Lennart Stieglitz

Directional deep brain stimulation: an intraoperative double-blind pilot study

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinsons disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.

The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors.

OBJECT Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. METHODS A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively. RESULTS The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. CONCLUSIONS Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

Reliability of intraoperative high-resolution 2D ultrasound as an alternative to high–field strength MR imaging for tumor resection control: a prospective comparative study

OBJECT Ultrasound may be a reliable but simpler alternative to intraoperative MR imaging (iMR imaging) for tumor resection control. However, its reliability in the detection of tumor remnants has not been definitely proven. The aim of the study was to compare high-field iMR imaging (1.5 T) and high-resolution 2D ultrasound in terms of tumor resection control. METHODS A prospective comparative study of 26 consecutive patients was performed. The following parameters were compared: the existence of tumor remnants after presumed radical removal and the quality of the images. Tumor remnants were categorized as: detectable with both imaging modalities or visible only with 1 modality. RESULTS Tumor remnants were detected in 21 cases (80.8%) with iMR imaging. All large remnants were demonstrated with both modalities, and their image quality was good. Two-dimensional ultrasound was not as effective in detecting remnants<1 cm. Two remnants detected with iMR imaging were missed by ultrasound. In 2 cases suspicious signals visible only on ultrasound images were misinterpreted as remnants but turned out to be a blood clot and peritumoral parenchyma. The average time for acquisition of an ultrasound image was 2 minutes, whereas that for an iMR image was approximately 10 minutes. Neither modality resulted in any procedure-related complications or morbidity. CONCLUSIONS Intraoperative MR imaging is more precise in detecting small tumor remnants than 2D ultrasound. Nevertheless, the latter may be used as a less expensive and less time-consuming alternative that provides almost real-time feedback information. Its accuracy is highest in case of more confined, deeply located remnants. In cases of more superficially located remnants, its role is more limited.

Microvascular decompression for trigeminal neuralgia in the elderly: long-term treatment outcome and comparison with younger patients.

OBJECTIVEMultiple studies have proved that microvascular decompression (MVD) is the treatment of choice in cases of medically refractory trigeminal neuralgia (TN). In the elderly, however, the surgical risks related to MVD are assumed to be unacceptably high and various alternative therapies have been proposed. We evaluated the outcomes of MVD in patients aged older than 65 years of age and compared them with the outcomes in a matched group of younger patients. The focus was on procedure-related morbidity rate and long-term outcome. METHODSThis was a retrospective study of 112 patients with TN operated on consecutively over 22 years. The main outcome measures were immediate and long-term postoperative pain relief and neurological status, especially function of trigeminal, facial, and cochlear nerves, as well as surgical complications. A questionnaire was used to assess long-term outcome: pain relief, duration of a pain-free period, need for pain medications, time to recurrence, pain severity, and need for additional treatment. RESULTSThe mean age was 70.35 years. The second and third branches of the trigeminal nerve were most frequently affected (37.3%). The mean follow-up period was 90 months (range, 48–295 months). Seventy-five percent of the patients were completely pain free, 11% were never pain free, and 14% experienced recurrences. No statistically significant differences existed in the outcome between the younger and older patient groups. Postoperative morbidity included trigeminal hypesthesia in 6.25%, hypacusis in 5.4%, and complete hearing loss, vertigo, and partial facial nerve palsy in 0.89% each. Cerebrospinal fluid leak and meningitis occurred in 1 patient each. There were no mortalities in both groups. CONCLUSIONMVD for TN is a safe procedure even in the elderly. The risk of serious morbidity or mortality is similar to that in younger patients. Furthermore, no significant differences in short- and long-term outcome were found. Thus, MVD is the treatment of choice in patients with medically refractory TN, unless their general condition prohibits it.

The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery.

BACKGROUND Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. OBJECTIVE To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. METHODS Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. RESULTS After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. CONCLUSION After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.

Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures

Purpose:  Epileptic seizures typically reveal a high degree of stereotypy, that is, for an individual patient they are characterized by an ordered and predictable sequence of symptoms and signs with typically little variability. Stereotypy implies that ictal neuronal dynamics might have deterministic characteristics, presumably most pronounced in the ictogenic parts of the brain, which may provide diagnostically and therapeutically important information. Therefore the goal of our study was to search for indications of determinism in periictal intracranial electroencephalography (EEG) studies recorded from patients with pharmacoresistent epilepsy.

Fat implant is superior to muscle implant in vestibular schwannoma surgery for the prevention of cerebrospinal fluid fistulae.

OBJECTIVE Meticulous sealing of opened air cells in the petrous bone is necessary for the prevention of cerebrospinal fluid (CSF) fistulae after vestibular schwannoma surgery. We performed a retrospective analysis to determine whether muscle or fat tissue is superior for this purpose. METHODS Between January 2001 and December 2006, 420 patients underwent retrosigmoidal microsurgical removal by a standardized procedure. The opened air cells at the inner auditory canal and the mastoid bone were sealed with muscle in 283 patients and with fat tissue in 137 patients. Analysis was performed regarding the incidence of postoperative CSF fistulae and correlation with the patients sex and tumor grade. RESULTS The rate of postoperative CSF leak after application of fat tissue was lower (2.2%) than after use of muscle (5.7%). Women had less postoperative CSF leakage (3.4%) than men (5.6%). There was an inverse correlation with tumor grade. Patients with smaller tumors seemed to have a higher rate of CSF leakage than those with large tumors without hydrocephalus. Only large tumors with severe dislocation of the brainstem causing hydrocephalus showed a higher incidence of CSF leaks. CONCLUSION Fat implantation is superior to muscle implantation for the prevention of CSF leakage after vestibular schwannoma surgery and should, therefore, be used for the sealing of opened air cells in cranial base surgery.

Localization of primary language areas by arcuate fascicle fiber tracking.

BACKGROUND To reduce the risk of disabling postoperative functional deficit in patients with lesions in the dominant hemisphere, information about the localization of eloquent language areas is mandatory. OBJECTIVE To demonstrate the feasibility of arcuate fascicle (AF) tractography for proper localization of eloquent language areas in the superior temporal (STG) and inferior frontal gyrus (IFG). METHODS Between January and June 2010, we performed surgery in 13 patients with highly eloquent lesions with close spatial relationship to the primary language areas. All of them received preoperative diffusion tensor imaging for AF tractography. The STG and IFG were delineated at the ends of the AF. Five patients underwent functional magnetic resonance imaging of the primary language areas. The results were compared with tractography. RESULTS Tractography of the AF without prior knowledge of the localization of the STG and IFG was feasible in all cases. In the cases with functional magnetic resonance imaging, the activation maps matched the tractography results. In all but 1 patient, preservation of the primary language areas was possible, proven by the good neurological outcome. One patient suffered from a language dysfunction caused by a lesion in the medial and inferior temporal gyrus along the surgical pathway. CONCLUSION Tractography of the AF is a useful tool for identification of parts of the main primary language areas. Using tractography as a localization procedure to determine the primary language areas aids in the delineation of the STG and IFG and thus may help reduce the risk of postoperative permanent neurological deficit.

Low-Threshold Monopolar Motor Mapping for Resection of Primary Motor Cortex Tumors

BACKGROUND: Microsurgery within eloquent cortex is a controversial approach because of the high risk of permanent neurological deficit. Few data exist showing the relationship between the mapping stimulation intensity required for eliciting a muscle motor evoked potential and the distance to the motor neurons; furthermore, the motor threshold at which no deficit occurs remains to be defined. OBJECTIVE: To evaluate the safety of low threshold motor evoked potential mapping for tumor resection close to the primary motor cortex. METHODS: Fourteen patients undergoing tumor surgery were included. Motor threshold was defined as the stimulation intensity that elicited motor evoked potentials from target muscles (amplitude > 30 &mgr;V). Monopolar high-frequency motor mapping with train-of-5 stimuli (HF-TOF; pulse duration = 500 microseconds; interstimulus interval = 4.0 milliseconds; frequency = 250 Hz) was used to determine motor response--negative sites where incision and dissection could be performed. At sites negative to 3-mA HF-TOF stimulation, the tumor was resected. RESULTS: HF-TOF mapping localized the motor neurons within the precentral gyrus by using variable, low-stimulation intensities. The lowest motor thresholds after final resection ranged from 3 to 6 mA, indicating close proximity of motor neurons. Postoperatively, 12 patients had no new motor deficit, 1 patient had a minor new temporary deficit (M4+, National Institutes of Health Stroke Scale 1), and another patient had a minor new permanent deficit (M4+, National Institutes of Health Stroke Scale 2). Thirteen patients had complete or gross total resection. CONCLUSION: These preliminary data demonstrate that a monopolar HF-TOF threshold > 3 mA was not associated with a significant new motor deficit. ABBREVIATIONS: CST, corticospinal tract fMRI, functional magnetic resonance imaging HF-TOF, high-frequency train-of-5 MEP, motor evoked potential NIHSS, National Institutes of Health Stroke Scale

Petrous bone pneumatization is a risk factor for cerebrospinal fluid fistula following vestibular schwannoma surgery.

BACKGROUND: For the prevention of postoperative CSF fistula a better understanding of origins and risk factors is necessary. OBJECTIVE: To identify the petrous bone air cell volume as a risk factor for developing CSF fistula, we performed a retrospective analysis. METHODS: From 2000 to 2007 519 patients had a retrosigmoidal surgical removal of a vestibular schwannoma. The 22 who had a postoperative CSF fistula were chosen for evaluation in addition to 78 patients who were randomly selected in 4 equally sized cohorts: male/female with small/large tumors. Preoperative CT scans were analyzed regarding petrous bone air cell volume, area of visible pneumatization at the level of the internal auditory canal (IAC), tumor grade, and sex. RESULTS: Women developed nearly half as many CSF fistulas (2.7%) as men (5.2%). The mean volume of the petrous bone air cells was 10.97 mL (SD, 4.9; range, 1.38-27.25). It was significantly lower for women (mean, 9.23 mL; SD, 3.8) than for men (mean, 12.5 mL; SD, 5.28; P = .0008). The mean air cell volume of CSF-fistula patients was 13.72 mL (SD, 5.22). The difference concerning the air cell volume between patients who developed CSF fistulas and patients from the control group was significant (P = .0042). There was a significant positive correlation between the air cell volume and the area of pneumatization in one CT slide at the level of the IAC. CONCLUSION: The higher incidence of CSF fistulas in men compared with women can be explained by means of differently pneumatized petrous bones. A high amount of petrous bone pneumatization has to be considered as a risk factor for the development of postoperative CSF fistula after vestibular schwannoma surgery.