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Use of an intracranial near-infrared probe for localization during stereotactic surgery for movement disorders.

Localization of targets during stereotactic surgery is frequently accomplished by identification of the boundaries between the gray matter of various nuclei and the surrounding white matter. The authors describe an intracranial probe developed for this purpose, which uses near-infrared (NIR) light. The probe fits through standard stereotactic holders and emits light at its tip. The scattered light is detected and analyzed by a spectrometer, with the slope of the trailing portion of the reflectance curve used as the measurement value. Near-infrared readings were obtained during 27 neurosurgical procedures. The first three operations were temporal lobectomies, with values obtained from tracks in the resected specimen and resection bed. In the next five procedures, the probe was inserted stereotactically to a depth of 1 to 2 cm with measurements obtained every 1 mm. The probe was then used in 19 stereotactic procedures for movement disorders, obtaining measurements every 0.5 to 1 mm to target depths of 6 to 8 cm to interrogate subcortical structures. The NIR signals were correlated to distances beneath the cortical surface measured on postoperative computerized tomography or magnetic resonance imaging by using angle correction and three-dimensional reconstruction techniques. The NIR values for white and gray matter obtained during the lobectomies were significantly different (white matter 2.5+/-0.37, gray matter 0.82+/-0.23 mean +/- standard deviation). The NIR values from the superficial stereotactic tracks showed initial low values corresponding to cortical gray matter and high values corresponding to subcortical white matter. There was good correlation between the NIR signals and postoperative imaging in the 19 stereotactic cases. Dips due to adjacent sulci, a plateau of high signal due to subcortical white matter, a dip in the NIR signal during passage through the ventricle, dips due to the caudate nucleus, and peaks due to the white matter capsule between ventricle and thalamus were constant features. The putamen-capsule boundary and the lamina externa and interna of the globus pallidus could be distinguished in three cases. Elevated signals corresponding to the thalamic floor were seen in 10 cases. Nuances such as prior lesions and nonspecific white matter changes were also detected. There was no incidence of morbidity associated with use of the probe. Data acquisition was straightforward and the equipment required for the studies was inexpensive. The NIR probe described in this article seems to be able to detect gray-white matter boundaries around and within subcortical structures commonly encountered in stereotactic functional neurosurgery. This simple, inexpensive method deserves further study to establish its efficacy for stereotactic localization.

Brain↗

[The rolandic line: a simple baseline for the identification of the central region. An MRI study and functional validation].

INTRODUCTION: The identification of the central region--i.e. the central sulcus, the pre- and post-central gyri, the paracentral lobule--on MRI and angiographic images may be necessary prior to stereotactic procedures such as biopsies or resection of centrally located tumors, depth electrode recordings for presurgical evaluation of drug-resistant epilepsies, or radiosurgery of arteriovenous malformations. Stereotactic methods, such as the Talairach's proportional grid based on the bicommissural system, demonstrated the statistical position of the central sulcus according to the Ac-Pc, Vac and Vpc baselines. However, the course and the spatial position of this sulcus have remarkable individual differences that sometimes make the sulcus difficult to identify on serial sagittal MRI or lateral angiographic images. In order to facilitate this identification, the authors propose a new oblique baseline, the rolandic (R) line. MATERIAL AND METHODS: The stereotactic MRI and angiography of 22 patients were reviewed for this study. Eleven of these patients had stereotactic biopsies for a low-grade tumor located in the central region, while eleven others had multiple intracerebral electrodes implantation and depth EEG recording (SEEG: stereoelectroencephalography) in the presurgical evaluation of drug-resistant partial epilepsy, prior to epileptogenic cortex resection. The Ac-Pc, Vac, Vpc baselines and segments of the central sulcus were drawn from the mid-sagittal and lateral T1-weighted MRI images and reported on an individual graph. Surface and deep margins as well as axis of the central sulcus were also reported along with corpus callosum baselines as defined by Olivier et al.: horizontal plane, anterior and posterior callosal planes. The rolandic line was then traced from the graph:it joined the intersection point between the anterior callosal plane and an orthogonal line passing through the floor of the temporal fossa, and the intersection point between posterior callosal plane and an orthogonal line passing through the top of the hemisphere. The rolandic line was then superimposed on any sagittal MRI image or lateral stereotactic angiographic film. Finally, the spatial position of electrode contracts through which electrical stimulations elicited motor and/or sensory responses, either from central electrode implanted for motor fibers identification prior to stereotactic biopsies or from SEEG electrodes implanted for epileptogenic zone identification and cortical mapping, was reported on the individual graph. Angular and linear measurements were taken from the graph, between the rolandic line, the central sulcus axis, the Ac-Pc and callosal baselines, and the central sulcus limits (top, bottom, anterior and posterior margins). RESULTS: Graph measurements indicated that the rolandic line was significantly closer to the inferior part of the central sulcus than to its superior part (average distance between the line and the inferior point of the sulcus: 1.86 +/- 1.87 mm; average distance between the line and the superior point of the sulcus: 4.5 +/- 2.3 mm; p < 0.001-t test); similarly, the rolandic line was closer to the deep margin of the sulcus rather than to its superficial border (average distance between the line and the most anterior point of the sulcus: 11.43 +/- 3.16 mm; average distance between the line and the most posterior point of the sulcus: 7.95 +/- 4.14 mm; p < 0.01-t test). In 90% of the cases, the rolandic line followed the deep or middle part of the sulcus, with an average angle of 4.18 degrees +/- 2.53 degrees between the line and the sulcus axis. The spatial position of the electrode contacts that elicited motor/or sensory responses to stimulations correlated topographically well in all cases with the position of the motor and sensory fibers defined according to the central sulcus, baselines and reference to stereotactic atlases. (ABSTRACT TRUNCATED)

Adolescent↗

Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury.

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years). Diffuse cortical Abeta deposits were observed in one third of subjects (aged 35-62 years) as early as 2 h after injury, with only one (35-year old) individual exhibiting "mature", dense-cored plaques. Plaque-like deposits, neurons, glia, and axonal changes were also immunostained with APP and apoE antibodies. In plaque-positive cases, the only statistically significant change in cellular immunostaining was increased neuronal APP (P = 0.013). There was no significant correlation between the distribution of Abeta plaques and markers of neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell soma, axons or glial cells in a larger subset of individuals. Tau-positive, neurofibrillary tangle (NFT)-like changes were detected in only two subjects, both of more advanced age and who were without Abeta deposits. Other neurodegenerative changes, evidenced by ubiquitin- and synuclein-immunoreactive neurons, were abundant in the majority of cases. Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Abeta plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury.

Adolescent↗

Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy.

PURPOSE: The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood-brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P-glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum. METHODS: Concentrations of carbamazepine (CBZ), 10-hydroxy-carbazepine (10-OH-CZ, metabolite of oxcarbazepine), lamotrigine (LTG), levetiracetam (LEV), topiramate, or phenytoin were determined by using one to four catheters during IOMD in the medial temporal gyrus. Furthermore, to calculate the individual recovery of every catheter, an in vitro microdialysis was performed with ultrafiltrate of serum concurrently obtained from the respective patient. In addition, AED levels were determined in the resected brain tissue, CSF, and serum of the same patients. Altogether 22 pharmacoresistant epilepsy patients (nine male, 13 female patients; age 15-54 years) with complex partial seizures or secondarily generalized seizures were involved. In a first series, IOMD samples 40 min after beginning of the microdialysis (flow rate, 1 microl/min), and in a second series, continuous measurements 25, 30, 35, and 40 min from the beginning were evaluated (flow rate, 2 microl/min). With in vitro recovery data of the individual catheters, the concentration in the extracellular space (ECS) was estimated. RESULTS: AED concentrations in the ECS of the cortex measured by catheters located at a distance of 0.6 cm differed markedly in some patients, whereas concentrations in the ultrafiltrate of the serum of the respective patients measured with the same catheters varied only slightly. Furthermore, ECS concentrations related to the ultrafiltrate of serum showed considerable interindividual variations. The high intra- and interindividual variation of ECS concentrations is demonstrated by the low correlation between concentrations in ECS and the ultrafiltrate of serum (CBZ, r= 0.41; 10-OH-CZ, r= 0.42; LTG, r= 0.27) in contrast to the high correlation between brain tissue concentration and the ultrafiltrate of serum (CBZ, r= 0.97; 10-OH-CZ, r= 0.88; LTG, r= 0.98) in the same group of patients. When comparing AED concentrations in the ECS with those in the CSF, ECS concentrations were significantly lower for CBZ, 10-OH-CZ, LTG, and LEV. CONCLUSIONS: The data demonstrate that AED concentrations show a considerable intraindividual and interindividual variation in the ECS of cortical regions. Furthermore, the ECS concentration of several AEDs is significantly lower than their CSF concentration in patients with intractable epilepsy. However, in the absence of data from nonepileptic tissues, it is not possible to judge whether the present findings relate to overexpression of multidrug transporters in the brain. Instead, the present study illustrates the methodologic difficulties involved in performing IOMD studies in patients and may thus be helpful for future approaches aimed at elucidating the role of multidrug transporters in epilepsy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗