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

Dystonia refers to involuntary, prolonged muscle contractions leading to sustained, often twisting, postures. High dose anticholinergic therapy for childhood onset dystonia, botulinum toxin injections for focal dystonia, and levodopa for diurnal dystonia provide symptomatic relief for some patients. Despite this, treatment of both idiopathic and secondary dystonia remains inadequate for many patients. Baclofen, a pre-synaptic acting GABA agonist, has been reported to benefit dystonia in a number of retrospective studies. Dramatic improvement in symptoms, especially in gait, was found in almost 30% of 31 children and adolescents with idiopathic dystonia in one retrospective study using doses ranging from 40 to 180 mg daily. The response to baclofen of adults with focal dystonia is less dramatic. One series of 60 adults with cranial dystonia found sustained benefit in 18%. Smaller series have not consistently found significant benefit in adults. Baclofen has been used to treat several secondary dystonias: tardive dystonia has occasionally been reported to improve and there are isolated reports of improvement in dystonia occurring in Parkinson's disease and in glutaric aciduria.
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PMID:Baclofen in the treatment of dystonia. 151 73

Baclofen benefits some patients with adult onset dystonia, but few reports document the response to baclofen of children with idiopathic dystonia. Sixteen of 80 patients less than age 21 years with idiopathic dystonia seen by the Movement Disorder Group at Columbia-Presbyterian Medical Center in New York were treated with baclofen. Five had substantial improvement in symptoms, two had moderate improvement, and nine failed to benefit. Three of the improved patients had transient improvement on high dose anticholinergics, but had sustained, dramatic improvement when baclofen was added. At last follow-up, five patients maintained improvement for a mean 3.8 years (19 months-8 years) on a mean 79 mg of baclofen (40-120 mg). Response to baclofen did not correlate with age at onset of dystonia or age at onset of therapy, but did correlate with duration of symptoms before therapy (3 years for those who improved vs 7.8 years for those who did not: p less than .002 by t-test). Baclofen can be an effective treatment for childhood dystonia.
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PMID:Baclofen in the treatment of idiopathic dystonia in children. 155 66

In a male infant with macrocephaly and dystonic cerebral palsy glutaric aciduria type I was detected by analysis of urine for organic acids. Glutaric aciduria type I is an inherited metabolic disorder of organic acids due to a defect of glutaryl-CoA-dehydrogenase in the intermediate metabolic step of lysine and tryptophan degradation. In the urine glutaric acid is usually accompanied by 3-hydroxy-glutaric acid in abnormal quantities. The enzyme defect in our patient was proved in cultured fibroblasts. In the cerebral computer tomography marked atrophy of bilateral frontotemporal regions could be demonstrated. The amount of urinary glutarat excretion decreased after protein but especially after lysine and tryptophan restriction in the diet. The administration of carnitine improved carnitine levels in blood and urine. Although the progression of neurological impairment could be stopped, dystonia and dyskinesis remained nearly unaltered. In spite of severe motor retardation, recognition and vocalisation were established. In the two year old patient mental retardation is relatively mild comparing with motor retardation. The administration of 100 or 200 mg Riboflavin/day was stopped, as it did not alter clinical symptoms or excretion of glutarat. Baclofen, an analogue of gamma-amino-butyric acid, was orally given (2 mg/kg/day) and improved dystonia, but did not influence organic aciduria. The neurological manifestations may be due in part to inhibition of neuronal glutamat decarboxylase by glutaric acid with decreased gamma-amino-butyric acid biosynthesis. The characteristic clinical symptoms with macrocephaly and dystonia and the very typical pattern of organic acids in urine are a challenge for rapid diagnosis and therapy.
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PMID:[Macrocephaly and dystonic cerebral palsy in a child with type I glutaric aciduria]. 194 71

A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.
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PMID:Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. 810 50

Baclofen, a gamma-aminobutyric acid agonist, acts at the spinal cord level to impede the release of excitatory neurotransmitters that cause spasticity. Oral baclofen improves cerebral spasticity mildly, but its activity is limited because of its poor lipid solubility. Cerebrospinal fluid baclofen levels after intrathecal administration are many times higher than those achieved after oral administration. Continuous intrathecal baclofen infusion has been used to treat cerebral spasticity in two patient groups: in older ambulatory children with inadequate underlying leg strength, and in patients with severe spasticity in both the upper and lower extremities. Responsiveness to intrathecal baclofen is confirmed by test injections before insertion of a programmable subcutaneous pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800 micrograms/day. Continuous intrathecal baclofen infusion reduces spasticity in the upper and lower extremities, and improves upper extremity function and activities of daily living but has no effect on athetosis in the dosages used to treat spasticity. Complications related to the intrathecal catheter occur in approximately 20% of patients, and infection requiring pump removal occurs in approximately 5%. Preliminary studies indicate that continuous intrathecal baclofen infusion alleviates some forms of generalized dystonia associated with cerebral palsy.
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PMID:Baclofen in the treatment of cerebral palsy. 888 81

Intrathecal baclofen reduces spasticity in individuals with cerebral palsy. Intrathecal doses are far lower than oral doses and the effects are considerably greater, and the side effects are fewer. Response to intrathecal baclofen must be confirmed by a screening trial before implantation of a pump for chronic infusion. Intrathecal baclofen reduces spasticity in the upper and lower extremities and is often associated with improved gait and upper extremity function. Quality of life improves for patients and caregivers. The Medtronic pump has been exceedingly reliable and typically functions for 4 or 5 years. The currently available intrathecal catheter is associated with far fewer complications than the initial catheter. Baclofen overdoses are unusual and are usually caused by pump programming errors rather than pump malfunction. Preliminary studies suggest that continuous intrathecal baclofen infusion reduces generalized dystonia in cerebral palsy. Screening to determine response of dystonia to intrathecal baclofen is by continuous infusion. The doses required to reduce dystonia are higher than those for cerebral spasticity. Additional investigations are underway to quantify the effects of continuous intrathecal baclofen infusion on communication, disability, and dystonia.
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PMID:Intrathecal baclofen in cerebral palsy movement disorders. 895 59

We studied the effects of intrathecal baclofen upon voluntary movements. Eleven patients with spasticity of different etiology and one patient with idiopathic dystonia were studied. Six patients participated in a double-blind trial. Kinematic/dynamic and electromyographic (EMG) patterns were recorded during attempts at single-joint elbow or ankle voluntary movements and isometric contractions. Reflex responses were also recorded. Baclofen suppressed spastic signs in 10 patients: it eliminated clonus and decreased the co-contraction of antagonist and distant muscle groups. Baclofen could induce weakness, particularly in patients with cerebral palsy (CP). Patients with hemi-syndromes did not notice any effects of baclofen in their 'unaffected' limbs. Intrathecal baclofen could improve voluntary movements in some patients with spasticity resulting in better walking and usage of arms. We hypothesize that spasticity induces an adaptive reaction at a segmental level that includes an increase in the number and/or affinity of GABA-sensitive receptors.
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PMID:Changes in voluntary motor control induced by intrathecal baclofen in patients with spasticity of different etiology. 923 40

A 15-year-old boy presented with a severe fluctuating foot and ankle dystonia resulting from a basal ganglia insult at the age of 4. This followed an embolic event related to an undiagnosed prolapsed mitral valve. Functionally, the patient was ambulatory with rocker bottom crutches and an ankle-foot orthosis, but there were periods of up to a year when pain and increased dystonic deformity required him to use a wheelchair. A new orthotic was made nearly every month because the orthotist could find no material that would withstand his tone without breaking, yet he could not ambulate without one. Multiple interventions, including biofeedback, contrast baths, stretching and strengthening, oral lioresal (Baclofen), diazepam (Valium), benztropine mesylate (Cogentin), carbidopa-levodopa (Sinemet), carbamazepine (Tegretol), and injections of botulism toxin (BOTOX) were tried, all with minimal effects. Amputation was recommended, based on anatomic and functional considerations. The patient and his family adjusted well to this decision, although not all orthopedists and therapists adjusted easily to the choice. The patient is now functionally independent with a prosthesis and has a normal teenage lifestyle for the first time.
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PMID:An aggressive approach to limb dystonia: a case report. 959 5

Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).
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PMID:Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia--a report of two cases. 1197 95

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.
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PMID:[Chronic high frequency deep brain stimulation of the globus pallidus internus for torsion dystonia]. 1209 79


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