Introduction
Learning Objectives:
- To review the pathophysiology and secondary causes of blepharoplasm
- To review the mechanism of action and administration of botox for patients with blepharoplasm
- To review other medical, surgical, and supportive treatments for blepharoplasm
Course Credit:
2 hours
Case
An 85
year old female presents to your clinic with a 5 year history of painful
“spasms” of her eyelids. Approximately 5
years ago, she started noticing intermitting “twitching” of her right
eyes. A few months later this was
followed by intermittent spasms that caused the eye to close completely. Over time she developed similar symptoms in
the left eye, and says the spasms have been increasing in both severity and
frequency. The symptoms are worse in the
right than left eyes. At worst they
occur several times a day and impair vision.
In between episodes she complains of grittiness of the eyes. She recalls no involvement of other facial
muscles.
The
patient’s past medical history is significant for hypertension and depression
for which he is on hydrochlorothiazide and Zoloft, respectively. There is no history of eye diseases or
surgeries.
On
exam visual acuity is 6/9 bilaterally.
There is excess skin in the eyelids as well as mild excoriations
presumably from the patient trying to manually open the lids during spasm. There is no weakness of facial muscles
noted. No spasms are noted during the
patient’s visit. A photograph of the
patient’s face is shown below (not during a spasm).
What
is the most likely etiology of this patient’s condition?
• Idiopathic
CORRECT
• Compression of the facial nerve
INCORRECT - Compression of the facial nerve along its course is the typical cause of hemifacial spasm, a related condition. However the clinical picture here is not consistent with hemifacial spasm, which is usually unilateral and associated with facial muscle weakness.
• Medication-induced
INCORRECT - Blepharospasm may be associated with several medications including antihistamines, dopaminergic drugs, and sympathomimetics. However both Zoloft and hydrocholorothiazide are unlikely to cause blepharospasm.
• Functional/hysterical blepharospasm
INCORRECT - Functional/hysterical blepharospasm is a diagnosis of exclusion that is characterized by blepharospasm in response to an emotionally traumatic event. The patient’s 5 year history makes this less likely, and such a diagnosis should not be considered unless there is no alternative explanation.
Introduction
Blepharospasm
is a form of dystonia characterized by spontaneous, spasmodic, bilateral,
intermittent or persistent, involuntary contractions of the orbicularis muscle.1
It is one of the more common types of dystonias, occurring at a
prevalence of 12-133 per million.2
Approximately 1 in every 10,000 people will develop the condition at
some point in their lives,3 and it affects more than 20,000
people in the United States.4
Blepharospasm
is more common in females with a male : female ratio of 1:2 to 1:3. It typically affects patients in the 5th-7th
decade of life,5 with a mean age of onset of 56,
and 2/3 of patients being age 60 or older. 6
Only rarely does it affect individuals below the age of 50.3
It may occur in isolation or as part of a spectrum of dystonic movements
of other facial or cervical muscles.7
Terminology
It is
important to clarify terminology related to facial dystonias. Briefly, some types of facial dystonias
include:
·
Blepharospasm: see above- abnormal, involuntary
spasms of the periocular musculature.1
·
Meige`s syndrome: Meige`s syndrome (also known as
idiopathic orofacial dystonia) is characterized by essential blepharospasm with
lower facial muscle involvement.7
Typical symptoms include dysarthria, dysphonia, involuntary chewing,
trismus, lip pursing, jaw deviation, and tongue protrusion.7
Meige’s syndrome is often seen in
patients on long-term neuroleptic treatment and also associated with
neurodegenerative disorders and chronic administration of levodopa. Over time, blepharospasm may evolve into
Meige’s syndrome.
·
Brueghel syndrome: Brueghel syndrome (also known
as oromandibular dystonia) is similar to Meige’s syndrome but characterized by
more extensive mandibular muscle involvement.7
Lower facial, mandibular, and cervical muscle involvement is typically severe. Blepharospasm, Meige’s syndrome, and
Brueghel’s syndrome are thought to involve a spectrum of facial dystonia.7
·
Hemifacial spasm: hemifacial spasm is a
unilateral disorder that usually begins as fasciculations of the periocular
orbicularis and surrounding muscles that spreads to involve spasms of the lower
facial muscles innervated by the facial nerve.7
Spasms are involuntary, aggravated by stress, and may persist during
sleep. Strictly speaking it is a myclonic
as opposed to dystonic disorder. A key
differentiating factor between hemifacial spasm and blepharospasm is underlying
facial weakness with hemifacial spasm.7
The etiology of hemifacial spasm is much different than the previously
mentioned dystonias and is typically caused by intracranial disease along the
course of the facial nerve.7
Typically causes include tumors of the cerebellopontine angle (e.g.
neuromas), compression of the nerve by aberrant arteries, compressing tumors or
edema of the temporal bone, demyelinating disease, and parotid tumors.7
Anatomy
The blink
reflex is an important ocular function that serves several purposes including
facilitation of tear flow, protection, and assistance with eye movements (i.e.
shifting targets). Multiple muscles are
involved in the control of blinking, the largest contributors of which are the
orbicularis oculi and levator palpebrae superioris. The orbicularis oculi muscle is typically
divided into the pre-tarsal portion (responsible for involuntary blinking), and
the periorbital portion responsible for voluntary closing.3
The levator palpebrae superioris,
originating on the lesser wing of the sphenoid bone and inserting on the upper
eyelid, is responsible for elevation and retraction of the upper eyelid. The Muller`s muscle (superior tarsal muscle)
in the upper eyelid and inferior palpebral muscle in the lower eyelid are also
important for eyelid opening.
A
normal blink is characterized by activation of protractor muscles and
inhibition of retractors. In addition to
the orbicularis, other protractors include the corrugators, procerus, and
depressor supercilli, while retractors including the levator palpebrae
superioris, superior tarsal, and frontalis muscles. Normal blinking function requires co-inhibition
of protractors and retractors.
The
nervous control for blinking is poorly understood. In general the reflex is thought to involve a
circuit consisting of a sensory limb, central control center, and motor
limb. Sensory stimuli may include dry or
irritated eyes, light, pain, emotion, stress, and other trigeminal stimulants. The location and function of the inferred “central
control centre” is debated. Likely it
includes structures in the midbrain and basal ganglia. Greater activation of dopaminergic pathways
in the striatum (a structure of the basal ganglia) is associated with a higher
rate of spontaneous blinking, while conditions with reduced dopamine (e.g.
Parkinson’s disease) have a lower rate of blinking. The motor limb involves the facial nucleus,
facial nerve, and corresponding muscles as previously discussed.
Given
the association of blepharospasm with other facial dystonias, a short
discussion of muscles of facial expression is important. Facial expression muscles are supplied by
terminal branches of the facial nerve (VII).3
These terminal branches are motor fibers, emerging from the inner part of
the parotid gland and dividing into two branches that innervate the upper,
medial, and lower thirds of the face and a portion of the neck- the
temporofacial division and cervicofacial division.3
Fibers tend to be intertwined so that one muscle can be supplied by more
than one nerve.3
Pathophysiology
In
the early part of the 20th century, blepharospasm was thought to be
a psychiatric disorder with many sufferers being sent to asylums rather than
doctors’ offices. Although the
pathophysiology continues to be poorly understood, recent studies have shown it
is in fact an organic neurologic disorder.
As
previously discussed, the blink reflex consists of a sensory component, central
control centre, and motor component. Patients
with blepharospasm have a hyperexcitable blink reflex, and may have
abnormalities at any one of these stages.
We will discuss some of the more common abnormalities which may
contribute to blepharospasm:8
Increased
excitability of brainstem interneurons
Increased
excitability of brainstem interneurons in the “central control centre” is
thought to be a key factor in the pathogenesis of blepharospasm. Studies have demonstrated abnormal
excitability of the R2 component of the blink reflex,9
and that sensory stimulation tricks lead to normal gating of this R2
component.10
It is thought that subclinical loss of striatal dopamine in the basal ganglia
causes the blink circuit to be vulnerable to excitation by environmental
insults or triggers.4
Such loss of dopamine occurs naturally with aging and is accelerated in
patients with Parkinson’s disease. A
central control centre prone to hyperexcitation by this and other causes may
create a permissive environment for development of blepharospasm.11
Increased
trigeminal sensory stimulus
Patients
with blepharospasm often have coexisting ocular abnormalities such as
orbicularis weakening which leads to ocular exposure and irritation. This increased sensory stimulus in the
setting of easily excitable interneurons initiates a cycle in which sensory
stimulus is increasingly able to incite uncontrolled motor activity. 5
Widespread
sensory abnormalities
It is
likely that patients with focal dystonias such as blepharospasm also have a
more widespread sensory disorder that is a contributing factor. For example, studies on patients with
blepharospasm have shown deficits in tactile temporal discrimination as a
result of loss of inhibitory sensory mechanisms, suggesting a fundamental
deficit in sensory inhibition as a contributing factor.12 13
Other sensory abnormalities noted in patients with blepharospasm include
an abnormal auditory startle and trigemino-sternomastoid reflex.14, 15
Abnormal
plasticity in blink reflex
It
has also been shown that patients with blepharospasm have abnormal plasticity
in the blink reflex circuit.16
Neuronal plasticity is the ability of the human brain to change in
response to intrinsic or extrinsic inputs and microscopically is characterized
by synaptic rearrangement. Mostly an
adaptive response (e.g. in response to damage, learning, etc.), abnormal
plasticity can cause deleterious effects such as blepharospasm.
Cortical
abnormalities
While
cortical areas are involved in blinking, their importance with blepharospasm is
debated. Studies using transcranial
magnetic stimulation (TMS) have shown a number of abnormalities in the primary
motor cortex of patients with blepharospasm including an abnormal cortical silent
period and short-interval intracortical inhibition, both signs of cortical
excitability.17
Other studies with functional MRI
have shown decreased activation of the primary and ventral premotor cortex and
increased activation of the cortical somatosensory areas, supplementary motor
area (SMA), thalamus, caudate, putamen, globus pallidus pars interna (Gpi) and
cerebellum).18
Etiology
Blepharospasm
may be either primary (i.e. no underlying etiology) or secondary. Often, primary blepharospasm is referred to
as “benign essential blepharospasm”, although this is somewhat of a misnomer as
such cases are thought to still have underlying neurologic abnormalities (see
pathophysiology) and many patients have severe disease that is not accurately
described to as being “benign”. On the
other hand, secondary blepharospasm is due to an underlying disease
process. The most common etiology for
blepharospasm overall is “reflex blepharospasm”, that is blepharospasm in
response to ocular surface disease (see diagnosis). Other causes of secondary blepharospasm are
rare.19
Genetics
are thought to play a key factor in risk of developing blepharospasm. Approximately 27% of patients with the
condition have at least one first degree relative with some form of focal
dystonia.20
Rarely, it may be inherited in an autosomal dominant fashion.
Several
medications are also associated with an increased risk of blepharospasm,
including benzodiazepines (acute withdrawal as well as prolonged use),
dopaminergic drugs (e.g. in patients with Parkinson’s disease), nasal
decongestants with antihistamine, and sympathomimetic drugs.3
Case reports have also described patients with B12 deficiency developing
blepharospasm that responds to B12 treatment.21
Various
neurological disorders are associated with blepharospasm. Examples include Parkinson’s disease,
Parkinson plus syndromes (e.g. supranuclear palsy and corticobasal degeneration),
Huntington’s disease, and cerebral diplegia.3 22
Symptoms/signs
Early
in the course of the disease, blepharospasm is often characterized by mild
symptoms including an increased blink rate in response to normal stimuli,
photophobia, tearing, and irritation.6
Usually patients are not diagnosed during early stages of disease. The etiology of photophobia in patients with
blepharospasm is poorly understood but may be due to central trigeminal sensitization
that produces an elevated response to intraocular nociceptors.23
Light is not only unpleasant, but also precipitates spasms.23
Photophobia is likely related to both the wavelength and intensity of
light exposure.23
Eyelid
spasm, the characteristic feature of blepharospasm, typically occurs a few
months to years after the onset of these early symptoms.3 At first it may occur unilaterally, but
usually eventually evolves to become bilateral.
Spasm typically lasts minutes to hours.
Often prior to spasm patients experience several episodes of excess
blinking lasting from a few seconds to a few minutes.3
Blepharospasm
typically has a variable course and may be intermittent or continuous. In most patients, it is slowly progressive.3
The severity of disease ranges from mild disease with a simple increased
blink rate with intermittent spasms to severe disease with frequent and long
spasms associated with severe pain and functional blindness. A high level of distress and psychosocial
impairment may be present in patients with severe disease, causing anxiety,
depression, avoidance of social contact, occupational problems, and even
suicide.
Often
patients can identify specific triggers for spasm attacks including intense
sunlight, polluted air, wind, noise, eye/head movements, stress, television,
reading and others.3
Patients may also develop sensory tricks to relieve symptoms (“geste
antagoniste”) such as tics/manners and movements of other muscles innervated by
the facial nerve (e.g. yawning, whistling, chewing gum, picking teeth,
coughing, and eating).17
Activities requiring mental concentration such as crossword, math, and
puzzles may also relieve symptoms.3
Other relieving factors may include relaxation, inferior gaze, and
traction on the eyelids. Usually
blepharospasm does not occur during sleep.
In
patients with blepharospasm there is also a high frequency of irritated and dry
eyes. Approximately 50% of patients
complain of dry eyes- interestingly the objective findings are often mild in
comparison to patient complaints.23
This is likely due to widespread sensory abnormalities in such
patients. Some patients also have
anterior segment disease such as blepharitis and keratoconjunctivitis which can
contribute. Commonly, ocular symptoms
are worse just prior to or during eyelid spasm.17
In as
many as 50% of patients, blepharospasm is associated with apraxia of eyelid
opening, 24 that is inhibition of proper
functioning of the levator palpebrae superioris. 17
Apraxia is especially common in parkinsonian disorders such as
Parkinson’s disease, supranuclear palsy, and corticobasilar degeneration (it
may also be seen in isolation).23
A
number of complications may be associated with longstanding blepharospasm,
including:
·
Dermatochalasis: dermatochalasis is defined as
excess skin in the eyelid and may occur in patients with blepharospasm due to
stretching of skin with loosening of its attachments to underlying muscle.24
·
Skin excoriation: secondary to manual attempts by
patient to open eyelids.
·
Eyebrow ptosis: may result from weakened
fascial support from longstanding spasm and stretching of fascia. 24
·
Blepharoptosis: ptosis of the eyelid may occur
from attenuation and disinsertion of the levator aponeurosis. 24
Significant ptosis may further compromise vision by affecting the
superior visual field.
·
Canthal tendon abnormalities: stretching of the medial and
lateral canthal tendons may lead to entropion or ectropion of the lower lids,
as well as phimosis or lid fissures. 24
As
previously discussed, blepharospasm, Meige’s syndrome, and Brueghel’s syndrome
are typically thought of as a spectrum of facial dystonias. Often, patients first develop blepharospasm
that later progresses to involve other facial muscles (i.e. Meige’s syndrome). Patients with blepharospasm have a risk of
having the dystonia spread to other parts of the body- one study found that 31%
of patients had spread past the head, mostly in the first 1-2 years of onset.25