Christopher R. Honey

A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression.

OBJECT Deep brain stimulation (DBS) has been recently investigated as a treatment for major depression. One of the proposed targets for this application is the subcallosal cingulate gyrus (SCG). To date, promising results after SCG DBS have been reported by a single center. In the present study the authors investigated whether these findings may be replicated at different institutions. They conducted a 3-center prospective open-label trial of SCG DBS for 12 months in patients with treatment-resistant depression. METHODS Twenty-one patients underwent implantation of bilateral SCG electrodes. The authors examined the reduction in Hamilton Rating Scale for Depression (HRSD-17) score from baseline (RESP50). RESULTS Patients treated with SCG DBS had an RESP50 of 57% at 1 month, 48% at 6 months, and 29% at 12 months. The response rate after 12 months of DBS, however, increased to 62% when defined as a reduction in the baseline HRSD-17 of 40% or more. Reductions in depressive symptomatology were associated with amelioration in disease severity in patients who responded to surgery. CONCLUSIONS Overall, findings from this study corroborate the results of previous reports showing that outcome of SCG DBS may be replicated across centers.

Medial forebrain bundle stimulation as a pathophysiological mechanism for hypomania in subthalamic nucleus deep brain stimulation for Parkinson's disease.

OBJECTIVEHypomania accounts for approximately 4% to 13% of psychotropic adverse events during subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinsons disease. Diffusion of current into the inferior and medial “limbic” STN is often reported to be the cause. We suggest a different explanation, in which the coactivation of the medial forebrain bundle (MFB), outside the STN, leads to hypomania during STN DBS. METHODSSix patients with advanced Parkinsons disease (age, 54 ± 11 years) underwent bilateral STN DBS surgery. Preoperative diffusion tensor imaging scans for fiber tracking of the MFB were conducted on a 3T magnetic resonance imaging scanner. After implantation, the electrode positions were determined with computed tomography and integrated in a diffusion tensor imaging software environment. RESULTSThe medial STN was shown to send tributaries to the MFB using it as a pathway to connect to the reward circuitry. One patient, who had a transient, stimulation-induced acute hypomanic episode, showed a direct contact between 1 active electrode contact and these putative limbic STN tributaries to the MFB unilaterally on the left. In 5 asymptomatic patients, the active contacts were between 2.9 and 7.5 mm distant from the MFB or its limbic STN tributaries. CONCLUSIONWe hypothesize that STN DBS-induced reversible acute hypomania might be elicited by inadvertent and unilateral coactivation of putative limbic STN tributaries to the MFB. These findings may provide insight into the neural pathways of hypomania and may facilitate future investigations of the pathophysiology of mood disorders.

Hypomania as an adverse effect of subthalamic nucleus stimulation: report of two cases

SummaryMania following subthalamic nucleus (STN) deep brain stimulation (DBS) is well described and obvious to both the patient and their physician. The authors describe two patients who developed hypomania following STN-DBS but were unaware of their mood disturbance. Two Parkinson’s patients with no previous mood disorders received bilateral STN electrodes. Both experienced dramatic improvement in their motor function and neither complained of any side effects. Their families reported detrimental hypomanic behaviour. Readjusting the stimulation parameters resolved the hypomania with continued motor benefits. The authors draw attention to potential adverse effects of STN-DBS that might be neglected by patients.

Reducing hardware-related complications of deep brain stimulation

BACKGROUND Deep brain stimulation (DBS) is used increasingly worldwide for the treatment of Parkinsons disease, dystonia, tremor and pain. As with any implanted system, however, DBS introduces a new series of problems related to its hardware. Infection, malfunction and lead migration or fracture may increase patient morbidity and should be considered when evaluating the risk/benefit ratio of this therapy. This work highlights several factors felt to increase DBS hardware complications. METHODS The authors undertook a prospective analysis of their patients receiving this therapy in two Canadian centres, over a four-year period. RESULTS One hundred and forty-four patients received 204 permanent electrode implants. The average follow-up duration was 24 months. Complications related to the DBS hardware were seen in 11 patients (7.6%). There were two lead fractures (1.4%) and nine infections (6.2%) including two erosions (1.4%). There was a significantly greater risk of infection in patients who underwent staged procedures with externalization. In patients with straight scalp incisions, the rate of infection was higher than that seen with curved incisions. CONCLUSION Hardware complications were not common. A period of externalization of the electrodes for a stimulation trial was associated with an increased infection rate. It is also possible that a straight scalp incision instead of curvilinear incision may lead to an increase in the rate of infection. With a clear understanding of the accepted DBS device indications and their potential complications, patients may make a truly informed decision about DBS technology.

Expectation and the placebo effect in Parkinson's disease patients with subthalamic nucleus deep brain stimulation

To determine whether the degree to which a patient with Parkinsons disease expects therapeutic benefit from subthalamic nucleus–deep brain stimulation (STN‐DBS) influences the magnitude of his or her improved motor response, 10 patients with idiopathic Parkinsons and bilateral STN‐DBS were tested after a 12‐hour period off medication and stimulation. Four consecutive UPDRS III scores were performed in the following conditions: (a) stimulation OFF, patient aware; (b) stimulation OFF, patient blind; (c) stimulation ON, patient aware; and (d) stimulation ON, patient blind. Statistical significance (P = 0.0001) was observed when comparing main effect ON versus OFF (mean ON: 32.55; mean OFF: 49.15). When the stimulation was OFF, patients aware of this condition had higher UPDRS motor scores than when they were blinded (mean: 50.7 vs. 47.6). With the stimulation ON, UPDRS motor scores were lower when the patients were aware of the stimulation compared with when they were blinded (mean: 30.6 vs. 34.5). The interaction between these levels was significant (P = 0.049). This variation was important for bradykinesia and was not significant for tremor and rigidity. The authors conclude that the information about the condition of the stimulation enhanced the final clinical effect in opposite directions. The results presented support the role of expectation and placebo effects in STN‐DBS in Parkinsons disease patients.

The treatment of trigeminal neuralgia in patients with multiple sclerosis using percutaneous radiofrequency rhizotomy

BACKGROUND Trigeminal neuralgia (TN) has a higher incidence among patients with multiple sclerosis (MS) than in the general population. This cohort of MS patients with TN presents a series of management challenges including poor tolerance of antineuralgic medications and occasional bilateral presentation. We analyzed our surgical series of MS patients presenting with TN who were treated with percutaneous radiofrequency rhizotomy to estimate the success, failure and recurrence rate of this procedure for those patients. METHODS Surgical reports were retrospectively reviewed between the years 1996-2000. Patients with MS and TN who received a percutaneous rhizotomy during that time were included in the study and followed until the end of 2002. Data regarding age, sex, duration of MS and pain, response to medical treatment, pain distribution and surgical outcome were evaluated. RESULTS There were thirteen patients with MS and medically refractory TN treated with percutaneous radiofrequency rhizotomy. The average age at diagnosis for MS was 41 with TN beginning an average of eight years later. Following rhizotomy, complete pain relief without the need for any medication was achieved in 81% of the patients. The addition of medications resulted in pain control in the remaining patients. During a mean follow-up period of 52 months, there was a 50% recurrence rate. There were no complications related to the procedure and the associated facial numbness was well-tolerated. CONCLUSIONS Percutaneous radiofrequency rhizotomy is a safe and effective method for the treatment of TN in patients with MS. The unique susceptibility of this cohort to the side effects of antineuralgic medications may require early consideration of rhizotomy.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial

BACKGROUND Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. METHODS Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. INTERPRETATION This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. FUNDING Abbott (previously St Jude Medical).

The importance of autonomic symptoms in trigeminal neuralgia. Clinical article.

OBJECT Autonomic symptoms can occur in association with the facial pain of trigeminal neuralgia (TN). The distinction between first division (V1) TN and trigeminal autonomic cephalgias, particularly short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), can be difficult. The goal in this study was to investigate the frequency of autonomic symptoms with TN and to determine their effect on surgical outcome. METHODS The authors sent questionnaires and reviewed the records of 92 patients who underwent surgical procedures for TN to obtain visual analog scale scores for pain before and after surgery and to determine the location of the pain and the presence of autonomic symptoms. RESULTS Sixty-seven percent of patients had at least 1 autonomic symptom, and 14% had 4 or more autonomic symptoms associated with their pain. With V1 pain, the most common autonomic symptoms were conjunctival injection, ptosis, and excessive tearing. With pain involving the second division (V2), facial swelling was the most common autonomic symptom. Excessive salivation occurred most often when the pain involved the third division (V3). In patients who underwent microvascular decompression (MVD), visual analog scores for pain showed significantly greater improvement postoperatively in those who had no preoperative autonomic symptoms than in those who reported autonomic symptoms. There was also a significantly greater number of patients who were pain free postoperatively in the group without autonomic symptoms. There were 3 patients with V1 facial pain associated with conjunctival injection and tearing who, in retrospect, fulfilled all the current diagnostic criteria for SUNCT. These patients underwent MVD, during which a vessel was found to compress the trigeminal nerve. Postoperatively, the 3 patients experienced complete and long-lasting pain relief. CONCLUSIONS The presence of autonomic symptoms in TN correlated with a worse prognosis for pain relief after MVD. First division TN with autonomic symptoms can present identically to SUNCT but can respond to MVD if there is a compressive vessel. Neurosurgeons should be aware of SUNCT, especially in patients with V1 TN and autonomic symptoms, to ensure that all potential medical therapies have been tried prior to surgical treatment.

Tract Identification by Novel MRI Signal Changes following Stereotactic Anterior Capsulotomy

Background: Five patients underwent magnetic resonance imaging (MRI) following MRI-guided stereotactic bilateral anterior capsulotomy to detect lesion-related anatomic changes. Methods: Five disabled and treatment-resistant patients with major depression (n = 4) and obsessive-compulsive disorder (n = 1) underwent stereotactic bilateral anterior capsulotomy. All patients had postoperative MRI at 2 months and at 1–4 years after surgery. An additional patient who had a pure motor deficit following a spontaneous basal ganglia hemorrhagic stroke was imaged as a comparator. Results: The 2-month postcapsulotomy MRI showed a previously undescribed increase in T1-weighted signal within similar neural pathways for each patient. These pathways showed no changes in T2-weighted or fluid-attenuated inversion recovery sequences. The signal changes are different from the expected changes associated with anterograde Wallerian degeneration and identify retrograde changes in the proximal segment of the interrupted axon. Conclusion: Previously undescribed T1-weighted signal alterations following stereotactic surgery identify retrograde non-Wallerian changes in interrupted axons and provide a new method in identifying and tracing lesioned pathways.

Neuroepithelial cysts presenting with movement disorders: two cases.

BACKGROUND The authors present two cases of movement disorders caused by neuroepithelial cysts and highlight their management. Neuroepithelial cysts are ependymal or epithelial lined fluid collections of unknown etiology within the central nervous system parenchyma with no obvious ventricular or subarachnoid connection. Most cysts are asymptomatic, however, some present with seizures, mass effect, or rarely with movement disorders. CASE REPORTS The first patient, a 27-year-old female, presented with progressive weakness, dystonic posturing, tremor, ballismus and choreoathetotic movements of her right upper extremity. Her symptoms improved after stereotactic drainage of a neuroepithelial cyst in her basal ganglia but recurred within a year. The second case, a 56-year-old female, presented with diplopia, nystagmus, gait imbalance and hemiparesis. Her symptoms improved after stereotactic drainage of a midbrain neuroepithelial cyst. The cyst reaccumulated over the next few years and she became symptomatic with left arm tremor and facial weakness. Aspiration was again performed with symptomatic improvement for nine months. Her tremor recurred and a cyst access device was placed stereotactically. She improved and has remained stable for over a year. CONCLUSION Simple stereotactic drainage of neuroepithelial cysts has a high recurrence rate. The authors recommend considering placement of a drainage device to facilitate aspiration of the cyst fluid during follow-up, if needed.