Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours.

BACKGROUND: There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection. MATERIALS AND METHODS: Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department. Among these patients we identified 51 patients, who underwent magnetic resonance (MR) based stereotactic biopsy and subsequent open resection within 30 days. Mortality and morbidity data as well as final histopathological diagnoses of both procedures were compared with regard to tumour grade and tumour cell type. Patients with discrepancies between the histological diagnosis obtained by biopsy and open resection were classified into three subgroups (same cell type but different grading; same grading but different cell type and different grading as well as different cell type). RESULTS: The mean number of tissue samples taken by stereotactic serial biopsy from each patient was 12 (range 7-21). Minor morbidity was 6% and major morbidity was 14% after open surgery compared to no morbidity after stereotactic biopsy. Mortality was 2% after stereotactic biopsy (one patient died after stereotactic biopsy as a result of a fatal bleeding) compared to 0% in the resection group. Silent bleeding rate without any clinical symptoms was 8% in the biopsy group. A complete correlation of histopathological findings between the biopsy group and the resection group was achieved in 76% and was increased to 90% by analyzing clinical and neuroradiological information. In patients with recurrence the correlation was higher (94%) than for patients with primary brain lesions (67%). The discrepancies between the open resection group and biopsy group were analysed. CONCLUSION: Stereotactic MR guided serial biopsy is a minimal invasive procedure with low morbidity and high diagnostic accuracy for diagnosis and grading of brain tumours. Diagnostic accuracy of stereotactic biopsy can be enhanced further by careful interpretation of neuroradiological and clinical information.

Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors.

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53-1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO degrees II vs. degrees III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additional risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.

Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy.

BACKGROUND: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. METHODS: Twenty-four consecutive patients (3-46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted (125)I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. RESULTS: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. CONCLUSION: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.

Interstitial radiosurgery in the treatment of gelastic epilepsy due to hypothalamic hamartomas.

The authors evaluated a new stereotactic radiosurgical approach in seven patients with gelastic epilepsy due to hypothalamic hamartomas. Stereotactic implantation of 125I-seeds into the hamartoma was feasible in six patients. At follow-up at least 1 year after interstitial radiotherapy, two patients had become seizure-free within 2 months, and two others had only persisting auras. There were no major perioperative or postoperative side effects.

Effect of interstitial stereotactic radiosurgery on behavior and subjective handicap of epilepsy in patients with gelastic epilepsy.

Patients with symptomatic epilepsy due to hypothalamic hamartomas often are compromised not only by pharmacoresistant epileptic seizures but also by behavioral disturbances and cognitive dysfunction. We report the effect of successful treatment with stereotactic interstitial radiosurgery by intrahypothalamic implantation of 125I seeds on behavior and subjective handicap. In all patients rendered seizure-free or suffering only from auras, improvement of behavior was reported by parents and colleagues or schoolteachers. Parents' ratings according to the Child Behavior Checklist showed improvements with respect to social problems and attention. Self-ratings of quality of life by adult patients showed improvements in activities, working situation, and self-perception. These improvements were not observed in patients in whom clinically manifest seizures and interictal EEG discharges persisted after radiosurgery.

Computer aided surgery with special focus on neuronavigation.

The term computer aided surgery (CAS) is now mainly used for an intraoperative navigation within the body combining a 3D-digitizer with preoperative CT/MR-imaging. This method has become indispensable in neurosurgery for the removal of deep-seated and/or critically located intracranial tumors and vascular malformations. Also ENT surgery within the paranasal sinuses and setting of pedicle screws in orthopedic surgery profit greatly from the high targeting precision of CAS. And still a growing number of surgical disciplines are employing this method. Today infrared-optical 3D-digitizers are state of the art, but electromagnetic spatial digitizing using novel, miniature localizers is promising, too. The results of our CAS study 1994-mid-1997 with 50 patients suffering from small intracranial lesions are presented.

Computer assisted brain surgery for small lesions in the central sensorimotor region.

The capacity of a new optical navigation device is demonstrated by six microsurgical procedures for small subcortical lesions within the central sensorimotor strip. This small series is aimed at less invasive resection in this functionally critical region, independently of primary diagnosis and outcome. Guided by high resolution CT imaging data five brain tumours and one cavernous angioma was selectively located and most sparingly removed without additional sensorimotor deficit. In two cases improvement of a pre-operative paresis was observed immediately after surgery. Thanks to light-weight freehand pointing instruments and a ranging accuracy of +/- 1 mm, damage to functionally important brain areas and vessels was avoided by using uncommonly oblique, e.g., transsulcal ways of access which would hardly have been possible even with guidance by conventional stereotaxy. The demanding systematic cortical stimulation of the precentral gyrus applied in three cases was only sensitive in infiltrating tumours-e.g., low grade astrocytomas-where for want of adjuvant therapy it was essential to proceed to the extreme limits of resection. In general, precise anatomical localisation by computer aided surgery (CAS) is sufficient in small central lesions which guarantees minimally invasive surgery. The potential of this new, soon commercially available optical navigation system in (neuro) surgery, quality control and teaching is discussed.

Modulation of sural nerve somatosensory evoked potentials during stance and different phases of the step-cycle.

In order to investigate the modulation of somatosensory processing during stance and locomotion, sural nerve somatosensory evoked potentials were recorded during both stance and different phases of the step-cycle. Characteristic sequences of negative-positive waves were elicited, consisting of an early component, N40, presumably of subcortical origin, followed by a P50-N80-P220 complex of cortical origin. The N40 and N40-P50 components had similar amplitudes in both gait and stance. However, the P50-N80 component was attenuated whereas the N80-P220 complex became biphasic during gait. Within the step-cycle, amplitudes of the cortical components P50-N80 and N80-P110 were larger prior to footfall and smaller at the beginning of the support phase. The results demonstrate that locomotion produces a modulatory effect on somatosensory input at a cortical level. Within the step-cycle, excitability of the somatosensory cortex is increased during the middle and late swing phases and decreased during the support phase. Such modulation may contribute to an improved detection of foot contact at touchdown.

Optically-navigable operating microscope for image-guided surgery.

In computer-assisted surgery (CAS), optical digitizing is state-of-the-art. Unfortunately standard navigation instruments, e.g. small, LED-equipped pointers are frequently shadowed by the operating microscope when the camera-array is ceiling- or rack-mounted. Thus, for microsurgery, a navigation module consisting of a reference panel mounted onto the housing of the microscope and an object distance measuring unit attached in front of the objective lens was developed. By means of this navigation module the microscope can be located in space with an accuracy of +/- 1-2 mm. Focusing errors due to the high depth of view of modern microscopes and individual refraction anomalies are eliminated by laser distance measurement. This device has been clinically tested since September 1994 and a typical case is reported.

Task-dependent modulation of short- and long-latency electromyographic responses in upper limb muscles.

Records were made of electromyographic (EMG) responses of both upper limb muscles and the corresponding elbow joint movements following sinusoidal (0.3 Hz) isometric displacement of the elbow joint itself. Two motor conditions were tested. Firstly, the subjects had to control elbow position and secondly control joint torque. Randomly timed, flexing or extending ramp impulses were induced at different displacement velocities and amplitudes. Following long duration displacements (> 100 msec) the recorded EMG responses could clearly be separated into 3 different components (M1-M3). The M1 component was of constant duration but M3 corresponded to the duration of the ramp displacement. It is proposed that the M1 component is "coded" by the acceleration signal and the M3 component by the velocity signal. Only the shape of the M2 component was dependent upon the actual motor condition. With the subjects controlling the elbow joint angle the M2 components in the arm flexor and extensor EMG responses exhibited a peak whose rate of rise was dependent on displacement velocity. However, when elbow torque was controlled by the subjects the M2 component exhibited a plateau whose amplitude was dependent on displacement velocity. The amplitude of the M2 component was significantly larger during position-control than during torque-control. We propose that the difference in the behaviour of the EMG responses may be achieved by the appropriate central regulation of gamma-motoneurone activity or, alternatively, by selective modulation of different receptor inputs between the two tasks.

Stretch-induced electromyographic activity and torque in spastic elbow muscles. Differential modulation of reflex activity in passive and active motor tasks.

Stretch-evoked electromyographic (EMG) activity and torque signals have been studied in elbow joint muscles of both sides of patients with spastic hemiparesis and healthy subjects. In order to reveal differences in the generation of muscle tone between clinical assessment and functional movement, stretches of different velocities and amplitudes were applied during passive and quasi-functional active motor tasks. In spastic patients the strength and duration of the EMG responses following stretching of flexor and extensor muscles during both passive and active tasks were dependent on the stretch velocity and duration, respectively. This effect was seen on both the spastic and unaffected side. Under passive conditions EMG activity after stretching was negligible in the limb muscles of healthy subjects, of small amplitude in unaffected limbs of the patients, but was strong in affected muscles. Under active conditions, the amplitude of the early (M1) component of the EMG signal was larger, while the later components (M2 and M3) were smaller. These differences were due more to a change in reflex gain than to a change in reflex threshold when the stretch velocity signal was the basis for calculation. It is suggested that in spastic paresis, modulation of stretch-induced EMG activity in the spastic limb becomes restricted to a smaller range with a poor ability to switch off under passive conditions. Furthermore, the reflex EMG activity suffers a reduced facilitation under active conditions. In comparison with unaffected limbs the stretch-evoked torque on the affected side was increased under passive conditions (due to the extra EMG activity) and decreased under active conditions (due to a reduced EMG activity). An increased torque to EMG ratio was found in spastic flexor and extensor muscles during active tasks. This is thought to be due to changes in mechanical muscle fibre properties suffered as a consequence of defective muscle activation following cerebral lesions. The consequences for clinical assessment of muscle tone and therapy of spastic movement disorder are discussed.

Increased amplitude of cutaneous reflexes during human running as compared to standing.

The amplitude of H-reflexes is decreased during walking as compared to standing and a further reduction is seen during running as compared to walking. Does a similar reduction occur for reflexes elicited by cutaneous stimulation? To answer this question, the electromyographic (EMG) responses in biceps femoris (BF) and tibialis anterior (TA) to a 20 ms train of 5 electrical pulses, were recorded. This stimulus was applied to the sural nerve at the ankle, either at 16 different phases of the step cycle in human volunteers running on a treadmill at 8 km/h or at different isometric contraction levels of TA and BF in the same subjects during standing, imitating the postures of different phases of the step cycle. The mean latency of the main responses in BF of all subjects was 76 ms. Similar responses (P2), with a latency of 79 ms were seen in TA in 6 of the 10 subjects. For a constant strength of stimulation (2 times perception threshold) during isometric contractions at different levels in early stance imitation, the mean reflex ratio's (reflex/background) of BF and TA responses were 1.07 and 0.53, respectively, while the ratio's for these 2 muscles during running were 1.78 and 1.1. The higher reflex ratio's in running were primarily due to the large facilitatory responses, which were present during most of the step cycle but rarely during voluntary contractions in the subjects during standing. At the end of the swing phase, however, the responses in BF and TA were predominantly suppressive, as were most of the responses to stimulation applied to the standing subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Human stance on a sinusoidally translating platform: balance control by feedforward and feedback mechanisms.

With subjects standing on a treadmill moving sinusoidally backward and forward, recordings of electromyographic (EMG) leg and trunk muscle activity, head and joint movements and platform torque were made with the subjects' eyes open or closed. The sinusoidal frequency was changed, stepwise and randomly, between 0.5, 0.3 and 0.25 Hz. The amplitude of the deflection was constant at +/- 12 cm. During an adapted sinus cycle, the maximum leg muscle EMG activity was recorded in the tibialis anterior around the posterior turning point and in the gastrocnemius around the anterior turning point in the treadmill cycle. This activity was associated with a forward inclination of the body around the posterior point and a straightening of the body at the anterior point. Both the degree of body inclination and the corresponding EMG activity were dependent upon the sinusoidal frequency. The programmed adjustment of the body inclination was such that the result of inertial and gravitational forces acting on the body coincided with the axis of the body at the posterior turning point. At the anterior point, the adjustment was achieved mainly by strong activation of the leg extensors. The latencies of the compensatory muscle responses to a change in treadmill frequency were significantly shorter at the posterior point for the gastrocnemius than for the tibialis anterior, and at the anterior point for the tibialis anterior than for the gastrocnemius. No correlated changes were seen in the corresponding head and joint movements. The difference in latency can best be attributed to the different body postures during the sinusoid. Early activation of the gastrocnemius is required due to the forward-directed impulse to the inclined body at the posterior point, and of the tibialis anterior muscle due to the backward-directed impulse to the erect body at the anterior point. It is suggested that afferent input from extensor load receptors provides information about the position of the body's centre of gravity relative to the support surface and determines the generation of the EMG responses. Adaptation of both the EMG and biomechanical patterns to a new sinusoidal frequency of the treadmill occurred within four cycles after the change. Biomechanically, this was reflected as a change in the body posture. Vision did not significantly affect these changes. In conclusion, standing on a sinusoidally moving platform, the nervous system acts to control the position of the body's centre of gravity relative to the feet. Body posture is adjusted in such a way that the forces acting on the body during the treadmill movements become minimised.(ABSTRACT TRUNCATED AT 400 WORDS)

Visually induced destabilization of human stance: neuronal control of leg muscles.

With subjects standing on a treadmill both the treadmill and an optical flow pattern were moved sinusoidally (0.25 Hz) and the effect of delaying the presentation of the image with respect to treadmill movement was analysed. Around the posterior turning point of treadmill movement a modulation of the tibialis anterior EMG was observed, the onset, duration and amplitude of which were dependent upon the phase-shift between the movements of the legs and the image. At times around the anterior turning point a corresponding modulation, but only of EMG amplitude, occurred in the extensor muscles. Little adaptational changes in EMG activity were seen during successive cycles. Consequently during a specific sensitive phase of the sinus tibialis anterior EMG, responses are evoked in which strength depended on the velocity of the optical flow pattern. The modulation of the extensor activity is necessary for a 'resetting' of the neutral body position.