Blepharospasm is considered to be a defect in the central neurological circuit that controls eyelid muscle activity and coordination.²⁰ This circuit has sensory input, central coordination control in the basal ganglia, and motor output components. Input factors such as light, ocular surface irritation, pain, emotion, and stress send sensory impulses to the central control center. A defect in this control center, presumably in the striatal dopamine 2 receptors,²¹,²² results in altered functional connectivity in widespread areas of the brain including the thalamus and cerebellum.

The corticobasal ganglia-thalamocortical loop is thought to be responsible for the regulation of voluntary movement. This motor circuitry is segregated into direct and indirect pathways that regulate stimulatory and inhibitory effects mediated and coordinated in the basal ganglia.²³ The direct pathway connects the motor cortex and caudate and putamen of the basal ganglia. Inhibitory signals are then sent to the globus pallidus internus (GPi) and substantia nigra that suppress the thalamus through gamma-aminobutyric acid (GABA)-mediated signals. This excites projections to the motor cortex, promoting muscle movement. The indirect pathway inhibits signals through the basal ganglia. It is responsible for disinhibiting the subthalamic nucleus, which ordinarily stimulates the GPi. This inhibitory signal suppresses muscle movement. In dystonia, it has been proposed that there is an imbalance between the direct and indirect pathways so that the indirect pathway becomes dysfunctional. This results in uninhibited stimulation of the direct pathway and muscle hypertonicity.²³

Basal ganglion dysfunction is thought to play a major role in the pathogenesis of dystonias. In EB, decreased gray matter has been found in structures related to sensorimotor processing, particularly in the putamen, caudate nucleus, and thalamus.²⁴ In case reports of focal dystonias, striatal gliosis and putaminal degeneration have been identified.²⁵,²⁶,²⁷ Also, studies on experimentally induced dystonias in animals suggest a role for the putamen and corpus striatum in blepharospasm.²⁸,²⁹ Positron emission tomography scans,³⁰ and diffusion tensor magnetic resonance imaging of the putamen, corpus callosum, pallidum, and caudate nuclei in EB patients support a role for the basal ganglion in a variety of focal dystonias.³¹ These findings support the hypothesis that increased activity in the direct striatopallidal pathway inhibits the internal globus pallidus, resulting in increased inhibition in the medial globus pallidus and reduced activity in pallidal output to the thalamus.³² The result is decreased inhibition of competitor muscles associated with the spastic muscles. Several studies have shown improvement in EB symptoms with the administration of oral methylphenidate, a drug that increases intrasynaptic dopamine by blocking dopamine transmitters.³³,³⁴ Some evidence has suggested that two factors, environmental and genetic, jointly underlie the pathophysiology of dystonia.³⁵ Environmental factors include things like local injury.³⁶,³⁷ In EB, up to 20% of patients have one or more family members with focal dystonia, essential tremor, or Parkinson disease.³⁸,³⁹ This suggests a genetic predisposition. Animal models and population studies have suggested that predisposing genes are inherited in an autosomal dominant fashion with low penetrance.⁴⁰,⁴¹,⁴² Studies have also shown polymorphisms in the D5 dopamine receptor (DRD5), and a group of DYT gene polymorphisms has been linked to some inherited dystonias.⁴²,⁴³,⁴⁴ However, no specific genetic factors have been identified specifically for EB.

EB is seen primarily among older individuals at a mean age of 64 years but rarely can be seen in children and adolescents.⁴⁵ Females are affected 2.5 times more frequently than males and tend on average to be 4 to 5 years older. Symptoms of EB range from increased frequency of blinking to sustained forceful, sometimes painful, squeezing of the eyelids that can lead to functional blindness. In many cases, the spasms may be localized to the eyelid protractor muscles alone as a focal dystonia (Figure 32.1). But with progression, spasms may also involve adjacent areas of the head and neck. Midfacial or lower-facial spasms are most often involved as a segmental dystonia (Figure 32.2A) or may spread even further to the neck as a regional dystonia (Figure 32.2B). Eyelid closure is bilateral and symmetrical and can range from increased frequency of blinking to occasional mild intermittent closure, to persistent forceful squeezing that may be difficult to overcome manually. Long-standing blepharospasm may be associated with anatomic eyelid changes, including dermatochalasis, eyelid and brow ptosis, entropion, and ectropion.⁵,⁴⁶ These frequently result from patients trying to manually open their eyes with their fingers or other devices such as tape or ptosis crutches (Figure 32.3). Upon careful questioning, patients frequently report certain precipitating factors such as driving, reading, stress, and bright lights.