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Peptide 1-42 and Incipient Alzheimer's Disease

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Peptide 1-42 and Incipient Alzheimer's Disease BRIEF COMMUNICATIONS (ioESM) is still the gold standard for the detection of Language Area Localization these essential language areas.2 Noninvasive functional neuroimaging techniques are emerging as promising with Three-Dimensional 4,5 clinical tools for this purpose. Functional Magnetic Functional magnetic resonance imaging (fMRI) is a completely noninvasive preoperative method of deter- Resonance Imaging Matches mining whole-brain functional neuroanatomy.6,7 It en- ables localization of brain function with high spatial Intrasulcal Electrostimulation and temporal resolution by monitoring the hemody- in Broca’s Area namic changes that are coupled with neuronal activity. We report successful identification of Broca’s area G. J. M. Rutten, MD,* P. C. van Rijen, MD, PhD,* within a sulcus 5 to 8 mm below the cortical surface C. W. M. van Veelen, MD, PhD,* and N. F. Ramsey, PhD† using three-dimensional (3D) fMRI and ioESM in a 14-year-old girl with a left inferior frontal desmoplastic ganglioglioma. In this study, intraoperative electrocortical stimulation mapping (ioESM), the current gold standard for the lo- Patient and Methods calization of critical language areas, is compared with Case Report functional magnetic resonance imaging (fMRI) in a 14- The 14-year-old patient has suffered from medically intrac- year-old girl with medically intractable epilepsy caused table complex partial seizures since she was 4 years old. by a tumor in the region of Broca’s area. Prior to the Computed tomography and MRI revealed a calcified, intra- operation, four different fMRI tasks that target inferior axial, noncontrast-enhancing lesion (diameter, 3 cm) within frontal language areas were applied. Prior to the resec- the left inferior frontal gyrus (Broca’s area) and within part tion, ioESM as well as fMRI detected no language areas of the left middle frontal gyrus. The tumor had remained at the exposed cortical area. After removal of the tumor, unchanged in successive MRI scans over a period of 3 years. a unique opportunity presented itself, where ioESM Electroencephalography suggested a left anterior frontal ictal could be performed in the depth of a now exposed and onset and a causal relationship with the lesion. The patient intact gyrus. One specific locus that was indicated to be a occasionally experienced a few minutes of postictal speech critical language area by multiple-task fMRI was targeted. problems. A neurological examination showed no abnormal- IoESM selectively confirmed the location of this language ities. A neuropsychological examination showed no language area to within an estimated 3 mm. We propose that the deficits. Hand preference was predominantly left-sided (20.5 combined use of different fMRI tasks increases the sen- on the Edinburgh Handedness Inventory).8 An intracarotid sitivity and specificity for the detection of essential lan- sodium amobarbital test (Wada test) showed a left hemi- guage areas. sphere dominance for language functions.9 Surgical removal of the tumor was decided on, with ioESM of the speech area Rutten GJM, van Rijen PC, van Veelen CWM, under local anesthesia. Ramsey NF. Language area localization with three-dimensional functional magnetic resonance imaging matches intrasulcal electrostimulation in fMRI Broca’s area. Ann Neurol 1999;46:405–408 fMRI was done 1 month prior to surgery using a 3D BOLD technique (navigated PRESTO sequence), implemented on a Philips ACS-NT 1.5-T scanner (Philips Medical Systems, 10,11 Neurosurgical resective procedures in the language- Best, The Netherlands) with standard hardware. Four vi- sually presented language tasks were used in the scanner: pic- dominant hemisphere must avoid the classic language ture naming, verb generation, repetitive reciting of the days areas of Broca (posterior part of the inferior frontal gy- of the week, and verbal fluency.4,12 The patient was in- rus) and Wernicke (perisylvian region of the tem- structed to use covert speech. During the control condition, poroparietal lobe) to prevent persistent language defi- the patient had to fixate her eyes on a small cross hair. Each 1–3 cits. Despite considerable practical disadvantages, task-control combination took about 10 minutes of imaging intraoperative electrocortical stimulation mapping time. A conventional T1-weighted MRI scan completed the session. Functional and anatomical scans were meticulously registered to each other prior to the statistical analysis. Sta- tistical maps were obtained on a voxel by voxel basis for each 10 From the Departments of *Neurosurgery and †Psychiatry, Univer- task (with reference to the control condition). sity Hospital Utrecht, Utrecht, The Netherlands. None of the individual tasks yielded activation at the cor- Received Jan 20, 1999, and in revised form Mar 29 and Apr 21. tical surface (Fig 1). A common area of activation for all four Accepted for publication Apr 23, 1999. tasks was found on the bank of a gyrus located directly Address correspondence to Dr Rutten, Department of Neuro- cranial-posterior to the tumor at a depth of 5 to 8 mm from surgery, University Hospital Utrecht, PO Box 85500, 3508 GA, the cortical surface (see Fig 1). The volume of this area was Utrecht, The Netherlands. 43 mm3 (ie, the volume of 1 functional voxel). Copyright © 1999 by the American Neurological Association 405 Fig 1. Composite result of multiple-task functional MRI (fMRI). Sagittal slices of the left hemisphere are shown. The most lateral slice is located in the bottom left corner, and the most medial slice is located in the upper right corner. Significant voxels (p , 0.05, Bonferroni corrected ) are colored and superimposed on anatomical images (in-plane resolution, 2 mm). The red voxel (ar- row) represents the area that is active during all four fMRI language tasks, the blue voxels represent the areas active during verb generation, the white voxels represent the areas active during picture naming, and the green voxel represents the area active during repetitive reciting of the days of the week. ioESM prior to the Resection The stimulus duration was 5 seconds, and the average cur- Local anesthetics were applied, and propofol was adminis- rent intensity was 9.5 mA (range, 8–13 mA). Arrest of tered as a transient hypnotic drug. A left-sided frontal crani- speech or anomia that could be elicited repetitively was con- otomy was performed. The lesion had partially displaced the sidered to represent a significant language error. During cranial-posterior gyri (Fig 2). Electrocorticography revealed ioESM, no language errors were observed during 29 stimuli no clear epileptic activity. IoESM was performed with bipo- at 17 different cortical sites covering the area of the craniot- lar electrodes that were placed 5 mm apart on the cortical omy, including the tumor. This finding was in concordance surface while the patient performed a picture-naming task.12 with the fMRI results. At two cortical sites, blinking of the Fig 2. Photographs of the craniotomy (A) before and (B) after resection. The head of the patient is facing toward the left and is aligned roughly along the canthomeatal line. The blue arrow on top of the sterile marker (white) points to the site where language errors were obtained with intraoperative electrocortical stimulation mapping (ioESM). The yellow arrows indicate the sites where ioESM did not induce language errors. 406 Annals of Neurology Vol 46 No 3 September 1999 right eye was elicited repetitively, indicating adequate current Pathology and Follow-Up intensity. At this point, the electrodes were removed, and Following histological and immunochemical analysis of the surgical removal commenced. removed tissue, the tumor was classified as a desmoplastic ganglioglioma. The postoperative clinical course was uncom- ioESM after the Resection plicated, and 6 months after her operation, the patient is still The tumor was radically removed (see Fig 2). As the wall of free of seizures. She has experienced no language deficits. the gyrus where fMRI had identified a critical language area was meticulously left intact and exposed, it was decided that Discussion this locus would be tested with ioESM. The patient was This study demonstrates an excellent agreement between again awakened and showed no signs of dysphasia. Electro- fMRI and ioESM of frontal language function in a 14-year- corticography revealed no epileptic activity. Speech arrest was old girl with a tumor in Broca’s area. The ioESM-derived then elicited repeatedly in the depth of the now exposed wall intrasulcal language area was located approximately 3 mm of a gyrus located cranial-posterior to the removed tumor at medial to the language area that was found with multiple- an estimated 10 mm from the cortical surface (see Fig 2). task fMRI. This difference may be explained by the fact that Intraoperative landmarks were compared with a surface ren- the brain surface shifts during surgery. Roberts and col- dering of the patient’s brain and with fMRI images (Fig 3). leagues13 reported an average brain shift of 10 mm as a result The site where speech arrest was elicited was located approx- of gravity alone, probably as a “consequence of displacement imately 3 mm medial to the locus where activity was found of cerebrospinal fluid and resulting loss of buoyancy.”13 with fMRI. ioESM at three other sites along this exposed To our knowledge, this is the first reported case in which gyrus (2 of which were located within 5 mm of the ioESM- fMRI of language areas has been validated with intrasulcal positive language site) induced no language errors, confirm- electrocortical stimulation. This case underscores the fact ing the fMRI results (see Fig 2). that routinely applied ioESM, as opposed to fMRI, cannot Fig 3. Photographs indicating concordance of intraoperative electrocortical stimulation mapping (ioESM) and functional MRI (fMRI) localization of Broca’s area. (Top row) Images from the neuronavigational apparatus. The yellow pointer indicates the lo- cation of the intrasulcal language area found with ioESM.
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