Pedunculopontine nucleus deep brain stimulation produces sustained improvement in primary progressive freezing of gait

Objective: To assess the efficacy of bilateral pedunculopontine nucleus (PPN) deep brain stimulation (DBS) as a treatment for primary progressive freezing of gait (PPFG). ------ ----- Methods: A patient with PPFG underwent bilateral PPN-DBS and was followed clinically for over 14 months. ------ ----- Results: The PPFG patient exhibited a robust improvement in gait and posture following PPN-DBS. When PPN stimulation was deactivated, postural stability and gait skills declined to pre-DBS levels, and fluoro-2-deoxy-d-glucose positron emission tomography revealed hypoactive cerebellar and brainstem regions, which significantly normalised when PPN stimulation was reactivated. ------ ----- Conclusions: This case demonstrates that the advantages of PPN-DBS may not be limited to addressing freezing of gait (FOG) in idiopathic Parkinson's disease. The PPN may also be an effective DBS target to address other forms of central gait failure.

Nutritional status in Parkinson's disease patients undergoing deep-brain stimulation surgery : a pilot study

People with Parkinson’s disease (PD) are at higher risk of malnutrition due to PD symptoms and pharmacotherapy side effects. Poorer outcomes are associated with higher amounts of weight loss (>5%) and lower levels of fat free mass. When pharmacotherapy is no longer effective for symptom control, deep-brain stimulation (DBS) surgery may be considered. People with PD scheduled for DBS surgery were recruited from a Brisbane neurological clinic (n=11 out of 16). The Scale for Outcomes of Parkinson’s disease –Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS), and a 3-day food diary were mailed to participants’ homes for completion prior to hospital admission. During admission, the Patient-Generated Subjective Global Assessment (PG-SGA), weight, height and body composition were assessed. Mean(±s.d.) PD duration from diagnosis and time since occurrence of PD symptoms was 9.0(±8.0) and 12(±8.8) years, respectively. Five participants reported unintentional weight loss (average loss of 15.6%). PD duration but not years since symptom onset significantly predicted PG-SGA scores (β=4.2, t(8)=2.7, p<.05). Both were positively correlated with PG-SGA score (r = .667, r=.587). On average, participants classified as well-nourished (SGA-A) (n=4) were younger, had shorter disease durations, lower PG-SGA scores, higher body mass (BMI) and fat free mass (FFMI) indices when compared to malnourished participants (SGA-B) (n=7). They also reported fewer non-motor symptoms on the SCOPA-AUT and MCAS. Three participants had previously received dietetic advice but not in relation to PD. These findings demonstrate that malnutrition remains unrecognised and untreated in this group despite unintentional weight loss and a high prevalence of malnutrition.

Nutritional status in Parkinson’s disease patients undergoing deep brain stimulation surgery : a pilot study

Objectives: People with Parkinson’s disease (PD) are at higher risk of malnutrition due to PD symptoms and pharmacotherapy side effects. When pharmacotherapy is no longer effective for symptom control, deep-brain stimulation (DBS) surgery may be considered. The aim of this study was to assess the nutritional status of people with PD who may be at higher risk of malnutrition related to unsatisfactory symptom management with optimised medical therapy. Design: This was an observational study using a convenience sample. Setting: Participants were seen during their hospital admission for their deep brain stimulation surgery. Participants: People with PD scheduled for DBS surgery were recruited from a Brisbane neurological clinic (n=15). Measurements: The Patient-Generated Subjective Global Assessment (PG-SGA), weight, height and body composition were assessed to determine nutritional status. Results: Six participants (40%) were classified as moderately malnourished (SGA-B). Eight participants (53%) reported previous unintentional weight loss (average loss of 13.3%). On average, participants classified as well-nourished (SGA-A) were younger, had shorter disease durations, lower PG-SGA scores, higher body mass (BMI) and fat free mass indices (FFMI) when compared to malnourished participants (SGA-B). Five participants had previously received dietetic advice but only one in relation to unintentional weight loss. Conclusion: Malnutrition remains unrecognised and untreated in this group despite unintentional weight loss and presence of nutrition impact symptoms. Improving nutritional status prior to surgery may improve surgical outcomes.

A head mountable deep brain stimulation device for laboratory animals

Deep brain stimulation has emerged as an effective method to treat certain medical conditions. Electrical charges are injected into the target tissue through a conducting electrode exciting the tissue. A variety of DBS devices have been developed based on different operation principles. Majority of these devices, however, employ complex circuitry and are bulky. In clinical trials, laboratory animals need to freely move around and perform activities whilst receiving brain stimulation for days. This paper presents a simple lightweight head mountable deep brain stimulation device that can be carried by the animal during the course of a clinical trial. The device produces continuous current pulses of specific characteristics. It employs passive charge balancing to minimize undesirable effects on the target tissue. The device is constructed and its performance tested.

Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's Disease : a review of the literature

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

Effect of deep brain stimulation on nucleus accumbens dopamine in a preclinicla model of antidepressant treatment-resistance

Background / Purpose: To determine if clinically effective deep brain stimulation (DBS) of neurosurgical targets for treatment-resistant depression regulates transient mesoaccumbens dopamine release in control and antidepressant-resistant animals (rats).

Main conclusion: In control rats, DBS stimulation of either the nucleus accumbens or infralimbic cortex significantly attenuated transient mesoaccumbens dopamine efflux, with nucleus accumbens DBS inducing a greater attenuation than infralimbic DBS. High frequency DBS of both targets induced long-term depression of transient accumbens dopamine release, lasting > 2hr post DBS.

Conversely, in antidepressant-resistant rats, infralimbic DBS significantly potentiated transient mesoaccumbens dopamine efflux during stimulation, but failed to induce long-lasting changes in neurotransmission. This suggests that a key mechanism of DBS for treatment-resistant depression is the regulation of dysfunctional mesoaccumbens dopamine neurotransmission.

Compact stacked planar inverted-F antenna for passive deep brain stimulation implants

A compact meandered three-layer stacked circular planar inverted-F antenna is designed and simulated at the UHF band (902.75 – 927.25 MHz) for passive deep brain stimulation implants. The UHF band is used because it offers small antenna size, and high data rate. The top and middle radiating layers are meandered, and low cost substrate and superstrate materials are used to limit the radius and height of the antenna to 5 mm and 1.64 mm, respectively. A dielectric substrate of FR-4 of εr= 4.7 and δ= 0.018, and a biocompatible superstrate of silicone of er= 3.7 and d= 0.003 with thickness of 0.2 mm are used in the design. The resonance frequency of the proposed antenna is 918 MHz with a bandwidth of 24 MHz at return loss of −10 dB in free space. The antenna parameter such as 3D gain pattern of the designed antenna within a skin-tissue model is evaluated by using the finite element method. The compactness, wide bandwidth, round shape, and stable characteristics in skin make this antenna suitable for DBS. The feasibility of the wireless power transmission to the implant in the human head is also examined.

Multi-layer implantable antenna for closed loop deep brain stimulation system

A multi-layer circular planar inverted-F antenna is designed and simulated at the industrial, scientific, and medical (ISM) band of 915 MHz for closed loop deep brain stimulation implant. The ISM band is considered due to the capabilities of small antenna size, high data rate, and long transmission range. In the proposed four-layer antenna, the top three radiating layers are meandered, and a high permittivity substrate and superstrate materials are used to limit the radius and the height of the antenna to 3.5 mm and 2.2 mm, respectively. The bottom layer works as a ground plate. The Roger RO3210 of εr = 10.2 and δ = 0.003 is used as a dielectric substrate and superstrate. The resonance frequency of the proposed antenna is 915 MHz with a bandwidth of 12 MHz at the return loss of -10 dB in free space. The stacked layered structure reduces the antenna size, and the circular shape makes it easily implantable into the human head. The antenna parameters (e.g. 3D gain pattern), SAR value, and electric field distribution within a six layers spherical head model are evaluated by using the finite element method (FEM). The feasibility of the wireless transmission of power, control and command signal to the implant in the human head is also examined. © 2012 IEEE.

A low power micro deep brain stimulation device for murine preclinical research

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

Closed loop deep brain stimulation: an evolving technology

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Development of a compact rectenna for wireless powering of a head-mountable deep brain stimulation device

Design of a rectangular spiral planar inverted-F antenna (PIFA) at 915 MHz for wireless power transmission applications is proposed. The antenna and rectifying circuitry form a rectenna, which can produce dc power from a distant radio frequency energy transmitter. The generated dc power is used to operate a low-power deep brain stimulation pulse generator. The proposed antenna has the dimensions of 10 mm × 12.5 mm × 1.5 mm and resonance frequency of 915 MHz with a measured bandwidth of 15 MHz at return loss of -10 dB. A dielectric substrate of FR-4 of εr = 4.8 and δ = 0.015 with thickness of 1.5 mm is used for both antenna and rectifier circuit simulation and fabrication because of its availability and low cost. An L-section impedance matching circuit is used between the PIFA and voltage doubler rectifier. The impedance matching circuit also works as a low-pass filter for elimination of higher order harmonics. Maximum dc voltage at the rectenna output is 7.5 V in free space and this rectenna can drive a deep brain stimulation pulse generator at a distance of 30 cm from a radio frequency energy transmitter, which transmits power of 26.77 dBm.