Constantine Constantoyannis

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.

Deep brain stimulation for secondary dystonia: results in 8 patients

BackgroundDystonia is a medically intractable condition characterized by involuntary twisting movements and/or abnormal postures. Deep Brain Stimulation (DBS) has been used successfully in various forms of dystonia. In the present study, we report on eight patients with secondary dystonia, treated with DBS in our clinic.MethodEight patients (five males, three females) underwent DBS for secondary dystonia. The etiology of dystonia was cerebral palsy (n = 2), drug-induced (n = 1), post encephalitis (n = 2) and postanoxic dystonia (n = 3). The functional capacity was evaluated before and after surgery with the use of Burke-Fahn-Mardsen Dystonia Rating Scale (BFM scale), both movement and disability scale (MS and DS, respectively). The target for DBS was the globus pallidus internus (GPi) in 7 patients and in one patient, with postanoxic damaged pallidum, the ventralis oralis anterior (Voa) nucleus. Brain perfusion scintigraphy using Single Photon Emission Computed Tomography (SPECT) was performed in two separate studies for each patient, one in the “off-DBS” and the other in the “on-DBS” state.FindingsPostoperative both MS and DS scores were found to be significantly lower compared to preoperative scores (p = 0.018 and p = 0.039, respectively). Mean improvement rate after DBS was 41.4% (0 – 94.3) and 29.5% (0 – 84.2) in MS and DS scores, respectively. The SPECT Scan, during the “on-DBS” state, showed a decrease in regional cerebral blood flow (rCBF), compared to the “off-DBS” state.ConclusionsOur results seem promising in the field of secondary dystonia treatment. More studies with greater number of patients and longer follow-up periods are necessary in order to establish the role of DBS in the management of secondary dystonia. Finally, the significance of brain SPECT imaging in the investigation of dystonia and functional effects of DBS should be further evaluated.

Vegetative State and Minimally Conscious State: A Review of the Therapeutic Interventions

Background/Aims: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. Methods: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. Results: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. Conclusion: The treatments proposed for disorders of consciousness have not yet gained the level of ‘evidence-based treatments’; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.

A double-blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation

Background –  Tardive dyskinesia (TD) is a neurological disorder typically induced by long‐term exposure to neuroleptics. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) may represent a therapeutic alternative for TD, which is often resistant to conservative treatment.

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.

Cross-cultural study of symptom expectation following minor head injury in Canada and Greece

OBJECTIVES The purpose of the present study is to compare the frequency and nature of expected symptoms in Greece (a country where the chronic post-concussive syndrome is largely unknown) with that in Canada. METHODS A symptom checklist was administered to two subject groups selected from local companies in Patras, Greece, and Edmonton, Canada, respectively. Subjects were asked to imagine having suffered head trauma with loss of consciousness in a motor vehicle accident and to check off symptoms, they expected might arise from the injury. For symptoms they anticipated, they were asked to select the period of time they expected those symptoms to persist. RESULTS In both the Greek and Edmontonian groups, the pattern of symptoms anticipated closely resembled the acute symptoms commonly reported by accident victims with minor head injury. Yet, while many Edmontonians also anticipated symptoms to last months or years, very few Greek subjects selected any symptoms as being likely to persist in a chronic manner. CONCLUSIONS In Greece, despite the frequent experience of minor head injury in motor vehicle accidents, there is a very low rate of expectation of any chronic sequelae from such an injury, contrasting greatly with the response shown in Canada, where the prevalence of the chronic post-concussive syndrome is higher. Symptom expectation in some countries may be an important factor in the development of the chronic post-concussive syndrome.

The Role of Ghrelin, Neuropeptide Y and Leptin Peptides in Weight Gain after Deep Brain Stimulation for Parkinson’s Disease

Background: The exact mechanism of weight gain (WG) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson’s disease remains unknown. Objectives: To investigate a possible involvement of ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS. Methods: Twenty-three Parkinson patients were submitted for body composition measurements and blood sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa equivalent daily dose. Patients were clinically evaluated using the Unified Parkinson’s Disease Rating Scale. Results: Three months after surgery, a significant WG was observed (3.09 ± 5.00 kg; p = 0.007) with no further increase at 6 months. Three months postoperatively, NPY circulating levels increased significantly (p = 0.05), while the increase of ghrelin levels reached statistical significance at 6 months (p = 0.001). WG was significantly associated with changes of ghrelin and leptin levels at 3 and 6 months, respectively. Conclusions: STN DBS seems to temporarily dysregulate the hypothalamic secretion of NPY and ghrelin. The variation of weight may be attributed to an increased production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted through the increase of ghrelin levels, should be further studied.

Meige's syndrome: A cranial dystonia treated with bilateral pallidal deep brain stimulation

BACKGROUND Meiges syndrome is a rare form of segmental dystonia characterized by blepharospasm and oromandibular dystonia. Medical treatment including botulinum toxin injections usually present disappointing results. The experience on Deep Brain Stimulation (DBS) in the treatment of Meiges syndrome and other segmental dystonias is still limited. At the moment, only a few cases of pallidal DBS have been reported to improve this rare form of dystonia. CASE DESCRIPTION We report on a case of a woman with a 7-year history of Meiges syndrome, which rendered her functionally blind. The treatment with botulinum toxin injections failed to improve her symptoms, whereas stereotactic bilateral DBS of the pallidum led to a dramatic clinical improvement. Clinical assessment using the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS) in a double-blind manner, showed an improvement of 70% in the Movement score and 93.33% in the Disability score (84% reduction of the total score) on the 3 and 6 month follow-up. CONCLUSIONS Stereotactic pallidal DBS might be considered as a potential treatment in the management of Meiges syndrome.

Effects of subthalamic nucleus deep brain stimulation on sweating function in Parkinson's disease

PURPOSE To assess the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on the sweating function in patients with advanced Parkinsons disease (PD). METHODS Nineteen patients with idiopathic PD (mean age+/-SD, 61.58+/-9.47) were examined immediately before and 6 months after DBS. Each examination session included registration of autonomic symptoms by means of a semi-structural questionnaire and recording of sympathetic skin response (SSR) from both palms and one sole. The neurophysiological measurements were compared to those of 19 matched for sex and age healthy controls. RESULTS Six months post-DBS motor improvement was amounted to 65.9% and the daily levodopa equivalent dose was decreased by 36.4%. Post-operatively, dyshidrosis manifestations were reduced by 66.7% (pre-DBS sudomotor dysfunction in 47.4% of patients and sudomotor fluctuation in 57.1% of the above patients). There were no significant differences in-between pre- and post-DBS results of SSR study. However, the number of patients with at least one abnormal SSR pre-operative was reduced from 6 to 3 post-operative. No correlation was found between this neurophysiological finding and the change of clinical symptoms of hyperhidrosis or the DBS motor improvement. CONCLUSIONS These results, although based on a small sample, suggest that STN DBS, in addition to the effect to the mobility, might also favorably regulate sweat in idiopathic PD.