Biomedical subjects

Oren Sagher

Publications and source records attributed to Oren Sagher.

6 recordsLinked to original sources

PubMed2005

Deep brain stimulation for refractory obsessive-compulsive disorder.

BACKGROUND: Neurosurgery (anterior capsulotomy) has been beneficial to many patients with debilitating, refractory obsessive-compulsive disorder (OCD), but the irreversibility of the procedure is an important limitation to its use. Nondestructive, electrical stimulation (deep brain stimulation; DBS) has proven an effective alternative to ablative surgery for neurological indications, suggesting potential utility in place of capsulotomy for OCD. METHODS: The effects of DBS for OCD were examined in four patients in a short-term, blinded, on-off design and long-term, open follow-up. The patients had incapacitating illness, refractory to standard treatments. Hardware developed for movement disorder treatment was surgically implanted, with leads placed bilaterally in the anterior limbs of their internal capsules. Patients received stimulation in a randomized "on-off" sequence of four 3-week blocks. Ongoing, open stimulation was continued in consenting patients after the controlled trial. RESULTS: Patients tolerated DBS well. Dramatic benefits to mood, anxiety, and OCD symptoms were seen in one patient during blinded study and open, long-term follow-up. A second patient showed moderate benefit during open follow-up. CONCLUSIONS: It appears that DBS has potential value for treating refractory psychiatric disorders, but additional development work is needed before the procedure is utilized outside of carefully controlled research protocols.

Adult↗

PubMed2004

Evidence for a central pathway in the cerebrovascular effects of spinal cord stimulation.

OBJECTIVE: Cervical spinal cord stimulation (SCS) augments cerebral blood flow (CBF) in a number of animal models. The mechanisms underlying the cerebrovascular effects of SCS are not yet well delineated. In this study, we analyzed two alternative pathways in CBF alterations induced by SCS in rats, one involving direct modulation of sympathetic outflow and the other through central vasomotor influence. METHODS: Resection of the superior cervical ganglion (SCG), SCS alone, or SCS after SCG removal was performed in adult male Sprague-Dawley rats. CBF was measured with (14)C-inosine monophosphate radiotracer studies. In another set of experiments, SCS was performed after spinalization at the cervicomedullary junction or after laminectomy alone. RESULTS: Baseline CBF in the SCG removal group was 71 +/- 8 ml/100 g/min, similar to controls. SCS alone significantly increased blood flow to 100 +/- 10 ml/100 g/min (P < 0.05). Animals that underwent SCS after SCG removal demonstrated a similar robust augmentation in CBF. SCS-induced changes in CBF were completely attenuated by spinalization. CONCLUSION: The profound effects of spinal cord transection on SCS-induced CBF augmentation, together with the lack of effect of surgical sympathectomy, suggest that the mechanisms underlying the effects of SCS involve central influences rather than cervical sympathetic outflow. These findings suggest a possible role for brainstem vasomotor centers in the cerebrovascular effects of SCS.

Animals↗

PubMed2003

Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients.

PURPOSE: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. METHODS: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. RESULTS: Baseline PSGs: One of 16 patients had an apnea-hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. CONCLUSIONS: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.

Adult↗

PubMed2003

Spinal cord stimulation reducing infarct volume in a model of focal cerebral ischemia in rats.

OBJECT: The authors previously showed that spinal cord stimulation (SCS) increases cerebral blood flow in rats, indicating that this technique may be useful in the treatment of focal cerebral ischemia. In the present study, the neuroprotective potential of SCS in the setting of middle cerebral artery occlusion (MCAO) was investigated. METHODS: The authors induced permanent, focal cerebral ischemia by using either suture-induced occlusion or direct division of the MCA in Sprague-Dawley rats. Electrical stimulation of the cervical spinal cord was performed during cerebral ischemia. Cerebral blood flow was assessed using both laser Doppler flowmetry (LDF) and quantitative radiotracer analysis. Stroke volumes were analyzed after 6 hours of ischemia. Spinal cord stimulation resulted in a 52.7 +/- 13.3% increase in LDF values (nine animals). Following MCAO, LDF values decreased by 64.1 +/- 3.6% from baseline values (10 animals). Spinal cord stimulation subsequently increased LDF values to 30.9 +/- 13.5% below original baseline values. These findings were corroborated using radiotracer studies. Spinal cord stimulation in the setting of transcranial MCAO significantly reduced stroke volumes as well (from 203 +/- 33 mm3 [control] to 32 +/- 8 mm3 [MCAO plus SCS], seven animals in each group, p < 0.001). Similarly, after suture-induced MCAO, SCS reduced stroke volumes (from 307 +/- 29 mm3 [control] to 78 +/- 22 mm3 [MCAO plus SCS], 10 animals in each group, p < 0.001). CONCLUSIONS: A strategy of performing SCS for the prevention of critical ischemia is feasible and may have the potential for the treatment and prevention of stroke.

Animals↗

PubMed2003

Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord stimulation.

OBJECT: Cervical spinal cord stimulation (SCS) has been found to augment cerebral blood flow (CBF) in a number of animal models, although the mechanisms underlying the cerebrovascular effects of SCS are poorly described. In this study, the authors examined the role of sympathetic tone in CBF alterations induced by SCS in rats. METHODS: Spinal cord stimulation was performed at three intervals while CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5, 10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2 mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously before the second stimulation. Changes in LDF values due to SCS were recorded as the percentage of change from baseline values and were analyzed. In vehicle-treated animals, SCS increased LDF values by 60.5 +/- 1.8% over baseline, whereas both high-dose hexamethonium and prazosin completely abolished the SCS-induced increases in LDF values. On the other hand, LDF values increased by 50.9 +/- 4% and 61.4 +/- 4% after SCS in the presence of idazoxan or propranolol, respectively. Administration of sympathetic nervous system blockers resulted in a variable degree of systemic hypotension as well. Nevertheless, induced hypotension without sympathetic blockade had only a minimal effect on SCS-induced augmentation of LDF values (48 +/- 1.4% over baseline). CONCLUSIONS: Sympathetic tone plays a major role in SCS-induced increases in CBF. This effect seems to be mediated primarily by alpha1-adrenergic receptors. Systemic hypotension alone cannot explain the effects of sympathetic blockade on the SCS response. Clinical use of SCS in the treatment of cerebral ischemia should take alpha1-adrenergic receptor sympathetic tone into account.

Adrenergic alpha-Antagonists↗

PubMed2002

Management of intrathecal catheter-tip inflammatory masses: a consensus statement.

OBJECTIVES: In a companion article, we synthesized current clinical and preclinical data to formulate hypotheses about the etiology of drug administration catheter-tip inflammatory masses. In this article, we communicate our recommendations for the detection, treatment, mitigation, and prevention of such masses. METHODS: We reviewed published and unpublished case reports and our own experiences to find methods to diagnose and treat catheter-tip inflammatory masses in a manner that minimized adverse neurological sequelae. We also formulated hypotheses about theoretical ways to mitigate, and possibly, prevent the formation of such masses. RESULTS: Human cases have occurred only in patients with chronic pain who received intrathecal opioid drugs, alone or mixed with other drugs, or in patients who received agents that were not labeled for long-term intrathecal use. Most patients had noncancer pain owing to their large representation among the population with implanted pumps. Such patients also had a longer life expectancy and exposure to intrathecal drugs, and they received higher daily doses than patients with cancer pain. Clues to diagnosis included the loss of analgesic drug effects accompanied by new, gradually progressive neurological symptoms and signs. When a mass was diagnosed before it filled the spinal canal or before it caused severe neurological symptoms, open surgery to remove the mass often was not required. Anecdotal reports and the authors' experiences suggest that cessation of drug administration through the affected catheter was followed by shrinkage or disappearance of the mass over a period of 2-5 months. CONCLUSIONS: Attentive follow-up and maintenance of an index of suspicion should permit timely diagnosis, minimally invasive treatment, and avoidance of neurological injury from catheter-tip inflammatory masses. Whenever it is feasible, positioning the catheter in the lumbar thecal sac and/or keeping the daily intrathecal opioid dose as low as possible for as long possible may mitigate the seriousness, and perhaps, reduce the incidence of such inflammatory masses.

Journal Article↗