Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vigabatrin was specifically designed to enhance gamma-aminobutyric acid (GABA) function in the CNS. By increasing brain concentrations of this inhibitory neurotransmitter the drug appears to decrease propagation of abnormal hypersynchronous discharges, thereby reducing seizure activity. At this stage in its development, clinical experience with vigabatrin is limited primarily to patients with refractory seizure disorders. In this difficult-to-treat population, 'add-on' therapy with vigabatrin greater than or equal to 2 g/day has shown impressive efficacy, reducing seizure frequency by greater than or equal to 50% in approximately half of patients. Clinical efficacy does seem to vary with seizure type with the best response reported in adults with complex partial seizures with or without generalisation and in children with cryptogenic partial epilepsy or symptomatic infantile spasm. Vigabatrin appears to have a negative effect on absences and myoclonic seizures. Some disorders of motor control may also be amenable to enhanced GABAergic function. In the small number of patients with tardive dyskinesia treated to date, vigabatrin produced mild to moderate improvement in hyperkinetic symptom scores but Parkinsonism or schizophrenic symptoms occasionally worsened. The best response was reported in a study of patients who had been withdrawn from neuroleptic therapy. In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis. Most adverse reactions to vigabatrin are mild and transient with central nervous system (CNS) changes being reported most frequently. Of particular note, serial evoked potential studies and the few available histology reports have not found evidence of intramyelinic oedema during therapeutic use, as was reported in rats and dogs on chronic high-dose treatment. Thus, vigabatrin is a promising new anticonvulsant drug. Current evidence supports a trial of this agent as adjunctive therapy in patients with refractory seizure disorders, and future investigation of vigabatrin monotherapy and its efficacy relative to established agents is awaited with interest. Wider experience should help to clarify which patients - by seizure type and concurrent CNS pathology - are likely to benefit from vigabatrin and ongoing monitoring should further clarify the potential detrimental effects, if any, of long term use. In the meantime, it is a welcome addition in the difficult setting of resistant epilepsy.
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PMID:Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. 171 66

Baclofen is widely used in the treatment of spasticity of spinal origin. It is relatively free of side effects or toxic actions on the nervous system or other organs. Agitation, personality change, and auditory and visual hallucinations have been described following its abrupt withdrawal. One patient with generalized seizures and one with complex partial seizures after baclofen withdrawal have been reported. This paper presents a patient who developed status epilepticus after baclofen withdrawal, and who sustained hypoxic cerebral injury. This observation further emphasizes the possibility of infrequent complications of baclofen therapy, and the advisability of gradual changes in baclofen dosage.
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PMID:Status epilepticus after baclofen withdrawal. 673 10

The aim of this study was to examine whether severity of epilepsy, motor functioning, and epilepsy-related restrictions change in children with medically intractable epilepsy who are ineligible for epilepsy surgery. The study was a prospective, longitudinal, 2-year follow-up of 28 children (14 females, 14 males). Their median age was 6 years 1 month (range 7mo-15y 4mo). Seizure types were: complex partial seizures (n=16), secondary generalized seizures (n=7), simple partial seizures (n=2), and mixed seizures (n=3). Severity of seizures, motor impairments, motor development, activities of daily life, and epilepsy-related restrictions were rated at baseline and 6, 12, and 24 months thereafter. Seizure severity did not change significantly, nor did muscle strength, range of motion, or muscle tone. Motor retardation was ubiquitous but did not increase in 20 children without spasticity. Motor function of eight children with spasticity improved (Gross Motor Function Measure: baseline 70.5 [SD 35.5]; 24 months later 81.6 [SD 29.6], p < 0.05) but remained below reference values in four children. In the entire group, functional skills increased and caregiver assistance lessened. Restrictions did not change significantly. We conclude that during a 2-year follow-up period, in children with medically intractable epilepsy who do not have surgical intervention, seizure severity does not deteriorate, motor impairments do not increase, motor development does not deflect negatively, and activities of daily living and restrictions do not worsen.
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PMID:No deterioration in epilepsy and motor function in children with medically intractable epilepsy ineligible for surgery. 1735 79