMS. Recordings of valid MEPs induced by nTMS were obtained in 10 patients. In the remaining patients, no MEPs could be elicited. Failure to generate MEPs was associated significantly with younger patient age (r = 0.8020, p = 0.0001863). The most frequent seizure control outcome was Engel Epilepsy Surgery Outcome Scale class I (9 patients).

Conclusions: Navigated TMS is a feasible, effective, and well-tolerated method for mapping the motor cortex of the upper and lower extremities in pediatric patients with epilepsy. Patient age modulates elicitability of MEPs, potentially reflecting various stages of myelination. Successful motor mapping has the potential to add to the existing presurgical diagnostic workup in this population, and further research is warranted.
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http://dx.doi.org/10.3171/2021.2.PEDS20901DOI Listing
June 2021

Direct brain recordings reveal occipital cortex involvement in memory development.

Neuropsychologia 2020 11 15;148:107625. Epub 2020 Sep 15.

Life-Span Cognitive Neuroscience Program, Institute of Gerontology and Merrill Palmer Skillman Institute, Wayne State University, Detroit, MI, USA; Department of Psychology, Wayne State University, Detroit, MI, USA. Electronic address:

Processing of low-level visual information shows robust developmental gains through childhood and adolescence. However, it is unknown whether low-level visual processing in the occipital cortex supports age-related gains in memory for complex visual stimuli. Here, we examined occipital alpha activity during visual scene encoding in 24 children and adolescents, aged 6.2-20.5 years, who performed a subsequent memory task while undergoing electrocorticographic recording. Scenes were classified as high- or low-complexity by the number of unique object categories depicted. We found that recognition of high-complexity, but not low-complexity, scenes increased with age. Age was associated with decreased alpha power and increased instantaneous alpha frequency during the encoding of subsequently recognized high- compared to low-complexity scenes. Critically, decreased alpha power predicted improved recognition of high-complexity scenes in adolescents. These findings demonstrate how the functional maturation of the occipital cortex supports the development of memory for complex visual scenes.
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http://dx.doi.org/10.1016/j.neuropsychologia.2020.107625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704894PMC
November 2020

Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor.

Acta Neuropathol Commun 2020 08 28;8(1):151. Epub 2020 Aug 28.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.

The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA or PIK3R1 mutation that characterizes RGNT. The glial component of LGNET with FGFR1 alterations typically has a predominantly oligodendroglial morphology, and many of the pilocytic astrocytomas with FGFR1 alterations lack the biphasic pattern, piloid processes, and Rosenthal fibers that characterize pilocytic astrocytomas with BRAF mutation or fusion. Together, this analysis improves the classification and histopathologic stratification of LGNET with FGFR1 alterations.
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http://dx.doi.org/10.1186/s40478-020-01027-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456392PMC
August 2020

Single-center series of boys with recurrent strokes and rotational vertebral arteriopathy.

Neurology 2020 09 20;95(13):e1830-e1834. Epub 2020 Jul 20.

From the Departments of Neurology (C.K.F., H.J.F.), Pediatrics (C.K.F., H.J.F., K.I.A., N.G.), Radiology and Biomedical Imaging (S.W.H., V.V.H.), and Neurological Surgery (K.I.A., M.T.L., N.G.), University of California San Francisco; and Department of Neurological Surgery (M.T.L.), Barrow Neurological Institute, Phoenix, AZ.

Objective: To describe a pediatric stroke syndrome with chronic focal vertebral arteriopathy adjacent to cervical abnormalities.

Methods: At a single pediatric stroke center, we identified consecutive children with stroke and vertebral arteriopathy of the V3 segment with adjacent cervical bony or soft tissue abnormalities. We abstracted clinical presentation, treatment, and follow-up data from medical charts.

Results: From 2005 to 2019, 10 children (all boys, ages 6-16 years) presented with posterior circulation strokes and vertebral arteriopathy with adjacent cervical pathology. Two children had bony abnormalities: one had a congenital arcuate foramen and one had os odontoideum with cervical instability. In children without bony pathology, vertebral artery narrowing during contralateral head rotation was visualized by digital subtraction angiography. Eight boys had recurrent ischemic events despite anti-thrombotic treatment (including 5 with multiple recurrences) and were treated surgically to prevent additional stroke. Procedures included vertebral artery decompression (n = 6), endovascular stent and spinal fusion (n = 1), and vertebral artery endovascular occlusion (n = 1). In boys treated with decompression, cervical soft tissue abnormalities (ruptured atlantoaxial bursa, ruptured joint capsule, or connective tissue scarring) were directly visualized during open surgery. No other etiology for stroke or dissection was found in any of the cases. Two boys without recurrent stroke were treated with activity restriction and antithrombotics. At a median follow-up of 51 months (range 17-84), there have been no additional recurrences.

Conclusions: Children with V3 segmental vertebral arteriopathy frequently have stroke recurrence despite antithrombotics. Cervical bone imaging and angiography with neck rotation can identify underlying pathology.
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http://dx.doi.org/10.1212/WNL.0000000000010416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682823PMC
September 2020

Extradural thoracic meningeal cyst without spinal dysraphism causing adulthood myelopathy: Case illustration and review of the literature.

J Clin Neurosci 2020 Aug 26;78:433-438. Epub 2020 Jun 26.

Department of Neurological Surgery, University of California San Francisco, United States.

Extradural spinal meningeal cysts are rare lesions in the adult spine and are an uncommon cause of neurologic deficits. We present the case of an adult who presented with myelopathic symptoms related to a dorsally based extradural thoracic meningeal cyst in the absence of any defect in the posterior spinal elements and no history of spinal dysraphism or trauma. We also performed a review of the literature to evaluate the surgical techniques for extradural meningeal cysts. Most thoracic cysts are intradural arachnoid cysts, yet this lesion is an extradural meningeal cyst, not an intradural arachnoid cyst. Because of the rarity of this lesion, its anatomic characterization can be difficult to conceptualize. An artist's illustration helps illustrate the anatomic characteristics of this cyst and our surgical management.
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http://dx.doi.org/10.1016/j.jocn.2020.05.039DOI Listing
August 2020

Meningiomas in children.

Handb Clin Neurol 2020 ;169:253-259

Division of Pediatric Neurosurgery, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States. Electronic address:

Meningiomas in children are poorly understood because they are rare. Recent reports have provided a more complete description of their incidence, genetics, imaging features, and outcome. In general, meningiomas in children are more likely to be higher grade, present in atypical locations, and have a higher risk of recurrence. The challenges encountered in children with respect to surgical and postoperative management are unique. Improved understanding of pediatric meningiomas, as well as the availability of new surgical, medical, and radiation therapies, creates opportunities to improve outcomes in this unique population.
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http://dx.doi.org/10.1016/B978-0-12-804280-9.00016-0DOI Listing
April 2021

Does Adult Neurogenesis Persist in the Human Hippocampus?

Cell Stem Cell 2018 12;23(6):780-781

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

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http://dx.doi.org/10.1016/j.stem.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800191PMC
December 2018

Responsive neurostimulation for treatment of pediatric drug-resistant epilepsy.

Epilepsy Behav Case Rep 2018 12;10:21-24. Epub 2018 Mar 12.

Department of Neurology, University of California, San Francisco, USA.

Responsive neurostimulation for epilepsy involves an implanted device that delivers direct electrical brain stimulation in response to detection of incipient seizures. Responsive neurostimulation is a safe and effective treatment for adults with drug-resistant epilepsy, but although novel treatments are critically needed for younger patients, responsive neurostimulation is currently not approved for children with drug-resistant epilepsy. Here, we report a 16-year-old patient with seizures arising from eloquent cortex, who was successfully treated with responsive neurostimulation. This case highlights the potential utility of this therapy for pediatric patients and underscores the need for larger studies.
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http://dx.doi.org/10.1016/j.ebcr.2018.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019859PMC
March 2018

Complications following pediatric cranioplasty after decompressive craniectomy: a multicenter retrospective study.

J Neurosurg Pediatr 2018 09 8;22(3):225-232. Epub 2018 Jun 8.

17Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.

OBJECTIVE In children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty. METHODS The authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty. RESULTS A total of 359 patients met the inclusion criteria. The patients' mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17-4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03-5.79), and ventilator dependence (OR 8.45, 95% CI 1.10-65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection. Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98-0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts. CONCLUSIONS This is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.
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http://dx.doi.org/10.3171/2018.3.PEDS17234DOI Listing
September 2018

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

Nature 2018 03 7;555(7696):377-381. Epub 2018 Mar 7.

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.
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http://dx.doi.org/10.1038/nature25975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179355PMC
March 2018

Laser ablative therapy of sessile hypothalamic hamartomas in children using interventional MRI: report of 5 cases.

J Neurosurg Pediatr 2018 05 16;21(5):460-465. Epub 2018 Feb 16.

Departments of1Neurological Surgery and.

Hypothalamic hamartomas (HHs) are benign lesions that cause medically refractory seizures, behavioral disturbances, and endocrine dysfunction. Open resection of HHs does not guarantee seizure freedom and carries a relatively high risk of morbidity. Minimally invasive stereotactic laser ablation has recently been described as an effective and safe alternative for HH treatment. Prior studies have not, however, assessed HH lesion size and morphology, 2 factors that may influence treatment results and, ultimately, the generalizability of their findings. In this paper, the authors describe seizure outcomes for 5 pediatric patients who underwent laser ablation of sessile HHs. Lesions were treated using a frameless, interventional MRI-guided approach, which facilitated laser targeting to specific components of these complex lesions. The authors' experiences in these cases substantiate prior work demonstrating the effectiveness of laser therapy for HHs, while elucidating HH complexity as a potentially important factor in laser treatment planning, and in the interpretation of early studies describing this treatment method.
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http://dx.doi.org/10.3171/2017.10.PEDS17292DOI Listing
May 2018

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

Proc Natl Acad Sci U S A 2017 06 22;114(23):E4530-E4538. Epub 2017 May 22.

Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, CA 94720-3190.

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.
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http://dx.doi.org/10.1073/pnas.1620669114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468648PMC
June 2017

Surgical management of medically refractory epilepsy in patients with polymicrogyria.

Epilepsia 2016 Jan 9;57(1):151-61. Epub 2015 Dec 9.

Department of Neurological Surgery, UCSF Comprehensive Epilepsy Center, University of California, San Francisco, California, U.S.A.

Objective: Polymicrogyria (PMG) is a malformation of cortical development characterized by formation of an excessive number of small gyri. Sixty percent to 85% of patients with PMG have epilepsy that is refractory to medication, but surgical options are usually limited. We characterize a cohort of patient with polymicrogyria who underwent epilepsy surgery and document seizure outcomes.

Methods: A retrospective study of all patients with PMG who underwent epilepsy surgery (focal seizure foci resection and/or hemispherectomy) at our center was performed by review of all clinical data related to their treatment.

Results: We identified 12 patients (7 males and 5 female) with mean age of 18 (ranging from 3 months to 44 years) at time of surgery. Mean age at seizure onset was 8 years, with the majority (83%) having childhood onset. Six patients had focal, five had multifocal, and one patient had diffuse PMG. Perisylvian PMG was the most common pattern seen on magnetic resonance imaging (MRI). Eight patients had other cortical malformations including hemimegalencephaly and cortical dysplasia. Scalp electroencephalography (EEG) often showed diffuse epileptic discharges that poorly lateralized but were focal on intracranial electrocorticography (ECoG). Eight patients underwent seizure foci resection and four underwent hemispherectomy. Mean follow-up was 7 years (ranging from one to 19 years). Six patients (50%) were seizure-free at last follow-up. One patient had rare seizures (Engel class II). Three patients were Engel class III, having either decreased seizure frequency or severity, and two patients were Engel class IV. Gross total resection of the PMG cortex trended toward good seizure control.

Significance: Our study shows that even in patients with extensive or bilateral PMG malformations, some may still be good candidates for surgery because the epileptogenic zone may involve only a portion of the malformation. Intracranial ECoG can provide additional localizing information compared to scalp EEG in guiding resection of epileptogenic foci.
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http://dx.doi.org/10.1111/epi.13264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237579PMC
January 2016

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 5: Effect of valve type on cerebrospinal fluid shunt efficacy.

J Neurosurg Pediatr 2014 Nov;14 Suppl 1:35-43

Department of Neurological Surgery, Saint Louis University, St. Louis, Missouri

Object: The objective of this systematic review was to examine the existing literature to compare differing shunt components used to treat hydrocephalus in children, find whether there is a superior shunt design for the treatment of pediatric hydrocephalus, and make evidence-based recommendations for the selection of shunt implants when placing shunts.

Methods: Both the US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words chosen to identify publications comparing the use of shunt implant components. Abstracts of these publications were reviewed, after which studies meeting the inclusion criteria were selected. An evidentiary table was compiled summarizing the selected articles and quality of evidence. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider evidence-based treatment recommendations.

Results: Two hundred sixty-nine articles were identified using the search parameters, and 43 articles were recalled for full-text review. Of these, 22 papers met the study criteria for a comparison of shunt components and were included in the evidentiary table. The included studies consisted of 1 Class I study, 11 Class II studies, and 10 Class III studies. The remaining 21 articles were excluded.

Conclusions: An analysis of the evidence did not demonstrate a clear advantage for any specific shunt component, mechanism, or valve design over another.

Recommendation: There is insufficient evidence to demonstrate an advantage for one shunt hardware design over another in the treatment of pediatric hydrocephalus. Current designs described in the evidentiary tables are all treatment options.

Strength Of Recommendation: Level I, high degree of clinical certainty.

Recommendation: There is insufficient evidence to recommend the use of a programmable valve versus a nonprogrammable valve. Programmable and nonprogrammable valves are both options for the treatment of pediatric hydrocephalus.

Strength Of Recommendation: Level II, moderate degree of clinical certainty.
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http://dx.doi.org/10.3171/2014.7.PEDS14325DOI Listing
November 2014

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 2: Management of posthemorrhagic hydrocephalus in premature infants.

J Neurosurg Pediatr 2014 Nov;14 Suppl 1:8-23

Department of Neurological Surgery, Saint Louis University, St. Louis, Missouri

Object: The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment strategies for posthemorrhagic hydrocephalus (PHH) in premature infants?

Methods: Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to PHH. Two hundred thirteen abstracts were reviewed, after which 98 full-text publications that met inclusion criteria that had been determined a priori were selected and reviewed.

Results: Following a review process and an evidentiary analysis, 68 full-text articles were accepted for the evidentiary table and 30 publications were rejected. The evidentiary table was assembled linking recommendations to strength of evidence (Classes I-III).

Conclusions: There are 7 recommendations for the management of PHH in infants. Three recommendations reached Level I strength, which represents the highest degree of clinical certainty. There were two Level II and two Level III recommendations for the management of PHH. Recommendation Concerning Surgical Temporizing Measures: I. Ventricular access devices (VADs), external ventricular drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment is required.

Strength Of Recommendation: Level II, moderate degree of clinical certainty. Recommendation Concerning Surgical Temporizing Measures: II. The evidence demonstrates that VSG shunts reduce the need for daily CSF aspiration compared with VADs.

Strength Of Recommendation: Level II, moderate degree of clinical certainty. Recommendation Concerning Routine Use of Serial Lumbar Puncture: The routine use of serial lumbar puncture is not recommended to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants.

Strength Of Recommendation: Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.

Strength Of Recommendation: Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents. II. Acetazolamide and furosemide are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.

Strength Of Recommendation: Level I, high clinical certainty. Recommendation Concerning Timing of Shunt Placement: There is insufficient evidence to recommend a specific weight or CSF parameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required.

Strength Of Recommendation: Level III, unclear clinical certainty. Recommendation Concerning Endoscopic Third Ventriculostomy: There is insufficient evidence to recommend the use of endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus.

Strength Of Recommendation: Level III, unclear clinical certainty.
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http://dx.doi.org/10.3171/2014.7.PEDS14322DOI Listing
November 2014

Fast dynamic imaging technique to identify obstructive lesions in the CSF space: report of 2 cases.

J Neurosurg Pediatr 2015 May 27;15(5):519-23. Epub 2015 Feb 27.

Department of Neurological Surgery, University of California, San Francisco; and.

Disorders of CSF dynamics such as syringomyelia and obstructive hydrocephalus can be caused by thin mobile obstructive lesions not visible on traditional MRI sequences. New imaging techniques with balanced steady-state free precession (bSSFP) and dynamic imaging with bSSFP cine allow visualization of these pulsatile structures within the CSF space. The authors present 2 cases involving pediatric patients-one who developed presumed idiopathic syringomyelia and one with presumed communicating hydrocephalus in association with Pfeiffer syndrome-who harbored thin dynamic obstructive lesions seen on bSSFP cine studies using 1.5-T MRI. In combination with traditional CSF cine studies and bSSFP, bSSFP cine sequence was able to detect dynamic membranous adhesions not seen on traditional MRI sequences. These previously undetectable lesions on traditional MRI sequences were the etiology of CSF obstruction, and tailored surgical approaches were performed to avoid shunting in both patients. These reports demonstrate the clinical utility for using these novel imaging tools for the detection of thin adhesions and dynamic lesions in the central nervous system. Balanced SSFP cine sequences can supplement conventional MR modalities to identify these otherwise poorly visualized lesions responsible for presumed communicating hydrocephalus or idiopathic syringomyelia.
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http://dx.doi.org/10.3171/2014.11.PEDS13620DOI Listing
May 2015

Unilateral holohemispheric central nervous system lesions associated with medically refractory epilepsy in the pediatric population: a retrospective series of hemimegalencephaly and Rasmussen's encephalitis.

J Neurosurg Pediatr 2014 Dec 10;14(6):573-84. Epub 2014 Oct 10.

Departments of Neurological Surgery.

Object: Cortical malformations and inflammatory encephalopathy are among common etiologies for medically refractory epilepsy in children. On rare occasions, lesions can affect an entire cerebral hemisphere while sparing the other; the 2 processes that can manifest in this manner are hemimegalencephaly (HME) and Rasmussen's encephalitis (RE). Although the clinical course and radiological appearance between the 2 disorders are distinct, there is occasional overlapping pathology between RE and cortical migration disorders. One question that arises from these observations is whether RE and HME, diseases with holohemispheric involvement but apparently different etiologies, have any overlapping characteristics.

Methods: The authors performed a retrospective review of all patients with presumed diagnosis of HME or RE who underwent hemispherectomy at University of California, San Francisco, and reviewed their clinical presentation, imaging, and pathology data.

Results: The authors present the clinicopathological features of 14 pediatric patients with unilateral holohemispheric lesions associated with medically refractory epilepsy. Radiological and pathological assessment classified 7 of the patients as having hemimegalencephaly, while the other 7 were diagnosed as having RE. Four of the patients had unusual features suggestive of overlapping developmental and inflammatory (dual) pathology. All patients underwent hemispherectomies. Eight patients (57%) became seizure free (Engel Class I), 5 patients (36%) had rare seizures (Engel Class II), and 1 patient had significant seizure reduction (Engel Class III).

Conclusions: Based on this case series, HME and RE can be distinguished on the basis of their radiological and histological appearance, even though some cases may have overlapping features. Hemispherectomy was effective at eliminating seizures for both HME and RE.
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http://dx.doi.org/10.3171/2014.8.PEDS13613DOI Listing
December 2014

Factors associated with failed focal neocortical epilepsy surgery.

Neurosurgery 2014 Dec;75(6):648-5;discussion 655; quiz 656

*Department of Neurological Surgery, ‡UCSF Comprehensive Epilepsy Center, and §Department of Neurology, University of California, San Francisco, California.

Background: Seizure outcomes after focal neocortical epilepsy (FNE) surgery are less favorable than after temporal lobectomy, and the reasons for surgical failure are incompletely understood. Few groups have performed an in-depth examination of seizure recurrences to identify possible reasons for failure.

Objective: To elucidate factors contributing to FNE surgery failures.

Methods: We reviewed resections for drug-resistant FNE performed at our institution between 1998 and 2011. We performed a quantitative analysis of seizure outcome predictors and a detailed qualitative review of failed surgical cases.

Results: Of 138 resections in 125 FNE patients, 91 (66%) resulted in freedom from disabling seizures (Engel I outcome). Mean ± SEM patient age was 20.0 ± 1.2 years; mean follow-up was 3.8 years (range, 1-17 years); and 57% of patients were male. Less favorable (Engel II-IV) seizure outcome was predicted by higher preoperative seizure frequency (odds ratio = 0.85; 95% confidence interval, 0.78-0.93), a history of generalized tonic-clonic seizures (odds ratio = 0.42; 95% confidence interval, 0.18-0.97), and normal magnetic resonance imaging (odds ratio = 0.30; 95% confidence interval, 0.09-1.02). Among 36 surgical failures examined, 26 (72%) were related to extent of resection, with residual epileptic focus at the resection margins, whereas 10 (28%) involved location of resection, with an additional epileptogenic zone distant from the resection. Of 16 patients who received reoperation after seizure recurrence, 10 (63%) achieved seizure freedom.

Conclusion: Insufficient extent of resection is the most common reason for recurrent seizures after FNE surgery, although some patients harbor a remote epileptic focus. Many patients with incomplete seizure control are candidates for reoperation.
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http://dx.doi.org/10.1227/NEU.0000000000000530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393951PMC
December 2014

Dynamic changes in phase-amplitude coupling facilitate spatial attention control in fronto-parietal cortex.

PLoS Biol 2014 Aug 26;12(8):e1001936. Epub 2014 Aug 26.

Department of Psychology, University of California, Berkeley, Berkeley, California, United States of America; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, United States of America.

Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70-250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2-5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.
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http://dx.doi.org/10.1371/journal.pbio.1001936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144794PMC
August 2014

Management of central nervous system teratoma.

J Clin Neurosci 2015 Jan 21;22(1):98-104. Epub 2014 Aug 21.

Department of Neurological Surgery, University of California at San Francisco, 505 Parnassus Avenue, Box 0112, San Francisco, CA 94143-0112, USA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Central nervous system (CNS) teratomas are very rare neoplasms that contain tissues derived from all three germ cell layers (endoderm, mesoderm, and ectoderm). Patients with teratomas usually have a good prognosis. Given the paucity of cases in the literature, we present a retrospective review of 15 CNS teratomas treated over a 25 year period at the University of California, San Francisco. We describe the presentation, location, treatment, and adjuvant therapy for these patients, and highlight three unique cases that emphasize the diverse presentation and treatment of these rare tumors.
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http://dx.doi.org/10.1016/j.jocn.2014.03.039DOI Listing
January 2015

Epilepsy surgery failure in children: a quantitative and qualitative analysis.

J Neurosurg Pediatr 2014 Oct 15;14(4):386-95. Epub 2014 Aug 15.

UCSF Comprehensive Epilepsy Center and 

Object: Resection is a safe and effective treatment option for children with pharmacoresistant focal epilepsy, but some patients continue experience seizures after surgery. While most studies of pediatric epilepsy surgery focus on predictors of postoperative seizure outcome, these factors are often not modifiable, and the reasons for surgical failure may remain unclear.

Methods: The authors performed a retrospective cohort study of children and adolescents who received focal resective surgery for pharmacoresistant epilepsy. Both quantitative and qualitative analyses of factors associated with persistent postoperative seizures were conducted.

Results: Records were reviewed from 110 patients, ranging in age from 6 months to 19 years at the time of surgery, who underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of patients were free of disabling seizures (Engel Class I outcome). Seizure freedom was predicted by temporal lobe surgery compared with extratemporal resection, tumor or mesial temporal sclerosis compared with cortical dysplasia or other pathologies, and by a lower preoperative seizure frequency. Factors associated with persistent seizures (Engel Class II-IV outcome) included residual epileptogenic tissue adjacent to the resection cavity (40%), an additional epileptogenic zone distant from the resection cavity (32%), and the presence of a hemispheric epilepsy syndrome (28%).

Conclusions: While seizure outcomes in pediatric epilepsy surgery may be improved by the use of high-resolution neuroimaging and invasive electrographic studies, a more aggressive resection should be considered in certain patients, including hemispherectomy if a hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment expectations is critical, and reoperation may be warranted in select cases.
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http://dx.doi.org/10.3171/2014.7.PEDS13658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393949PMC
October 2014

Intraoperative changes in transcranial motor evoked potentials and somatosensory evoked potentials predicting outcome in children with intramedullary spinal cord tumors.

J Neurosurg Pediatr 2014 Jun 4;13(6):591-9. Epub 2014 Apr 4.

Departments of Neurological Surgery and.

Object: Intraoperative dorsal column mapping, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) have been used in adults to assist with the resection of intramedullary spinal cord tumors (IMSCTs) and to predict postoperative motor deficits. The authors sought to determine whether changes in MEP and SSEP waveforms would similarly predict postoperative motor deficits in children.

Methods: The authors reviewed charts and intraoperative records for children who had undergone resection for IMSCTs as well as dorsal column mapping and TcMEP and SSEP monitoring. Motor evoked potential data were supplemented with electromyography data obtained using a Kartush microstimulator (Medtronic Inc.). Motor strength was graded using the Medical Research Council (MRC) scale during the preoperative, immediate postoperative, and follow-up periods. Reductions in SSEPs were documented after mechanical traction, in response to maneuvers with the cavitational ultrasonic surgical aspirator (CUSA), or both.

Results: Data from 12 patients were analyzed. Three lesions were encountered in the cervical and 7 in the thoracic spinal cord. Two patients had lesions of the cervicomedullary junction and upper spinal cord. Intraoperative MEP changes were noted in half of the patients. In these cases, normal polyphasic signals converted to biphasic signals, and these changes correlated with a loss of 1-2 grades in motor strength. One patient lost MEP signals completely and recovered strength to MRC Grade 4/5. The 2 patients with high cervical lesions showed neither intraoperative MEP changes nor motor deficits postoperatively. Dorsal columns were mapped in 7 patients, and the midline was determined accurately in all 7. Somatosensory evoked potentials were decreased in 7 patients. Two patients each had 2 SSEP decreases in response to traction intraoperatively but had no new sensory findings postoperatively. Another 2 patients had 3 traction-related SSEP decreases intraoperatively, and both had new postoperative sensory deficits that resolved. One additional patient had a CUSA-related SSEP decrease intraoperatively, which resolved postoperatively, and the last patient had 3 traction-related sensory deficits and a CUSA-related sensory deficit postoperatively, none of which resolved.

Conclusions: Intraoperative TcMEPs and SSEPs can predict the degree of postoperative motor deficit in pediatric patients undergoing IMSCT resection. This technique, combined with dorsal column mapping, is particularly useful in resecting lesions of the upper cervical cord, which are generally considered to be high risk in this population. Furthermore, the spinal cord appears to be less tolerant of repeated intraoperative SSEP decreases, with 3 successive insults most likely to yield postoperative sensory deficits. Changes in TcMEPs and SSEP waveforms can signal the need to guard against excessive manipulation thereby increasing the safety of tumor resection.
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http://dx.doi.org/10.3171/2014.2.PEDS1392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322892PMC
June 2014

Current management of choroid plexus carcinomas.

Neurosurg Rev 2014 Apr 26;37(2):179-92; discussion 192. Epub 2013 Sep 26.

Department of Neurological Surgery, University of California San Francisco, 505 Parnassus Ave., San Francisco, CA, 94117, USA.

Choroid plexus carcinoma (CPC) is a World Health Organization (WHO) grade III brain tumor with a poor prognosis that occurs mainly in children. Gross total resection of CPC is highly recommended and is associated with improved overall survival, although it is often associated with increased morbidity. The use of adjuvant therapies has yet to be standardized, although evidence suggests that for patients with incompletely resected CPCs, a combination of chemotherapy and radiation therapy may be beneficial. The use of radiation therapy for younger children (<3 years old) with CPC, however, is not recommended, due to the potential negative neurological sequelae associated with radiation to the developing brain. Given that the majority of CPC patients are young children, questions regarding optimal radiation dose, chemotherapy agents, and how to combine these two adjuvant treatment modalities to achieve the best outcomes remain unanswered. In this paper we summarize the current management of CPC in the literature. Further studies are needed to standardize the treatment paradigm for this malignant brain tumor.
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http://dx.doi.org/10.1007/s10143-013-0499-1DOI Listing
April 2014

Seizure types and frequency in patients who "fail" temporal lobectomy for intractable epilepsy.

Neurosurgery 2013 Nov;73(5):838-44; quiz 844

*UCSF Epilepsy Center, University of California, San Francisco, California; ‡Department of Neurological Surgery, University of California, San Francisco, California; §Department of Neurology, University of California, San Francisco, California; ¶Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana; ||Children's Hospital and Research Center Oakland, Oakland, California.

Background: Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who "fail" surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency?

Objective: To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures.

Methods: We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010.

Results: Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5).

Conclusion: Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.
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http://dx.doi.org/10.1227/NEU.0000000000000120DOI Listing
November 2013
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