Marwan Hariz

Deep Brain Stimulation for Parkinson Disease: An Expert Consensus and Review of Key Issues

OBJECTIVE To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). DATA SOURCES AND STUDY SELECTION An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. DATA EXTRACTION AND SYNTHESIS A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. CONCLUSIONS (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.

High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinsons disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the β (13–30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local β activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP β activity for 12 s after the end of stimulation and a decrease in motor cortical–STN coherence in the β band over the same time period. The reduction in LFP β activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of β activity was associated with better task performance. These features were absent when power in the 5–12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological β activity in PD.

Adaptive Deep Brain Stimulation In Advanced Parkinson Disease

Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.

Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease†

We report the 5 to 6 year follow‐up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinsons disease (PD) patients. Thirty‐five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinsons Disease Rating Scale (UPDRS) assessed with a prospective cross‐over double‐blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off‐ and on‐medication states with and without stimulation, activities of daily living (ADL), anti‐PD medications, and dyskinesias. In double‐blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off‐stimulation, regardless of the sequence of stimulation. In open assessment, both STN‐ and GPi‐DBS significantly improved the off‐medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti‐PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long‐term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN‐DBS patients and fewer adverse events in the GPi‐DBS group.

Long-term efficacy of thalamic deep brain stimulation for tremor: double-blind assessments.

Thalamic deep brain stimulation (DBS) is proven to suppress tremor in Parkinsons disease (PD) and essential tremor (ET). However, there are few reports on its long‐term efficacy. We studied the efficacy of DBS at 2 years and 6–7 years after electrode implantations in the ventrointermediate nucleus of the thalamus in 39 patients (20 PD, 19 ET) with severe tremor. Twenty‐five of the patients completed the study. Evaluations were done in a double‐blind manner with the Unified Parkinsons Disease Rating Scale (UPDRS) and Essential Tremor Rating Scale (ETRS). DBS decreased tremor sum scores in PD (P < 0.025) compared to the preoperative baseline (median, 7; Q25–75, 6–9) both at 2 years (median, 2; Q25–75, 2–3.5; n = 16) and at 6 to 7 years (median, 2.5; Q25–75, 0.5–3; n = 12). Stimulation on improved tremor sum as well as sub scores (P < 0.025) compared to stimulation off conditions. In ET, thalamic stimulation improved (P < 0.025) kinetic and positional tremor at both follow‐up periods (n = 18 and n = 13, respectively) with significant improvements (P < 0.025) in hand‐function tests. PD but not ET patients showed a general disease progression. Stimulation parameters were remarkably stable over time. We conclude that high‐frequency electric thalamic stimulation can efficiently suppress severe tremor in PD and ET more than 6 years after permanent implantation of brain electrodes.

Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson’s disease

Both phenotype and treatment response vary in patients with Parkinsons disease. Anatomical and functional imaging studies suggest that individual symptoms may represent malfunction of different segregated networks running in parallel through the basal ganglia. In this study, we use a newly described, electrophysiological method to describe cortico-subthalamic networks in humans. We performed combined magnetoencephalographic and subthalamic local field potential recordings in thirteen patients with Parkinsons disease at rest. Two spatially and spectrally separated networks were identified. A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band, whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band. Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex. Subthalamic activity was predominantly led by activity in the cortex in both frequency bands. The cortical topography and frequencies involved in the alpha and beta networks suggest that these networks may be involved in attentional and executive, particularly motor planning, processes, respectively.

Deep brain stimulation: from neurology to psychiatry?

Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinsons disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ganglia-thalamocortical loops underlies these various disorders, which might now be amenable to DBS treatment.

Ventroposterolateral Pallidotomy Can Abolish All Parkinsonian Symptoms

Stereotactic ventroposterolateral pallidotomy in 46 parkinsonian patients resulted in a complete or almost complete and long-lasting relief of rigidity and hypokinesia in 91% of the patients. Good tremor effect was obtained in 80% of them. The L-dopa-induced dyskinesias, gait and speech improved in most patients. Complications were observed in 7 cases after 51 pallidotomies, i.e. 14% (partial homonymous hemianopia in 6 and transient dysphasia and facial weakness in 1). We believe that the good effect of surgery is based on interruption of some striopallidal or subthalamopallidal pathways.

Complications of deep brain stimulation surgery.

Currently, DBS is a commonly performed surgery for treatment of movement disorders, especially Parkinsons disease. Although nonablative and minimally invasive, this procedure may give rise to many complications and side effects, some of which are neither reversible nor adaptable. This study reviews the potential complications of DBS along the entire path of this procedure, from patient selection through the postoperative period. Although intraoperative complications such as paralysis and hematoma are rare, other serious complications due to the hardware, such as lead fracture, dislocation, and infection, are not uncommon. Complications or side effects as a result of chronic stimulation itself may be the most common. It is concluded that every member of the surgical team, including the referring neurologist, has an important role in the avoidance of such complications. Proper and careful patient selection, matching each patient to the specific DBS procedure appropriate for his/her symptom profile and suitable for his/her social and cognitive condition, along with experienced and careful intraoperative surgical routine, may be the best way to prevent the complications of DBS procedures.

Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review Clinical article

OBJECT Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue. METHODS The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery. RESULTS The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test). CONCLUSIONS Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit.