Biomedical subjects

Pantaleo Romanelli

Publications and source records attributed to Pantaleo Romanelli.

At least 19 recordsLinked to original sources

PubMed2006

Interlaced x-ray microplanar beams: a radiosurgery approach with clinical potential.

Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-microm thick and spaced 100-300 microm on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90-degree angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm(3) exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-microm dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.

Animals↗

PubMed2006

Radiosurgery for epilepsy.

Radiosurgery is an emerging therapeutic approach for the treatment of medically intractable epileptogenic foci. A favourable seizure outcome was first reported in studies of the effects of radiosurgery in the treatment of arteriovenous malformations and tumours. Radiosurgery has since been applied to the treatment of complex partial seizures with mesial-temporal-lobe onset. Nearly simultaneously, experimental evidence supporting the usefulness of radiosurgery to improve or abolish seizures has confirmed that stereotactic irradiation can preferentially affect epileptogenic versus normal cortex. Further work is clearly needed, but this technique might become an important approach in the management of mesial-temporal and extratemporal epilepsy, especially if refractory seizures arise from eloquent cortex or surgically challenging regions of brain.

Epilepsy↗

PubMed2006

Atlas-based identification of targets for functional radiosurgery.

Functional disorders of the brain, such as Parkinson's disease, dystonia, epilepsy, and neuropathic pain, may exhibit poor response to medical therapy. In such cases, surgical intervention may become necessary. Modern surgical approaches to such disorders include radio-frequency lesioning and deep brain stimulation (DBS). The subthalamic nucleus (STN) is one of the most useful stereotactic targets available: STN DBS is known to induce substantial improvement in patients with end-stage Parkinson's disease. Other targets include the Globus Pallidus pars interna (GPi) for dystonia and Parkinson's disease, and the centromedian nucleus of the thalamus (CMN) for neuropathic pain. Radiosurgery is an attractive noninvasive alternative to treat some functional brain disorders. The main technical limitation to radiosurgery is that the target can be selected only on the basis of magnetic resonance anatomy without electrophysiological confirmation. The aim of this work is to provide a method for the correct atlas-based identification of the target to be used in functional neurosurgery treatment planning. The coordinates of STN, CMN, and GPi were identified in the Talairach and Tournoux atlas and transformed to the corresponding regions of the Montreal Neurological Institute (MNI) electronic atlas. Binary masks describing the target nuclei were created. The MNI electronic atlas was deformed onto the patient magnetic resonance imaging-T1 scan by applying an affine transformation followed by a local nonrigid registration. The first transformation was based on normalized cross correlation and the second on optimization of a two-part objective function consisting of similarity criteria and weighted regularization. The obtained deformation field was then applied to the target masks. The minimum distance between the surface of an implanted electrode and the surface of the deformed mask was calculated. The validation of the method consisted of comparing the electrode-mask distance to the clinical outcome of the treatments in ten cases of bilateral DBS implants. Electrode placement may have an effect within a radius of stimulation equal to 2 mm, therefore the registration process is considered successful if error is less than 2 mm. The registrations of the MNI atlas onto the patient space succeeded in all cases. The comparison of the distance to the clinical outcome revealed good agreement: where the distance was high (at least in one implant), the clinical outcome was poor; where there was a close correlation between the structures, clinical outcome revealed an improvement of the pathological condition. In conclusion, the proposed method seems to provide a useful tool for the identification of the target nuclei for functional radiosurgery. Also, the method is applicable to other types of functional treatment.

Journal Article↗

PubMed2006

Image-guided radiosurgical ablation of intra- and extra-cranial lesions.

For decades since its introduction, stereotactic radiosurgery (SRS) was used only to treat intracranial lesions because intracranial targets could be immobilized and located relative to a rigid metal frame affixed to the patient's head. Lesions outside the head were generally not treated with SRS because it is difficult to immobilize extracranial lesions and to attach stereotactic frames elsewhere on the body. Advances in computerized image guidance and robotics allowed the development of systems, such as the CyberKnife SRS System (Accuray, Inc, Sunnyvale, CA), that could target intracranial lesions without the stereotactic frame. Enhancements have resulted in a radiation delivery system that can accurately deliver high-dose, focal radiation to lesions in the spine, chest, and abdomen, even if they move during respiration. In this review we will describe the technical features of frameless SRS systems and briefly review their application to treating intracranial and extracranial lesions, focusing in particular on spinal lesions.

Brain Neoplasms↗

PubMed2006

Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia.

OBJECTIVE: Frame-based radiosurgical rhizotomy has been shown in clinical studies to be effective for managing trigeminal neuralgia (TN). To date, however, only a small pilot study has been published for the frameless, image-guided CyberKnife system. We present our preliminary experience with 29 trigeminal neuralgia patients treated with the frameless CyberKnife using X-ray image-guided targeting, a novel CT method for target definition, and non-isocentric planning. MATERIALS AND METHODS: All 29 patients failed previous medical therapy and 14 had undergone prior surgical procedures. CT iohexal cisternography was used to identify the 6- to 8-mm segment of nerve to be lesioned. The marginal dose ranged from 60 to 70 Gy (median 66.4 Gy) as defined at an average 79th percentile. The corresponding Dmax varied from 71.4 to 86.4 Gy (median 77.91 Gy). RESULTS: After a median 10-month follow-up, 26 of 29 (90%) patients rated their pain control as excellent and 3 (10%) reported no improvement. Median time to improvement was 6 days. No or only minor progression in numbness was reported by 22 of 29 (76%) patients, 4 of 29 (14%) patients reported worsening, and 3 of 29 (10%) reported the onset of severe ipsilateral facial numbness. Two patients whose target volume inadvertently included the semi-lunar ganglion developed painful dysethesias in the distribution of their numbness. CONCLUSION: Although the optimal dose and length of nerve to be lesioned are still being refined, this preliminary experience suggests that image-guided robotic radiosurgery can effectively lesion the trigeminal nerve. Further follow-up is needed to determine whether our method has advantages over the more commonly used procedure for radiosurgical trigeminal rhizotomy.

Adult↗

PubMed2006

Computer aided robotic radiosurgery.

Radiosurgery involves the precise delivery of sharply collimated high-energy beams of radiation to a distinct target volume along selected trajectories. Historically, accurate targeting required the application of a stereotactic frame, thus limiting the use of this procedure to single treatments of selected intracranial lesions. However, the scope of radiosurgery has undergone a remarkable broadening since the introduction of image-guided robotic radiosurgery. Recent developments in real-time image guidance provide an effective frameless alternative to conventional radiosurgery and allow both the treatment of lesions outside the skull and the possibility of performing hypofractionation. As a consequence, targets in the spine, chest and abdomen can now also be radiosurgically ablated with submillimetric precision. Meanwhile, the combination of image guidance, robotic beam delivery, and non-isocentric inverse planning can greatly enhance the conformality and homogeneity of radiosurgery. The aim of this article is to describe the technological basis of image-guided radiosurgery and provide a perspective on future developments. The current clinical usage of robotic radiosurgery will be reviewed with an emphasis on those applications that may represent a major shift in the therapeutic paradigm.

Brain Neoplasms↗

PubMed2005

CyberKnife radiosurgery for idiopathic trigeminal neuralgia.

OBJECT: Gamma knife surgery is an accepted treatment option for trigeminal neuralgia (TN). The safety and efficacy of CyberKnife radiosurgery as a treatment option for TN, however, has not been established. METHODS: Forty-one patients were treated between May 2002 and September 2004 for idiopathic TN at Stanford University and the Rocky Mountain CyberKnife Center. Patients with atypical pain, multiple sclerosis, or previous radiosurgical treatment or a follow-up duration of less than 6 months were excluded. Patients were evaluated for the level of pain control, response rate, time to pain relief, occurrence of hypesthesia, and time to pain recurrence with respect to the length of the nerve treated and the maximum and the minimum dose to the nerve margin. Thirty-eight patients (92.7%) experienced initial pain relief at a median of 7 days after treatment (range, 24 hours-4 months). Pain control was ranked as excellent in 36 patients (87.8%), moderate in two (4.9%), and three (7.3%) reported no change. Six (15.8%) of the 38 patients with initial relief experienced a recurrence of pain at a median of 6 months (range 2-8 months). Long-term response after a mean follow-up time of 11 months was found in 32 (78%) of 41. Twenty-one patients (51.2%) experienced numbness after treatment. CONCLUSIONS: CyberKnife radiosurgery for TN has high rates of initial pain control and short latency to pain relief compared with those reported for other radiosurgery systems. The doses used for treatment were safe and effective. Higher prescribed doses were not associated with improvement in pain relief or recurrence rate. The hypesthesia rate was related to the length of the trigeminal nerve treated.

Adult↗

PubMed2005

Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels.

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps.

Animals↗

PubMed2005

Multistage epilepsy surgery: safety, efficacy, and utility of a novel approach in pediatric extratemporal epilepsy.

OBJECTIVE: To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy. METHODS: Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections. RESULTS: Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8-14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients). CONCLUSION: In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy.

Adolescent↗

PubMed2004

The functional organization of the sensorimotor region of the subthalamic nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is viewed by many as the ultimate therapy targeting severe advanced stages of Parkinson's disease (PD). A fundamental constituent of the mechanisms underlying the therapeutic effects of DBS is clearly the functional organization of the STN; however, there is limited understanding of the organization of this structure in humans. Data from primates suggest that different domains can be identified in the STN, including a sensorimotor area with a segregated body map, as well as nonmotor areas. Recent clinical studies have used microelectrode recording to investigate the presence of a body map in the sensorimotor STN of PD patients. This paper will review and compare experimental and clinical data regarding the functional organization of the STN and discuss the clinical implications for PD patients undergoing STN DBS.

Animals↗

PubMed2004

Asymptomatic transient MRI signal changes after unilateral deep brain stimulation electrode implantation for movement disorder.

Deep brain stimulation (DBS) is an accepted treatment of movement disorders, but little research on tissue changes induced by these devices has been made. We report findings of MRI signal changes in patients with unilateral DBS implantation and no clinically detectable symptoms. A retrospective review of preoperative stereotactic MRI scans for staged placement of second-side DBS was performed in 38 patients to assess the frequency of signal changes along the previously implanted DBS track. No abnormal signal changes were noted in 23 patients (61%). Increased subcortical signals on T2-weighted fast spin echo MRI sequences along the DBS track were noted in 15 patients (39%) and varied from circumferential hyperintensity along the electrode track to significant involvement of the subcortical white matter. The changes were only detected in scans performed within 3 months of DBS implantation (15 of 27 patients). Despite these changes, the patients were totally asymptomatic. The etiology of the changes is unknown but may reflect a transient tissue response to the implantation of the electrode.

Brain↗

PubMed2004

Patient-controlled deep brain stimulation can overcome analgesic tolerance.

We report a technique based on patient-controlled stimulation to restore analgesia after development of tolerance to deep brain stimulation (DBS). A 45-year-old female with neurogenic pain after cerebellar stroke underwent DBS implantation in the right ventralis caudalis (VC) thalamus with excellent stimulus-controlled analgesia for 29 months, followed by development of tolerance and loss of analgesia. Analgesia was restored when a stimulation module that allowed patient-controlled stimulation was implanted.

Analgesia, Patient-Controlled↗

PubMed2004

Postoperative EEG and seizure outcome in temporal lobe epilepsy surgery.

OBJECTIVE: To assess the prognostic value of scalp electroencephalogram (EEG) after epilepsy surgery, we investigated whether postoperative EEG abnormalities (interictal epileptiform discharges, IED; interictal slow activity, ISA) were associated with seizure outcome and other patient characteristics after resective surgery in patients with temporal lobe epilepsy (TLE). METHODS: Sixty-two patients with medically refractory TLE who underwent surgery were studied. Patients were categorized according to etiology (mesiotemporal sclerosis vs. tumors/cortical dysplasias); extent of surgical resection (extensive vs. limited); and amount of preoperative IED on wake EEG (oligospikers, <1 IED/h, vs. spikers). Patients were also classified as seizure-free (SF) or having persistent seizures/auras (not-SF) during follow up visits 1 month and 1 year after surgery. Preoperative 60-min interictal EEGs were evaluated for IED and ISA, and compared to postoperative wake EEGs. RESULTS: Seizures/auras persisted in 16/62 (25.8%) patients at 1 month and in 8/62 (12.9%) at 1 year follow up. ISA was not significantly related to outcome. Of 42 patients with EEG negative for IED at 1 month, 4 were not-SF; at 1 year, one of 44 such patients was not-SF. IED was significantly associated with seizure/aura persistence in patients categorized as mesiotemporal sclerosis and with extensive surgery. Oligospikers and spikers on preoperative EEG showed no differences in the postoperative seizure outcome, excellent in both cases; moreover, the presence of postoperative IEDs indicated auras/seizures persistence apart from the preoperative EEG spike frequency. CONCLUSIONS: Our study showed that the presence of IED of postoperatve EEG strongly indicates seizure/aura persistence. Therefore, serial EEGs should be included in postoperative follow up schedules as a crucial tool in evaluating seizure outcome.

Adolescent↗

PubMed2004

Ablative procedures for chronic pain.

The advent of neuroaugmentative techniques has reduced the application of neuroablative procedures, especially as regards pain of functional origin. Although intracranial ablative procedures are now rarely performed, spinal ablative procedures, such as anterolateral cordotomies or midline myelotomies, remain important in the management of cancer pain. These procedures produce immediate and satisfactory pain relief with acceptable complication rates. An important future trend will be the application of radiosurgery guided by functional imaging (eg,fMRI, PET) to place such intracranial lesions as cingulotomies or medial thalamotomies.

Catheter Ablation↗

PubMed2004

The functional anatomy of neuropathic pain.

The generation of neuropathic pain is a complex phenomenon involving a process of peripheral and central sensitization producing enhanced transmission of nociceptive inputs to the brain associated with the loss of discriminatory processing of noxious and innocuous stimuli. This increased flow of abnormally processed nociceptive inputs to the brain may overcome the ability of descending modulatory pathways to produce analgesia, causing further worsening of the pain. Several crucial locations involved in the physiologic generation of pain inputs (eg, peripheral nociceptors, dorsal horns, thalamus, cortex) show evidence of functional reorganization and altered nociceptive processing in association with chronic pain. These locations present the best targets for therapeutic intervention, including systemic administration of drugs able to counteract the chemical storm induced by neural injuries in the nociceptive afferents and dorsal horns, or for more focused intervention, such as neuroablative procedures; intrathecal drug delivery; and spinal cord, deep brain, or motor cortex stimulation.

Afferent Pathways↗

PubMed2004

Epilepsy surgery for tuberous sclerosis.

Tuberous sclerosis complex is often associated with medically refractory epilepsy secondary to cortical tubers. Previous studies have identified an association between early seizure onset, greater seizure burden, and mental retardation in childhood. Early effective seizure control could therefore significantly reduce the adverse developmental effects of chronic epilepsy in tuberous sclerosis complex. In medically intractable epileptic patients, surgical treatment has been demonstrated to reduce or abolish seizures and the associated burden for the child and its environment. Epilepsy surgery has not been widely used in patients with tuberous sclerosis complex thus far, mostly because of the concern that the multifocal nature of the cortical lesions could be associated with the development of independent epileptogenic zones. Advances in electroencephalographic techniques, functional neuroimaging, and invasive cortical mapping are changing this view and allowing an increased number of tuberous sclerosis complex patients to be evaluated for resective surgery. Additional techniques emerging in the neurosurgical field may add further treatment options to the current state of the art.

Anticonvulsants↗

PubMed2004

Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease.

OBJECT: The subthalamic nucleus (STN) is a key structure for motor control through the basal ganglia. The aim of this study was to show that the STN in patients with Parkinson disease (PD) has a somatotopic organization similar to that in nonhuman primates. METHODS: A functional map of the STN was obtained using electrophysiological microrecording during placement of deep brain stimulation (DBS) electrodes in patients with PD. Magnetic resonance imaging was combined with ventriculography and intraoperative x-ray film to assess the position of the electrodes and the STN units, which were activated by limb movements to map the sensorimotor region of the STN. Each activated cell was located relative to the anterior commissure-posterior commissure line. Three-dimensional coordinates of the cells were analyzed statistically to determine whether those cells activated by movements of the arm and leg were segregated spatially. Three hundred seventy-nine microelectrode tracks were created during placement of 71 DBS electrodes in 44 consecutive patients. Somatosensory driving was found in 288 tracks. The authors identified and localized 1213 movement-related cells and recorded responses from 29 orofacial cells, 480 arm-related cells, 558 leg-related cells, and 146 cells responsive to both arm and leg movements. Leg-related cells were localized in medial (p < 0.0001) and ventral (p < 0.0004) positions and tended to be situated anteriorly (p = 0.063) relative to arm-related cells. CONCLUSIONS: Evidence of somatotopic organization in the STN in patients with PD supports the current theory of highly segregated loops integrating cortex-basal ganglia connections. These loops are preserved in chronic degenerative diseases such as PD, but may subserve a distorted body map. This finding also supports the relevance of microelectrode mapping in the optimal placement of DBS electrodes along the subthalamic homunculus.

Brain Mapping↗

PubMed2003

Surgical treatment of multifocal epilepsy involving eloquent cortex.

PURPOSE: This report describes our long-term follow-up for combined resective surgery and multiple subpial transections (MSTs) in patients with refractory epilepsy involving eloquent and noneloquent cortex in multiple lobes. Multiple independent seizure foci made these patients poor candidates for conventional surgery. METHODS: MST and resective surgery were used in 13 patients to treat localization-related refractory epilepsy involving eloquent and noneloquent cortex of two or more lobes. Preoperative investigation was followed by invasive monitoring. RESULTS: Eleven patients had MST plus resection involving two different lobes, and two patients had MST plus resection involving three different lobes. MSTs were performed on the primary sensorimotor cortex (eight patients), temporal language area (two patients), Broca's area (one patient), and on both frontal motor and temporal language areas (two patients). Nine patients had a two-stage procedure, and four patients had a three-stage procedure (two consecutive subdural grid studies followed by resections). Average follow-up was 59.2 months (range, 42-98 months). With a modified Engel Outcome Scale, four patients (31%) had a class I outcome; three (23%), class II; three (23%), class III; and three (23%), class IV. Ten (77%) patients had a >50% reduction of seizure burden. CONCLUSIONS: Combined MST and resection can meaningfully improve seizure control in patients with multifocal epilepsy involving eloquent cortex. Prospective randomized studies are needed.

Adolescent↗