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.

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.

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 postural reflexes and gravity--an under water simulation.

This study represents the first attempt to investigate the influence of gravity on postural adjustments. Subjects were displaced while standing under water on a movable platform, while the buoyancy of the body was adjusted by using a variety of lead vests. Under water, an approximately linear relationship was found between body weight and impulse directed electromyographic response amplitudes in the leg and thigh muscles. Loading of the subjects out of water resulted in a saturation of the response amplitude. The biomechanical signals recorded during the displacements indicated that neither vestibulospinal nor muscle proprioceptive reflex mechanisms can account for the effect observed under water. It is suggested that the EMG responses are mediated by reflexes which are activated by pressure receptors within the body in order to hold the centre of gravity over the feet.

Compensation of human stance perturbations: selection of the appropriate electromyographic pattern.

Perturbations of stance evoke purposive EMG patterns which are directed to hold the body's centre of gravity over the feet. Dorsiflexing rotation of the feet is followed by a monosynaptic stretch reflex response in the gastrocnemius muscle, succeeded by a late compensatory tibialis anterior activation. Backward translation of the feet elicits only a compensatory polysynaptic EMG response in the gastrocnemius muscle, while an early gastrocnemius response is absent. The amplitude modulation of the gastrocnemius H-reflex has been investigated during the early part of the two modes of perturbation. Only during translational perturbation a progressive decrease in gastrocnemius H-reflex amplitude started within 5 ms after onset of displacement. The degree of the reduction in amplitude in the former perturbation was dependent on the displacement velocity. Only the contact forces (torques) differed between the two modes of perturbations within the first 10 ms after onset of perturbations. It is suggested that signals from pressure receptors within the body are responsible for the early change in H-reflex amplitude during translational perturbations and it is concluded that the simplest spinal reflex is under very rapid and powerful moment-to-moment control by changes in peripheral feedback. In view of a strong reciprocal modulation of monosynaptic and polysynaptic reflex responses, the later purposive EMG responses may be determined by early changes in presynaptic inhibition of group I afferents.

Influence of subjects' height on the stabilization of posture.

In order to investigate the influence of subjects' height in stabilization of body sway, postural EMG reactions were analysed following perturbation of posture during stance on a force measuring platform. Perturbing momenta of different strengths were unexpectedly applied at the back (level of the center of gravity) after being matched to the body weight of each subject. EMG activity of the antagonistic leg muscles and head, hip and ankle joint movements were recorded. There was a close correlation between displacement amplitude at the ankle joint and height of the subject, with the largest displacements in small subjects. The consequence of this relationship was that 1) The compensatory reactions consisted of larger gastrocnemius responses and a stronger coactivation of the tibialis anterior; 2) Momenta of increasing strength resulted in a larger increment of both ankle joint displacement and gastrocnemius EMG responses in small compared to larger subjects. In analogy to tip-toeing movements, it is concluded that the coactivation pattern is typical for stance conditions with a restricted area of support in order to reduce body sway. On the basis of latency measurements it is suggested that the response pattern is induced by proprioceptive information from the impact site of the momentum.

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.

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.

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.

Reflex activity and muscle tone during elbow movements in patients with spastic paresis.

Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis. During sinusoidal (0.3-Hz) isometric or isotonic elbow tracking, with a control either of joint position or of torque, randomly timed displacements were induced (at one of three velocities) stretching either the activated flexor or the extensor muscles. On the spastic side, exaggerated short-latency reflexes were apparent, but in contrast, the amplitude of long-latency electromyography (EMG) responses was reduced. The latter responses were differentially modulated on the unaffected side, predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque, while the mode of muscle contraction (isometric or isotonic) had little influence on this behavior. This difference in reflex modulation was lost on the spastic side. The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements. The ratio of torque to EMG activity during displacements was higher for both background and reflex-induced EMG on the spastic limb than on the unaffected side. This effect was more pronounced for the flexor than for the extensor muscles. Consequently, the development of spastic muscle hypertonia cannot be attributed to an increase in EMG activity. It is suggested that secondary to a supraspinal lesion, mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched.

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.

Amplitude modulation of the human quadriceps tendon jerk reflex during gait.

Amplitude modulation of the quadriceps tendon jerk reflex was investigated during the step cycle in normal human subjects. Reflex amplitude was compared with that obtained during a control stance condition, with "equivalent" levels of EMG activity and limb position. During gait there was a progressive decrease in the reflex amplitude early in the stance phase, i.e. during yielding of the knee, and it remained reduced throughout the step cycle. This pattern of changes in reflex amplitude correlated with neither the quadriceps EMG activity nor with the knee joint movements. The behavior of the tendon reflex was similar to that described for the modulation of the quadriceps H-reflex during the early stages of the stance phase of gait. In the latter study it was argued that changes in presynaptic inhibition of quadriceps la terminals could account for the amplitude modulation. We conclude that there is no dramatic change in the gamma drive to quadriceps muscle spindles: tendon reflexes are modulated during the step cycle in much the same way as H-reflexes, in spite of the peripheral and central differences between them. Similar behavior has been described for the soleus H-reflex and Achilles tendon reflex during gait although the modulation of these reflexes followed a different pattern than that seen in the quadriceps.

Phase-dependent reversal of reflexly induced movements during human gait.

To investigate whether phase-dependent reversals in reflex responses on electromyography (EMG) are accompanied by movement reversals, a series of human volunteers were studied for their behavioural responses to sural nerve stimulation during running or walking on a treadmill. Low-intensity stimulation (less than 2.5 x perception threshold, T) of the sural nerve yielded facilitatory responses in the tibialis anterior muscle (TA), correlated with an induced ankle dorsiflexion (mean maximum 4 degrees) in early swing. The same stimuli yielded primarily TA suppression and weak ankle plantar flexion (mean maximum 1 degree) at end swing. The correlated induced knee angle changes did not precede the ankle changes, and they were relatively small. Mean maximum flexion in early swing was 6.2 degrees, while mean maximum extension was 3.7 degrees. High-intensity stimulation of the sural nerve (greater than 2.5 x T) always gave rise to suppression of the ongoing activity. This resulted in a second type of movement reversal. During late stance and early swing the responses in TA were suppressive (i.e. below background activity) and related to ankle plantar flexion. In contrast, the responses during early and middle stance consisted of suppression in extensor activity (gastrocnemius medialis and soleus) and ankle dorsiflexion. The data are discussed in terms of a new hypothesis, which states that the responses to electrical stimulation of cutaneous nerves during locomotion do not correspond directly to corrections for stumbling following mechanical perturbations during the step cycle. Instead, the data invite a reinterpretation in terms of the opening and closing of reflex pathways, presumably by a central pattern generator for locomotion.