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PubMed2005

[Novel brain stimulation techniques: therapeutic perspectives in psychiatry].

Recent advances have allowed the development of new physical techniques in neurology and psychiatry, such as Transcranial Magnetic Stimulation (TMS), Vagus Nerve Stimulation (VNS), and Deep Brain Stimulation (DBS). These techniques are already recognized as therapeutic approaches in several late stage refractory neurological disorders (Parkinson's disease, tremor, epilepsy), and currently investigated in psychiatric conditions, refractory to medical treatment (obsessive-compulsive disorder, resistant major depression). In Paralell, these new techniques offer a new window to understand the neurobiology of human behavior.

Deep Brain Stimulation↗

PubMed2005

Bilateral subthalamic stimulation improves gait initiation in patients with Parkinson's disease.

Impaired gait initiation is one of the typical sign of advanced Parkinson's disease (PD). This is the first study to examine quantitatively the effect of deep brain stimulation of the subthalamic nucleus on the performance of gait initiation for patients with advanced PD. A total of 11 patients after surgery of bilateral deep brain stimulation of the subthalamic nucleus (STN) were tested in both the deep brain stimulation (DBS) ON and OFF conditions and/or in both the medication ON (i.e., with the usual dosage of antiparkinsonian medications administered) and OFF (i.e., with the usual dosage of antiparkinsonian medications withheld) conditions. DBS had no effect on the onset of anticipatory postural adjustment (APA). The effect of DBS approached significant level for the onset of swing foot lifting, but reached significant level for the delay of swing foot lifting. DBS significantly increased the amplitude of the APA, amplitude of reactive shear forces on both feet, and amplitude of COP in both anterior-posterior and medial-lateral directions. It is concluded that DBS significantly improved the performance of patients with advanced PD in gait initiation.

Adult↗

PubMed2006

The burden of severe depression: a review of diagnostic challenges and treatment alternatives.

Among the factors making recognition of severe depression problematic for clinicians are the heterogeneous nature of the condition, lack of standardized definitions, and concomitant comorbidities that confound differential diagnosis of symptoms. The spectrum of severity in depressive disorders is extraordinarily broad, and severity assessment is comprised of several metrics including symptom intensity, diagnostic subtypes, suicidality risk, and hospitalization status. The overall diagnosis is achieved through consideration of symptom types and severities together with the degree of functional impairment as assessed by the psychiatric interview. It is likely that no single fundamental neurobiological defect underlies severe depression. The chronicity and heterogeneity of this disorder lead to frequent clinic visits and a longer course of treatment; therefore, successful approaches may require an arsenal of treatments with numerous mechanisms of action. The categories of drugs used to treat severe depression are detailed herein, as are several non-pharmacologic options including a number of experimental treatments. Pharmacotherapies include tricyclic antidepressants, selective serotonin reuptake inhibitors, atypical antidepressants such as serotonin-norepinephrine reuptake inhibitors and monoamine oxidase inhibitors, and combination and augmentation therapies. Drugs within each class are not equivalent, and efficacy may vary with symptom severity. Patient adherence makes tolerability another critical consideration in antidepressant choice. The role of non-pharmacological treatments such as electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation remain active avenues of investigation. Improved knowledge and treatment approaches for severe depression are necessary to facilitate remission, the ideal treatment goal.

Complementary Therapies↗

PubMed2002

Novel physical treatments for the management of neuropsychiatric disorders.

OBJECTIVE: To briefly describe the novel non-drug physical interventions currently in use in the investigation and treatment of neuropsychiatric disorders regarding their efficacy and potential future applications. METHODS: A systematic review of the literature concerning transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), vagus nerve stimulation (VNS) and neurosurgery for mental disorders (NMD) was conducted using Medline and literature known to the authors. RESULTS: A summary of each procedure is provided giving a succinct overview of efficacy, current applications and possible future indications. CONCLUSION: Novel and innovative physical interventions are currently being used to study brain function in health and disease. In particular, TMS has quickly established itself as a useful investigational tool and is emerging as a possible antidepressant therapy. Similarly, VNS has been applied successfully in the management of intractable epilepsy and is undergoing evaluation in the management of patients with treatment-resistant depression. DBS has shown significant promise in the treatment of Parkinson's disease and may have use in the management of obsessive-compulsive disorder. Finally, neurosurgical procedures for the treatment of mental disorders have been sufficiently refined to stage a comeback, although rigorous scientific study of their efficacy and indications is still necessary.

Brain Diseases↗

PubMed2003

Psychologic evaluation for patients undergoing neuroaugmentative procedures.

Neuroaugmentative and neuromodulation therapy continues to expand. New applications are being found for existing technology, such as the use of SCS therapy in the treatment of head pain. The potential impact of existing therapies is enhanced by new discoveries as exemplified by the availability and demonstrated efficacy of different pharmacologic agents and combinations of agents in intrathecal therapy [39]. Increased attention is being paid to cortical stimulation, including motor cortex stimulation and deep brain stimulation. We must, however, not let our fascination for gadgets betray sound sense. The role of psychosocial factors in the outcome of more "objective" and measurable problems, such as spasticity and tremor versus pain, remains an open area of investigation. Although psychologic issues may not be as prevalent in the amelioration of such problems, they may influence the patient's overall level of satisfaction with the therapy and improvement in quality of life.

Electric Stimulation Therapy↗

PubMed2001

Neural prostheses.

Assuming that neural regeneration after spinal cord injury (SCI) will eventually become a clinical reality, functional recovery will probably remain incomplete. Assistive devices will therefore continue to play an important role in rehabilitation. Neural prostheses (NPs) are assistive devices that restore functions lost as a result of neural damage. NPs electrically stimulate nerves and are either external or implanted devices. Surface stimulators for muscle exercise are now commonplace in rehabilitation clinics and many homes. Regarding implantable NPs, since 1963 over 40 000 have been implanted to restore hearing, bladder control and respiration. Epidural spinal cord stimulators and deep brain stimulators are routinely implanted to control pain, spasticity, tremor and rigidity. Implantable NPs have also been developed to restore limb movements using electrodes tunnelled under the skin to muscles and nerves. Spinal cord microstimulation (SC[mu]stim) is under study as an alternative way of restoring movement and bladder control. Improvement in bladder and bowel function is a high priority for many SCI people. Sacral root stimulation to elicit bladder contraction is the current NP approach, but this usually requires dorsal rhizotomies to reduce reflex contractions of the external urethral sphincter. It is possible that the spinal centres coordinating the bladder-sphincter synergy could be activated with SC[mu]stim. Given the large and growing number of NPs in use or development, it is surprising how little is known about their long-term interactions with the nervous system. Physiological research will play an important role in elucidating the mechanisms underlying these interactions.

Animals↗

PubMed1991

Electrical stimulation of peripheral and central pathways for the relief of musculoskeletal pain.

One method for the treatment of chronic musculoskeletal pain involves stimulation of the peripheral or central nervous system. Such stimulation includes transcutaneous electrical nerve stimulation, dorsal column stimulation, and deep brain stimulation. This review discusses the clinical use of electrical stimulation for the relief of musculoskeletal pain, and describes the results of studies conducted in our laboratory suggesting that such stimulation reduces pain transmission along sensory-discriminative pathways.

Animals↗

PubMed2001

Motor cortex stimulation for phantom limb pain: comprehensive therapy with spinal cord and thalamic stimulation.

The effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) were analyzed in 19 patients with phantom limb pain. All of the patients underwent SCS and, if the SCS failed to reduce the pain, the patients were considered for DBS and/or MCS. Satisfactory pain control for the long-term was achieved in 6 of 19 (32%) by SCS, 6 of 10 (60%) by DBS and 1 (20%) of 5 by MCS. SCS and DBS of the VC sometimes produced a dramatic effect on the pain, leading to a long pain-free interval and infrequent use of stimulation. The effects of both DBS of the VC and MCS were tested in four. One patient of them reported better pain control by MCS than by DBS, whereas two reported the opposite results. There is no evidence at present for an advantage of MCS over SCS and DBS of the VC in controlling phantom limb pain.

Adult↗

PubMed2001

Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation.

We analyzed the effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) in 45 patients with post-stroke pain. Satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels (7% by SCS, 25% by DBS and 48% by MCS). A painful sensation was sometimes produced by stimulation of the VC as well as the post-central, pre-central and pre-frontal cortices. Such a sensation occurred less frequently as the stimulation site was moved to higher levels (50% at the VC, 39% at the post-central cortex, 6% at the pre-central cortex and 3% at the pre-frontal cortex). These findings imply that abnormal processing of nociceptive information develops at the level of deafferentation and spreads to higher levels to a varying extent. This may be one of the reasons why satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels.

Analgesia↗

PubMed2006

Current and emerging somatic treatment strategies in psychotic major depression.

Psychotic major depressive disorder (MDD) is a mood disorder characterized by severe affective and neurovegetative symptoms together with the presence of delusions and/or hallucinations. It is a common disorder seen in a quarter of consecutively admitted depressed patients and is often associated with severe symptomatology, increased suicide risk, poor acute response to antidepressants and poor acute and long-term treatment outcome. It is possible that poor response in psychotic depression is caused by the fact that we have yet to identify the most efficacious treatment protocol for psychotic MDD. Multiple studies have shown that modifications in the treatment paradigm may increase treatment efficacy in psychotic MDD. It has been generally accepted that, during the acute treatment phase, antidepressant-antipsychotic drug combination therapy is more effective than either treatment alone, although this strategy has recently been challenged. The question of the optimal duration of pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of current investigation. This article will review currently recommended treatment strategies for the acute, continuation and maintenance phases of therapy. In particular, it will address the role of newer-generation antidepressants, the role of second-generation antipsychotics, the use of mood stabilizers and indications for electroconvulsive therapy. Other possible treatment strategies such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will be discussed. Current recommendations for the prevention of relapse and improvement of long-term outcome will be reviewed.

Affective Disorders, Psychotic↗

PubMed2026

Epilepsy: Bridging Epidemiological Landscapes, Molecular Mechanisms, and Emerging Precision Therapeutics.

Epilepsy ranks among the most prevalent neurological disorders worldwide, and recent years have witnessed significant advancements in understanding its epidemiological features, pathophysiological mechanisms, diagnostic methodologies, and therapeutic approaches. This review systematically examines the epidemiology of epilepsy, highlighting pronounced regional and population-based disparities, particularly the substantial treatment gap observed in low-income countries. Regarding pathogenesis, epilepsy development involves aberrant ion channel function, neuroinflammatory processes, dysregulation of the mTOR signaling pathway, and genetic predispositions. Diagnostic innovations, including ultra-high field magnetic resonance imaging, artificial intelligence-enhanced electroencephalogram analysis, and liquid biopsy techniques, have markedly enhanced the precision of epileptogenic focus localization and etiological identification. Genetic investigations have uncovered numerous epilepsy-associated genes, thereby underpinning the advancement of targeted therapies. Therapeutically, novel antiepileptic drugs, neuromodulation modalities such as vagus nerve stimulation and deep brain stimulation, alongside gene therapy, have expanded treatment options for refractory epilepsy. Nonetheless, global epilepsy management continues to confront challenges including limited drug accessibility, social stigma, and pharmacoresistance. The future trajectory emphasizes individualized and precision medicine approaches, integrating genomics, biomarker discovery, and intelligent monitoring technologies to foster comprehensive improvements in epilepsy diagnosis and treatment.

epidemiology↗

PubMed2004

Effect of stimulation frequency on tremor suppression in essential tremor.

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.

Adult↗

PubMed2004

How does DBS work?

Deep brain stimulation (DBS) produces striking effects in patients with various disorders including Parkinson's disease and dystonia, yet its precise mechanism of action is not clear. Because the clinical benefits of lesioning target structures such as the thalamus, globus pallidus and subthalamic nucleus appear to be similar to those achieved by chronic application of stimulation at these structures, it has been surmized that deep brain stimulation produces a functional inactivation or block of the target. This simplistic proposal has supporting and detracting evidence. In the present work we consider the mechanism of action of DBS and provide arguments for and against the stimulation or inhibition of target neural structures.

Animals↗

PubMed1999

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Cognition↗

PubMed2004

Long-term results of bilateral pallidal stimulation in Parkinson's disease.

We followed up 11 patients for up to 5 years after bilateral pallidal deep brain stimulation for advanced Parkinson's disease. Dyskinesias remained significantly reduced until the last assessment. The initial improvement of off-period motor symptoms and fluctuations, however, was not sustained and gradually declined. Beneficial effects of pallidal deep brain stimulation on activities of daily living in the on- and off-period were lost after the first year. Replacement of pallidal electrodes into the subthalamic nucleus in four patients could restore the initial benefit of deep brain stimulation and allowed a significant reduction of dopaminergic drug therapy.

Activities of Daily Living↗

PubMed2004

Laryngeal findings in advanced Parkinson's disease.

Parkinson's disease is a major source of neurologic morbidity. A majority of patients with Parkinson's disease complain of problems with voice, speech, and swallowing. Treatments for these problems center on the improvement of vocal fold adduction through either speech therapy or vocal fold augmentation. No prior study has looked at laryngeal improvement after neurologic surgery, specifically deep brain stimulation, performed to treat Parkinson's disease. The goal of this study was to establish a baseline of laryngeal findings in patients who are considering deep brain stimulation. Fifteen patients underwent physical examination with videostroboscopy and fiberoptic endoscopic evaluation of swallowing before deep brain stimulation. In addition, they were asked to self-report voice handicap. Eighty-seven percent of patients demonstrated significant vocal fold bowing. All patients had some degree of pharyngeal residue of solids noted on evaluation of swallowing. All but one patient had a significant self-reported voice handicap. These findings are reviewed and established as a baseline for further study.

Aged↗

PubMed2001

Surgical management of Parkinson's disease: a critical review.

Parkinson's disease is a progressive disabling movement disorder that is characterised by three cardinal symptoms: resting tremor, rigidity, and bradykinesia. Before the availability of effective medical treatment with levodopa and stereotactic neurosurgery, the objective of surgical management was to alleviate symptoms such as tremor at the expense of motor deficits. Levodopa was the first effective medical treatment for Parkinson's disease, and surgical treatment such as stereotactic thalamotomy became obsolete. After one decade of levodopa therapy, however, drug-induced dyskinesia had become a source of additional disability not amenable to medical treatment. Renewed interest in stereotactic functional neurosurgery to manage Parkinson's disease has been seen since the 1980s. Local experience of deep-brain stimulation is presented and discussed in this paper. Deep-brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease, although evidence from randomised control trials is lacking.

Humans↗

PubMed2002

Camptocormia treated with bilateral pallidal stimulation.

The authors report the neurological, neurophysiological, and neuropsychological effects of using long-term bilateral pallidal high-frequency deep brain stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation electrodes were implanted stereotactically to target the globus pallidus internus (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS electrodes and concurrent abdominal flexor electromyography (EMG) potentials during camptocormic episodes. Videotaped assessments of the movement disorder and neuropsychological evaluations of the patient before implantation and 6 months after initiation of pallidal stimulation were recorded. There was significant functional improvement following long-term pallidal stimulation, and some improvement was noted in neuropsychological scores. A temporal correlation between the GPi FPs and EMG-recorded rectus abdominis potentials was evident. There were no treatment-related adverse effects. The authors have found that long-term pallidal stimulation was safe and offered functional benefit to a patient with this severely disabling condition. The physiological studies may help further the understanding of the pathophysiology of this rare entity.

Adult↗