Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects.

BACKGROUND: Major depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD). OBJECTIVE: We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD. METHODS: In a multicenter, double blind study, 331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA current, 130 µs pulse width), MEDIUM (0.5-1.0 mA, 250 µs), or HIGH (1.25-1.5 mA, 250 µs). A highly treatment-resistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically warranted. Assessments then continued until Week 50 (end of long-term phase). RESULTS: VNS therapy was well tolerated. During the acute phase, all groups showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose. CONCLUSIONS: TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline, and the effect was durable over 1 year. Higher electrical dose parameters were associated with response durability.

Marked improvement of heart failure upon adequate titration of continuous positive airway pressure in a patient with obstructive sleep apnea.

Sleep disordered breathing (SDB) is frequently present in heart failure (HF), and it may take the form of obstructive (OSA) and central (CSA) sleep apnea. The use of continuous positive airway pressure (CPAP) in patients with OSA and HF is associated with an improved neuroendocrine profile and cardiac function. The degree of upper airway obstruction and the airway closing pressure (and the PAP pressure used to relieve it) may all be highly variable in a setting of uncontrolled HF, mostly due to variable airway oedema. We present a case of a man with HF whose cardiac symptoms radically improved after adequate treatment of his OSA with an auto-adjusting PAP device.

Successful bilateral subthalamic nucleus stimulation for segmental dystonia after unilateral pallidotomy.

BACKGROUND: Several subcortical structures have been targeted for surgical treatment of dystonia, including motor thalamus, internal segment of globus pallidus (GPi), and more recently, the subthalamic nucleus (STN). Deep brain stimulation of GPi is currently the preferred surgical treatment, but it is unclear if targeting other structures would yield better results. Patients who have already had a pallidotomy yet continue to experience dystonic symptoms may be limited in further treatment options. METHODS: A patient with medically intractable, segmental, early-onset, primary torsion dystonia presented for surgical consultation after exhausting nearly all treatment options. Medications, botulinum toxin injections, cervical denervation surgery, and left-sided pallidotomy failed to give adequate relief. The patient was implanted with STN stimulating leads bilaterally according to standard procedures. RESULTS: The patient received a 36% improvement in dystonic symptoms as measured by several dystonia rating scales. These benefits persisted for 2 years after surgery despite several hardware-related complications, and the patient reported being very satisfied with the outcome. CONCLUSION: This result supports the efficacy of STN deep brain stimulation in dystonia patients, even those with prior pallidotomy.

Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson's disease.

Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

Lethal pontine hemorrhage in postpartum syndrome of hemolysis, elevated liver enzyme levels, and low platelet count.

BACKGROUND: HELLP syndrome (a combination of hemolysis, elevated liver enzyme levels, and low platelet count) is a severe variant of preeclampsia that generally occurs before delivery but can occur post partum. This syndrome is more common than eclampsia and frequently leads to devastating neurological consequences such as intracerebral hemorrhage. OBJECTIVE: Although mentioned in the obstetric literature, there has been sparse reporting in the neurology literature specifically regarding intracerebral hemorrhage in HELLP syndrome. We illustrate such a case and review the existing literature regarding this severe complication. SETTING: Obstetric unit at an academic medical center. PATIENT: A 34-year-old primigravida experienced a pontine hemorrhage and subsequent respiratory arrest 22 hours after a normal delivery. This hemorrhage occurred 7 hours after the sudden onset of hypertension, severe headache, and intermittent abdominal pain. RESULTS: Laboratory and postmortem evidence suggested HELLP syndrome with disseminated intravascular coagulation as the cause of her intracerebral hemorrhage. CONCLUSIONS: Our case suggests the importance of the neurology consultant's familiarity with HELLP syndrome and the need for thorough laboratory testing and close monitoring in the puerperal patient with headache and hypertension.

Carotid endarterectomy with routine electroencephalography and selective shunting: Influence of contralateral internal carotid artery occlusion and utility in prevention of perioperative strokes.

OBJECTIVE: Carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia during carotid clamping, particularly in the face of contralateral internal carotid artery (ICA) occlusion. We examined the results of CEA with continuous electroencephalography in patients without and with contralateral ICA occlusion. DESIGN AND SETTING: We reviewed 564 primary CEAs with routine electroencephalography and general anesthesia performed between April 1, 1989, and March 31, 1999, in a community teaching medical center. Main outcome measures were perioperative stroke, temporary lateralizing neurologic deficit, and death. Shunts were placed primarily for significant electroencephalographic changes after carotid clamping but also selectively for contralateral ICA occlusion, prior stroke, or surgeon choice. CEA was performed for asymptomatic disease in 35% of cases. RESULTS: Significant electroencephalographic changes occurred in 16% versus 39% (P <.001) and shunts were placed in 13% versus 55% (P <.001) of patients with patent (n = 507) versus occluded contralateral ICA (n = 57), respectively. The fraction of CEAs with significant electroencephalographic changes during clamping was stable, but shunt use declined slightly over time as our confidence in electroencephalography increased. Patches were placed more often (86% versus 65%; P =.002), but other operative details were similar when the contralateral ICA was occluded. Five early (30 days) strokes (0.9%) and eight early temporary postoperative neurologic events (1.4%) occurred, all ipsilateral to CEA and all after the patient left the operating room with none in patients with contralateral ICA occlusion. Two perioperative deaths occurred, one in a patient without and one in a patient with contralateral ICA occlusion. Neither of these deaths was related to ipsilateral stroke. No increase in stroke rate with decreased shunt use over time was seen. CONCLUSION: Routine use of electroencephalography was associated with apparent complete elimination of intraoperative strokes and less than 1% risk of perioperative strokes. These observations appear to be true even in the face of contralateral ICA occlusion. Electroencephalography is a sensitive detector of cerebral ischemia and a valuable tool for determination of need for shunting during CEA. Surgeons should consider routine use of electroencephalography and selective shunting for significant electroencephalographic changes with clamping.