Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Absorption of wireless radiation in the child versus adult brain and eye from cell phone conversation or virtual reality.

Children's brains are more susceptible to hazardous exposures, and are thought to absorb higher doses of radiation from cell phones in some regions of the brain. Globally the numbers and applications of wireless devices are increasing rapidly, but since 1997 safety testing has relied on a large, homogenous, adult male head phantom to simulate exposures; the "Standard Anthropomorphic Mannequin" (SAM) is used to estimate only whether tissue temperature will be increased by more than 1 Celsius degree in the periphery. The present work employs anatomically based modeling currently used to set standards for surgical and medical devices, that incorporates heterogeneous characteristics of age and anatomy. Modeling of a cell phone held to the ear, or of virtual reality devices in front of the eyes, reveals that young eyes and brains absorb substantially higher local radiation doses than adults'. Age-specific simulations indicate the need to apply refined methods for regulatory compliance testing; and for public education regarding manufacturers' advice to keep phones off the body, and prudent use to limit exposures, particularly to protect the young.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

The role of modern imaging modalities on deep brain stimulation targeting for mental illness.

INTRODUCTION: The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. METHODS: Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. RESULTS: Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. CONCLUSIONS: Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.

Radiosurgery from the brain to the spine: 20 years experience.

INTRODUCTION: Radiosurgery evolved from brain to spine. Mechanical and computer advances in linear accelerator (LINAC) radiosurgery apply precise single/fractional stereotactic radiation to multiple pathologies. METHODS: During a 10-year span the senior author used proton-beam radiosurgery in over 300 lesions, followed by gamma-knife, adapted and dedicated LINACS, including cyber-knife, in another 700 patients. The last 10 years, experience was accumulated with the Novalis in over 3,000 patients. Novalis uses a beam-shaper in a high-speed delivery LINAC. It operates using conventional circular arc, conformal static beam, dynamic conformal or intensity modulated modes. Patients treated with Novalis at the UCLA since 1997 were evaluated regarding effectiveness, complications and failure. These results were compared with previous 1997 data. RESULTS: Over 4,000 patients with trigeminal neuralgia/intractable pain, arteriovenous malformations/angiomas, metastases, ependymomas, gliomas, meningiomas hemangiopericytomas, schwannomas, adenomas, hemangioblastomas, and chordoma were treated. Spinal lesions were treated with frameless stereotaxis and on-line precision checks. Treatment was expeditious, comfortable and with reduced complications. Success is similar or superior to published data. Reduced treatment time of complex lesions and highly homogeneous dose compares favorably to other radiosurgery. CONCLUSIONS: The senior author's experience validates the novel shaped-beam approach. Long-term follow-up supports safety and effectiveness and capability to treat brain and spine.

Experimental radiosurgery simulations using a theoretical model of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: A novel biomathematical arteriovenous malformation (AVM) model based on electric network analysis was used to investigate theoretically the potential role of intranidal hemodynamic perturbations in elevating the risk of rupture after simulated brain AVM radiosurgery. METHODS: The effects of radiation on 28 interconnected plexiform and fistulous AVM nidus vessels were simulated by predefined random or stepwise occlusion. Electric circuit analysis revealed the changes in intranidal flow, pressure, and risk of rupture at intervals of 3 months during a 3-year latency period after simulated partial/complete irradiation of the nidus using doses <25 and >/=25 Gy. An expression for risk of rupture was derived on the basis of the functional distribution of the critical radii of component vessels. The theoretical effects of radiation were also tested on AVM nidus vessels with progressively increasing elastic modulus (E:) and wall thickness during the latency period, simulating their eventual fibrosis. RESULTS: In an AVM with E=5. 0x10(4) dyne/cm(2), 4 (14.3%) of a total 28 sets of AVM radiosurgery simulations revealed theoretical nidus rupture (risk of rupture >/=100%). Three of these were associated with partial nidus coverage and 1 with complete treatment. All ruptures occurred after random occlusion of nidus vessels in AVMs receiving low-dose radiosurgery. Intranidal hemodynamic perturbations were observed in all cases of AVM rupture; the occlusion of a fistulous component resulted in intranidal rerouting of flow and escalation of the intravascular pressure in adjacent plexiform components. Risk of rupture was found to correlate with nidus vessel wall strength: a low E: of 1.9x10(4) dyne/cm(2) resulted in a 92.8% incidence of AVM rupture, whereas a higher E: of 7.0x10(4) dyne/cm(2) resulted in only a 3.6% incidence of AVM rupture. A dramatic reduction in rupture incidence was observed when increasing fibrosis of the nidus was modeled during the latency period. CONCLUSIONS: It was found that the theoretical occurrence of AVM hemorrhage after radiosurgery was low, particularly when radiation-induced fibrosis of nidus vessels was considered. When rupture does occur, it would appear from a theoretical standpoint that the occlusion of intranidal fistulas or larger-caliber plexiform vessels could be a significant culprit in the generation of critical intranidal hemodynamic surges resulting in nidus rupture. The described AVM model should serve as a useful research tool for further theoretical investigations of cerebral AVM radiosurgery and its hemodynamic sequelae.

Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction: preliminary study.

OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. DESIGN AND METHODS: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Implications of tissue heterogeneity for radiosurgery in head and neck tumors.

PURPOSE: This study was undertaken to investigate the perturbation of small radiation beams by low density heterogeneities and to evaluate the ability of a Monte Carlo code to account for such perturbation. Performance of an inexpensive film scanning system was also evaluated. METHODS AND MATERIALS: Film and diode measurements were made in an acrylic phantom in which the size and position of an air gap were varied. Monte Carlo analysis was used to obtain additional verification of the measurements, to provide insight into photon and electron transport phenomena not directly measurable, and as a benchmark for the code. RESULTS: With 10 MV photons and a 1 cm circular field, a small 3-mm air cavity placed 2.6 cm deep in acrylic (full buildup) results in a reduction in central axis dose of 21% immediately following the cavity. Equilibrium is then reestablished over the next centimeter, after which the dose exceeds that of the homogeneous case by 3-4%. The loss in central axis equilibrium is highly field-size dependent, with some loss occurring even for the largest (32 mm) collimator. In addition, the presence of the air cavity produces a significant increase in dose up to 2 cm lateral and outside the primary field. CONCLUSIONS: Tissue heterogeneities are not presently accounted for in radiosurgery calculations, yet have the ability to perturb dose significantly. Targets may potentially be underdosed, and adjacent critical structures overdosed. Inability to account for tissue heterogeneities may limit the use of the radiosurgery approach in some areas. A Monte Carlo approach may be the method of choice for small field dose calculation when tissue heterogeneities are encountered.

Arteriovenous malformation animal model for radiosurgery: the rete mirabile.

PURPOSE: To study the effects of single-dose radiation on the porcine rete mirabile, a tangle of microvessels that mimics human arteriovenous malformations of the brain. METHODS: Eight retia mirabilia received a single dose of radiation under stereotactic location with digital angiography and CT. The following doses were applied: 20, 30, 40, 50, 60, 70, 80, and 90 Gy. The animals were followed up for a period of 7 months. Findings at neurologic examination, serial angiography, and histopathologic examination were analyzed. RESULTS: Progressive occlusion as observed by angiography corresponded to the histopathologic finding of intimal hyperplasia; that is, marked thickening of the vessel wall, progressing to occlusion of the vascular lumen, and associated thrombosis. A direct dose response was noted for these changes. Neurologic findings were related to the dose distribution and to histologic findings in structures adjacent to the rete mirabile. CONCLUSION: The rete mirabile is an excellent model by which to study the radiologic and histologic effects of single-dose radiation to the microvasculature of the central nervous system.

Hyperglycemia, cerebrospinal fluid lactic acidosis, and cerebral blood flow in severely head-injured patients.

Cerebrospinal fluid (CSF) lactate concentration is known to increase during the acute phase after severe head injury. To determine the influence of glycemia or cerebral ischemia on this lactate increase, we studied 69 head-injured patients aged 28.7 +/- 15.4 (SD) years with a mean Glasgow coma score of 5.7 +/- 1.7 (SD). They were intubated, paralyzed, and artificially respired. We measured lactate and glucose concentrations in ventricular CSF (VCSF), arterial blood, and jugular bulb blood for 5 days. Samples were obtained within 12 hours after injury and at regular 12-hour intervals. These patients were not treated for hypo- or hyperglycemia. Cerebral blood flow (CBF) was also measured within 12 hours and at 12- to 48-hour intervals. Hyperglycemia was found consistently within 12 hours after injury (224 +/- 98 mg/dl, P less than 0.001), and mild hyperglycemia persisted during the entire period of study. The VCSF glucose course was parallel to that in blood (the initial VCSF glucose value was 128 +/- 37 mg/dl, P less than 0.001). The blood lactate value was also elevated during the first 12 hours (4.2 +/- 2.0 mmol/litre, P less than 0.001), normalizing within 24 to 36 hours. The VCSF lactate course was independent from that of the blood lactate value. It was significantly elevated within 12 hours after injury (5.3 +/- 2.6 mmol/litre, P less than 0.001) and remained so during the 5 days of study. A high initial VCSF glucose value was associated with a high initial VCSF lactate value. However, a high VCSF lactate concentration was present even when the glucose value was close to the normal level.(ABSTRACT TRUNCATED AT 250 WORDS)

Early postoperative appearance of radiofrequency lesions on magnetic resonance imaging.

Eleven patients who underwent stereotactic radiofrequency lesions in the central nervous system had magnetic resonance imaging follow-up within 72 hours of surgery to determine the early appearance of their lesions. Eight patients with severe tremor, one with chronic pain, and two with dystonia were analyzed. There were six female patients and five male patients, age 7 to 75 years (mean +/- standard deviation = 42 +/- 21). Magnetic resonance imaging was performed postoperatively at 32 +/- 25 hours (range, 3-72). Postoperative T1-weighted spin echo images demonstrated foci of iso- to hyperintensity surrounded by an edge of hypointensity, and corresponding T2-weighted images showed a lesion with three concentric zones consisting of inner hypointense, middle hyperintense, and outer hypointense zones. Gadolinium increased T1-weighted image lesion visibility, and a ring of enhancement around the zone of hypointensity was observed. Lesions could be seen as early as 3 hours after surgery. The lesions were best shown on gadolinium-enhanced T1-weighted images and on T2-weighted images. The edema surrounding the lesion increased over time, up to the 72 hours studied. These data provide important information on the development of lesion appearance, which may be applied in the development of real-time magnetic resonance imaging monitoring of radiofrequency lesion formation. This technique associated with electrophysiological response and the real-time visualization of the anatomic correlation of the probe may allow for a very precise and selected lesion in the central nervous system for the treatment of functional disorders and brain tumors.

Arteriovenous malformation hemodynamics: a transcranial Doppler study.

Congenital arteriovenous malformation (AVM) of the brain represents a defect in capillary development resulting in a high flow fistula between arterial and venous systems. In this study, AVM hemodynamics were related with clinical findings. Volume flow was calculated based on transcranial Doppler (TCD) and angiographic data. Forty patients admitted to the Massachusetts General Hospital for proton beam therapy (33 +/- 10 yr old; mean +/- SD) were studied. Four symptoms were considered: intracranial bleeding, progressive neurological deficit, seizures, and headache. Fourteen control subjects aged 30 +/- 7 years (mean +/- SD) were normal volunteers. Angiography with calibrated markers permitting magnification correction was available for all patients. Lateral and medial depth limits of the intracranial basal arteries in relation to the TCD temporal window were determined by TCD and angiogram with excellent correlation. Selected depth for data acquisition was determined independently in the angiogram and by TCD. The difference between the two techniques was less than 4 mm. Mean flow velocity, pulsatility index, and vessel diameter were studied. Flow volume was calculated from these data. Mean flow velocity, pulsatility index, vessel diameter, and flow volume were significantly different among AVM feeders, non-feeders, and control arteries. The non-feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 254 +/- 13, 136 +/- 14, and 79 +/- 8 ml/min, respectively. Accordingly, the estimated cerebral flow volume was 938 ml/min. The feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 552 +/- 47, 369 +/- 70, and 484 +/- 67 ml/min, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

CO2 reactivity in arteriovenous malformations of the brain: a transcranial Doppler ultrasound study.

Arteriovenous malformations (AVM's) are congenital tangles of vessels that have a high blood flow through a low-resistance nidus. The vessels in the nidus may lack normal vasoreactivity in response to changes in PaCO2 or perfusion pressure (autoregulation). Arteriovenous malformation hemodynamics have been assessed based on the response of AVM feeding arteries to hypocapnia. Twenty-five AVM patients, aged 34 +/- 11 years (mean +/- standard deviation), were admitted to the Massachusetts General Hospital for proton-beam radiation therapy. Fourteen healthy volunteers aged 30 +/- 7 years served as control subjects. Angiograms with calibrated markers permitting magnification correction were available for all patients. The limits of the middle cerebral artery, as determined by transcranial Doppler ultrasonography, were compared to measurements made on the angiograms. Hyperventilation was induced at a rate set by a metronome. Fixed bilateral Doppler probes allowed almost simultaneous sampling of two vessels. Volunteer control subjects were hyperventilated in two steps. The two PaCO2 step decreases were significant (mean resting PaCO2 40.6 +/- 3.5 mm Hg, Step 1 level 29.4 +/- 3.5 mm Hg and Step 2 level 23.8 +/- 3.5 mm Hg; p < 0.01). These decreases induced a significant decrease in mean flow velocity (Vm) and an increase in the pulsatility index (p < 0.001). Mean carbon dioxide reactivity (% delta Vm/delta PaCO2) was 2.74 +/- 1.0 for Step 1 and 1.44 +/- 1.8 for Step 2 (p < 0.003). The mean PaCO2 decrease in patients was from 39.5 +/- 4.0 mm Hg to 27.0 +/- 3.5 mm Hg. Carbon dioxide reactivity was 0.92 +/- 1.12 for feeding vessels and 2.59 +/- 1.78 for nonfeeding vessels (p < 0.001). Transcranial Doppler ultrasound and angiographic depth measurements correlated well. Hyperventilation induced significantly more hemodynamic changes in control and nonfeeding middle cerebral arteries than in feeding vessels. Impaired CO2 reactivity may help to identify AVM feeding vessels as well as the relative magnitude of the flow provided to the malformation.

Radiosurgery performed with the aid of a 3-mm collimator in the subthalamic nucleus and substantia nigra of the vervet monkey.

OBJECT: Radiosurgery for functional neurosurgery performed using a linear accelerator (LINAC) has not been extensively characterized in preclinical studies. In the present study, the properties of a newly designed 3-mm-diameter collimator were evaluated in a dedicated LINAC, which produced lesions in the basal ganglia of vervet monkeys. Lesion formation was determined in vivo in three animals by examining magnetic resonance (MR) images to show the dose-delivery precision of targeting and the geometry and extent of the lesions. Postmortem immunohistochemical studies were conducted to determine the extent of lesion-induced radiobiological effects. METHODS: In three male vervet monkeys, the subthalamic nucleus (STN; one animal) and the pars compacta of the lateral substantia nigra (SN; two animals) were targeted by a Novalis Shaped Beam Surgery System that included a 3-mm collimator and delivered a maximum dose of 150 Gy. Magnetic resonance images obtained 4, 5, and 9 months posttreatment were reviewed, and the animals were killed so that immunohistological characterizations could be made. CONCLUSIONS: The generation of precise radiosurgical lesions by a 3-mm collimator was validated in studies that targeted the basal ganglia of the vervet monkey. The extent of the lesions created in all animals remained restricted in diameter (< 3 mm) throughout the duration of the studies, as assessed by reviewing MR images. Histological studies showed that the lesions were contained within the STN and SN target areas and that there were persistent increases in glial fibrillary acidic protein immunoreactivity. Increases in immunoreactivity for tyrosine hydroxylase, the serotonin transporter, and the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor in penumbral regions of the lesion were suggestive of compensatory neuronal adaptations. This radiosurgical approach may be of particular interest for the induction of lesions of the STN and SN in studies of experimental parkinsonism, as well as for the development of potential radiosurgical treatments for Parkinson disease.

Delayed internal capsule infarctions following radiofrequency pallidotomy. Report of three cases.

The authors report on a series of patients with idiopathic Parkinson's disease (IPD) who underwent stereotactic radiofrequency (RF) pallidotomies, three of whom suffered delayed postoperative strokes. These three belonged to a group consisting of 42 patients with medically intractable IPD in whom 50 pallidotomies were performed. All three patients had significant previous vascular disease and were in a high-risk group for cerebral infarction. A postoperative magnetic resonance (MR) image was obtained immediately after the pallidotomy was performed to document the placement of the RF lesion and to rule out any hematoma. The delayed strokes occurred on postoperative Days 10, 51, and 117 in patients with previous vascular disease (Group 1, 11 patients). No strokes occurred in the group with the vascular disease risk factor (Group 2, 11 patients) or in the group with no risk factors for vascular disease (Group 3, 20 patients). This observation is statistically significant (p < 0.05). The T2-weighted MR images showed the lesions as high-intensity signals extending to the posterior limb of the internal capsule ipsilateral to the pallidotomy site. The poststroke T1-weighted images obtained in two patients showed persistent contrast enhancement of the RF lesion and no enhancement around the stroke lesion. Clinically and radiographically, these discrete new lesions represent delayed infarctions, suggesting that RF lesioning can induce delayed injury in adjacent tissue. Patients with previously identified vasculopathy may be at risk for delayed capsular infarction following RF pallidotomy.

MRI of thermally denatured blood: methemoglobin formation and relaxation effects.

Focal regions of T1-shortening have been observed in magnetic resonance imaging (MRI)-monitored thermal ablations of perfused tissues. The aims of this study were two-fold: to find evidence for heat-induced conversion of hemoglobin (Hb) to methemoglobin (mHb), and to investigate the effects of heat treatment of in-vitro blood components upon their MR relaxation times. Spectrophotometric studies were performed to confirm the heat-induced formation of methemoglobin. Preparations of whole and fractionated blood, previously submitted to elevated temperatures of 40 degrees C to 80 degrees C, were imaged and the relaxation times were calculated. Optical absorption spectra of samples containing free Hb, heated to 60 degrees C, showed increased light absorption at 630 nm, evident of mHb presence. Short T1 values in whole blood (1.13 s) and packed red blood cell (0.65 s) compartments, heated at 60 degrees C, compared to their baseline values (1.62 s and 0.83 s, respectively), were attributed to mHb formation. In relation to MRI-guided thermal interventions, these results suggest a possible explanation for observation of hyperintense regions on T1-weighted images.

Role of stereotaxis in the treatment of cerebral palsy.

There is a renewed interest in basal ganglia surgery for improvement of motor symptoms in cerebral palsy. Rigidity, choreoathetosis, and tremor can be improved or abolished by a well-placed radiofrequency lesion, either in the ventrolateral nucleus of the thalamus or ventroposterior pallidum. The target is chosen based on the predominance of the symptoms in a given patient. A review of the main reports on surgery of the basal ganglia for cerebral palsy, as well as the author's data, shows that the surgery can have a remarkable impact on patients' quality of life when motor dysfunction is improved. An update of the physiopathology of cerebral palsy motor symptoms related to anatomic findings on experimental work, magnetic resonance imaging, and autopsy is used to rationalize surgery of the basal ganglia. Modern stereotactic technique based on exquisite demonstration of the basal ganglia anatomy by magnetic resonance imaging is described and supported by intraoperative electricophysiologic studies. The author stresses the importance of a multidisciplinary approach to provide the cerebral palsy patient with a comprehensive treatment plan before stereotactic surgery.

Primary central nervous system lymphoma. Results at the University of California at Los Angeles and review of the literature.

The authors report 24 patients with primary central nervous system lymphoma (PCNSL) treated from 1977 to 1992. There were 13 females and 11 males. Median age was 57 (range: 17-84). Patients were symptomatic for a median of 3 months. Headache was the most common complaint. Median Karnofsky performance score was 70. There were 19 patients with solitary PCNSL, and 5 had multiple deposits. Disease was confined to the supratentorium in 23 patients. Cerebrospinal fluid cytology was positive in 5 of 22 patients examined. All patients received whole-brain irradiation with or without supplemental tumor boost. Tumor doses ranged from 10 to 60 Gy. Intrathecal chemotherapy was administered to 16 patients and 7 received systemic agents. After follow-up ranging from 1 to 66 months, median survival and progression-free survival were each 8 months. One- and 3-year actuarial survival rates were 50% and 36%, respectively. One- and 3-year actuarial progression-free rates were 41% and 15%, respectively. Relapse occurred in 18 patients, and in 17 there was a component of local progression. Lesions recurred in the spinal meninges in 1 patients and in the vitreous in 1. Patients with Karnofsky performance status > or = 70 demonstrated median progression-free survival of 27 months, compared to 4 months for patients < 70 (p = .024). No other significant patient or treatment-related prognostic factors were identified. Clinical dementia occurred in 2 of 11 patients surviving at least 1 year. Review of the literature indicates PCNSL demonstrates relative radioresistance. The most immediate improvement in prognosis for patients with PCNSL can be achieved by properly sequencing systemic and intrathecal chemotherapy with radiation therapy.

Thalamic pain syndrome: anatomic and metabolic correlation.

We report a patient with thalamic pain induced by stereotactic biopsy; therefore, the location of the anatomical lesion causing the syndrome is precisely known. The location of the lesion was confirmed by postoperative magnetic resonance imaging and computed tomography. The metabolic consequences of the anatomic lesion were documented by positron emission tomography using as marker 18F-fluoro-2desoxy-glucose. The anatomic, metabolic, and clinical findings are discussed, as well as the neurophysiologic theories of the mechanisms of the thalamic pain syndrome.