Deep brain stimulation in early Parkinson's disease: enrollment experience from a pilot trial.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson's disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. METHODS: We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. RESULTS: 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. CONCLUSION: This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long-term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD.

Visual field defects after selective amygdalohippocampectomy and standard temporal lobectomy.

BACKGROUND: Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures. METHODS: Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level. RESULTS: All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH. CONCLUSIONS: Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.

Intraventricular monitoring for temporal lobe epilepsy: report on technique and initial results in eight patients.

OBJECTIVE AND IMPORTANCE: Resective surgery is an effective treatment for refractory temporal lobe epilepsy. In difficult cases, invasive monitoring may be needed to precisely lateralise and localise seizure foci of mesial temporal origin. The authors present a modified technique for image guided, endoscopic placement of an intraventricular electrode array (IVE) that abuts the amygdalo-hippocampal complex. METHODS: Eight patients with suspected mesial temporal lobe epilepsy had placement of an IVE in conjunction with other invasive electrodes. Seven of these patients also had subdural grid or strip electrodes and four had foramen ovale electrodes. Frameless image guidance was used to place a custom 10-contact depth electrode through a rigid neuroendoscope within the atrium of the lateral ventricle. Once proper orientation towards the temporal horn was confirmed, the IVE array was advanced into the temporal horn to the temporal tip. The endoscope was removed and electrode placement was confirmed through an intraoperative lateral skull radiograph and on visual inspection at the time of resection in two cases. RESULTS: The IVE was crucial for localisation in one patient and helped localisation in four others. Surgery was offered to seven patients. The only serious complication of IVE placement was a thalamic contusion presumably from an errant electrode tip. One electrode was inadvertently placed into the frontal horn. There were no deaths and no permanent morbidity associated with the procedure. CONCLUSION: Endoscopically placed temporal horn, intraventricular electrodes provide an alternative to transcortical depth electrode placement. The technique hopefully can avoid complications associated with multiple depth electrode placements, especially when bilateral amygdalo-hippocampal electrical recordings are desired, although there may be a steep learning curve.

Low-dose stereotactic radiosurgery is inadequate for medically intractable mesial temporal lobe epilepsy: a case report.

The successful surgical treatment of medically refractory epilepsy is based on one of three different principles: (1) elimination of the epileptic focus, (2) interruption of the pathways of neural propagation, and (3) increasing the seizure threshold through cerebral lesions or electrical stimulation. Temporal lobe epilepsy, being the most common focal epilepsy, may ultimately require temporal lobectomy. This is a case report of a 36-year-old male with drug-resistant right mesial temporal lobe epilepsy who failed to obtain seizure control after stereotactic radiosurgery to the seizure focus. Complex-partial seizures occurred 6-7 times monthly, and consisted of a loss of awareness followed by involuntary movements of the right arm. EEG/CC TV monitoring indicated a right mesial temporal lobe focus, which was corroborated by decreased uptake in the right temporal lobe by FDG-PET and by MRI findings of right hippocampal sclerosis. Stereotactic radiosurgery was performed with a 4MV linac, utilizing three isocenters with collimator sizes of 10, 10, and 7 mm respectively. A dose of 1500 cGy (max dose 2535 cGy) was delivered in a single fraction to the patient's right amygdala and hippocampus. There were no acute complications. Following radiosurgery the patient's seizures were improved in both frequency and intensity for approximately 3 months. Antiepileptic medications were continued. Thereafter, seizures increased in both frequency and intensity, occurring 10-20 times monthly. At 1 year post radiosurgery, standard right temporal lobectomy including amygdalohippocampectomy was performed with subsequent resolution of complex-partial seizures. Histopathology of the resected temporal lobe revealed hippocampal cell loss and fibrillary astrocytosis, consistent with hippocampal sclerosis. No radiation-induced histopathologic changes were seen. We conclude that low-dose radiosurgery doses temporarily changed the intensity and character of seizure activity, but actually increased seizure activity long-term. If radiosurgery is to be an effective alternative to temporal lobectomy for medically intractable temporal lobe epilepsy, higher radiosurgery doses will be required. The toxicity and efficacy of higher-dose radiosurgery is currently under investigation.

Magnetic stimulation of the spine to produce lower extremity EMG responses. Significance of coil position and the presence of bone.

STUDY DESIGN: Magnetic stimulation of the spinal cord in 14 pigs was performed, and compound muscle action potentials (CMAPs) were recorded from lower extremities before and after nerve root and spinal cord lesioning. OBJECTIVES: The authors determined whether magnetic stimulation of the spinal cord produced lower extremity CMAPs. SUMMARY OF BACKGROUND DATA: Previous studies indicated that the magnetic stimulation of the spinal cord would result in lower extremity CMAP if appropriate amounts of spinal bone were removed to expose the spinal cord. RESULTS: Our findings demonstrated that the presence of intervening bone did not affect the reliability or presence of lower extremity CMAPs. Additionally, magnetic stimulation did not result in spinal cord activation but produced activity in nerve roots lateral to nerve root foramen. Lesioning of the spinal cord and complete rhizotomies did not affect magnetically elicited CMAPs. CONCLUSIONS: Magnetic stimulation of the spinal canal does not result in activation of spinal cord motor tracts. Lower extremity CMAPs were elicited by stimulation of nerve roots lateral to nerve root foramen and not of the spinal cord. Magnetic stimulation of the spinal cord is not appropriate for monitoring spinal cord motor tract function.

Correlation of motor-evoked potential response to ischemic spinal cord damage.

The prevalence of morbidity is a major deterrent to the success of aortic aneurysm replacement operations. We have developed a model of spinal cord ischemia, based on the amplitude reduction of the motor-evoked potential, which produces approximately a 90% prevalence of paraplegia. Regional blood flow was studied with the use of radioactive microspheres, and results showed that there was a significant decrease in flow to the lumbar cord (85% reduction) during aortic occlusion, followed by a twofold to threefold hyperemia that persisted for 24 hours. Histopathologic examination of the cord revealed that the greater portion of microgliosis, spongiosis, and neuronal damage was confined to the gray matter of the cord, and its severity increased as one progressed caudally. The somatosensory-evoked potential disappeared before the motor-evoked potential L-2 signal in all dogs, with a mean disappearance time of 10.9 +/- 5.6 minutes, compared with 21 +/- 6.6 minutes for the motor-evoked potential. Both the sensory-evoked potential and the motor-evoked potential cord signal were present 24 hours later in all dogs tested. The peripheral nerve motor-evoked potential disappeared within 1 minute of cord ischemia, was not present 24 hours later, and hence appears to be too sensitive to use as an indicator of spinal cord damage. Plotting spinal cord motor-evoked potential amplitude reduction versus both histopathologic damage and regional blood flow revealed a positive correlation between motor-evoked potential amplitude reduction, decreased cord perfusion, and increased histopathologic damage. In addition, it may be possible to make inferences about the neurologic status of a subject based on the magnitude and time-course of the motor-evoked potential's amplitude reduction and wave morphology.

Amplitude and latency characteristics of spinal cord motor-evoked potentials in dogs.

The motor-evoked potential can be reliably recorded in anesthetized dogs by use of percutaneous placement of active recording electrodes near the dorsal lamina of the vertebral column. Two types of responses were observed in this study; short (less than 5.5 ms at T9-10)- and long (greater than 5.8 ms at T9-10)-latency waves. Short-latency waves are larger in amplitude and appear with higher stimulus intensities than do long-latency waves. Short-latency waves are conducted at greater than 80 m/s and may not reflect pyramidal tract activation. The safety of using higher intensity stimuli to generate short-latency waves has not been determined.

Suprathreshold brain stimulation activates non-corticospinal motor evoked potentials in cats.

In the feline model of the motor evoked potential (MEP) test, a multiphasic spinal cord signal can be elicited in response to bipolar or transcranial brain stimulation. Previous studies have shown that signals produced by threshold stimulation travel mostly in the corticospinal tract. However, from this study we show that suprathreshold stimulation produces very large amplitude MEPs which travel in the ventral funiculus and therefore are most likely associated with extrapyramidal tract activation. The data supporting this conclusion are: (1) apparent conduction velocities of the first two large amplitude peaks are at least 80 m/s with transcranial stimulation; (2) latency of the transcranial MEP at L2 in the cord is less than or equal to 3.50 ms; (3) large amplitude, positive monophasic potentials are recorded in the ventral but not dorsal-lateral funiculus for either bipolar or transcranial MEPs; (4) both bipolar and transcranial MEPs are significantly reduced or abolished by selective lesion of the ventral funiculus. The two tracts which we believe are responsible for mediating the suprathreshold MEP in the cat are the reticulospinal and vestibulospinal tracts. This is significant because suprathreshold MEPs can be used to monitor feline ventral cord function. Furthermore, combining the use of threshold and suprathreshold MEPs may provide a differential diagnostic test for pyramidal vs. extrapyramidal motor function.

Amplitude and latency characteristics of spinal cord motor evoked potentials in the rat.

The motor evoked potential (MEP) has become a valuable component of neurophysiological monitoring. A better understanding of the characteristics of the normal MEP is needed before one can fully appreciate the effects of injury on the MEP. We describe characteristic patterns of spinal cord MEPs, recorded epidurally, in response to transcranial (dura-to-palate) brain stimulation in a rat model. Series of signal averaged MEP responses at a duration of 100 microseconds were recorded at T10/11, T12/13, and L1/2 in 8 normal rats. We used a much greater range of current intensities (0.5-65 mA) than has been studied previously. Also, we studied the gradual development of the MEP wave form using smaller increments of current strength than have been reported previously. We confirmed in rats our earlier report in cats that long latency peaks appear first at low intensities while short latency peaks appear with higher intensities (Konrad et al. 1988). We also report average peak latencies over the range of stimulus intensities used for each recording level in each rat. In some rats, conduction velocities of several MEP peaks were calculated, and they range from 35 to 42 m/sec. These velocities are consistent with values reported in the literature for extrapyramidal pathways. Our rat model provides a method of measuring spinal cord potentials at three levels with no trauma to the spinal cord. Therefore, it can be used to repeatedly test motor function in chronic studies of spinal cord injury.

Existence of a strength-duration curve for spinal cord motor evoked potentials in cats.

A new technique has been developed to estimate the chronaxie of fibers carrying action potentials that are responsible for short latency motor evoked potentials (MEPs). In a 6-cat study, electrical stimuli were applied to the exposed motor cortex, and spinal cord potentials (at the vertebral level of T9/10 and L2/3) were recorded with needle electrodes using signal averaging. From a plot of MEP amplitude versus stimulus current amplitude for stimuli of 70, 100, 200 and 500 microseconds duration, it was possible (by extrapolation and using the linear relationship between charge and duration) to estimate chronaxie for the first 2 prominent peaks in MEP recordings. Mean chronaxie values ranging from 190 to 337 microseconds were obtained. This study describes acquisition of strength-duration curves for short latency MEP peaks, but does not address the origin of these peaks.

Motor evoked potentials in the dog: effects of global ischemia on spinal cord and peripheral nerve signals.

Motor evoked potentials (MEPs) in cats, rats, and humans have been reported. They appear promising as a test of central nervous system function, and they are sensitive not only to mechanical injury but also to ischemia. In mechanical trauma, the peripheral nerve response is much more sensitive to damage than the cord response, with a lower threshold and an earlier disappearance. We are reporting that the MEP can also be produced in the dog and that, under conditions of cardiac arrest induced by fibrillation, the peripheral nerve response disappears first at about 30 seconds and then the spinal cord response disappears at about 10 to 13 minutes. The late disappearance of the spinal cord response raises serious questions about its role as an adequate injury monitor. The most useful warning feature of the spinal cord response is an increase in amplitude during the critical first 2 minutes of arrest. Latency changes in the cord and peripheral nerve response did not seem as useful as amplitude changes in terms of providing adequate detection of injury. We also evaluated the peripheral nerve signals to determine whether they are partially volume-conducted weak muscle responses, and evidence substantiates their nonmuscle origin.