✓ 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.
Experimental study in cats
Antonio A. F. DeSalles, Yoichi Katayama, Donald P. Becker, and Ronald L. Hayes
Michael J. Alexander, Antonio A. F. DeSalles, and Uwamie Tomiyasu
✓ 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.
Timothy D. Solberg, Steven J. Goetsch, Michael T. Selch, William Melega, Goran Lacan, and Antonio A. F. DeSalles
Object. The purpose of this work was to investigate the targeting and dosimetric characteristics of a linear accelerator (LINAC) system dedicated for stereotactic radiosurgery compared with those of a commercial gamma knife (GK) unit.
Methods. A phantom was rigidly affixed within a Leksell stereotactic frame and axial computerized tomography scans were obtained using an appropriate stereotactic localization device. Treatment plans were performed, film was inserted into a recessed area, and the phantom was positioned and treated according to each treatment plan. In the case of the LINAC system, four 140° arcs, spanning ± 60° of couch rotation, were used. In the case of the GK unit, all 201 sources were left unplugged. Radiation was delivered using 3- and 8-mm LINAC collimators and 4- and 8-mm collimators of the GK unit. Targeting ability was investigated independently on the dedicated LINAC by using a primate model.
Measured 50% spot widths for multisource, single-shot radiation exceeded nominal values in all cases by 38 to 70% for the GK unit and 11 to 33% for the LINAC system. Measured offsets were indicative of submillimeter targeting precision on both devices. In primate studies, the appearance of an magnetic resonance imaging—enhancing lesion coincided with the intended target.
Conclusions. Radiosurgery performed using the 3-mm collimator of the dedicated LINAC exhibited characteristics that compared favorably with those of a dedicated GK unit. Overall targeting accuracy in the submillimeter range can be achieved, and dose distributions with sharp falloff can be expected for both devices.
Nader Pouratian, Zhong Zheng, Ausaf A. Bari, Eric Behnke, W. Jeff Elias, and Antonio A. F. DeSalles
Due to the lack of internal anatomical detail with traditional MR imaging, preoperative stereotactic planning for the treatment of tremor usually relies on indirect targeting based on atlas-derived coordinates. The object of this study was to preliminarily investigate the role of probabilistic tractography–based thalamic segmentation for deep brain stimulation (DBS) targeting for the treatment of tremor.
Six patients undergoing bilateral implantation of DBS electrodes in the thalamus for the treatment of upper-extremity tremor were studied. All patients underwent stereotactic surgical implantation using traditional methods (based on indirect targeting methodologies and intraoperative macrostimulation findings) that were programmed for optimal efficacy, independent of tractography-based segmentations described in this report. Connectivity-based thalamic segmentations were derived by identifying with which of 7 cortical target regions each thalamic voxel had the highest probability of connectivity. The authors retrospectively analyzed the location of the optimal contact for treatment of tremor with connectivity-based thalamic segmentations. Findings from one institution (David Geffen School of Medicine at UCLA) were validated with results from 4 patients at another institution (University of Virginia Health System).
Of 12 electrodes implanted using traditional methodologies, all but one resulted in efficacious tremor control. Connectivity-based thalamic segmentation consistently revealed discrete thalamic regions having unique connectivity patterns with distinct cortical regions. Although the authors initially hypothesized that the most efficacious DBS contact for controlling tremor would colocalize with the thalamic region most highly connected with the primary motor cortex, they instead found it to highly colocalize with those thalamic voxels demonstrating a high probability of connectivity with premotor cortex (center-to-center distance: 0.36 ± 0.55 mm). In contrast to the high degree of colocalization with optimal stimulation site, the precise localization of the premotor cortex–defined thalamic region relative to the anterior and posterior commissures was highly variable. Having defined a connectivity-based target for thalamic stimulation in a cohort of patients at David Geffen School of Medicine at UCLA, the authors validated findings in 4 patients (5 electrodes) who underwent surgery at a different institution (University of Virginia Health System) by a different surgeon.
This report identifies and provides preliminary external validation of a novel means of targeting a patient-specific therapeutic thalamic target for the treatment of tremor based on individualized analysis of thalamic connectivity patterns. This novel thalamic targeting approach is based on identifying the thalamic region with the highest probability of connectivity with premotor and supplementary motor cortices. This approach may prove to be advantageous over traditional preoperative methods of indirect targeting, providing patient-specific targets that could improve the precision, efficacy, and efficiency of deep brain stimulation surgery. Prospective evaluation and development of methodologies to make these analyses more widely available to neurosurgeons are likely warranted.
Alessandra A. Gorgulho, Donald C. Shields, Dennis Malkasian, Eric Behnke, and Antonio A. F. DeSalles
High-frequency stimulation of the subthalamic nucleus (STN) in patients with parkinsonian symptoms is often used to ameliorate debilitating motor symptoms associated with this condition. However, individual variability in the shape and orientation of this relatively small nucleus results in multiple side effects related to the spread of electrical current to surrounding structures. Specifically, contraction of the muscles of facial expression is noted in a small percentage of patients, although the precise mechanism remains poorly understood.
Facial muscle contraction was triggered by high-frequency stimulation of 49 contacts in 18 patients undergoing deep brain stimulation of the STN. The mean coordinates of these individual contacts relative to the anterior commissure–posterior commissure midpoint (also called the midcommissural point) were calculated to determine the location or structure(s) most often associated with facial contraction during physiological macrostimulation.
The x, y, and z coordinates associated with contraction of the facial musculature were found to be 11.52, 1.29, and 1.15 mm lateral, posterior, and inferior to the midcommissural point, respectively. This location, along the lateral-anterior-superior border of the STN, may allow for the spread of electrical current to the fields of Forel, zona incerta, and/or descending corticospinal/corticobulbar tracts. Because stimulation of corticobulbar tracts produces similar findings, these results are best explained by the spread of electrical current to nearby internal capsule axons coursing lateral to the STN.
Thus, if intraoperative deep brain stimulation lead testing results in facial musculature contraction, placement of the electrode in a more medial, posterior position may reduce the amount of current spread to corticobulbar fibers and resolve this side effect.
J. Patrick Johnson, Samuel S. Ahn, William C. Choi, Jeffery E. Masciopinto, Kee D. Kim, Aaron G. Filler, and Antonio A. F. DeSalles
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.
Donald C. Shields, Alessandra Gorgulho, Eric Behnke, Dennis Malkasian, and Antonio A. F. Desalles
Deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease is often very effective for treatment of debilitating motor symptoms. Nevertheless, the small size of the STN and its proximity to axonal projections results in multiple side effects during high-frequency stimulation. Contralateral eye deviation is produced in a small percentage of patients, but the precise mechanism of this side effect is at present poorly understood.
Contralateral eye deviation was produced by high-frequency stimulation of 22 contact sites in nine patients undergoing deep brain stimulation of the STN. The precise locations of these contacts were calculated and compiled in order to locate the stimulated structure responsible for eye deviation.
The mean x, y, and z coordinates associated with contralateral eye deviation were found to be 11.57, 2.03, and 3.83 mm lateral, posterior, and inferior to the anterior commissure–posterior commissure midpoint, respectively. The point described by these coordinates is located within the lateral anterosuperior border of the STN.
Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule axons.
Joshua R. Dusick, Felice Esposito, Daniel F. Kelly, Pejman Cohan, Antonio DeSalles, Donald P. Becker, and Neil A. Martin
Object. The extended transsphenoidal approach, which requires a bone and dural opening through the tuberculum sellae and posterior planum sphenoidale, is increasingly used for the treatment of nonadenomatous suprasellar tumors. The authors present their experiences in using the direct endonasal approach in patients with nonadenomatous suprasellar tumors.
Methods. Surgery was performed with the aid of an operating microscope and angled endoscopes were used to assess the completeness of resection. Bone and dural defects were repaired using abdominal fat, collagen sponge, titanium mesh, and, in most cases, lumbar drainage of cerebrospinal fluid (CSF).
Twenty-six procedures for tumor removal were performed in 24 patients (ages 9–79 years), including two repeated operations for residual tumor. Gross-total removal could be accomplished in only 46% of patients, with near-gross-total removal or better in 74% of 23 patients (five of eight with craniopharyngiomas, six of seven with meningiomas, five of six with Rathke cleft cysts, and one of two with a dermoid or epidermoid cyst); a patient with a lymphoma only underwent biopsy. Of 13 patients with tumor-related visual loss, 85% improved postoperatively. The complications that occurred included five patients (21%) with postoperative CSF leaks, one patient (4%) with bacterial meningitis; five patients (21%) with new endocrinopathy; and two patients (8%) who needed to undergo repeated operations to downsize suprasellar fat grafts. The only permanent neurological deficit was anosmia in one patient; there were no intracranial vascular injuries.
Conclusions. The direct endonasal skull-base approach provides an effective minimally invasive means for resecting or debulking nonadenomatous suprasellar tumors that have traditionally been approached through a sublabial or transcranial route. Procedures in the supraglandular space can be performed effectively with excellent visualization of the optic apparatus while preserving pituitary function in most cases. The major challenge remains developing consistently effective techniques to prevent postoperative CSF leaks.
Antonio A. F. DeSalles, Pauline G. Newlon, Yoichi Katayama, C. Edward Dixon, Donald P. Becker, Henry H. Stonnington, and Ronald L. Hayes
✓ 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.