Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi.

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD.

OBJECTIVE: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi). RESULTS: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states. CONCLUSIONS: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed.

Pathology of ilioinguinal neuropathy produced by mesh entrapment: case report and literature review.

Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.

Management of chronic severe pain: cerebral neuromodulatory and neuroablative approaches.

Two approaches are utilized when targeting the brain to treat pain. The first, a non-destructive approach, uses either electrical stimulation of brain targets thought to modulate the process of pain perception, or pharmacological agents are introduced into ventricular spaces to target pain modulating receptors. Electrical stimulation targets include; the thalamic nuclei, the periventricular and periaqueductal grey (PVG and PAG) matter or the motor cortex. Currently, the pharmacological agent of choice for intracerebroventricular injection is morphine. In general, electrical stimulation is used for nonmalignant type pain, and pharmacological modulation for malignant type pain. The second, a destructive approach, is usually employed with the goal of interrupting the signals that lead to pain perception at various levels. Neuroablation is usually performed on cellular complexes such as "nuclei, or gyri" or on tracts with the aim of disrupting the sensory and limbic pathways involved in the emotional processes associated with pain. Specific cerebral neuroablation targets include; the thalamic medial group of nuclei, the cingulated gyrus, and the trigeminal nucleus and tract. There are fewer reports in the literature detailing the brain, when compared to the spine, as a target to treat pain, and further research is required.

Management of chronic severe pain: spinal neuromodulatory and neuroablative approaches.

The spinal cord is the target of many neurosurgical procedures used to treat pain. Compactness and well-defined tract separation in addition to well understood dermatomal cord organization make the spinal cord an ideal target for pain procedures. Moreover, the presence of opioid and other receptors involved in pain modulation at the level of the dorsal horn increases the suitability of the spinal cord. Neuromodulative approaches of the spinal cord are either electrical or pharmacological. Electrical spinal cord modulation is used on a large scale for various pain syndromes including; failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), neuropathic pain, angina, and ischemic limb pain. Intraspinal delivery of medications e.g. opioids is used to treat nociceptive and neuropathic pains due to malignant and cancer pain etiologies. Neuroablation of the spinal cord pain pathway is mainly used to treat cancer pain. Targets involved include; the spinothalamic tract, the midline dorsal column visceral pain pathway and the trigeminal tract in the upper spinal cord. Spinal neuroablation can also involve cellular elements such as with trigeminal nucleotomy and the dorsal root entry zone (DREZ) operation. The DREZ operation is indicated for phantom type pain and root avulsion injuries. Due to its reversible nature spinal neuromodulation prevails, and spinal neuroablation is performed in a few select cases.

Microelectrode recording: lead point in STN-DBS surgery.

BACKGROUND: Microelectrode recording is an integral part of many surgical procedures for movement disorders. We evaluate the Lead point compared to the NeuroTrek system. We used NeuroTrek in 18 Parkinsonian patients, Lead point-4 in 12 patients, during STN-DBS surgery. We compared MR-Stir image with Microelectrode recording. METHOD: The MicroGuide system with its integrated screen display provides the user with all the information needed during the surgery on its screen. Microelectrode recordings showed characteristic neuronal discharges on a long trajectory (5-6 mm), intraoperative stimulation induces dramatic improvement of Parkinsonian motor symptoms. FINDINGS: Microrecording data of the Leadpoint showed high background activity, and firing rate of 14-50 Hz. The discharge pattern is typically chaotic, with frequent irregular bursts and pauses. DISCUSSION: The microelectrode recording of the neuroTrek and Lead point-4 showed unique results of the typical STN spike. The DBS effect is maximized associated by MER mapping.

Temporal lobe magnetic resonance spectroscopic imaging following selective amygdalohippocampectomy for treatment-resistant epilepsy.

OBJECTIVES: Magnetic resonance spectroscopic imaging (MRSI) may show circumscribed or extensive decreased brain N-acetyl aspartate (NAA)/creatine and phosphocreatine (Cr) in epilepsy patients. We compared temporal lobe MRSI in patients seizure-free (SzF) or with persistent seizures (PSz) following selective amygdalohippocampectomy (SAH) for medically intractable mesial temporal lobe epilepsy (mTLE). We hypothesized that PSz patients had more extensive temporal lobe metabolite abnormalities than SzF patients. MATERIALS AND METHODS: MRSI was used to study six regions of interest (ROI) in the bilateral medial and lateral temporal lobes in 14 mTLE patients following SAH and 11 controls. RESULTS: PSz patients had more temporal lobe ROI with abnormally low NAA/Cr than SzF patients, including the unoperated hippocampus and ipsilateral lateral temporal lobe. CONCLUSION: Postoperative temporal lobe MRSI abnormalities are more extensive if surgical outcome following SAH is poor. MRSI may be a useful tool to improve selection of appropriate candidates for SAH by identifying patients requiring more intensive investigation prior to epilepsy surgery. Future prospective studies are needed to evaluate the utility of MRSI, a predictor of successful outcome following SAH.

Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD.

OBJECTIVE: To assess the safety, tolerability, and biological activity of glial cell line-derived neurotrophic factor (GDNF) administered by an implanted intracerebroventricular (ICV) catheter and access port in advanced PD. BACKGROUND: GDNF is a peptide that promotes survival of dopamine neurons. It improved 6-OHDA- or MPTP-induced behavioral deficits in rodents and monkeys. METHODS: A multicenter, randomized, double-blind, placebo-controlled, sequential cohort study compared the effects of monthly ICV administration of placebo and 25, 75, 150, 300, and 500 to 4,000 microg of GDNF in 50 subjects with PD for 8 months. An open-label study extended exposure up to an additional 20 months and maximum single doses of up to 4,000 microg in 16 subjects. Laboratory testing, adverse events (AE), and Unified Parkinson's Disease Rating Scale (UPDRS) scoring were obtained at 1- to 4-week intervals throughout the studies. RESULTS: Twelve subjects received placebo and seven or eight subjects were assigned to each of the other GDNF dose groups. "On" and "off" total and motor UPDRS scores were not improved by GDNF at any dose. Nausea, anorexia, and vomiting were common hours to several days after injections of GDNF. Weight loss occurred in the majority of subjects receiving 75 microg or larger doses of GDNF. Paresthesias, often described as electric shocks (Lhermitte sign), were common in GDNF-treated subjects, were not dose related, and resolved on discontinuation of GDNF. Asymptomatic hyponatremia occurred in over half of subjects receiving 75 microg or larger doses of GDNF; it was symptomatic in several subjects. The open-label extension study had similar AE and lack of therapeutic efficacy. CONCLUSIONS: GDNF administered by ICV injection is biologically active as evidenced by the spectrum of AE encountered in this study. GDNF did not improve parkinsonism, possibly because GDNF did not reach the target tissues--putamen and substantia nigra.

Interactions between deep brain stimulation and levodopa in Parkinson's disease.

OBJECTIVE: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. BACKGROUND: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. METHODS: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and 1 day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. RESULTS: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. CONCLUSION: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.

DBS and diathermy interaction induces severe CNS damage.

Pulse-modulated radiofrequency diathermy treatment to the maxilla produced permanent diencephalic and brainstem lesions and a vegetative state in a patient with PD with implanted subthalamic electrodes for deep brain stimulation.

Assessments of axial motor control during deep brain stimulation in parkinsonian patients.

OBJECTIVE: We tested the hypothesis that bilateral deep brain stimulation (DBS) in the globus pallidus internus or the subthalamic nucleus improves various components of postural and oromotor function and that some of the components correlate with changes in the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease. METHODS: Six patients with Parkinson's disease were evaluated for four postural and two orofacial UPDRS items, and quantitative tests of posture adjustments and oromotor control were performed while the patients were on and off DBS. Measurements of postural adjustments included reactive force and latency before a voluntary step. The oromotor assessments involved velocity and amplitude changes during voluntary jaw movement. RESULTS: DBS significantly improved the total UPDRS motor score by an average of 44%, which included improvement of 18 to 54% in the postural and orofacial items. DBS also decreased foot lift-off latency significantly, but it produced a variable response to the preparatory postural force in the swing limb. DBS significantly improved jaw-opening velocity by 14 to 50% and jaw opening amplitude by 5 to 41%. Significant correlations for the percentage change from off and on DBS occurred among a few UPDRS items and foot lift-off latency and jaw-opening velocities. CONCLUSION: DBS in either the globus pallidus internus or the subthalamic nucleus induces improvements in bradykinesia of specific components of postural and oromotor control, which also can be measured by the postural and orofacial UPDRS items. In some Parkinson's disease patients, DBS results in improvements in force or amplitude control, although these changes are not reflected in changes in UPDRS postural and orofacial items. A battery of quantitative and clinical tests must be used to evaluate the effects of DBS on axial motor control adequately.

Intrathecal hydromorphone for chronic nonmalignant pain: a retrospective study.

OBJECTIVE: Ten percent to 15% of patients with chronic pain experience intolerable side effects or inadequate analgesia with continuous intrathecal morphine therapy. Although clinical experience suggests that rotation to hydromorphone (Dilaudid) can reduce side effects and recapture analgesia, there have been only scattered reports of long-term intrathecal hydromorphone use in patients with nonmalignant pain. The purpose of this study is to review the safety and effectiveness of continuous intrathecal hydromorphone in the management of patients with nonmalignant pain in whom continuous intrathecal morphine therapy has failed. DESIGN: A retrospective review of 37 patients with chronic nonmalignant pain managed with intrathecal hydromorphone after failure of intraspinal morphine. RESULTS: The mean age of patients was 64 years +/- 12 SD. All patients suffered from severe nonmalignant pain, most from failed lumbosacral spine operations (19/37; 51%). Morphine was replaced with hydromorphone because of pharmacological complications (21/37; 57%) or inadequate analgesic response (16/37; 43%) after an average of 11 months +/- 11 SD of intrathecal therapy. Pharmacological complications, particularly nausea and vomiting, pruritus, and sedation were reduced by hydromorphone in most patients. Peripheral edema was improved by hydromorphone but tended to recur with prolonged hydromorphone exposure. Analgesic response was improved by at least 25% in six of 16 patients who were switched to hydromorphone because of poor pain relief. CONCLUSIONS: Hydromorphone can be a safe, analgesic alternative for long-term intrathecal management of nonmalignant pain among patients in whom morphine fails because of pharmacological side effects or inadequate pain relief.

Pain and spasticity after spinal cord injury: mechanisms and treatment.

STUDY DESIGN: A comprehensive survey of literature on the proposed mechanisms and treatment of pain and spasticity after spinal cord injury (SCI) was completed. OBJECTIVES: To define the current understanding of these entities and to review various treatment options. SUMMARY OF BACKGROUND DATA: The neurophysiologic basis of spasticity after SCI is well established. The mechanism of neuropathic pain after SCI remains conjectural, although considerable new data, much of it from animal models, now add to our understanding of this condition. METHODS: A comprehensive search and review of the published literature was undertaken. RESULTS: Treatment options for spasticity are effective and include oral medication (baclofen, tizanidine), intrathecal baclofen, and rarely, surgical rhizotomy or myelotomy. Selected patients with post-SCI pain can respond to surgical myelotomy (DREZ lesions) or intrathecal agents (e.g., morphine + clonidine), but the majority continue to suffer. CONCLUSIONS: Medical and surgical treatments for spasticity are established and highly successful. Management of post-SCI pain remains a clinical challenge, as there is no uniformly successful medical or surgical treatment.

Outcome of unilateral and bilateral pallidotomy for Parkinson's disease: patient assessment.

OBJECTIVE: Pallidotomy has recently regained acceptance as a safe and effective treatment for Parkinson's disease symptoms. The goal of this study was to obtain the patients' perspective on their results after undergoing this procedure. Special attention was focused on the potential complications and the respective advantages and risks of unilateral versus bilateral pallidotomy. METHODS: Fifty-six patients were studied during a 2-year period; 44 completed the evaluation, with a median follow-up of 7 months. Of these patients, 22 underwent unilateral pallidotomy, and 17 had bilateral simultaneous pallidotomy. Five patients who underwent staged bilateral pallidotomy were excluded from the statistical analysis, because the number of patients was considered too small for analysis. The procedures were performed with magnetic resonance imaging determination of the target, combined with physiological confirmation, including microelectrode recording. RESULTS: According to Visual Analog Scale scores, unilateral pallidotomy significantly improved dyskinesias (P < 0.05) but no other symptoms. Simultaneous bilateral pallidotomy improved slowness, rigidity, tremor, and dyskinesias (P < 0.05) but worsened speech function (P < 0.05). According to the patients' most frequently chosen answers to multiple-choice questions, unilateral pallidotomy improved night sleep, muscle pain, freezing, overall "on," overall "off," and the duration of "off periods," but it worsened the volume of the voice and articulation, increased drooling, and reduced concentration. Bilateral pallidotomy improved night sleep, muscle pain, freezing, overall "on," overall "off," duration of "off periods," and the amount of medication taken, but it increased drooling and worsened the volume of the voice, articulation, and writing. Subjective visual disturbance was noted in 36 and 41% of patients who underwent unilateral and simultaneous bilateral pallidotomy, respectively. Globally, the result of the procedure was rated "good" or "excellent" by 64% of the patients who underwent unilateral pallidotomy and by 76% of the patients who underwent bilateral pallidotomy. An age less than 70 years was a positive prognostic factor for the global outcome (P < 0.05), as were severe preoperative dyskinesias (P < 0.05). CONCLUSION: This study confirms that, from a patient standpoint, unilateral and simultaneous bilateral pallidotomy can reduce all the key symptoms of Parkinson's disease (i.e., akinesia, tremor, and rigidity) and the side effects of L-dopa treatment (i.e., dyskinesias). Preoperative severe dyskinesias and younger age are positive prognostic factors for a successful outcome. Simultaneous bilateral pallidotomy was more effective than unilateral pallidotomy regarding tremor, rigidity, and dyskinesias, but it conferred a higher risk of postoperative speech deterioration.

On the natural history of trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia is usually considered a separate entity from atypical trigeminal neuralgia. The exact relationship among these two and several other syndromes of facial pain remains unknown. There is no long-term prospective study of the natural history of trigeminal neuralgia nor any explanation for the existence of different, albeit somewhat similar, facial pain syndromes. DESCRIPTION OF CONCEPT: On the basis of our clinical experience, we propose a theory that may explain different facial pain syndromes as sequential stages of the same disease process. Typical trigeminal neuralgia caused by microvascular compression of the trigeminal nerve root in the posterior fossa may become transformed over time into atypical trigeminal neuralgia, if left untreated. This transformation involves change in the character of pain and development of sensory impairment. Two representative cases are presented to support this theory. CONCLUSION: If the theory of progressive change in character of pain and degree of sensory impairment in the course of otherwise typical trigeminal neuralgia is correct, trigeminal neuralgia, atypical neuralgia, and trigeminal neuropathic pain may represent different degrees of injury to the trigeminal nerve, therefore comprising a continuous spectrum rather than discrete diagnoses.

Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study.

OBJECTIVE: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) and subthalamic nucleus (STN) has been reported to be effective in alleviating the symptoms of advanced Parkinson's disease (PD). Although recent studies suggest that STN stimulation may be superior to GPi stimulation, a randomized, blinded comparison has not been reported. The present study was designed to provide a preliminary comparison of the safety and efficacy of DBS at either site. METHODS: Ten patients with idiopathic PD, L-dopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Neurological condition was assessed preoperatively with patients on and off L-dopa and on DBS at 10 days and 3, 6, and 12 months after implantation. Patients and evaluating clinicians were blinded to stimulation site throughout the study period. Complete follow-up data were analyzed for four GPi patients and five STN patients. RESULTS: When off-L-dopa, both GPi and STN groups demonstrated a similar response, with approximately 40% improvement in Unified PD Rating Scale motor scores after 12 months of DBS. Rigidity, tremor, and bradykinesia improved in both groups. In combination with L-dopa, Unified PD Rating Scale motor scores were more improved by GPi stimulation than by STN stimulation. On-L-dopa axial symptoms were clinically improved in the GPi but not the STN group. L-Dopa-induced dyskinesia was reduced by DBS at either site, although medication requirement was reduced only in the STN group. There were no serious intraoperative complications among patients in either group. CONCLUSION: Pallidal and STN stimulation appears to be safe and efficacious for the management of advanced PD. A larger study is needed to investigate further the differences in symptom response and the interaction of L-dopa with stimulation at either site.