The current study demonstrates that combining two mild alterations to the rat trigeminal reflex blink system reproduces the symptoms of benign essential blepharospasm, a cranial dystonia characterized by uncontrollable spasms of blinking. The first modification, a small striatal dopamine depletion, reduces the tonic inhibition of trigeminal reflex blink circuits. The second alteration, a slight weakening of the lid-closing orbicularis oculi muscle, begins an adaptive increase in the drive on trigeminal sensory-motor blink circuits that initiates blepharospasm. By themselves, neither of these modifications causes spasms of lid closure, but combined, they induce bilateral forceful blinking and spasms of lid closure. A two-factor model based on these rodent experiments may explain the development of benign essential blepharospasm in humans. The first factor, a subclinical loss of striatal dopamine, creates a permissive environment within the trigeminal blink circuits. The second factor, an external ophthalmic insult, precipitates benign essential blepharospasm. This two-factor model may also be applicable to the genesis of other cranial dystonias.
This study characterizes trigeminal blinks in normal human subjects between 20 and 80 years of age, 60-year-old Parkinson's disease patients, and young and old guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the excitability and latency of the trigeminal reflex blink increase significantly relative to younger subjects. Aged guinea pigs appear to display similar increases in reflex blink duration and latency. Reflex blink amplitude, however, does not change consistently with age. For subjects less than 70 years of age, a unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds exhibit blinks of equal amplitude. In all cases, blink duration is identical for the two eyelids. If normal, age-related loss of dopamine neurons explains these trigeminal blink modifications, then Parkinson's disease should exaggerate age-related changes in these blink parameters. Preliminary data show that Parkinson's disease increases blink duration and excitability relative to age-matched control subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons accounts for increases in trigeminal blink excitability and duration. A previously uncharacterized type of trigeminally evoked blink appears after age 40 in humans and in aged guinea pigs. In subjects less than 40 years old, a single trigeminal stimulus elicits a single reflex blink. In subjects over age 40, however, a single stimulus frequently evokes a reflex blink and additional blinks that occur at a fixed interval relative to the preceding blink. These "blink oscillations" may arise from oscillatory processes within trigeminal reflex blink circuits. The presence of exaggerated blink oscillations in subjects with dry eye and benign essential blepharospasm suggests that an alteration of blink oscillation mechanisms plays a critical role in these disorders.
Keywords dry eye; blinking; blepharospasm; eyelid movements; blink oscillations; brainstemThe primary purpose of the eyelids is to ensure corneal integrity. An important component of this protective function is maintaining the corneal tear film. Blink characteristics can determine tear film stability. Increasing blink amplitude thickens the lipid layer that overlies the aqueous layer of the tear film. This thickening reduces evaporation of the aqueous layer. Because each blink reforms the tear film, increasing blink frequency reduces tear film breakup. [1][2][3][4] Both innocuous stimuli such as air across the eyelashes, and noxious stimuli such as touching the cornea, elicit trigeminal reflex blinks. If abnormal corneal afferent activity caused by corneal irritation acts as an "error signal" that adjusts the amplitude and frequency of reflex blinks evoked by both innocuous and corneal stimuli, then corneal irritation creates an adaptive blink response regardless of whether a corneal or an innocuous trigeminal stimulus elicits the blink.An investigation of the effects of aging on trigeminal blinks 5 supports the hypothesis that corneal irritation modifies trigeminal reflex blinks evoked by innocuous stimuli. In people over age 40 years, a single innocuous, supraorbital (SO) nerve stimulus frequently evokes a reflex blink and additional blinks that occur at a nearly constant interval relative to the onset of the preceding blink, blink oscillations. Because blink oscillations are more frequent and larger than reflex blinks, this modification increases tear film stability. Peshori and colleagues 5 propose that the development of consistent blink oscillations in many individuals over age 40 years is a blink adaptation that compensates for the subclinical reduction in corneal wetting that accompanies aging. 6 This hypothesis predicts that innocuous SO stimuli should produce more blink oscillations in people with dry eye than in age-matched control subjects. We test this prediction by comparing the SO-evoked blinks of individuals with dry eye with those of age-matched controls. Given the frequent occurrence of dry eye at the onset of benign essential blepharospasm (BEB), 7 blink modifications associated with dry eye may play a role in the origin of BEB. We present a hypothesis that links the adaptive processes initiated by dry eye with the origin of BEB. METHODSMeasurements of eyelid movement and orbicularis oculi electromyographic (OOemg) activity were made on seven subjects, ranging in age from 44 to 72 years of age. Five female subjects had been diagnosed with dry eye at the SUNY Stony Brook Ophthalmology Clinic. The data from these subjects were compared with those from age-matched control subjects in another study. 5 Two normal subjects, a man and a woman, participated in an experimental paradigm described below. Apart from dry eye, no subject had any ocular disorders other than the need for corrective lenses. A previous study 8 detailed measurement of lid movements and OOemg used in the current study. Upper eye...
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