Search Results for: deep brain stimulation

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Is deep brain stimulation neuroprotective if applied early in the course of Parkinson’s Disease?

dbs221

This is an important question. until now all medication for Parkinson’s disease relieved the symptoms of this disease for a while. The medication couldn’t prevent the progression of the disease resulting in lack of efficacy of the medication. Increasing the dosage until side-effects or adding another therapeutic temporarily resolved the symptoms until the progression again decreased their efficacy.

Hundreds of putative neuroprotective agents have been tested in clinical trials over the past two decades, but none of these agents has been successful at preventing the progression of PD.

In a recent Viewpoint in Nature Clinical Practice Neurology the authors claim that:

We believe that DBS will be the first therapy proven to slow PD progression, and that it must be applied in the earliest stages of the disease to have such an effect.

They base their opinion on the results of animal research. From these animal models it was learned that high frequency deep brain stimulation can be neuroprotective. The animals received DBS during ongoing neurodegeneration, which more accurately represents clinical practice and DBS at high frequency has inhibitory effects on this neurodegeneration.

Results from clinical trials are contradictory. In some trials no significant clinical deterioration during 4 years of DBS therapy could be found, while many trials have noted clinically and statistically significant deterioration of motor symptoms after initiation of DBS therapy.

The authors have stron arguments for these conflicting results:

First, continued functional decline does not eliminate the possibility of positive disease modification—it only eliminates the possibility that DBS might result in a complete halt in progression. Furthermore, none of the studies so far has included a control group that was treated with standard drug therapy, and, thus, progression rates between the two groups have not been compared.

An additional limitation is that all studies to date have been in patients with features of advanced PD, including motor complications of therapy. Currently, patients do not receive DBS therapy until they have developed intractable symptoms and motor complications of therapy; electrode implantation both in clinical trials and in standard of care takes place at an average of 11 years after diagnosis, at which point considerable cell death has occurred, and potentially neuroprotective strategies are unlikely to demonstrate a clear benefit.

The authors have started a pilot clinical trial (ClinicalTrials.gov identifier NCT00282152) to study the neuroprotective effects of DBS in Parkinson’s Disease. They will test the hypothesis that DBS slows the progression of early stage PD.

You can read some more about this trial on Viewpoint in Nature Clinical Practice Neurology.

Hope they will succeed in confirming their hypothesis for such a debilitating disease.

ResearchBlogging.org
Charles, P., Gill, C., Davis, T., Konrad, P., & Benabid, A. (2008). Is deep brain stimulation neuroprotective if applied early in the course of PD? Nature Clinical Practice Neurology, 4 (8), 424-426 DOI: 10.1038/ncpneuro0848

 

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Deep Brain Stimulation for Treatment Resistant depression

deep brain stimulation

New data are being published about deep brain stimulation and treatment resistant depression. Especially longer follow up is of importance. In recent published research about deep brain stimulation for treatment resistant depression, six months after surgery, 60% of patients were responders and 35% met criteria for remission, benefits that were largely maintained at 12 months. Moreover, there was no significant loss of effect requiring dose adjustments over time. So once a good stimulus dose, high change that it will remain that way over a long period of time.

With DBS for TRD symptoms typically return rapidly if the device is turned off, if a lead breaks, or if the battery dies. From other areas of neuroscience it is learned that intermittent stimulation of brain areas could provoke longer-term neuroplastic brain changes in these circuits (LTD or LTP), thus moving brain circuits into a more resilient and healthy mode, making symptom recurrence less likely if stimulation is stopped or withdrawn. Exciting trials with intermittent DBS are underway testing these new hypotheses and probably after some time it is probable that the devices can be switched of for good or until recurrence.

In this study twenty patients with TRD underwent serial assessments before and after Subcallosal Cingulate Gyrus DBS. They determined the percentage of patients who achieved a response (50% or greater reduction in the 17-item Hamilton Rating Scale for Depression or remission (scores of 7 or less) after surgery. They also examined changes in brain metabolism associated with DBS, using positron emission tomography.

limbischesysteem

Results from PET scans. The results indicate that SCG DBS produces striking changes in cognitive and limbic brain areas and they provide a biological basis for the observed improvements in depression in these patients. There is a direct activation of the white matter at target that can lead to either metabolic activation or inhibition in distinct remote brain areas. Antidepressant medications, cognitive behavioral therapy, and electroconvulsive therapy produce similar changes in many of these same brain regions.

Adverse Effect

  • Wound Infection and Hardware removal 3 patients
  • Reinsertion of DBS Hardware 1 patient
  • Wound Infection Managed with Antibiotics Alone 1 patient
  • Perioperative Seizure 1 patient
  • Worsening Mood/Irritability 2 patients
  • Perioperative Headache 4 patients
  • Pain at Pulse Generator Site 1 patient
  • No Adverse Effects 7 patients

Limitation of this study is the open label assessment of outcomes

DBS is tried with many more indications. Parkinson’s disease and Obsessive compulsive disorder are the most well known. The Food and Drug Administration has approved deep brain stimulation as a therapy for Obsessive compulsive disorder. In case reports DBS is also tried with addiction, Alzheimers disease, Tourette’s syndrom and even coma. This are all case reports, not evidence based. For a recent overview and intervied about DBS for different indications please read at the Chigaco Tribune, with thanks to @dsaarinen for reminding me on the use of DBS for Alzheimer’s disease.

For a short but very informative video:Deep Brain stimulation for Parkinson’s disease

ResearchBlogging.org
A LOZANO, H MAYBERG, P GIACOBBE, C HAMANI, R CRADDOCK, S KENNEDY (2008). Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression Biological Psychiatry, 64 (6), 461-467 DOI: 10.1016/j.biopsych.2008.05.034

 

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Hands on Experience with Deep Brain Stimulation for Depression

dbs

Recently I found a hands on experience blog for someone undergoing deep brain stimulation for parkinson’s disease. Now another blogger who blogs about the participation in a trial: 278-005 DBS Trial. This trial is done in St. Jude’s. It’s the DBS study for TRD (treatment resistant depression). Surgery is scheduled for next week.

The trial is a blind study – which means I won’t know if the gizmo they give me is turned on or not. At least for 6 months I won’t know. from what I understand 2 out of 3 of the gizmos implanted will be turned on. The other 1/3 won’t be turned on for 6 months and NONE of us will know which one we are.

 

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Hands on Blog For Deep Brain Stimulation

deep brain stimulation

There is a new blog with the written hands on experience of undergoing deep brain stimulation surgery: Focus on a Cure’s Deep Brain Stimulation (DBS) Journal


This blog is created in the hopes that my experiences will give others inspiration to take a risk and have the courage to face the unknown in order to accomplish the impossible as others have done for me.
Stay Focused,

Incredible good insight and information about the whole procedure, especially the whole process before deciding to undergo the procedure.

One thing I was surprised about that after all my research and all my conversations with other DBS patients and doctors no one mentioned the steel ball ear plug portion of the halo/frame procedure. During this portion I asked the surgeon why no one ever mentioned this part he told me it was because most people do not remember it. Well let me be truthful I remember ever second of it and I told him I was going blog about it and let the secret out.

On this blog plenty of posts about the use and indications for Deep Brain Stimulation and on Mind Hacks a short list of things that deep brain stimulation has been used to treat.

Thanks Jan at Medblog.nl

 

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Deep Brain Stimulation for Addiction?

deep brain stimulation

With the expanding knowledge of the neuronal circuits responsible for the behavioral disorders associated with addiction, though, DBS could become a future treatment option for patients suffering from addiction and being part of an Addiction Recovery Therapy.

In people addicted to psychoactive substance it has been shown by Positron emission tomography studies that, when they take the psychoactive substance, dopamine is released in the nucleus accumbens, which causes “the high.”

They lack the decrease of the output neurons on this dopamine release. There is no brake on the “high” elicited by the drug and the subsequent dopamine release. This lack of inhibition causes activation of the reward system. The increased dopamine release is located in the nucleus accumbens. This reward circuit consists of dopaminergic neurons that project from the ventral tegmental area to the ventral striatum (including nucleus accumbens), the amygdala and septal nuclei, and prefrontal and cingulate cortices.

The feeling of well-being produced by activation of the reward system can be seen as positive reinforcement. Negative reinforcement involves escaping from or avoiding intensive outpatient treatment symptoms, which occur after cessation of the substance use. In addicted individuals both positive and negative reinforcement involve disruption of the reward system by repeated administration of the substance.

Other brain regions involved in addiction are:

  • The amygdala. The amygdala couples the rewarding qualities of the substance and the environment in which the abuse takes place. This could explain why an environment with substance-
    associated stimuli causes the craving reported by addicted individuals
  • The prefrontal cortex and the anterior cingulate gyrus. Dysfunction of the dopaminergic transmission in these structures leads to impairment of inhibitory control and decision making. This may cause an inability to resist substance-abusing behavior in addicted individuals, even
    though they are explicitly aware of the negative consequences.

A recent review described the different psychosurgical procedures used in an addiction treatment clinic as treatments. Moreover this review also discusses the first reports on the treatment of substance-related addictive disorders by using Deep Brain Stimulation.

They found three cases in two publications. Two patients with Parkinson’s disease and Dopamine dysregulation syndrome.

Dopaminergic medications, share some of the stimulant properties of commonly abused drugs such as amphetamine and cocaine. These have the potential to be compulsively used by a small group of susceptible individuals with Parkinson’s disease, causing harmful social, psychological, and physical effects. Patients with this condition, termed “dopamine dysregulation syndrome”, meet clinical criteria for substance dependence and addiction. They frequently also show behavioural compulsions, such as compulsive gambling, eating and hyper-sexuality.

In both cases there was a good effect of deep brain stimulation on motor disability, but also on Dopamine Dysregulation Syndrome and related behavior characteristics. They both underwent bilateral subthalamic nucleus deep brain stimulation. The other case report was about a man with severe agoraphobia with panic attacks, secondary depressive disorder, and alcohol dependency. After bilateral deep brain stimulation of the nucleus accumbens the substance abuse disappeared. The nucleus accumbens is part of the “addictive circuit” in the brain.

Psychosurgery for the Newport Beach Addiction Treatment has been done and published. Never in randomized controlled trials and the procedure is irreversible.

DBS is reversible and makes randomized placebo controlled trials for this indication feasible. Nevertheless, the evidence so far is circumstantial and limited

What do you think, should DBS be tried with addiction?

ResearchBlogging.org
Bianca M. L. Stelten, Lieke H. M. Noblesse, Linda Ackermans, Yasin Temel, Veerle Visser-Vandewalle (2008). The neurosurgical treatment of addiction Neurosurgical FOCUS, 25 (1) DOI: 10.3171/FOC/2008/25/7/E5

 

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Potential surgical targets for deep brain stimulation in treatment-resistant depression

Deep brain stimulation has shown promise in the treatment of treatment resistant depression(TRD) in some small series and case reports. The definition of TRD is still a matter of debate. There isn’t one clear classification scheme of TRD. TRD shouldn’t be mixed up with pseudoresistant depression . The recent research with deep brain stimulation showed some promising results and in the future might add this treatment to the 9 steps for treatment resistant depression.

Since this treatment for TRD is in it’s infancy

The most appropriate target, optimal stimulation parameters, and long-term effects and efficacy remain uncertain.

About the targets for deep brain stimulation in treatment resistant depression some options are available:

  • The reward circuitry of the ventral striatum and Nucleus Accumbens has been associated with drug addiction and depression for many years. Some case reports showed some partial effect on TRD. One case report with obsessive-compulsive disorder and concomitant major
    depression and three cases with TRD.

    Nucleus Accumbens Ventral Striatum

  • Subgenual Cingulate Cortex: Area 25. Helen Mayberg found the switch that lifts depression in area 25, a spot deep in the cortex. This area is the key conduit of neural traffic between the thinking frontal cortex or forebrain and the central limbic region that plays a role in emotions and which appeared earlier in our evolutionary development. This area is overactive during depression or sadness. This form of DBS was doen in a Randomized Controlled Trial with 6 patients with overall response of 60%.

    Broadman area 25

  • Inferior Thalamic Peduncle. The ITP has proven to be hyperactive in depression, a phenomenon that reverses with effective pharmacological treatment. Successful use of this target in DBS stimulation has been published in one case report. One initial case report indicates promise, large-scale trials of implantation are necessary to determine the efficacy and safety of this target.

    inferior thalamic peduncle

  • Rostral Cingulate Cortex: Area 24a. No electrode has yet been implanted in the rostral cingulate cortex in humans; however, stereotactic lesioning of this area has shown beneficial effects.

    Rostral Cingulate cortex

  • Lateral Habenula. Only used in animal models with some suggestion that functional inhibition of this area using high-frequency DBS may have therapeutic benefit

    lateral habenula

These localizations have been described on this blog in another posts: 5 different locations for deep brain stimulation in depression, but now it appears in a peer reviewed article with excelent graphics.

Only three have been tried with patients with TRD or obsessive-compulsive disorder and concomitant major depression. The other anatomical targets are tentative. The most impressive results done with a proper study design was with Broadman area 25 by Helen Mayberg.

I think the following quote by Dr. Cosgrove sums it up as far as the progress and future of DBS is concerned:

“deep brain stimulation may provide a unique opportunity to help patients who suffer horribly from the consequences of severe depression…. early efforts must go forward only with the highest ethical, moral, and scientific standards to ensure that this historic opportunity is not wasted…. much is at stake.”

What do you think?

ResearchBlogging.org
Jason S. Hauptman, Antonio A. F. DeSalles, Randall Espinoza, Mark Sedrak, Warren Ishida (2008). Potential surgical targets for deep brain stimulation in treatment-resistant depression Neurosurgical FOCUS, 25 (1) DOI: 10.3171/FOC/2008/25/7/E3

 

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Deep Brain Stimulation for Depression

CNN’s Dr. Sanjay Gupta reports on new research showing deep brain stimulation may ease severe depression.

In a very short video a short introduction to Deep Brain Stimulation with nice animation. It is explained as a pacemaker to the brain. The pacemaker regulates mood circuits, potentially easing deep depression no other treatments can touch. Also about who are candidates for this treatment. Answer: When all else fails.

Alas the video is not always available or other technical problems exist.

For a more detailed video and article about Deep Brain Stimulation read on globeandmail.com: Mending a broken mind.

Thanks Therapeutic Neuromodulation Blog

 

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New Trial On Deep Brain Stimulation for Treatment Resistant Depression

Deep Brain Stimulation

The current study is the largest clinical trial to date of the efficacy of DBS as a treatment for severe depression. Between May 2003 and November 2006, Andrez M. Lozano and his colleagues implanted electrodes into the brains of a total of 20 patients (9 men and 11 women) with major depressive disorder, all of whom were referred to the researchers from hospitals or community psychiatrists, after failing to respond to antidepressants, psychotherapy or electroconvulsive therapy.

On Neurophilosophy a post about this new trial with this new treatment for treatment resistant depression.

12 out of the 20 patients reported significant long-term improvements in their condition. This was corroborated by neuropsychological assessments which measured, among other things, the patients’ mood, anxiety levels and sleeping patterns. These improvements were observed within 1 month and, importantly, persisted for at least 12 months after the treatment, by which time 7 of the patients had gone into full remission.

Time for some randomized controlled trial with switching on and off?

Related posts on this blog about Deep Brain Stimulation

 

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Cognitive Safety of Deep Brain Stimulation for Treatment Resistant Depression


Apart from a transient mild decline in manual motor speed, there seems to be no
adverse cognitive effects associated with chronic Deep Brain Stimulation (DBS) in Cg25 for Treatment Resistant Depression (TRD) in this sample of 6 patients with a follow-up of 12 months.

Another important conclusion from this research:

Several areas of cognition that were below average or impaired at baseline improved over follow-up, and these changes were not correlated with improvements in mood.

Broadman Area 25 as target for deep brain stimulation in treatment resistant depression. This area in the brain is from the most important publication about DBS and depression in Neuron march 2005 by Helen Mayberg. This is the location used in the largest trial with DBS in TRD. Other locations for DBS in TRD appear as well but these publications concern individual cases.

Functional neuroimaging as well as antidepressant treatment effects suggest that this area plays an important role in modulating negative mood states. Clinical response was demonstrated in 4 of 6 patients using standardized psychiatric end points. These results suggest that modulation of pathological activity in specific limbic-cortical circuits by electrical stimulation of Cg25 can effectively reverse symptoms in previously TRD patients.

Comparison to ECT

Moreover, in contrast to the memory deficits consistently reported with
ECT, no consistent declines in memory for either verbal or visual material were noted after onset or maintenance of DBS over baseline.


Limitations

  • small sample size (n=6)

  • the lack of a matched control group

  • the lack of control (on-off) conditions for stimulation

  • impact of repeat testing or regression toward the mean may have nonetheless affected the results

  • patients were not free of psychopharmacological drugs

Other indications for DBS:

ResearchBlogging.org
McNeely, H.E., Mayberg, H.S., Lozano, A.M., Kennedy, S.H. (2008). Neuropsychological Impact of Cg25 Deep Brain Stimulation for Treatment-Resistant Depression. The Journal of Nervous and Mental Disease, 196(5), 405-410. DOI: 10.1097/NMD.0b013e3181710927

 
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