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Objective: In this study, the authors describe their 10-year single-institution experience with single-step complete corpus callosotomy (CCC) for seizure management in pediatric and adult patients with catastrophic, medically refractory, nonlocalizing epilepsy at Advent Health Orlando., Methods: The authors conducted a retrospective observational study of patients aged 6 months to 49 years who underwent clinically indicated CCC for drug-resistant nonlocalizing epilepsy at Advent Health Orlando between July 2011 and July 2021. Follow-up ranged from 12 months to 10 years., Results: Of the 101 patients (57% of whom were male) who met eligibility criteria, 81 were pediatric patients and 20 were ≥ 18 years. All patients had seizures that appeared poorly lateralized on both electroencephalograms and clinical semiological studies. Of 54 patients with drop seizures before CCC, 29 (54%) achieved stable freedom from drop seizures after CCC. Of the 101 patients, 14 (13.9%) experienced stable resolution of all types of clinical seizures (International League Against Epilepsy classes 1 and 2). The most common postoperative neurological complication was a transient disconnection syndrome, observed in 50% of patients; of those patients, 73% experienced syndrome resolution within 2 months after surgery, and all resolved by the 2-year follow-up. Formal neuropsychological test results were stable in 13 patients assessed after CCC., Conclusions: CCC is an effective and well-tolerated palliative surgical technique. In this study, drop attacks were reduced after CCC but could recur for the first time as late as 44 months after surgery. Other seizure types were also reduced postoperatively but could recur for the first time as late as 28 months after surgery. Nearly 14% of patients achieved stable and complete freedom from seizures after CCC. Re-evaluation after CCC can reveal lateralized seizure onset in some patients.

While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Epilepsy is one of the most common chronic neurological disorder affecting 6-7 per 1000 worldwide. Nearly one-third of patients with newly diagnosed epilepsy continue to have recurrent seizures despite adequate trial of more than two anti-seizure drugs : drug-resistant epilepsy (DRE). Children with DRE often experience cognitive and psychosocial co-morbidities requiring more urgent and aggressive treatment than adults. Epilepsy surgery can result in seizure-freedom in approximately two-third of children with improvement in cognitive development and quality of life. Understanding fundamental differences in etiology, co-morbidity, and neural plasticity between children and adults is critical for appropriate selection of surgical candidates, appropriate presurgical evaluation and surgical approach, and improved overall outcome.

Pyruvate kinase plays a central role in glucose catabolism in bacteria, and efficient utilization of this hexose has been linked to the virulence of Brucella strains in mice. The brucellae produce a single pyruvate kinase which is an ortholog of the Bradyrhizobium manganese (Mn)-dependent pyruvate kinase PykM. A biochemical analysis of the Brucella pyruvate kinase and phenotypic analysis of a Brucella abortus mutant defective in high-affinity Mn import indicate that this enzyme is an authentic PykM ortholog which functions as a Mn-dependent enzyme in vivo The loss of PykM has a negative impact on the capacity of the parental 2308 strain to utilize glucose, fructose, and galactose but not on its ability to utilize ribose, xylose, arabinose, or erythritol, and a pykM mutant displays significant attenuation in C57BL/6 mice. Although the enzyme pyruvate phosphate dikinase (PpdK) can substitute for the loss of pyruvate kinase in some bacteria and is also an important virulence determinant in Brucella , a phenotypic analysis of B. abortus 2308 and isogenic pykM , ppdK , and pykM ppdK mutants indicates that PykM and PpdK make distinctly different contributions to carbon metabolism and virulence in these bacteria. IMPORTANCE Mn plays a critical role in the physiology and virulence of Brucella strains, and the results presented here suggest that one of the important roles that the high-affinity Mn importer MntH plays in the pathogenesis of these strains is supporting the function of the Mn-dependent kinase PykM. A better understanding of how the brucellae adapt their physiology and metabolism to sustain their intracellular persistence in host macrophages will provide knowledge that can be used to design improved strategies for preventing and treating brucellosis, a disease that has a significant impact on both the veterinary and public health communities worldwide., (Copyright © 2018 American Society for Microbiology.)

Background and Objectives: Sensorineural hearing loss (SNHL) in children is associated with neurocognitive morbidity. The cause of SNHL is a loss of hair cells in the organ of Corti. There are currently no reparative treatments for SNHL. Numerous studies suggest that cord blood mononuclear cells (human umbilical cord blood, hUCB) allow at least partial restoration of SNHL by enabling repair of a damaged organ of Corti. Our objective is to determine if hUCB is a safe treatment for moderate to severe acquired SNHL in children. Subjects and., Methods: Eleven children aged 6 months to 6 years with moderate to severe acquired SNHL were treated with intravenous autologous hUCB. The cell dose ranged from 8 to 30 million cells/kg body weight. Safety was assessed by measuring systemic hemodynamics during hUCB infusion. Infusion-related toxicity was evaluated by measuring neurologic, hepatic, renal and pulmonary function before and after infusion. Auditory function, auditory verbal language assessments and MRI with diffusion tensor imaging (DTI) were obtained before and after treatment., Results: All patients survived, and there were no adverse events. No infusionrelated changes in hemodynamics occurred. No infusion-related toxicity was recorded. Five subjects experienced a reduction in auditory brainstem response (ABR) thresholds. Four of those 5 subjects also experienced an improvement in cochlear nerve latencies. Comparison of MRI with DTI sequences obtained before and after treatment revealed increased fractional anisotropy in the primary auditory cortex in three of five subjects with reduced ABR thresholds. Statistically significant (p<0.05) reductions in ABR thresholds were identified., Conclusions: TIntravenous hUCB is feasible and safe in children with SNHL.

Background: The insular cortex is not routinely removed in modified functional hemispherectomy due to the risk of injury to the main arteries and to deep structures. Our study evaluates the safety and usefulness of applying intraoperative electrocorticography (ECoG) on the insular during the hemispherectomy., Methods: We included all patients who underwent insular ECoG during a modified functional hemispherectomy from 2012 to 2015. After the surgery, the decision for further resection of the insular cortex was made based on the presence of electrographic seizures on ECoG., Results: The study included 19 patients (age, 6.4 ± 4.7 years, mean ± standard deviation). Electrographic seizures were identified in 5 patients (26.3%). Sixteen of the 19 patients (84.2%) became seizure-free with a follow-up duration of 3.1 ± 0.6 years and no vascular complication occurred., Conclusions: Intraoperative insular ECoG monitoring can be performed safely while providing a tailored approach for insular resection during modified hemispherectomy.

Hemispherectomy is a complex multistep procedure with a steep learning curve. Several surgical approaches have been developed, but each requires considerable practice to master. Four experienced pediatric neurosurgeons, who participated in the 2014 Gothenburg Pediatric Epilepsy Surgery Meeting, provided succinct technical summaries of four hemispherectomy approaches: modified functional hemispherectomy, peri-insular hemispherotomy, parasagittal hemispherotomy, and endoscopic-assisted hemispherotomy. No clinical or outcome data are included. Our intention is to reduce the slope and length of the learning curve for surgeons and to improve the understanding of the technical details of hemispherectomy surgery by nonsurgeonmembers of epilepsy teams., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Purpose: To evaluate the use of the cortiQ-based mapping system (g.tec medication engineering GmbH, Austria) for real-time functional mapping (RTFM) and to compare it to results from electrical cortical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI)., Methods: Electrocorticographic activity was recorded in 3 male patients with intractable epilepsy by using cortiQ mapping system and analyzed in real time. Activation related to motor, sensory, and receptive language tasks was determined by evaluating the power of the high gamma frequency band (60-170 Hz). The sensitivity and specificity of RTFM were tested against ESM and fMRI results., Results: "Next-neighbor" approach demonstrated [sensitivity/specificity %] (1) RTFM against ESM: 100.00/79.70 for hand motor; 100.00/73.87 for hand sensory; -/87 for language (it was not identified by the ESM); (2) RTFM against fMRI: 100.00/84.4 for hand motor; 66.70/85.35 for hand sensory; and 87.85/77.70 for language., Conclusions: The results of the quantitative "next-neighbor" RTFM evaluation were concordant to those from ESM and fMRI. The RTFM correlates well with localization of hand motor function provided by ESM and fMRI, which may offer added localization in the operating room and guidance for extraoperative ESM mapping. Real-time functional mapping correlates with fMRI language activation when ESM findings are negative. It has fewer limitations than ESM and greater flexibility in activation paradigms and measuring responses.

Objectives: The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls., Design: The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow-derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19)., Setting: The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008., Patients: Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8., Interventions: The treatment group received 6 million autologous bone marrow-derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines., Measurements and Main Results: The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear predictions identified a significant reduction in the Pediatric Intensity Level of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05). This divergence was also reflected in the Pediatric Logistic Organ Dysfunction score following the first week. The duration of intracranial pressure monitoring was 8.2 ± 1.3 days in the treated group and 15.6 ± 3.5 days (p = 0.03) in the time-matched control group., Conclusions: IV autologous bone marrow-derived mononuclear cell therapy is associated with lower treatment intensity required to manage intracranial pressure, associated severity of organ injury, and duration of neurointensive care following severe traumatic brain injury. This may corroborate preclinical data that autologous bone marrow-derived mononuclear cell therapy attenuates the effects of inflammation in the early post-traumatic brain injury period.

The purpose of this retrospective study was to evaluate the long-term outcomes of using the microscopic minimally invasive approach for the treatment of nonsyndromic craniosynostosis. During the last 10 years, 180 consecutive patients with nonsyndromic craniosynostosis were treated: 67 patients were treated with microscopic minimally invasive approach, and 113 were treated with the open approach. In the microscopic group, there was 1 intraoperative complication (1.5%). There were 10 postoperative complications (14.9%), of which 9 required major reoperations and 1 required a minor procedure. The major complications occurred in 7 unicoronal patients (58.3%) and 2 metopic patients (25.0%). In the open-approach group, there were 8 complications (7.1%), 2 patients required major reoperations and 6 required minor procedures. Chi-squared test showed that there was no statistically significant difference in the overall complication rate between the microscopic and open approaches. However, in the unicoronal patients, the complication rate was significantly higher in the microscopic group (P < 0.001). In conclusion, the microscopic approach is our treatment of choice in nonsyndromic patients with sagittal and lambdoidal craniosynostosis. We no longer use the microscopic approach in patients with unicoronal or metopic craniosynostosis because of the high complication rate.

The question we address here is whether the invasive presurgical brain mapping approaches of direct cortical stimulation and of the Wada procedure can be replaced by noninvasive functional neuroimaging methods (functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], transcranial magnetic stimulation and [TMS]). First, we outline the reasons for contemplating such a replacement. Second, we present evidence to the effect that the efficacy of the invasive and noninvasive methods, while suboptimal, is comparable. Third, we discuss additional advantages of noninvasive presurgical brain mapping and conclude that there are no longer compelling reasons for opting for invasive mapping in many if not most cases provided that the non-invasive methods are available., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

The organic hydroperoxide resistance protein Ohr has been identified in numerous bacteria where it functions in the detoxification of organic hydroperoxides, and expression of ohr is often regulated by a MarR-type regulator called OhrR. The genes annotated as BAB2&#95;0350 and BAB2&#95;0351 in the Brucella abortus 2308 genome sequence are predicted to encode OhrR and Ohr orthologs, respectively. Using isogenic ohr and ohrR mutants and lacZ promoter fusions, it was determined that Ohr contributes to resistance to organic hydroperoxide, but not hydrogen peroxide, in B. abortus 2308 and that OhrR represses the transcription of both ohr and ohrR in this strain. Moreover, electrophoretic mobility shift assays and DNase I footprinting revealed that OhrR binds directly to a specific region in the intergenic region between ohr and ohrR that shares extensive nucleotide sequence similarity with so-called "OhrR boxes" described in other bacteria. While Ohr plays a prominent role in protecting B. abortus 2308 from organic hydroperoxide stress in in vitro assays, this protein is not required for the wild-type virulence of this strain in cultured murine macrophages or experimentally infected mice.

The gene designated BAB1&#95;0591 in the Brucella abortus 2308 genome sequence encodes the manganese-cofactored superoxide dismutase SodA. An isogenic sodA mutant derived from B. abortus 2308, designated JB12, displays a small colony phenotype, increased sensitivity in vitro to endogenous superoxide generators, hydrogen peroxide and exposure to acidic pH, and a lag in growth when cultured in rich and minimal media that can be rescued by the addition of all 20 amino acids to the growth medium. B. abortus JB12 exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, but this attenuation is limited to the early stages of infection. Addition of the NADPH oxidase inhibitor apocynin to infected macrophages does not alleviate the attenuation exhibited by JB12, suggesting that the basis for the attenuation of the B. abortus sodA mutant is not an increased sensitivity to exogenous superoxide generated through the oxidative burst of host phagocytes. It is possible, however, that the increased sensitivity of the B. abortus sodA mutant to acid makes it less resistant than the parental strain to killing by the low pH encountered during the early stages of the development of the brucella-containing vacuoles in macrophages. These experimental findings support the proposed role for SodA as a major cytoplasmic antioxidant in brucella. Although this enzyme provides a clear benefit to B. abortus 2308 during the early stages of infection in macrophages and mice, SodA appears to be dispensable once the brucellae have established an infection.

Background: Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection., Objective: To determine whether autologous BMMNCs are a safe treatment for severe TBI in children., Methods: Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6×10 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures., Results: All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability., Conclusion: Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.

Brucella strains are exposed to potentially toxic levels of H2O2 both as a consequence of their aerobic metabolism and through the respiratory burst of host phagocytes. To evaluate the relative contributions of the sole catalase KatE and the peroxiredoxin AhpC produced by these strains in defense against H2O2-mediated toxicity, isogenic katE, ahpC, and katE ahpC mutants were constructed and the phenotypic properties of these mutants compared with those of the virulent parental strain B. abortus 2308. The results of these studies indicate that AhpC is the primary detoxifier of endogenous H2O2 generated by aerobic metabolism. KatE, on the other hand, plays a major role in scavenging exogenous and supraphysiologic levels of H2O2, although this enzyme can play a supporting role in the detoxification of H2O2 of endogenous origin if AhpC is absent. B. abortus ahpC and katE mutants exhibit wild-type virulence in C57BL/6 and BALB/c mice, but the B. abortus ahpC katE double mutant is extremely attenuated, and this attenuation is not relieved in derivatives of C57BL/6 mice that lack NADPH oxidase (cybb) or inducible nitric oxide synthase (Nos2) activity. These experimental findings indicate that the generation of endogenous H2O2 represents a relevant environmental stress that B. abortus 2308 must deal with during its residence in the host and that AhpC and KatE perform compensatory roles in detoxifying this metabolic H2O2.

Purpose: The purpose of this retrospective study was to present the results of the authors' microscopic minimally invasive approach in the treatment of nonsyndromic craniosynostosis., Methods: From 2001 to 2007, the authors treated a cohort of 67 infants with nonsyndromic sagittal, unicoronal, bicoronal, and metopic craniosynostosis, either with the microscopic (n = 40) or the open (n = 27) approach. In the microscopic approach, incisions were placed over the premature suture, and using a surgical microscope, the appropriate synostectomy was performed. The open approach used a traditional coronal incision with cranial vault reconstruction. Both groups of patients had postoperative molding helmet therapy. Finally, anthropometric measurements were used to evaluate the treatment results. The measurement used for the patients with sagittal and bicoronal craniosynostoses was the divergence from the norm of the age-adjusted cephalic index. The (FZr-EUl/FZl-EUr) and (FZr-EUr)/(FZl-EUl) were used for the patients with unicoronal craniosynostosis. The divergence from the norm of age-adjusted (FTr-FTl)/(Tr-Tl) was used for the patients with metopic craniosynostosis. (FZr = right frontozygomaticus, EUl = left eurion, FZl = left frontozygomaticus, Eur = right eurion, FTr = right frontotemporale, FTl = left frontotemporale, Tr = tragion, Tl = left tragion)., Results: The median surgical times for microscopic and open approaches were 108 and 210 minutes, the volumes of blood loss were 75 and 220 mL, the durations of hospital stay were 2 and 4 days, the numbers of helmet were 2 and 1, and the durations of helmet therapy were 10.5 and 8 weeks, respectively. The analysis of variance for repeated measures showed that there was no statistically significant difference between the 2 groups in any of the craniosynostoses., Conclusions: The treatment outcomes from the microscopic minimally invasive approach to craniosynostosis are equal to those seen with the open approach. The microscopic approach results in less operative time, blood loss, and hospitalization.

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent National Institutes of Health consensus statement recommends research into multimodality treatments for TBI. This article will review the complex pathophysiology of TBI as well as the possible therapeutic mechanisms of progenitor cell transplantation, hypertonic saline infusion, and controlled hypothermia for possible utilization in multimodality clinical trials.

RET/PTC rearrangements are one of the genetic hallmarks of papillary thyroid carcinomas. RET/PTC oncoproteins lack extracellular or transmembrane domains, and activation takes place through constitutive dimerization mediated through coiled-coil motifs in the NH(2) terminus of the chimeric protein. Based on the observation that the epidermal growth factor receptor (EGFR) kinase inhibitor PKI166 decreased RET/PTC kinase autophosphorylation and activation of downstream effectors in thyroid cells, despite lacking activity on the purified RET kinase, we proceeded to examine possible functional interactions between RET/PTC and EGFR. Conditional activation of RET/PTC oncoproteins in thyroid PCCL3 cells markedly induced expression and phosphorylation of EGFR, which was mediated in part through mitogen-activated protein kinase signaling. RET and EGFR were found to coimmunoprecipitate. The ability of RET to form a complex with EGFR was not dependent on recruitment of Shc or on their respective kinase activities. Ligand-induced activation of EGFR resulted in phosphorylation of a kinase-dead RET, an effect that was entirely blocked by PKI166. These effects were biologically relevant, as the EGFR kinase inhibitors PKI166, gefitinib, and AEE788 inhibited cell growth induced by various constitutively active mutants of RET in thyroid cancer cells as well as NIH3T3 cells. These data indicate that EGFR contributes to RET kinase activation, signaling, and growth stimulation and may therefore be an attractive therapeutic target in RET-induced neoplasms.

Context: Mutually exclusive mutations of RET, RAS, or BRAF are present in about 70% of papillary thyroid carcinomas, whereas only the latter two are seen in poorly differentiated and anaplastic cancers. Although the signal output common to these oncoproteins is ERK, a recent report showed that only BRAF mutations consistently predicted responsiveness to MAPK kinase (MEK) inhibitors., Objectives: Here we investigated whether sensitivity to MEK inhibition was determined by oncogene status in 13 human thyroid cancer cell lines: four with BRAF mutations, four RAS, one RET/PTC1, and four wild type., Results: Growth of BRAF (+) cells was inhibited by the MEK antagonist PD0325901 with an IC(50) of less than 5 nm. By contrast, RAS, RET/PTC1, or wild-type cells had IC(50) of 4 nm to greater than 1000 nm. Sensitivity was not predicted by coexisting mutations in PIK3CA or by PTEN status. Similar effects were obtained with the MEK inhibitor AZD6244. PD0325901 induced a sustained G1/S arrest in BRAF (+) but not BRAF (-) lines. PD0325901 was equipotent at inhibiting pERK1/2 after 2 h, regardless of genetic background, but pERK rebounded at 24 h in most lines. MEK inhibitor resistance was associated with partial refractoriness of pERK to further inhibition by the compounds. AZD6244 was more potent at inhibiting growth of NPA (BRAF +) than Cal62 (KRAS +) xenografts., Conclusion: Thyroid cancers with BRAF mutation are preferentially sensitive to MEK inhibitors, whereas tumors with other MEK-ERK effector pathway gene mutations have variable responses, either because they are only partially dependent on ERK and/or because feedback responses elicit partial refractoriness to MEK inhibition.

Objective: To evaluate the long-term effectiveness of helmet therapy in the correction of deformational plagiocephaly and to assess the early occlusal abnormalities seen in these patients., Design: A prospective study with blinded measurements., Patients: Twenty-eight patients with deformational plagiocephaly who were treated with molding helmet therapy with at least 5 years of follow-up., Interventions: The average length of molding helmet treatment was 6.2 months. At the time of this follow-up evaluation, the mean interval since completing the molding helmet therapy was 5.6 years., Main Outcome Measures: Anthropometric measurements of cranial asymmetry included cranial vault asymmetry (CVA), orbitotragial depth asymmetry (OTDA), and cranial base asymmetry (CBA). A dental examination was also performed., Results: At the completion of therapy, the most improvement was seen in the measurement of CBA, followed by CVA and OTDA. However, in evaluating the long-term stability of molding treatment, OTDA tended to continue improving after the initial treatment, while CBA and CVA appeared to regress, although none of the changes reached statistically significant levels. In dental measurements, all the dental midline and chin deviations were toward the unaffected side with respect to occipital deformation., Conclusion: This study demonstrated that helmet remodeling with the dynamic orthotic cranioplasty band is effective in the correction of cranial asymmetry, with some nonstatistically significant changes in long-term cranial vault symmetry. Dental observations indicated the possibility of occlusal abnormalities that may affect dental, especially orthodontic, diagnosis and treatment planning.

Landau-Kleffner syndrome is characterized by a regression in receptive language. The factors that affect the clinical expression of this syndrome remain unclear. This study presents neuroimaging findings in 2 patients showing different clinical evolutions. Linguistic regression persisted in 1 patient and evolved positively in the other. In patient A (with severe linguistic regression) there was an overlap between areas engaged during word recognition and those involved in generating the epileptiform activity; in patient B (with better linguistic evolution), receptive language was predominantly represented in the right hemisphere (unaffected). Patient A underwent multiple subpial transections. The 2-year follow-up indicated linguistic improvement, absence of epileptiform activity, and activation of the left temporal cortex during word comprehension. These results suggest that the resolution of the linguistic deficit in Landau-Kleffner syndrome may be modulated by the language-specific cortex freed from interfering epileptiform activity or by reorganization of the receptive language cortex triggered by the epileptic activity.

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.

Corpus callosotomy has a long history as a palliative treatment for intractable epilepsy. Identification of a single epileptogenic zone is critical to performing successful resective surgery. We describe three patients in which corpus callosotomy allowed recognition of unapparent seizure foci, leading to subsequent successful resection. We retrospectively reviewed our epilepsy surgery database from 2003 to 2005 for children who had a prior callosotomy and were candidates for focal resection. All underwent magnetic resonance imaging and scalp video electroencephalograph monitoring, and two had magnetoencephalography, electrocorticography and/or intracranial video electroencephalograph monitoring. The children were 8 and 9 years old, and seizure onset varied from early infancy to early childhood. One child had a history of head trauma preceding seizure onset, one had a large intracerebral infarct and dysplastic cortex in the contralateral frontal lobe, and the other had an anterior temporal lobe resection without improvement in seizure frequency. After medical management failed, callosotomy was performed with the expectation of decreasing the seizure types affecting both hemispheres. Following transection of the callosal fibers, a single focus was recognized and resected, with resultant dramatic improvement in seizure control. In medically refractory epilepsy, where rapid secondary bisynchrony is suspected but the electroencephalograph is non-localizing, callosotomy should be considered as a means of treating generalized seizure types, but may also assist in identifying potentially operable seizure foci. Study limitations include its retrospective nature and cohort size. The findings, however, suggest the need for prospective, systematic, well-controlled studies of the use of corpus callostomy in this intractable patient population.

Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Correlating genotypes with phenotypes should facilitate the disease management of tuberous sclerosis complex.

The purpose of this study is to describe a minimally invasive approach using a microscope and the subsequent helmet therapy. The authors have treated 14 patients with the microscopic technique between May 2001 and November 2003. In this group of patients, there were 3 females and 11 males with an average age of 10.5 weeks and a range of 4 to 28 weeks. The study included 8 patients with sagittal synostosis and 6 patients with other synostoses. In the latter group, there were 3 patients with metopic, one with unicoronal, one with bicoronal, and one with lambdoidal. The approach used limited incisions over the affected sutures. The craniotomy/craniectomy was completed using a 5-mm burr. Postoperative helmet therapy was begun within 2 weeks after surgery. In patients with sagittal synostosis, a mean of 1.5 helmets for a duration of 11.4 weeks was used. In the other groups of patients with craniosynostosis, a mean of 2.3 helmets for a duration of 13.5 weeks was used. A microscopic variation to the "minimally invasive" approach to craniosynostosis is presented. It provides excellent visualization, illumination, and control of the surgical field. When compared with traditional surgery, it results in shorter hospitalization and operative time and decreased blood loss. The authors note that critical to this approach is the postoperative helmet therapy. Early results are encouraging.

Two-dimensional gel electrophoretic analysis of cell lysates suggests that stationary phase production of wild-type levels of an ortholog of the low pH dependent chaperone HdeA in Brucella abortus 2308 during growth in a minimal medium requires the presence of the RNA binding protein Hfq. Although mutational analysis demonstrated that HdeA contributes to acid resistance in this bacterium, this protein is not required for wild-type virulence in the BALB/c mouse model. These experimental findings indicate that the brucellae rely upon additional gene products to resist the acidic conditions they encounter in the phagosomal compartment of host macrophages.

Object: Scaphocephaly is a common craniofacial abnormality that results from craniosynostosis of the sagittal suture. The authors have treated a group of infants who presented with nonsynostotic scaphocephaly, or a so-called sticky sagittal suture. The purpose of this study was to describe these patients with nonsynostotic scaphocephaly, the natural history of the disease, and its treatment., Methods: At the University of Texas-Houston Medical School between 1996 and 2002, nine patients presented with nonsynostotic scaphocephaly. When the abnormality in patients was diagnosed prior to 12 months of age, the majority (seven of eight) were successfully managed by molding helmet therapy. The only child in this group in whom this therapy failed to correct the deformity was noted on repeated computerized tomography scanning to have true sagittal synostosis, which required surgical correction. One child with nonsynostotic scaphocephaly, who presented after 1 year of age, required surgical correction followed by postoperative molding helmet therapy., Conclusions: Patients with nonsynostotic scaphocephaly appear to have sagittal synostosis. If treated early (at < 12 months of age), head shape in these patients can be normalized by molding helmet therapy. Surgery is reserved for older patients (> 12 months of age) or those with sagittal synostosis.

Objective: The authors evaluated the sensitivity and selectivity of interictal magnetoencephalography (MEG) versus prolonged ictal and interictal scalp video-electroencephalography (V-EEG) in order to identify patient groups that would benefit from preoperative MEG testing., Methods: The authors evaluated 113 consecutive patients with medically refractory epilepsy who underwent surgery. The epileptogenic region predicted by interictal and ictal V-EEG and MEG was defined in relation to the resected area as perfectly overlapping with the resected area, partially overlapping, or nonoverlapping., Results: The sensitivity of a 30-minute interictal MEG study for detecting clinically significant epileptiform activity was 79.2%. Using MEG, we were able to localize the resected region in a greater proportion of patients (72.3%) than with noninvasive V-EEG (40%). MEG contributed to the localization of the resected region in 58.8% of the patients with a nonlocalizing V-EEG study and 72.8% of the patients for whom V-EEG only partially identified the resected zone. Overall, MEG and V-EEG results were equivalent in 32.3% of the cases, and additional localization information was obtained using MEG in 40% of the patients., Conclusion: MEG is most useful for presurgical planning in patients who have either partially or nonlocalizing V-EEG results.

Considerable evidence supports the idea of magnetoencephalography (MEG) being a valuable noninvasive tool for presurgical mapping of sensory and motor functions. In this study, we test the validity and replicability of a new experimental paradigm for simultaneous sensory and motor mapping using MEG recordings. This comprehensive sensorimotor protocol (CSSMP), where external mechanic stimulation serves as a cue for voluntary movements, allows the recording of sensory and motor cortical responses during a single activation task. The stability and replicability of MEG-derived recordings during this paradigm were tested in a group of eight neurologically normal volunteers and six patients with perirolandic lesions. We found that a common sensorimotor cortical network, engaging sensory (S1, S2) and motor (M1) areas, was reliably activated in all subjects and patients and that the results remained exceptionally stable over time. Additionally, the clinical validity of the MEG-derived maps of activation was tested through intraoperative electrocortical stimulation mapping in the group of patients. The MEG-derived anatomical maps for specific sensory (S1) and motor (M1) responses were verified, by direct cortical mapping, and confirmed with the patient's surgical outcome. The results of this validation study show that the so-called CSSMP is a reliable and reproducible method for assessing simultaneously sensory and motor areas. This method minimizes methodological problems and improves our knowledge of the spatiotemporal organization of the sensorimotor cortical network and helps to optimize the surgical management of patients with perirolandic lesions.

The purpose of this study was to compare the use of molding helmet therapy in the treatment of positional brachycephaly and posterior positional plagiocephaly. Four hundred twenty-eight children with positional brachycephaly or plagiocephaly were included in this study. In this group of patients, 132 (32%) were treated with positioning alone. Of the 292 (68%) patients who were treated with molding therapy, 64 (21.9%) were treated for positional brachycephaly and 248 (78.1%) were treated for posterior positional plagiocephaly. All children were evaluated by a craniofacial surgeon and a pediatric neurosurgeon. Anthropomorphic measurements were used to assess the efficacy of treatment. Measurements were made before initiation of therapy and at 2-month intervals until the completion of therapy. Results showed that statistically significant improvements (P < 0.01) were seen in all patients treated with molding helmet therapy. Overall, the children with posterior plagiocephaly normalized their head shapes; however, the head shapes of the children with positional brachycephaly did not normalize despite statistically significant improvements in their Cephalic Index. It is concluded that molding helmet therapy is an effective treatment of position-induced head shape abnormalities. Helmet therapy is more effective in children with posterior positional plagiocephaly than in children with positional brachycephaly.

Lesions consistent with cavernous angiomas (CAs) of the brain are sometimes seen on MRI scans of the brains of patients who received radiation therapy for brain tumors as children. The lesions appear years later within brain tissue that was included in radiation fields. It is unclear whether these MRI-detected lesions are true CAs or a pathological variant. This study reports the clinical, radiographical, and pathological findings in 3 cases of radiation-induced CAs of the brain. From 1995 to 1997, 3 patients previously treated with radiation therapy (45-55 Gy) for pediatric brain tumors (medulloblastoma, ependymoma, and a presumed midbrain astrocytoma) underwent resections of symptomatic and enlarging lesions that were consistent with a CA of the brain. All of the lesions occurred within fields of prior irradiation. None of the patients had received chemotherapy as part of their cancer treatment. CA-presenting symptoms included seizures, cranial nerve deficits, and headaches. The lesions appeared 7-19 years after radiation therapy and slowly enlarged on subsequent imaging studies. MRI scans of the lesions revealed characteristics typical of CA. The lesions became symptomatic 1-5 years after they were initially noted. Surgical resection was performed 1-2 years after symptoms began. The age at resection ranged from 15 to 23 years (10-21 years after radiation therapy). Pathological analysis of the three lesions showed typical CA characteristics. Some CAs may be caused by radiation therapy for pediatric brain tumors. They are radiologically and pathologically similar to sporadically occurring CAs of the brain and may enlarge over time and become symptomatic. CAs can be safely resected using standard microsurgical techniques., (Copyright 2003 S. Karger AG, Basel)

Epidermal nevus syndrome is a kind of neurocutaneous syndrome that is associated with epidermal nevus and a variety of congenital CNS disorders. Clinical presentations include seizures, paresis, mental retardation, and developmental delay. We report three cases with MR imaging and magnetoencephalography findings; one patient underwent ictal and interictal single photon emission CT. Both structural and functional imaging studies indicated that the frontal lobes had lesser involvement or were intact. One patient underwent hemispherectomy because of the medically intractable seizure. He remained seizure free with topiramate monotherapy.

The purpose of this study is to investigate if multimodality neuroimaging evaluation increases the detection of subtle focal cortical dysplasia as part of an epilepsy surgery evaluation. Three patients with normal magnetic resonance imaging and histopathological findings of focal cortical dysplasia were reviewed. Their magnetoencephalography recordings were performed on whole-head magnetoencephalography system. Magnetic resonance images were re-evaluated with special inspection in limited regions guided by magnetoencephalography spike localization. Two patients had ictal and interictal single photon emission computed tomography study after administration of Tc99m ECD. In two patients we found tiny focal abnormalities including slightly increased cortical thickness and blurred gray-white matter junction at the locations of interictal events after re-evaluation of the MR images indicating focal cortical dysplasia. The third patient showed focal atrophic change. All patients are seizure free after surgery. Both ictal and interictal single photon emission computed tomography showed hyperperfusion in the dysplastic cortex regions. Multimodality neuroimaging study can improve the detection of focal cortical dysplasia. Normal magnetic resonance images should be re-evaluated for subtle signs of focal cortical dysplasia especially when magnetoencephalography recording demonstrate focal epileptic discharges.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In such cases, interictal frequent rhythmic bursting epileptiform activity (FBREA) on both scalp electroencephalography (EEG) and electrocorticography (ECoG) is generally accepted to be identical to the ictal epileptiform activity. We used magnetoencephalography (or Magnetic Source Imaging (MSI)) to determine the epileptogenic zone in a 6-year-old patient with histopathologically proven FCD and normal magnetic resonance imaging (MRI). MSI was used to localize the sources of both ictal activity and FRBEA, which was then compared with ECoG findings. The intracranial sources of both types of activity co-localized in the left inferior frontal and superior temporal gyri. The location and extent of the epileptogenic area determined by MSI was essentially identical to that determined directly through extra-operative ECoG. In the absence of structural abnormalities detectable on MRI, the noninvasive method of MSI provided valuable information regarding the location and extent of the primary epileptogenic area. This was critical for pre-surgical planning regarding placement of intracranial electrodes and for risk-benefit evaluation.

The current surgical treatment of sagittal craniosynostosis often fails to produce a normal cephalic index; however, recent reports of early endoscopic suture release and postoperative helmet therapy promise improved cranial symmetry. The role of helmet therapy is critical in this approach, but there are few reports on the use of helmet therapy after craniosynostosis surgery. The authors present a retrospective review comparing the results of surgery alone versus surgery and postoperative banding in treating children diagnosed with sagittal synostosis. Cephalic index (CI) measurements and the divergence of the CI from the norm (DFN) were used to compare the banded and the non-banded groups. Included in the study were 21 children with sagittal craniosynostosis of whom 6 were treated with surgery alone and 15 were treated with surgery and postoperative banding. Preoperatively, both groups were significantly different from the norm (non-banded, P < 0.05; banded, P < 0.01), while postoperatively they were not significantly different from the norm. Statistically significant changes were present in the CIs of the banded group in the preoperative-follow-up interval (P < 0.01), while no significant changes occurred in the non-banded group during this same interval. Statistically significant changes in the DFN occurred in the preoperative-postoperative and preoperative-follow-up intervals of the banded group; however, these changes were not significant in the non-banded group during the same intervals. Correction toward a normal CI was seen in the banded group throughout the course of treatment, while this trend was not present in the non-banded group. Therefore, molding helmet therapy maintains the operative correction obtained and promotes more normal cranial growth patterns.

Somatosensory maps were determined in three patients with hemimegalencephaly using magnetic resonance imaging (MRI) and magnetoencephalography (MEG). MRIs were characterized by thickened gray matter with clearly aberrant lamination patterns. Somatosensory Evoked Fields (SEFs), as measured by MEG, were absent from the affected hemisphere in the two patients with severe cortical lamination defects. The third patient presented with relatively preserved cortical lamination in the frontal lobe and clear cortical SEFs in this region, indicating somatotopical reorganization. These findings suggest that the presence and location of MEG-derived somatosensory maps reflect the severity of the cortical lamination defects in hemimegalencephaly.

Rasmussen's encephalitis (RE) is a cryptogenic progressive inflammatory disorder of the brain that causes severe neurological problems, including intractable focal epilepsy. In select patients, aggressive treatment using cerebral hemispherectomy may ameliorate the devastating cognitive decline that accompanies this disease, even if the epileptic focus appears broadly distributed. We present a case of histopathologically-confirmed RE evaluated using a multimodal process that explored the physical and functional aspects of the associated epilepsy. This process included magnetic resonance imaging, single photo emission computed tomography, electroencephalography, and magnetoencephalography (MEG). The findings indicate that functional brain imaging data may greatly assist the surgical treatment decision-making process in RE, especially when structural imaging fails to reveal definitive localizing information. In addition, MEG may provide insights about the cortical reorganization of somatosensory cortex following hemispherectomy.

The presentation of anaplastic large cell lymphoma in bone is uncommon. We report a case of anaplastic large cell lymphoma of the skull that was diagnosed after head trauma. Biopsy revealed significant destruction of the outer table of the frontal bone. Histopathologically, the initial evaluation suggested osteomyelitis because of a mixed inflammatory infiltrate with large numbers of neutrophils. However, several clusters and individual mononuclear cells were atypical. The tumor cells had large, pleomorphic nuclei; these cells stained positively with antibodies to Ki-1 (CD 30), ALK-1, and EMA. Fluorescence in situ hybridization (FISH) showed rearrangement of the ALK gene, which usually results from the t(2;5) translocation, present in most anaplastic large cell lymphomas. There was no evidence of systemic disease. The patient has tolerated chemotherapy and is free of disease 12 months later.

In this report, the newest of the functional imaging methods, magnetoencephalography, is described, and its use in addressing the issue of brain reorganization for basic sensory and linguistic functions is documented in a series of 10 children and young adults. These patients presented with a wide variety of conditions, ranging from tumors and focal epilepsy to reading disability. In all cases, clear evidence of reorganization of the brain mechanisms of either somatosensory or linguistic functions or both was obtained, demonstrating the utility of magnetoencephalography in studying, completely noninvasively, the issue of plasticity in the developing brain.

This study evaluated the validity of data derived from magnetic source imaging regarding hemispheric dominance for language in children and adolescents with intractable seizure disorder by comparison with results of the intracarotid amobarbital procedure. Functional imaging of the receptive language cortex using a whole-head neuromagnetometer was performed in 19 consecutive epilepsy patients, ages 8 to 18 years, who also underwent the intracarotid amobarbital procedure. During magnetic source imaging recordings, patients engaged in a continuous recognition memory task for words in visual and auditory modalities. This task has previously been shown to be valid for the purpose of lateralization and localization of language cortex in adult epilepsy patients who undergo the intracarotid amobarbital procedure and intraoperative language mapping allowing confirmation of magnetic source imaging findings. Results indicated that language laterality indices formed for the intracarotid amobarbital procedure and magnetic source imaging procedures were highly correlated (R = .87). In addition, clinical judgments regarding cerebral dominance for language made by independent raters using the two methods were in excellent agreement. We conclude that magnetic source imaging is a promising method for determination of cerebral dominance for language in children and adults.

The role of surgery in the treatment of refractory epilepsy (RE) in tuberous sclerosis complex (TSC) is poorly defined. Four patients with RE and TSC were evaluated for epilepsy surgery from 1994 to 1996. Three of four patients developed infantile spasms within 5 months of birth. These progressed to frequent complex partial and generalized tonic/myoclonic seizures refractory to antiepileptic drug therapy. Neuroimaging revealed typical findings of TSC including calcified lesions consistent with hamartomas. Clinical and EEG evidence suggested an epileptic focus near a prominent lesion in each child. This was confirmed using magnetic source imaging in 1 case. All patients underwent inpatient continuous video-EEG monitoring followed by temporal lobectomy or focal cortical resection with intraoperative EEG. Age at operation ranged from 5 to 13 years. Three out of 4 patients experienced a greater than 90% decrease in seizure activity. One patient continues to have rare complex partial seizures, and 1 has rare simple partial seizures. Tumor DNA analysis revealed mutations in the TSC1 gene in case 1 and the TSC2 gene in case 2; no mutations have been identified yet in cases 3 and 4. Temporal lobectomy and focal cortical resection can result in improved seizure control in patients with TSC and RE.

To identify factors influencing outcome and morbidity in patients selected for corpus callosotomy, we retrospectively reviewed 23 patients with intractable generalized seizures who underwent corpus callosotomy between 1991 and 1994. Three patients had a complete corpus callosotomy, while 20 had an anterior callosotomy. Three of those patients subsequently had completion of the anterior callosotomy. Overall, 41% of patients were nearly or completely free of the seizure types targeted for surgical treatment, while another 45% had seizures less than half as frequently. Four patients developed simple partial motor seizures after callosotomy. A transient disconnection syndrome was observed in 57% of patients. The best predictor of good outcome was a normal preoperative MRI. Mentally retarded patients had poorer outcomes. Outcome was not predicted by extent of callosal section or lateralization on neurological examination, EEG, MRI, and SPECT. Completion of anterior callosotomy resulted in significant reductions in seizure frequency. Though most patients do not become seizure-free after corpus callosotomy, worthwhile palliation of an otherwise intractable illness can be achieved. An analysis of prognostic factors should lead to better selection of patients for surgery.

Pediatric meningiomas are rare. They are usually seen in association with neurofibromatosis type 2 (NF-2) or following radiation therapy. The tumors are more frequently intraventricular, cystic, and infratentorial than are those in adult patients. Pathologically they are more histologically aggressive than in adults and tend to recur more frequently. Complete resection is the surgical goal. The treatment of subtotally resected meningiomas, particularly in NF-2, remains controversial.

The effects of early hydrocephalus and related brain anomalies on cognitive skills are not well understood. In this study, magnetic resonance scans were obtained from 99 children aged from 6 to 13 years with either shunted hydrocephalus (n = 42) or arrested (unshunted) hydrocephalus (n = 19), from patient controls with no hydrocephalus (n = 23), and from normal, nonpatient controls (n = 15). Lateral ventricle volumes and area measurements of the internal capsules and centra semiovale in both hemispheres were obtained from these scans, along with area measurements of the corpus callosum. Results revealed reductions in the size of the corpus callosum in the shunted hydrocephalus group. In addition, lateral ventricle volumes were larger and internal capsule areas were smaller in both hemispheres in children with shunted and arrested hydrocephalus. The centra semiovale measurements did not differentiate the groups. Correlating these measurements with concurrent assessments of verbal and nonverbal cognitive skills, motor abilities, and executive functions revealed robust relationships only between the area of the corpus callosum and nonverbal cognitive skills and motor abilities. These results support the theory of a prominent role for the corpus callosum defects characteristic of many children with shunted hydrocephalus in the spatial cognition deficits commonly observed in these children.

Hemangiopericytomas (HPs) are rare tumors, about 10% of which occur in children. Since 1988, 2 children with intracranial HP have been seen at the University of Texas M.D. Anderson Cancer Center. The patients presented at ages 2 weeks and 1 month. Both were treated with surgery alone. We also review 4 cases previously reported in the literature; at presentation, those patients were ages 2 days to 9 months. Infantile HPs have a better prognosis than do those that occur in adults, and an improved outcome is also evident for intracranial lesions. Tumors that occur in the neonatal period may be treated with surgery alone; however, those that occur after the neonatal period may be more likely to recur.

Tissue diagnosis is necessary for optimal treatment of pineal region tumors in children. Preoperative staging should include craniospinal MR imaging with and without gadolinium DTPA enhancement, CSF sampling for cytology, and measurement of biologic tumor markers in serum and CSF. Surgical approach is determined by results of preoperative MR imaging and the extent of resection by the results of staging and intraoperative frozen-section histopathologic evaluation. There is no longer a role for the radiation test dose (2000 cGy) in the management of these tumors. Postoperative treatment is based on histopathology and extent of disease. Benign tumors are treated with surgery only, and nondisseminating focal tumors with surgery and focal radiation therapy. Non-germinoma malignant germ cell tumors are best treated with neoadjuvant chemotherapy followed by radiation therapy given focally for focal disease; craniospinal radiation therapy is reserved for patients with evidence of disseminated disease at the completion of induction chemotherapy.

In castrated male goats, two flexible catheters, one open ended for reference and the other ending in a 1-mm-diam glass bulb pH electrode, were advanced ventrally through a left posterior fossa craniotomy into the subarachnoid space between the 9th and 10th cranial nerve roots, passing medially into cerebrospinal fluid (CSF) over the medullary ventral surface (MVS). They were anchored to dura and fascia, tunneled under the scalp, and terminated in connectors on the left horn. After several days for recovery, while the animals were awake, the effects of CO2 and hypoxia on pH of the film of CSF between the pia and arachnoid (pHMVS) were recorded along with end-tidal PCO2 and PO2 (mass spectrometer), ventilation (pneumotachometer) through a permanent tracheostomy, and, when possible, ear arterial O2 saturation (SaO2). High PCO2 acidified MVS as expected: delta pH MVS/delta log PCO2. = -0.64 +/- 0.14, producing a ventilatory response slope delta VI/delta pHMVS = 372 l/min. Hypoxia resulted in acid shifts even when PCO2 was allowed to fall. The development of hypoxic acidosis was related to the location of pH electrodes determined at necropsy. In isocapnic hypoxia, pH over putative chemoreceptor surfaces fell in proportion to desaturation: delta pHMVS = 0.0033(SaO2)-0.34, r = 0.80, Sy.x = 0.025. With uncontrolled arterial PCO2, similar acidosis occurred when SaO2 fell below 85-90%: delta pHMVS = 0.0039(SaO2)-0.34, r = 0.88, Sy.x = 0.032. With constant hypoxia, pH fell (tau = 3.7 +/- 2.2 min) to a plateau after 10-20 min and showed rapid recovery (tau = 2.0 +/- 1.3 min).(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of primary central nervous system (CNS) lymphoma has increased rapidly in patients with acquired immunodeficiency syndrome (AIDS) and is predicted to exceed 1800 cases annually by 1991. To characterize the natural history and response to radiation therapy (RT) of these lesions, the authors have reviewed the clinical histories of 55 AIDS patients with biopsy-proven primary CNS lymphomas. The tumors responded both clinically and radiologically to whole-brain RT consisting of 4000 rad in 267-rad fractions over 3 weeks or an equivalent neuroret dose. The mean duration of survival from the appearance of symptoms consistent with the mass lesion was significantly greater in patients who received RT than in those who did not (42 vs. 134 days, p less than 0.5; median 27 vs. 119 days). Autopsy findings showed that patients who did not receive RT died from tumor progression, whereas those who completed RT died of opportunistic infections. Patients with AIDS who are suspected of having primary CNS lymphoma should therefore immediately undergo biopsy and, if the diagnosis is confirmed, whole-brain RT. With early diagnosis and treatment, these tumors respond to, and patients benefit from, RT. Survival of such patients may in future be prolonged by more effective treatments for systemic opportunistic infections.