Dynamic arc radiosurgery field shaping: a comparison with static field conformal and noncoplanar circular arcs.

PURPOSE: Recent advances in field-shaping technology and linac multileaf collimator (MLC) integration have resulted in new approaches to performing stereotactic radiosurgery. We present a modeling study comparing the absolute dose distributions from three radiosurgery delivery techniques: a conventional approach utilizing noncoplanar circular arcs, a static field conformal approach, and a dynamic arc field-shaping approach. In the latter, the MLC leaves more in a continuous fashion, conforming to the beam's-eye-view projection of the target at every increment along the path of an arc. METHODS AND MATERIALS: For the analysis, we devised a simulated target consisting of three overlapping spheres. This was chosen because it offered a straightforward planning approach for all three techniques, primarily the multiple isocenter approach. In addition, three representative cases were selected from the prior radiosurgery experience. These range in increasing size, from 0.50 to 9.79 cm(3), and in complexity, requiring from 3 isocenters to 16 in the case of circular arcs. In each situation, the goals were twofold: (1) to cover the entire volume with as high an appropriate isodose level (90% in the case of the conformal and dynamic arc techniques, 50% in the case of circular collimators) while (2) minimizing the dose to normal brain and where applicable, any adjacent radiation-sensitive structures. Because of the latter requirement, a single isocenter circular arc approach was ruled out for the analysis. RESULTS: In the case of large or irregularly shaped lesions, the circular arc technique requires multiple isocenters, producing a high level of dose heterogeneity within the target volume. Both the static field and dynamic arc conformal techniques, as with all single isocenter approaches, produce a highly homogeneous dose throughout the target region. For a given large dose, peripheral dose is decreased as additional beams or arc degrees are added with either of the conformal approaches. Dose--volume histogram analysis evaluating the peripheral dose shows that, in many cases, dose to surrounding structures can be reduced through the use of a conformal static or dynamic arc approach over the conventional multiple isocenter, circular arc techniques. CONCLUSIONS: Dynamic arc shaping is an efficient and effective method for accurately delivering a homogeneous target dose while simultaneously minimizing peripheral dose in radiosurgery applications.

Monte Carlo treatment planning for stereotactic radiosurgery.

OBJECTIVES: In radiosurgery treatment planning there is general acceptance that the target volume can be assumed to be homogeneous and that corrections for variations in contour are unnecessary. Thus, dose algorithms employed in radiosurgery treatment planning are quite unsophisticated; in almost every case the algorithms are the simple product of tissue-maximum and off-axis ratios and an output factor. In small photon beams, however, the lack of side scatter equilibrium compromises these assumptions. METHODS: In this work we have employed Monte Carlo techniques in an attempt to obtain a more accurate representation of radiosurgical dose distributions. Specifically, the Monte Carlo system which we have devised traces the paths of primary and secondary radiation through a patient-specific anatomical representation defined by computed tomography data. In this manner the perturbation effects from external contour changes and internal tissue heterogeneities are accounted for completely. The ability to precisely mimic multi-beam multi-arc stereotactic delivery has been incorporated into our Monte Carlo treatment planning interface. RESULTS: Subsequent calculations show that substantial differences can exist when homogeneity is not assumed. Tissue heterogeneities produce a lateral broadening of the beam, resulting in a smaller volume contained within the higher isodose levels (80-90%) with a corresponding increase in the volume treated at the lower isodose levels (<50%). CONCLUSIONS: These results suggest that further investigation and refinement of radiosurgery dose algorithms is in order.

The origin of brainstem afferents of the paramedian pontine reticular formation in the cat.

Transcannular microinjections of horseradish peroxidase (HRP) were made into the paramedian pontine reticular formation (PPRF) in adult cats to determine the origin of the principal sources of inputs to this important preoculomotor center for the production of saccadic eye movements. Retrogradely labeled cells were observed in numerous oculomotor-related structures, including the prerubral field (rostral interstitial nucleus of the medial longitudinal fasciculus), nucleus of Darkschewitsch, nucleus of the posterior commissure, deep superior colliculus, supraoculomotor ventral periaqueductal gray, contralateral paramedian pontine reticular formation, pontine raphe and dorsal medial pontine tegmentum medial to the abducens nucleus (purported to contain omnipause neurons), cell group Y, and the perihypoglossal complex (nucleus prepositus hypoglossi). Other sources of afferents to the region included the zona incerta, lateral and medial habenular nuclei, medial hypothalamus, medial mammillary nucleus, nucleus cuneiformis, medial medullary reticular formation, and the medial and lateral cerebellar nuclei. The results are discussed in terms of the potential influence of these nuclei on the control of eye movement.

The frontal eye field and prefrontal cortex project to the paramedian pontine reticular formation in the cat.

Transcannular microinjections of horseradish peroxidase were made into the paramedian pontine reticular formation (PPRF) in adult cats to identify regions of the cerebral cortex having direct influence on this important center for the production of saccadic eye movements. The majority of retrogradely labeled cortico-(ponto)reticular neurons were located in lamina V of the dorsomedial precruciate shoulder cortex and presylvian sulcal cortex, the medial and lateral frontal eye fields of the cat respectively. In most cases, labeled cells also extended into the gyrus proreus, the cat prefrontal cortex.

Afferent and efferent connections of the cholinoceptive medial pontine reticular formation (region of the ventral tegmental nucleus) in the cat.

Following minor concussive brain injury when there is an otherwise general suppression of CNS activity, the ventral tegmental nucleus of Gudden (VTN) demonstrates increased functional activity (32). Electrical or pharmacological activation of a cholinoceptive region in this same general area of the medial pontine tegmentum contributes to certain components of reversible traumatic unconsciousness, including postural atonia (31, 32, 45). Therefore, in an effort to examine the neuroanatomical basis of the behavioral suppression associated with a reversible traumatic unconsciousness, the afferent and efferent connections of the VTN and putative cholinoceptive medial pontine reticular formation (cmPRF) were studied in the cat using the retrograde horseradish peroxidase (HRP), HRP/choline acetyltransferase (ChAT) double-labeling immunohistochemistry, and anterograde HRP and autoradiographic techniques. Based upon retrograde HRP labeling, the principal afferents to the VTN region of the cmPRF originated from the medial and lateral mammillary nuclei, and lateral habenular nucleus, and to a lesser extent from the interpeduncular nucleus, lateral hypothalamus, dorsal tegmental nucleus, superior central nucleus, and contralateral nucleus reticularis pontis caudalis. Other afferents, which were thought to have been labeled through spread of HRP into the medial longitudinal fasciculus (MLF), adjacent paramedian pontine reticular formation, or uptake by transected fibers descending to the inferior olive, included the nucleus of Darkschewitsch, interstitial nucleus of Cajal, zona incerta, prerubral fields of Forel, deep superior colliculus, nucleus of the posterior commissure, nucleus cuneiformis, ventral periaqueductal gray, vestibular complex, perihypoglossal complex, and deep cerebellar nuclei. In HRP/ChAT double labeling studies, only a very small number of cholinergic VTN afferent neurons were found in the medial parabrachial region of the dorsolateral pontine tegmentum, although the pedunculopontine and laterodorsal tegmental nuclei contained numerous single-labeled ChAT-positive cells. Anterograde HRP and autoradiographic findings demonstrated that the VTN gave rise almost exclusively to ascending projections, which largely followed the course of the mammillary peduncle (16,21) and medial forebrain bundle, or the tegmentopeduncular tract (4). The majority of fibers ascended to terminate in the medial and lateral mammillary nuclei, interpeduncular complex (especially paramedian subnucleus), ventral tegmental area, lateral hypothalamus, and the medial septum in the basal forebrain. Labeling that joined the mammillothalamic tract to terminate in the anterior nuclear complex of the thalamus was thought to occur transneuronally. Some projections were also observed to nucleus reticularis pontis oralis and caudalis, superior central nucleus, and dorsal tegmental nucleus adjacent to the VTN...

Brain tissue pH in severely head-injured patients: a report of three cases.

It is well established that low cerebrospinal fluid (CSF) pH and high CSF lactate concentration indicate the development of brain acidosis after severe human head injury. However, there is no direct evidence that tissue acidosis actually occurs. We measured brain extracellular pH (pHe) in three patients undergoing operation for the evacuation of acute subdural hematomas. A pH-sensitive polymer membrane electrode was inserted 500 micron into the cerebral cortex close to the damaged area. The pHe values obtained were correlated with ventricular CSF acid-based parameters and extension of the brain lesion. The CSF pH was higher than the pHe in all cases; the pHe was particularly low in areas of contusion or compression by mass lesion. The effect of focal brain tissue acidosis on clinical course after severe head injury is discussed.

Surgical outcomes in pure frontal lobe epilepsy and foci that mimic them.

In this study we examined 37 subjects with a diagnosis of intractable frontal lobe epilepsy (FLE) based on non-invasive pre-surgical evaluation. Twenty-six underwent chronic intracranial ictal recordings (CIR) with video monitoring; 20 of these went on to surgical resection. Eleven underwent surgery without CIR. Retrospectively, we determined that 19 had pure FLE, 12 had frontal plus extrafrontal epileptogenic zones, and six others did not have FLE. We analysed the whole group and individual categories to evaluate the determinants of surgical outcome. Sixty percent of the pure frontal group is seizure free with all having > or = 75% reduction. The frontal-plus group had only 10% seizure free with 70% having > or = 75% reduction. Being in the pure frontal group was associated with better outcomes than the 'frontal-plus' group (P < 0.05; chi-square). Subjects with FSIQ > or = 85, focal pathologies and 18FDG-PET scans which were normal or had focal abnormalities (P < or = 0.05, all, chi-square) were more likely to have excellent outcomes. MRI abnormalities, surface EEG, and location and size of resection were not predictive of surgical outcomes. Rasmussen's encephalitis, incomplete surgical strategies and bilateral foci were apparent in those with poor outcomes, and surgical size predicted post-operative deficits (chi-square; P < 0.001). We conclude that careful, hypothesis-driven implants and operating procedures can result in good surgical outcomes for frontal lobe epilepsy subjects even when lesions are not apparent on routine neuroimaging.

Thalamostriate artery aneurysm within the third ventricle. Case report.

The authors report the case of a 7-mm saccular aneurysm, located within the third ventricle and arising from the distal portion of a thalamostriate artery. The patient presented with an intraventricular hemorrhage and was treated via a frontotemporal craniotomy with translamina-terminalis approach for resection of the aneurysm. The etiology of the aneurysm was presumed to be idiopathic. Previously only one other third ventricular aneurysm has been reported. An intraventricular aneurysm arising from a perforating artery should therefore be considered as a rare cause of an intraventricular hemorrhage. Potential surgical approaches to third ventricular aneurysms are discussed.

Multiple radiation-induced intracranial lesions after treatment for pituitary adenoma. Case report.

This 53-year-old man presented with a syncopal episode 31 years after undergoing craniotomy and external-beam radiation for a pituitary macroadenoma. A gadolinium-enhanced magnetic resonance (MR) image of the brain demonstrated a 2.5-cm enhancing mass in the right caudate region that had not been seen on previous studies. A stereotactically guided biopsy procedure was performed to obtain specimens from the mass, which were consistent with ependymoma. The MR image also revealed two additional lesions that appeared to be within the radiation fields: a right temporal meningioma and a left frontal cavernous malformation. A review of the literature found three previous reports in which ependymomas presented after radiation therapy.

Pain suppression induced by electrical stimulation of the pontine parabrachial region. Experimental study in cats.

Cholinergic stimulation by microinjection of drugs into a region surrounding the lateral half of the brachium conjunctivum selectively produces a non-opiate form of pain suppression in the cat. Since this suppression does not appear to involve neural systems that mediate morphine analgesia, stimulation of this pontine parabrachial region (PBR) may potentially be useful for control of human pain resistant or tolerant to opiate treatment. Because of technical problems associated with the clinical use of microinjection techniques in the human brain, we investigated whether electrical stimulation of the PBR can produce pain suppression similar to pain suppression produced by cholinergic stimulation. The results indicate that electrical stimulation of an area generally corresponding to the PBR can also produce significant pain suppression. Although the PBR is a region previously implicated in a variety of behavioral and physiological functions, the stimulation parameters that produce maximal pain suppressive effects (namely, low frequency and relatively low intensity) were not associated with noticeable changes in such functions. The prolonged onset period and persistent analgesic effects outlasting the period of stimulation--features that have been reported in other studies of brain stimulation-produced pain suppression--were observed in the present study. The time course of pain suppression did not parallel other changes in behavioral and physiological functions. These data indicate that electrical stimulation of the PBR, under certain stimulation parameters, can activate previously demonstrated neural populations related to pain suppression without affecting neural elements contributing to other behavioral or physiological functions. The authors suggest that electrical stimulation of the PBR may be clinically applicable for treatment of human pain.

Transient suppression of event-related evoked potentials produced by mild head injury in the cat.

Studies in humans have shown that sensory stimuli, presented in the context of certain tasks, can elicit a late positive component (LPC), namely P300, in the scalp-recorded evoked potential believed to reflect neural activity related to attentional processes. A similar LPC has been reported in cats and monkeys. In this study, the LPC of the auditory evoked potential (AEP) in the cat was used to detect impairment in attention to a relevant stimulus after low levels of cerebral concussion produced by a fluid percussion device. A hollow screw (for fluid percussion) and stainless steel screws (for AEP recording) were surgically placed in the skull. After recovery from surgery, animals were trained in the paradigm to obtain an LPC. Pupillary dilation was conditioned to tones. A random sequence of two discriminable tones was presented. The lower tone had a probability of 0.1 and was followed by a tail shock (tone-shock). After 400 to 1000 tone-shock presentations, animals attended to the lower tone stimulus as inferred by selective pupillary dilation. In the AEP an early positive component at 50 to 120 msec related to an alerting response was enhanced, and an LPC at 250 to 450 msec appeared in response to the paired tone-shock. Animals were then subjected to cerebral concussion. Complete recovery of normal reflexes, motor coordination, and orienting response was seen within 2 hours after injury. The LPC was suppressed for a period of at least 3 days, suggesting that low magnitudes of brain injury can disrupt higher-order neural activities. This disruption can persist despite recovery of other neurological functions.

Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI.

The literature suggests that in children with severe head injury, cerebral hyperemia is common and related to high intracranial pressure (ICP). However, there are very few data on cerebral blood flow (CBF) after severe head injury in children. This paper presents 72 measurements of cerebral blood flow ("CBF15"), using the 133Xe inhalation method, with multiple detectors over both hemispheres in 32 children aged 3 to 18 years (mean 13.6 years) with severe closed head injury (average Glasgow Coma Scale (GCS) score 5.4). In 25 of the children, these were combined with measurements of arteriojugular venous oxygen difference (AVDO2) and of cerebral metabolic rate of oxygen (CMRO2). In 30 patients, the first measurement was taken approximately 12 hours postinjury. In 18 patients, an indication of brain stiffness was obtained by withdrawal and injection of ventricular cerebrospinal fluid and calculation of the pressure-volume index (PVI) of Marmarou. The CBF and CMRO2 data were correlated with the GCS score, outcome, ICP, and PVI. Early after injury, CBF tended to be lower with lower GCS scores, but this was not statistically significant. This trend was reversed 24 hours postinjury, as significantly more hyperemic values were recorded the lower the GCS score, with the exception of the most severely injured patients (GCS score 3). In contrast, mean CMRO2 correlated positively with the GCS score and outcome throughout the course, but large standard deviations preclude making predictions based on CMRO2 measurements in individual patients. Early after injury, there was mild uncoupling between CBF and CMRO2 (CBF above metabolic demands, low AVDO2) and, after 24 hours, flow and metabolism were completely uncoupled with an extremely low AVDO2. Consistently reduced flow as found in only four patients; 28 patients (88%) showed hyperemia at some point in their course. This very high percentage of patients with hyperemia, combined with the lowest values of AVDO2 found in the literature, indicates that hyperemia or luxury perfusion is more prevalent in this group of patients. The three patients with consistently the highest CBF had consistently the lowest PVI: thus, the patients with the most severe hyperemia also had the stiffest brains. Nevertheless, and in contrast to previous reports, no correlation could be established between the course of ICP or PVI and the occurrence of hyperemia, nor was there a correlation between the levels of CBF and ICP at the time of the measurements. The authors argue that this lack of correlation is due to: 1) a definition of hyperemia that is too generous, and 2) the lack of a systematic relationship between CBF and cerebral blood volume

Prognostic significance of ventricular CSF lactic acidosis in severe head injury.

Brain-tissue acidosis inferred by cerebrospinal fluid (CSF) lactic acidosis is considered to play an important role in the clinical course of severe head injury. Ventricular CSF lactate concentration was studied in 19 patients during the first 5 days after severe head injury. All patients were intubated, paralyzed, and artificially ventilated so that PaCO2 was kept at 33.2 +/- 5.0 mm Hg and PaO2 at 122 +/- 18 mm Hg (mean +/- standard deviation). The mean Glasgow Coma Scale score on admission was 5.73 +/- 2.42. The first CSF sample was drawn within 18 hours after head injury. Over the first 4 days postinjury, patients with a poor outcome had significantly higher ventricular CSF lactate levels than did those with moderate disabilities or a good outcome. Patients showing favorable outcome had a significant decrease in ventricular CSF lactate levels 48 hours after injury. This decrease was not observed in patients with a poor outcome. Increased ventricular CSF lactate concentration was also reliably associated with increased intracranial pressure (ICP). Ventricular CSF lactate levels did not correlate with the magnitude of intraventricular bleeding. Arterial and jugular venous blood lactate levels, although high after head injury, were usually lower than the levels in the ventricular CSF and reached a normal range by the 3rd day following head trauma. At that time, the ventricular CSF lactate concentration was still above normal in patients with a poor outcome but had decreased to normal in patients with moderate disabilities or a good outcome. Ventricular CSF pH did not generally correlate with the ventricular CSF lactate concentration in patients under controlled ventilation; however, in a few patients close to death or with ventricular infection, a correlation was noted. Ventricular CSF lactate levels were not related to cerebral blood flow. In this study, profiles of ventricular CSF lactate concentration are defined in relation to the patients' clinical course and outcome. High ventricular CSF lactate concentration is present within 18 hours after severe head injury. Its decrease to normal in the following 48 hours is a reliable sign of clinical improvement; however, ventricular CSF lactate levels that are persistently high or that increase over time indicate the patient's deterioration. Serial assessment of ventricular CSF for acid-base status and metabolites in head-injured patients with a ventricular catheter already placed for ICP monitoring is useful in the evaluation of prognosis and clinical course.

Cerebellar venous angioma associated with angiographically occult brain stem vascular malformation. Report of two cases.

We studied two patients with angiographically documented cerebellar venous angioma (malformation) and angiographically occult vascular malformation of the brain stem. One patient had recurrent hemorrhage in the pontine tegmentum. The second patient had recurrent hemorrhage in the midbrain. None had hemorrhage originating from the abnormal cerebellar venous channels. The more benign nature of angiographic venous malformations is supported by the cases we are presenting, as well as from a review of the literature, which includes an autopsy study of similar cases. The management of multiple vascular brain lesions is contingent on the verification of symptomatic pathological blood vessels. It is emphasized that angiographically occult vascular malformation could possibly exist in the vicinity of angiographic venous malformation when the patient with intracerebral hemorrhage, especially in the posterior fossa, was diagnosed as having venous malformation.

Thoracoscopic sympathectomy: techniques and outcomes.

Thoracic sympathectomy is an important option in the treatment of palmar hyperhidrosis and pain disorders. Earlier surgical procedures were highly invasive with known morbidity, acceptable outcome, and established recurrence rates that were the limitations to considering surgical treatment. Thoracoscopic sympathectomy is a minimally invasive procedure that allows detailed visualization of the sympathetic ganglia and minimal postoperative morbidity; however, outcome studies of this technique have been limited. The authors treated 39 patients with 60 thoracoscopic procedures, and the outcomes in this small series were equivalent to previously established open surgical techniques; however, operative moribidity rates, hospital stay, and time of return to normal activity were substantially reduced. Complications and recurrence of symptoms were also comparable to previous reports. Overall patient satisfaction and willingness to repeat the operative procedure ranged from 66 to 96% in all patients. Patients and physicians can consider minimally invasive thoracoscopic sympathectomy procedures as an option to treat sympathetically mediated disorders because of the procedure's reduced morbidity and at least equivalent outcome rates in comparison to other treatments.

Fractionated stereotactic radiotherapy: rationale and methods.

Stereotactic radiosurgery (SRS) has become a widely accepted technique for the treatment intracranial neoplasms. Combined with modern imaging modalities, SRS has established its efficacy in a variety of indications. From the outset, however, it was recognized that the delivery of a single large dose of radiation was essentially "bad biology made better by good physics." To achieve the accuracy required to compensate for this biological shortcoming, the application of SRS has required that a neurosurgical head frame of some sort be rigidly attached to the patients head. Historically, this prerequisite has, primarily for practical reasons, precluded the delivery of multiple fractions over multiple days. With recent improvements in immobilization and repeat fixation, the good biology of fractionated delivery has been realized. This technique, which has come to be known as stereotactic radiotherapy (SRT), has significantly expanded the efficacy of the technique through the use of accurate physical targeting coupled with the basic radiobiological principles gleaned from decades of clinical experience.

Stereotactic radiotherapy for the treatment of pituitary adenomas.

PURPOSE: The aim of this study was to retrospectively review local control and morbidity following stereotactic radiotherapy (SRT) for pituitary adenoma. METHODS: Between 1997 and 2004, 39 patients with pituitary adenomas received SRT. Median age was 56 years (range: 13 to 90 years). Thirty-three patients underwent incomplete transsphenoidal surgery prior to SRT and six had unresectable tumors. The largest tumor dimension varied from 1.7 to 6 cm (median: 3 cm). Tumor volume varied from 1.2 to 56 mL (median 10.5 mL). Thirty-five tumors were < or = 1 mm from the optic chiasm/nerve. Thirty-three tumors were non-functional. SRT was delivered by a dedicated linear accelerator (Novalis, Heimstetten, Germany). Beam collimation was achieved by a fixed circular collimator (five patients) or a micro-multileaf collimator (34 patients). Total dose varied from 4500 to 5040 cGy (median: 4860 cGy) and was prescribed at the 90 % isodose line. RESULTS: After a median follow-up of 32 months (range: 12 to 94 months), the local control rate was 100 %. Tumor size was stable in 26 patients and decreased in 13 patients. Hormone normalization did not occur following SRT. New endocrine deficiency occurred in six patients. No patient developed cranial nerve injury or second malignancy following treatment. CONCLUSIONS: SRT achieves a high rate of local control and a low rate of treatment-induced morbidity. SRT is applicable to pituitary adenomas in close proximity to the optic apparatus and tumors in excess of three centimeters in the greatest dimension. Further follow-up is necessary to establish the long-term outcome following SRT for pituitary adenomas.

Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma.

PURPOSE: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. METHODS: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. CONCLUSIONS: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.

Long-term methamphetamine-induced decreases of [(11)C]WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey.

The effects of glial cell line-derived neurotrophic factor (GDNF) pretreatment on methamphetamine (METH)-induced striatal dopamine system deficits in the vervet monkey were characterized with [(11)C]WIN 35,428 (WIN)-positron emission tomography (PET). WIN, a cocaine analog that binds to the dopamine transporter (DAT), was used to provide an index of striatal dopamine terminal integrity. In two subjects, GDNF (200 microg/40 microl) was injected into the caudate and putamen unilaterally vs. saline contralaterally. After 1-2 weeks, + and -GDNF striatal WIN-PET binding values were equivalent as calculated by multiple time graphic analysis, suggestive of an absence of unilateral DAT up-regulation. Three other subjects (n = 3) received GDNF injections into the caudate and putamen unilaterally and one week later, were administered METH HCl (2 x 2 mg/kg; i.m., 24 hours apart; a neurotoxic dosage for this species). At 1 week post-METH, WIN-PET studies showed that mean WIN binding was decreased by 72% in the +GDNF and by 92% in the -GDNF striatum relative to pre-drug assessment values. Thus, GDNF pretreatment reduced the extent of METH-induced decreases in WIN binding. Subsequent WIN-PET studies (1.5-9-month range) showed a protracted recovery of WIN binding in each striatum, indicative of long-term but partially reversible METH neurotoxicity. Further, at each time point, WIN binding remained relatively higher in the +GDNF vs. -GDNF striatum. These results provide further evidence that the adult non-human primate brain remains responsive to exogenously administered GDNF and that this pharmacotherapy approach can counteract aspects of neurotoxic actions associated with methamphetamine.

Percutaneous stereotactic brain tumour biopsy and cyst aspiration with a non-invasive frame.

A non-invasive Stereoadapter was used for stereotactic CT-guided percutaneous brain biopsy in 18 patients with 16 solid tumours and four cysts. The Stereoadapter was mounted on the patient's head using ear plugs and a nasion support. After the CT study, the Stereoadapter was detached. The target was simulated on a phantom base and a probe carrier attached to the Stereoadapter. For surgery, the Stereoadapter with the probe carrier was remounted to the patient's head. Local anaesthesia was mainly used. Tissue samples were aspirated with a 2 mm diameter Sedan-Nashold biopsy cannula, introduced through a twist drill hole. Conclusive histological/cytological diagnosis was obtained in 16 of the 20 lesions. The new method proved to be reliable and quick. Since the imaging study and the surgery could be separated in time and place, the biopsy procedure was less time-consuming than previous methods of stereotactic biopsy using an invasive frame.