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.

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.

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.

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.

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.

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.

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.

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.

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery.

Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated an acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci.

Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys.

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[18F]fluoro-L-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (Ki) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPA Ki ratios differed less than 5% between studies conducted at 1-2, 5-7, and 9-11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5-7 and 9-11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9-11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAKi ratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.

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.

Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology.

The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction.

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.

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.

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

Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy?

A case of angiographically occult brainstem vascular malformation presenting solely with pathological laughing and crying is reported. Although this emotional syndrome has been seen in association with several different pathological entities, review of the literature failed to identify its occurrence as the only clinical expression of angiographically occult brainstem vascular malformation, or as a solitary symptom in any disease. Our data suggest that pathological laughing and crying can occur without any other manifestation of pseudobulbar palsy. An attempt is made to correlate this patient's clinical and radiological findings. This case was treated by stereotactic Bragg-peak proton beam therapy.

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...