Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008

revealed that closure of the palpebral aperture, named the blink completeness, is higher in healthy subjects than in soft lens wearers.49 Blepharoptosis can be induced by rigid contact lenses and can reduce eyelid motility. A study of the effect of aging on rigid contact lens wearers revealed that lid saccades in both groups have smaller amplitudes and lower peak velocities.50

In order to study the effect of aging in healthy subjects and in subjects with schizophrenia and other neuropsychiatric disorders, prepulse inhibition of the acoustic startle response was used. The combination of a 30-500 ms weak prestimulus preceding a startle stimulus enables measurements of startle plasticity and habituation. A decrease of the startle amplitude and an increase of the startle latency were measured in a large group of non-psychiatric subjects.51

In Parkinson’s patients and in patients with dry eye, prepulse inhibition experiments caused an increased excitability of the reflex blinks.52 The authors concluded that prepulse inhibition reflects the intrinsic characteristics of the blink reflex circuit.

Lid saccades of upper and lower eyelids can also be affected by aging. In a study of two groups, one 20-30 years of age and the other 60-91 years of age, no significant difference in saccade amplitude was found. However, in the elderly group, a clear decline in peak velocity of the upper eyelid and an increase of the amplitude of the lower eyelid were measured.53

Facial Movement Disorders

Hemifacial paralysis (Bell’s palsy)

Facial nerve palsy may have a variety of causes such as trauma, nerve compression, toxins, and infection. In over 50 percent of facial nerve palsy patients the cause is unknown. The syndrome is then termed idiopathic facial nerve palsy, or Bell’s palsy. The most common infectious agents that may cause facial palsy are the herpes simplex and varicella zoster viruses. However, a recent study about the detection of herpes simplex (HSV-1) and varicella-zoster (VZV) viruses in patients with Bell’s palsy revealed that HSV-1 or VZV DNA was detected in only two of the 20 patients.54 This proportion is much smaller than that found in the study of Murakami and coworkers,55 indicating that it is still unclear whether the assumption of viral involvement in the etiology of Bell’s palsy is valid.

Some authors reported an enhanced blink rate in Bell’s palsy patients.56,57 Others postulated that reduced eyelid motility may produce increased trigeminal blink reflex excitability after stimulation of the supraorbital nerve ipsilateral to the palsied eyelid.58 The chance of affliction increases with age but is gender independent.

In patients with a substantial distal degeneration of the facial nerve, R1 is absent during electrical supraorbital nerve stimulation, and the M wave is markedly reduced in amplitude for several months, and in some cases for a few years.

Fig. 19.7 In severely affected Bell’s palsy patients, the OO-muscle activity on the palsied side is normal one year, while the concomitant eyelid movement remains deviated

In the nineteenth century Sir Charles Bell observed in facial nerve palsy patients an upward eye movement during blinking in the palsied eye.59 He noted that only the eye at the palsied side rotates in a delayed upward direction, but not that both eyes rotate! Later this misinterpretation was quoted world-wide.

This observation must not be confused with Bell’s phenomenon observed in 1823.60 Bell’s phenomenon exists during forceful voluntary eyelid closure and can be described as a slow upward and outward deviation of the eyes.46 This phenomenon is also seen in healthy subjects during spontaneous blinking.61

In a longitudinal study of severely affected Bell’s palsy patients the direction of the eye movements during voluntary (and often during spontaneous) blinking remained impaired throughout recovery, which was a year and a half after the onset of the affliction.1 Interestingly, the direction of eye movement during reflex blinking was normal after one year, indicating that structural changes may take place in the somatosensory and motor cortex.

The preliminary results of a longitudinal recovery study of blink and mouth movements in severely affected Bell’s palsy patients using the functional MRI technique revealed that the representation fields in the motor cortex and probably the somatosensory cortex for blinking and mouth movements change in size. Monitoring the distinct motor cortex regions which are directly or indirectly involved in blinking and mouth movements on the palsied side revealed no significant changes in the first three months. Subsequently, a strong enhancement of the blink area and a less prominent enhancement of the mouth region were observed between four months and one year (unpublished results; see Fig. 19.8). The results of this ongoing study have now been monitored for a year and a half. The plasticity noted in the motor cortex representation areas in the study implies that Bell’s palsy is not purely a peripheral affliction; it should be realized that central reorganizations in the motor cortex can influence an optimal recovery. This is supported by a study about motor cortex plasticity, which revealed that rehabilitation is very important for an optimal facial function after brain injury.62

The major complications of peripheral facial nerve palsy are synkinesia, facial weakness, and the occurrence of corneal ulceration due to an incomplete closure of the palsied eyelid, the lagophthalmos.

Fig. 19.8 A strong enhancement of the blink area and a less prominent enhancement of the mouth region were observed between four months and one year

Directly after the paresis of the orbicularis oculi muscle, eyelid closure is imperative, and gentle closure of the palsied eyelid by gravity is inhibited by the tonic activity of the levator palpebrae superioris muscle.

In addition lid saccades, mainly executed by the levator palpebrae superioris muscle, are also affected in Bell’s palsy patients. This phenomenon, named thixotropy, can be eased by regular stretching of the levator palpebrae superior muscle.45

In order to improve facial symmetry of late or partially recovered Bell’s palsy patients, non-surgical intervention with facial physiotherapy, botulinum toxin injections, or surgical treatment can be necessary63. Botulinum toxin is often used to diminish synkinesia of facial structures. However, the result is temporary and often unsatisfactory; but alternatives are few.

Electrical stimulation of facial muscles during recovery may be one of these alternatives although improvement of eyelid movement is often very poor.64 An electrophysiological study in Bell’s palsy patients showed that patients with residual facial weakness showed enhanced blink reflex recovery after electrical SO nerve

stimulation on the palsied side.57 Cossu and coworkers65 suggested starting “treatment” about 3 months after onset of complete facial nerve palsy, the period when the first connections are made between growing axons and denervated muscles. At this stage very little muscle activity was detected in these patients. Starting therapy at that stage risks an overstimulation (activation) of facial muscles at the non-palsied side, which could result in pronounced facial asymmetry. In order to prevent the overstimulation, prudence should be used regarding the start of the training. VanderWerf and coworkers1 recommend starting therapy directly after the first signs of innervation of both the OO and orbicularis oris muscles.

Apraxia

Another effect of aging was seen in a large group of subjects over 60 years of age who suffered from apraxia of eyelid opening or closure.

Patients with apraxia of eyelid opening have difficulty initiating the act of eyelid opening on command.66,67 Many of these patients also exhibit an inability to keep the eyelids open for long period of time. Aramideh and coworkers68 found that involuntary inhibition of the palpebrae superioris muscle activity causes an inability to keep the eyelids open or to reopen them after involuntary closure. This form of apraxia accompanies the focal dystonia blepharospasm and is more frequently seen in patients with extrapyramidal disorders. However, dystonia is unlikely to account for all cases of apraxia of eyelid opening.69 In one population study of apraxia of eyelid opening, the affliction coincided with adult-onset blepharospasm in 75 percent and with atypical Parkinsonism in 25 percent of the cases.70

Apraxia of eyelid closure is characterized by the inability of the patient to close the the eyelids on command. However, spontaneous blinking is preserved and several patients deny that the eyelids remain open on attempts to close them. The affliction is often associated with parietal lobe lesions.

Hemifacial spasm

Hemifacial spasm is characterized by involuntary, paroxysmal bursts of tonic and clonic contractions of muscles on one side of the face. It is named primary or idiopathic when it does not follow Bell’s palsy, and secondary or postparalytic when it does.71

The most common cause of primary facial spasm is compression of vascular malformation: for instance, a cerebellar artery, impinging on the facial nerve at the exit of the pontine level. Several types of posterior fossa tumours have also been reported in association with hemifacial spasm.72

The “postparalytic” hemifacial spasm, though less frequent, should be differentiated from the “primary” hemifacial spasm, as well as from synkinesia due to aberrant regeneration after Bell’s nerve palsy (post-Bell’s palsy synkinesia).

A

LP

OO

B

LP

OO

LP

OO

Fig. 19.11 Another feature is the constant in shape and kinematics of blink profiles after repeated exposure to a given stimulus (with courtesy of Dr. M. Aramideh).

reflex recovery curves in blepharospasm patients is used to determine the abnormal excitability enhancement of interneurons in the brainstem and the motor cortex. Reduction of the inhibition of the R2 response can also be detected.78

A minority of patients also have involuntary levator palpebrae inhibition. In all of these patients the R2 is enhanced in the recovery curves, indicating an abnormal processing of sensory inputs, and leading to excessive activity in premotor circuits.

Compelling evidence is presented in the literature that the cerebellum is also involved with leg and blink reflexes.30,32,79

The main functional role of the cerebellum is its involvement with associative learning and memory39 and balance control.80 Associative learning and memory can be studied with eyeblink conditioning using the delay, the trace, or the startle conditioning paradigms. Delay conditioning is used to study the functioning and involvement of the cerebellum. Trace conditioning is used to study the involvement of the hippocampus in learning, and startle conditioning is used to investigate the involvement of the amygdala.

For the delay conditioning paradigm, a 500 ms tone is used as the conditioning stimulus, and a 20 ms air puff, as the unconditioned stimulus, is presented at the end of the tone. Both stimuli end simultaneously.39 For the trace conditioning paradigm, a 20 ms air puff is used as the conditioned stimulus, followed 250 ms later by a 100 ms air puff as the unconditioned stimulus,6

Aging influences awareness during the trace conditioning, especially when the trace time is increased.81 This was confirmed by a study on the effects of age and awareness using eyeblink conditioning, which revealed that increased age is associated with a decline in the overall eyeblink conditioned response frequency.82

One of the main features of a reflex blink is the exact timing of the onset of the movement in response to a stimulus. Another feature is the constancy in shape and kinematics of blink profiles after repeated exposure to a given stimulus (Fig. 19.11). Both parameters are modulated by the cerebellum, but knowledge of the blink reflex modulation is limited, and different interpretations of the role of the cerebellum do not always agree with each other. The major studies support the concept that the cerebellum modulates both conditioned and reflex blinks. Two cerebellar structures are most often mentioned, the cortex83 and the nucleus.84

A study of various cerebellar ataxia patients reveals impaired eyeblink conditioning in several subtypes of cerebellar ataxia. Besides their inability to learn during delay eyeblink conditioning and their decreased blink rate, spinocerebellar ataxia (SCA) 3 and 7 and multiple system atrophy patients are unable to time their blink reflex (unpublished results; see Fig. 19.12). In another study of the maximal amplitude of unconditioned eyeblink responses, “the blinks” varied using the same paradigms. This might indicate also that a brainstem structure like the olivary body is involved in the feedback control of reflex blinking, and not the deep cerebellar nuclei as suggested by Welsh.83

Conclusion

The world of blinking and blinking-related movements is generated, regulated, and controlled by many brain structures. External factors, such as the environment, or internal factors, such as aging, can have great consequences for the normal function of the blink.

Fig. 19.12 Spinocerebellar ataxia (SCA) 3 and 7, and multiple system atrophy patients are unable to time their blink reflex

References

1.VanderWerf F, Reits D, Smit AE, Metselaar M (2007) Blink recovery in patients with Bell’s palsy: a neurophysiological and behavioural longitudinal study. Invest Ophthalmol Vis Sci 48:203-213

2.Sullivan BD, Evans JE, Dana R, Sullivan DA (2006) Influence of aging on the polar and neutral lipid profiles in human meibomiam gland secretions. Arch Ophthalmol 124: 1286-1292

3.Lander T, Wirtschafter JD, McLoon LK (1996) Orbicularis oculi muscle fibers are relatively short and heterogeneous in length. Invest Ophthalmol Vis Sci 37:1732-1739