Tratamento da doença de Meige com droga agonista de receptores GABA

Abstract

The spontaneous occurrnce of blepharospasm and dystonic movements in face muscles, particularly those of the perioral and mandibular regions, has been named Meige's disease. Other dystonic features as spasmodic torticollis, dysphagia, spasmodic dysphonia and segmental dystonia of the limbs may, eventually, be present in the same patient. There is very little knowledge about the pathology of this disease. Many hypotheses concerning the pathophysiology of this entity have been put forward, most of them correlating the clinical response to several drugs with known action on the neurotransmitter system of the brain. There are some evidences that it may exist a dopaminergic preponderance in the disease. In the nigro-striatal pathway, one of the retrograde loops in the feed-back control of dopamine synthesis by nigral neurons is dependent on GABA. Increasing GABA activity through GABA agonists that cross the blood-brain barrier could result in a decreased dopaminergic action in the nigro-striatal pathway and, thus, ameliorate the dystonic symptoms which might have been produced by its increased function. We have used baclofen, a GABA-agonist drug, to treat five patients with Meige's disease, in a single-blinded trial. These were four females and one male, with age ranging from 50 to 63 years. The drug was started at 20mg/day, being increased by 10mg each three days reaching a maximum dose of 70mg/day. One of the patients showed marked improvement of blepharospasm and orofacial dystonia and a second patient had a moderate improvement in the same symptoms. Another patient showed moderate improvement of limb dystonia, but had no benefit in the facial movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortical Silent Period Reveals Differences Between Adductor Spasmodic Dysphonia and Muscle Tension Dysphonia

“…Clozapine, a GABA receptor antagonist, has also reportedly reduced symptoms of oromandibular dystonia and laryngeal dystonia in single case reports 54,55 . Due to the limited randomized, controlled trials of the effectiveness of GABA modifying drugs in the treatment of focal dystonia and the inconsistent and unpredictable outcomes, GABA modifying drugs have not been adopted into routine clinical practice 56,57,58 .…”

Shortened cortical silent period in adductor spasmodic dysphonia: Evidence for widespread cortical excitability

“…The source of this altered inhibitory process is beyond the scope of this project and not fully understood. Research suggests the mechanism may be due to a loss of thalamic input to motor cortices as a result of alterations in basal ganglia excitability [21] or a decrease in GABA B in the primary motor cortex [11,17]. The impaired inhibition distant from the affected musculature in AdSD suggests this impairment is widespread beyond the cortical bulbar system into the cortical spinal system.…”

Meige Syndrome: An Eternal Diagnostic Confusion

“…Though studied for a long time, the cause of Meige syndrome still remains elusive and treatment remains debatable. Basal ganglion dysfunction has been postulated with involvement of dopamine receptors [5]. In the nigro-striatal pathway, one of the retrograde loops in the feed-back control of dopamine synthesis by nigral neurons is dependent on GABA.…”

“…In the nigro-striatal pathway, one of the retrograde loops in the feed-back control of dopamine synthesis by nigral neurons is dependent on GABA. Increasing GABA activity through GABA agonists that cross the blood-brain barrier could result in a decreased dopaminergic action in the nigro-striatal pathway and, thus, ameliorate the dystonic symptoms which might have been produced by its increased function [5]. Baclofen, a GABA agonist, has been tried in dystonias for the above reason and has shown variable results.…”