Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim, first used in our group in 1987 as a treatment of tremor of various origins, has been used over the last ten years in 137 patients. Since 1993, this method has been extended to two other targets (subthalamic nucleus (STN): 137 patients and the medial pallidum (GPi): 12 patients), based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then also suppresses levodopa induced dyskinesias. The stereotactic technique is based on the determination of the target using ventriculography, MRI and electrophysiology, with both microrecording of single neuron activity and microstimulation inducing therapeutic symptom suppression and side effects. Chronic electrodes are then placed bilaterally at the best physiologically defined location and then connected to implantable stimulators (either 2 Itrel II or the new double channel Kinetra), operated at 130-185 Hz, 60 ms pulse width, 2.5 to 3.5 volts. There was no operative mortality and permanent morbidity was observed in 3 patients. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of neural network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. Mechanisms within an individual target are also probably different for tremor or for other symptom alleviation. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. This strong improvement allows the decrease of the drug dosage to approximately 30% of the preoperative level, which suppresses the levodopa-induced dyskinesias. The off period dystonias are also suppressed as well as freezings and falls. The effects remain stable over more than 5 years and in the same period, the off stimulation-off medication UPDRS remains stable and does not increase at the usual rate The low rate of permanent complications, the minor side effects and their immediate reversibility, the possibility of bilateral implantation in one session and the long-term persistence of symptom relief are strong arguments which support chronic HFS of STN as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsy. It is therefore possible that DBS in STN as well as in other targets could become a potent therapeutic tool in the near future for neurological disorders.
 ...
PMID:Deep brain stimulation of the corpus luysi (subthalamic nucleus) and other targets in Parkinson's disease. Extension to new indications such as dystonia and epilepsy. 1169 87

A patient with severe postanoxic dystonia and bilateral necrosis of the basal ganglia, who was confined to a wheelchair, underwent bilateral ventralis oralis anterior deep brain stimulation (Voa-DBS) after 6 weeks of unsuccessful bilateral pallidal DBS (GPi-DBS). After 4 months of high intensity Voa-DBS, cognitively unimpaired, he showed major improvement in dystonia, became ambulant, but committed suicide. Brain examination confirmed the correct location of the electrodes in GPi and Voa on both sides.
 ...
PMID:Postanoxic generalized dystonia improved by bilateral Voa thalamic deep brain stimulation. 1180 66

Deep Brain Stimulation (DBS, chronic high frequency stimulation) is well established for Parkinson's disease and tremordominant movement disorders. Generalized dystonia is known as a type of movement disorder in which therapeutic options are very limited. A case of generalized dystonia is reported which was successfully treated by DBS in the Globus pallidus internus (GPI). A 26 years old male suffered from severe torsion dystonia of the lower limbs. The onset of symptoms was at age 7. It started with dystonia of the left foot. He very fast developed severe dystonia of the lower limbs. These complaints were initially treated by diazepam, later by baclofen (Lioresal ((R))) p.o em leader There was no L-DOPA response. Because of the rapid progression of the disease a cervical spinal cord stimulator was implanted with a transient success. Due to further progression of the disease the patient became wheelchair bounded and resistant for oral medication. Limited improvement of symptoms was achieved using continuous intrathecal administration of baclofen. Finally the patient was treated with 980 microgram intrathecal Baclofen (Lioresal ((R))) daily and up to 100 mg diazepam. Under these conditions the patient remained wheelchair bounded with severe lower limb dystonia. As an ultima ratio it was decided to treat the patient with stereotactic implantation of two electrodes (Medtronic 3387) and two neurostimulators (Medtronic ITREL ((R))II). The GPI was the bilateral target point. Intraoperative computerized tomography and ventriculography were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode positioning. Surgery was performed under sedation. Two weeks after surgery first improvement of symptoms was observed. Patient was able to stand with assistance. At the three months follow-up he could walk without assistance. Slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The oral medication has been continuously reduced. After 6 months it was stopped. The intrathecal administered baclofen was diminished to 250 microgram daily. At the 24 months follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (3,5 V, 400 microseconds 145 Hz for both sides). Deep Brain Stimulation of the Globus Pallidus internus is an alternative approach for severe cases of generalized dystonia.
 ...
PMID:[Chronic high frequency deep brain stimulation of the globus pallidus internus for torsion dystonia]. 1209 79

Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson's disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications.
 ...
PMID:Complications of deep brain stimulation surgery. 1237 60

Surgical treatments for dystonia have been available since the early 20th century, but have improved in their efficacy to adversity ratio through a combination of technologic advances and better understanding of the role of the basal ganglia in dystonia. The word "dystonia" describes a phenotype of involuntary movement that may manifest from a variety of conditions. Dystonia may affect only certain regions of the body or may be generalized. It appears to be critical to determine whether the etiology underlying the dystonia is "primary" (ie, occurring from a genetic or idiopathic origin) or "secondary" (ie, occurring as a result of structural, metabolic, or neurodegenerative disorders). Secondary dystonias are far more common than primary dystonias. Primary dystonias respond well to pallidotomy or deep brain stimulation of the internal segment of the globus pallidum, whereas secondary dystonias appear to respond partially at best. Limited historic and current data suggest that the thalamus may be a promising target for the treatment of secondary dystonias, but more careful, prospective, randomized studies are needed. Combinations of bilateral targets are possible with the current technology of DBS, but not widely used due to surgical morbidity and expense. This article reviews the surgical treatment of dystonia from past to present, with a focus on separating the outcomes for primary versus secondary and generalized versus cervical dystonia.
 ...
PMID:Surgical therapy for dystonia. 1293 Jun 99

The net output of the basal ganglia is tightly regulated by the activity and balance of driving and inhibitory circuitry. In pathologic states, disrupted activity in the main outflow nucleus, the globus pallidus interna (GPi), is relayed to the motor areas of the thalamus and brainstem. The behavior of these targets receiving this disrupted outflow is consequently also disrupted, which in turn produces the profound disturbances in motor function that are characteristic of parkinsonian states and certain forms of dystonia. Therapeutic efforts are directed at reversing or canceling the pathologic basal ganglia output. When drugs are ineffective or have shortcomings, surgical approaches can be considered. It is interesting and paradoxical that elimination of this abnormal activity with destruction of the motor GPi is usually well tolerated and produces little in the way of overt motor deficit. Indeed having no motor pallidum appears to be preferable to having a pallidum generating and transmitting pathologic inputs to down-stream targets. This observation brings into question the mysterious role of the GPi in normal motor function. Nevertheless, bilateral pallidal lesions can be associated with significant adverse effects including speech difficulties and cognitive disturbances. It is for this reason that neurosurgeons have sought to develop surgical procedures that offer the efficacy of selective pallidal lesions but have a better index of safety. With the introduction of DBS to treat first chronic pain and then PD, it became logical to apply DBS to treat dystonia. There is now increasing experience in the use of DBS to treat various forms of dystonia. The initial results suggest that certain primary dystonias can show a strong improvement with GPi DBS.
 ...
PMID:Pallidal stimulation for dystonia. 1450 87

Our experience of deep brain stimulation of the globus pallidus internus (GPi-DBS) for dystonia is summarized. A total of 5 patients with primary generalized dystonia underwent GPi-DBS. There were 3 males and 2 females. The age at onset of dystonia ranged from 8 to 45 years and the age at surgery for GPi-DBS ranged from 17 to 59 years. Two of the patients had been treated previously by bilateral thalamotomy or unilateral pallidotomy at other clinics and then developed new symptoms or recurrence. All were stimulated bilaterally. No surgical complications were encountered. The symptoms of dystonia were scored by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). The scores ranged from 18 to 62 before surgery. An improvement in the symptoms of dystonia was observed soon after the initiation of GPi-DBS, and additional progressive improvement was noted during a period of months or even years after surgery. The score at 6 months after surgery reached a level ranging from 4 to 23. The improvement in score ranged from -51% to -92%. GPi-DBS produced a marked effect even in patients who had previously undergone thalamotomy or pallidotomy. At 6 months after surgery, all patients were receiving bipolar stimulation with a wide interpolar distance, using contact 0 or 1 as the cathode and contact 2 or 3 as the anode. Stimulation was being performed at an intensity of around 2.0 V with a pulse width of 0.21 ms at a high frequency ranging from 120 to 140 Hz. GPi-DBS represents an important therapeutic option in many patients with primary generalized dystonia.
 ...
PMID:Chronic stimulation of the globus pallidus internus for control of primary generalized dystonia. 1451 38

Primary generalized dystonia (PGD) associated with the early-onset generalized dystonia gene (DYT1) can cause severe disability, compromising an individual's ability to perform activities of daily living. Pharmacological treatment has been inadequate in alleviating the motor dysfunctions. Deep brain stimulation of the bilateral globus pallidus internus (DBS B-GPi) has been documented to reduce these debilitating motor abnormalities. This report details the successful treatment of a DYT1-positive 13 year-old boy suffering from PGD.
 ...
PMID:Bilateral globus pallidus internus deep brain stimulation therapy for primary generalized dystonia. 1535 20

Pantothenate kinase-associated neurodegeneration (PKAN) causes a progressive generalized dystonia which remains pharmacologically intractable. We performed bilateral internal globus pallidus stimulation in six patients with genetically confirmed PKAN who obtained a major and long-lasting improvement of their painful spasms, dystonia, and functional autonomy. This study shows the benefits of pallidal DBS for the dystonia of PKAN patients.
 ...
PMID:Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. 1585 5

Globus pallidus deep brain stimulation (GPi-DBS) is a useful alternative in the treatment of dystonia. Patients selected for GPi-DBS were prospectively rated with the Unified Dystonia Rating Scale (UDRS). Also, "blinded" videotape assessments were performed. Eleven patients were identified. Compared with pre-DBS scores, there were improvements in mean total UDRS score (15.3%) and in the following subscores: neck (18.18%), trunk (32.9%), arm (17.9%), and leg (19.9%). One patient developed a skin infection and erosion requiring surgical debridement. GPi-DBS is a safe and effective treatment for generalized dystonia in patients who remained impaired, despite optimal medical therapy.
 ...
PMID:Globus pallidus deep brain stimulation in dystonia. 1634 55


1 2 3 4 5 6 7 Next >>