Brain Changes in Blepharospasm

Objectives

This proposal will evaluate the role of an increase in excitability of the orbicularis oculi (OO) muscle representation in the medial frontal areas (supplementary motor areas, SMA) and anterior rostral cingulate: M3) in excessive blinking in patients with benign essential blepharospasm (BEB). We hypothesize that:

• at rest, the decrease of the MEP after 15 minutes of 1Hz rTMS, targeting the SMA-M3, is more prominent in patients with BEP than in healthy control subjects,
• at rest, the decrease of the MEP after 15 minutes of 1Hz rTMS targeting M1, is almost the same in patients with BEP and in healthy control subjects,
• at rest, sICI of OO muscle will be decreased and ICF increased after stimulation of the SMA-M3 facial cortical area, in patients with BEP compared to healthy control subjects,
• at rest sICI and ICF of the OO muscle will be the same after stimulation of the M1 facial area in patients with BEP and healthy control subjects,
• in healthy control subjects facilitation of the MEPs evoked from M1 is more prominent during voluntary blinking,
• in healthy control subjects facilitation of the MEP evoked from SMA-M3 is more prominent during involuntary blinking,
• in patients with BEB there is facilitation of MEPs evoked from M1 and SMA-M3 during voluntary and involuntary blinking.
• it is possible to evoke consistent and reproducible motor evoked responses (MEP) in the orbicularis oculi (OO) muscles by stimulating the two main cortical representations of upper facial region: in the medial frontal wall (SMA and cingulate cortex - its rostral part, M3) and in the primary motor cortex (M1) with transcranial magnetic stimulation (TMS).

Study population

36 patients with BEB but without severe forceful closure of eyelids, 36 normal volunteers.

Study design

Subjects will have 3 visits:

Visit 1: screening and blepharospasm score

Visit 2: stimulation of the OO muscle representation in SMA-M3 using low frequency rTMS (1Hz) with the Hesed coil (designed to stimulate deep brain).

Visit 3: stimulation of the OO muscle representation in M1 using low frequency rTMS (1Hz) using a standard eight-shaped coil.

Visits 2 and 3: single pulse TMS will be used to evoke MEPs from OO muscles. Paired pulse TMS will be used to assess sICI from OO muscles. The order of visits 2 and 3 will be randomly assigned.

Outcome measures

The main outcome measures will be the sizes of OO muscle MEPs and the amount of sICI assessed before and after 15 minutes of low frequency rTMS. The secondary outcome measures will be the sizes of OO muscle MEPs assessed before and during voluntary and involuntary blinks.

• INCLUSION CRITERIA:
• Healthy volunteers (aged 18 or older) who are willing to participate.
• Patients (aged 18 and older) with benign essential blepharospasm

Exclusion criteria

FOR HEALTHY VOLUNTEERS:

• Subjects with a history of neurological or psychiatric disorder, current use or a history of alcohol or drug abuse, psychiatric disorders requiring hospitalization or prolonged treatment, head injury with loss of consciousness, or epilepsy.
• Subjects receiving drugs acting primarily on the central nervous system

Exclusion criteria

FOR PATIENTS:

• Subjects with a history of neurological disorders other than blepharospasm
• Subjects with a history of a psychiatric disorder, current use or a history of alcohol or drug abuse, psychiatric disorders requiring hospitalization or prolonged treatment, head injury with loss of consciousness, or epilepsy.
• Subjects receiving drugs acting primarily on the central nervous system
• Subjects who have been treated with botulinum toxin injections within 3 months prior to their participation in the study
• Subjects who are taking any medication for dystonia at the time of the study
• Subjects with severe forceful closure of eyelids, subjects scoring more than 20 on the Blepharospasm Disability scale (Lindeboom et al., 1995).
• Patients for whom participation in the study would, in the opinion of the investigators, cause undue stress or excessive apprehensiveness will also be excluded. The reason for that is that, in some patients, any stressful situation (like a medical exam or experiment) may cause a strong increase in the involuntary blink rate leading to a severe functional discomfort.

The following exclusion criteria are due to the use of transcranial magnetic stimulation and repetitive transcranial magnetic stimulation up to 1Hz (Hallett 1999) for healthy volunteers and patients:

• Subjects with cardiac pacemakers, intracardiac lines, implanted medication pumps.
• Subjects with eye, blood vessel, cochlear, or eye implants.
• Subjects with increased intracranial pressure as evaluated by clinical means
• Subjects with metal in the cranium
• Subjects with dental braces (but dental fillings are not a problem), metal fragments from occupational exposure or surgical clips in or near the brain.
• Subjects with a personal or family history of hearing loss