BACKGROUND: Blepharospasm (BSP) is a common form of focal dystonia, but the etiology and underlying pathophysiological mechanisms are still obscure. BSP is characterized by excessive involuntary closure of the eyelids. Pathological changes in excitability in the primary motor cortex (MC) and secondary motor areas, such as the anterior cingulate (AC), pre-and supplementary cortex (PMC, SMA) are suggested from electrophysiological and brain imaging studies. It is conceivable that modulation of excitability in some of these areas may lead to amelioration of the symptoms of BSP. Cortical excitability can be experimentally changed by various well-established electrophysiological techniques non-invasively. METHODS: In this pilot protocol, studying 30 patients with BSP, we will use repetitive transcranial magnetic stimulation (rTMS) over the AC, PMC, SMA and MC in two different inhibitory modes: low frequency rTMS ((lf) rTMS) and continuous theta burst stimulation cTBS. Furthermore, we will apply transcranial direct stimulation (tDCS) in an inhibitory mode (cathodal tDCS) over the MC and low intensity high frequency supraorbital electrical stimulation; the latter will be performed in patients and in 7 healthy subjects. The effects on blepharospasm will be objectively measured by electrophysiological measures (blink reflex recovery curve (BRR), blink rate observation by an investigator blinded to the intervention, and a subjective rating by the patient. OBJECTIVES: We hypothesize that we will find variable amounts of clinical improvement in BSP patients with these different methods. With this study, we aim to get more insight to the underlying pathophysiological mechanisms of BSP and identify which method of non-invasive brain stimulation may be clinically most efficacious.
- INCLUSION CRITERIA PATIENTS: - Patients with idiopathic BSP or Meige-Syndrome (=BSP plus oromandibular dystonia). - Age 18 years or older. - Normal findings in the medical history, physical and neurological examination, except for dystonia (in cases that patients have not had an H& P at the NIH within the last 12 months; they will undergo all these exams on the first study day). - Last treatment with botulinum toxin more than three months ago. INCLUSION CRITERIA CONTROLS: - Age 18 years or older - Normal findings in the medical history, physical and neurological examination - No history of neuroleptic medications/ prior use of neuroleptics (such as Haldol(Registered Trademark)) - Not been treated or taken anti-depressants, anti-seizure medication, anticholinergic drugs (such as Artane(Registered Trademark)) and muscle relaxants within the past 4 weeks EXCLUSION CRITERIA PATIENTS: Any of the following will exclude a patient from the study: - Other disease with involuntary blinking (Hemifacial spasm, Tic disorder, Tardive Dyskinesia, Tardive dystonia, etc). - BSP and normal recovery of R2 in BRR. - Participation in a clinical trial in the 2 weeks preceding the study. - History of seizure disorder. - Pregnancy- a pregnancy test will be performed for women of childbearing potential. - Symptoms of a clinically relevant illness in the 4 weeks before the first study day, including history of any other neurological disorders or conditions requiring the use of anti-depressants, neuroleptic medications or anti-seizure meds., anticholinergic drugs and muscle relaxants. - History of neuroleptic medications/prior use of neuroleptics. EXCLUSION CRITERIA CONTROLS: A botulinum toxin injection within 3 months of starting the protocol Any condition that requires the use of anti-depressants, anti-psychotic or anti-seizure medications Cannot follow the instruction through the entire recording Not able to provide consent to participate in the study Patients will be screened and recruited from the outpatient clinic of the HMCS, NINDS. Age matched volunteers will be recruited from the NIH Patient Recruitment and Public Liaison Office.