Handbook of Clinical Neurology, Vol.

100 (3rd series)

Hyperkinetic Movement Disorders
W.J. Weiner and E. Tolosa, Editors
# 2011 Elsevier B.V. All rights reserved

Chapter 48

Hemifacial spasm
GIOVANNI ABBRUZZESE, 1* ALFREDO BERARDELLI, 2 AND GIOVANNI DEFAZIO 3
1
Department of Neurosciences, University of Genoa, Genoa, Italy
2
Department of Neurological Sciences, La Sapienza University of Rome, Rome, Italy
3
Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

EPIDEMIOLOGY among the clinical series. Notwithstanding such diffi-

Hemifacial spasm (HFS) is a peripherally induced
movement disorder characterized by involuntary
clonic or tonic contractions involving the upper and
lower facial muscles (including the platysma). HFS is
typically unilateral except for uncommon (<1% of
the cases) bilateral cases. Two forms of HFS are recog-
nized: primary and secondary HFS.
Primary hemifacial spasm (HFS) is more common in
women than in men (ratio 1.5:1) and the mean age at dis-
ease onset is around 55 years but with a wide range,
including juvenile to late-life forms. In one study (Auger
and Whisnant, 1990) the prevalence rate was 7.4 per 100
000 population in men and 14.5 per 100 000 in women.
The prevalence was highest in subjects aged 4079 years.
Another study gave a similar prevalence of 9.8 per 100
000 (Nilsen et al., 2004). Although HFS cases are report-
edly more frequent in Asian populations (Poungvarin
et al., 1995), no epidemiological studies support this
observation. Most HFS cases are sporadic, but familial
cases have been reported (Micheli et al., 1994; Miwa
et al., 2002), suggesting a possible genetic contribution.
Some case-control studies found a significantly
higher prevalence of hypertension among patients with
primary HFS than among patients with other neurolog-
ical diseases or healthy controls (Defazio et al., 2000,
2003). Yet other series failed to find a significant
difference in the prevalence of arterial hypertension
in patients with primary HFS (Colosimo et al., 2003;
Tan et al., 2003).
Epidemiological studies have mainly concentrated
on primary HFS, the major form. The relative propor-
tion of primary and secondary HFS varies substantially
culties, available studies suggest that secondary HFS
may also be a frequent neurological problem. Second-
ary HFS frequently follows peripheral facial palsy or
may be more rarely secondary to facial nerve or brain-
stem damage after tumors, demyelinating disorders,
trauma, and infections (Table 48.1).
CLINICAL FEATURES
Facial muscle contractions in HFS are usually brief and
repetitive, often occurring in flurries. More prolonged
and sustained muscle spasms may also be present
(separated by periods of absent muscle activity). The
movements occur spontaneously or can be triggered
by relaxing the face after voluntary and forceful facial
muscle contractions. The symptoms may be exacer-
bated by stress, fatigue, and anxiety. In secondary
forms, synkinesis is most frequently observed during
speaking or eating.
HFS may affect the upper and lower face, but
the disorder typically begins around the eye (the
orbicularis oculi muscle in 90% of cases) (Wang
and Jankovic, 1998) with involuntary closure of the
eyelid and eyebrow elevation. This interferes with
vision and may cause social embarrassment. The con-
tractions may later spread to the cheek or to the peri-
oral region (orbicular oris and zygomatic muscles)
and also involve the frontalis, corrugator, mentalis,
and platysma. The involuntary facial twitches can
persist during sleep, causing insomnia in some cases.
Eventually a mild facial weakness may develop,
particularly in patients with secondary HFS who may
have nerve demyelination. In rare cases of bilateral

*Correspondence to: Giovanni Abbruzzese, Dipartimento di Neuroscienze Universita di Genova, Via De Toni 5 16132, Genova,
Italy. Tel: 39 010 3537039, Fax: 39 010 3538631, E-mail: giabbr@unige.it
676 G. ABBRUZZESE ET AL.
Table 48.1
Causes of secondary hemifacial spasm

Postparalytic (Bells facial palsy)

Cerebellopontine angle mass lesions
Meningioma
Schwannoma
Arteriovenous malformation
Brainstem lesions
Trauma
Demyelinating disorders
Infections
Parotid gland tumor

HFS (Tan and Jankovic, 1999), the spasms occur asyn-

chronously on the two sides. Unilateral or bilateral
hearing loss has been reported in one series (Wang
and Jankovic, 1998).
Little information is available on the possible
similarities or differences in the demographic and
clinical features between primary and secondary HFS.
A study of 214 consecutive outpatients demonstrated
that primary and secondary HFS share a number of
demographic and clinical features, such as age of
onset, gender distribution, side preference, synkinesias,
and rarity of familial cases. Conversely, the two
forms differ in clinical presentation, since most
patients with secondary HFS (72%) report simulta-
neous involvement of the upper and lower facial mus-
cles at the onset of disease (Colosimo et al., 2006),
whereas patients with primary HFS present with
contractions that involve the periocular muscles alone
but subsequently spread to the lower facial muscles
and platysma.
The natural history of HFS is highly variable. Tran-
sient spontaneous remissions rarely occur (Mauriello
et al., 1996) and the course is usually characterized by
progressive accentuation of the symptoms. HFS should
be regarded as a chronic and socially embarrassing
condition that can affect health-related quality of life
(emotional distress, visual or speech disability) (Tan
et al., 2004, 2006).
ETIOLOGY
Primary HFS is mainly attributed to vascular abnormal-
ities in the posterior fossa, compressing the seventh
cranial nerve at its exit zone from the pons (Jannetta,
1982; Tan and Chan, 2004). The most common abnor-
mality is an aberrant or ectatic intracranial artery, most
commonly an overriding superior cerebellar artery or
anterior inferior cerebellar artery, but a vein may also
Fig. 48.1. (A) Axial and (B) coronal three-dimensional con-
structive interference in steady-state (3D CISS) magnetic
resonance imaging of a patient with left hemifacial spasm.
The arrows indicate the left anterior inferior cerebellar artery
forming a vascular loop around the facialacoustic nerve
complex.
be involved (Naraghi et al., 2007). Neurovascular
conflict is a pathophysiologic phenomenon which is
implicated in several cranial neuropathies. The most
common are trigeminal neuralgia and HFS, but other
pathologies such as glosopharyngeal neuralgia, dis-
abling positional vertigo, and limited cases of tinnitus
may be due to neurovascular compression as well.
Although the development of magnetic resonance
imaging (MRI) and magnetic resonance angiography
has allowed the detection of possible neurovascular
conflicts (NVC) (Adler et al., 1992; Girard et al.,
1997) (Fig. 48.1), an NVC alone is probably insufficient
to produce HFS (Tan et al., 1999). Hypertension could
over time contribute to the development of the arterial
vessel ectasia, eventually leading to a critical NVC.
This process might explain the association between
HFS and arterial hypertension highlighted by some
case-control studies. Alternatively, vascular compression
at the ventrolateral medulla (VLM) may contribute to
the development of arterial hypertension. Supporting
this view, studies using high-resolution MRI techniques
show that hypertensive HFS patients have a greater
likelihood of VLM compression than nonhypertensive
HFS patients and healthy controls (Chan et al., 2008).
 HEMIFACIAL SPASM 677

Fig. 48.2. Surface electromyographic (EMG) recordings in two patients with hemifacial spasm. In case A, low-frequency
myokymic discharges can be observed in the orbicularis oculi and in the depressor labii inferioris muscles of the right side.
In case B, high-frequency repetitive firing of action potentials is present in the orbicularis oculi and levator labii superioris
muscles of the left side. Note that in both cases EMG activity is highly synchronized in the two muscles.

PATHOPHYSIOLOGY stimulation of the supraorbital nerve, an electromyogram

(EMG) response is also present in the orbicularis oculi
Neurophysiological studies provided important infor-
muscle (Valls-Sole, 2007). The recovery cycle of the blink
mation for understanding the pathophysiology of
reflex, at least in some patients, demonstrates that hyper-
HFS. Standard needle electromyogram shows parox-
excitability of facial nerve motoneurons and trigemino-
ysmal bursts of high-frequency motor unit discharges
facial interneurons are contributing factors (Valls-Sole
(up to 300 Hz). This activity may be synchronous
and Tolosa, 1989; Eekhof et al., 1996).
in upper and lower facial muscles (Fig. 48.2). Facial
Alternatively, it has been proposed that peripheral
nerve stimulation elicits a normal compound muscle
lesions may cause hyperexcitability of the facial moto-
action potential that can be followed by after-activity
neurones via an antidromic barrage of impulses
consisting of single or trains of motor unit potentials.
(nucleus origin hypothesis). The reverberant activity
These ectopic discharges are probably generated by
within the nucleus would be responsible for the abnor-
axonoaxonal ephaptic transmission, due to local demye-
mal discharges.
lination at the entry zone of the facial nerve root, possibly
owing to nerve damage caused by a compressing cerebral
INVESTIGATIONS
vessel (Nielsen, 1984a, b). The foregoing findings led
some to suggest the nerve origin hypothesis as the All patients with HFS should have a detailed
main pathophysiological mechanism in HFS. Studies neurological examination to detect possible focal
investigating the blink reflex show that, after electrical neurological deficits. An EMG examination should
678 G. ABBRUZZESE ET AL.
be performed in order to differentiate primary forms synkinesias are always triggered by movements (eye
from HFS secondary to facial nerve lesions. An closure may occur with voluntary mouth opening)
MRI scan should be obtained to rule out a secondary and are absent at rest. Neurophysiological studies show
origin or to document the NVC. Advanced MRI that in synkinesias every burst of activity induced in
techniques (Girard et al., 1997) (or magnetic reso- the orbicularis oculi spreads to the orbicularis oris,
nance angiography) provide information about the whereas in HFS activity spreads on many, but not on
presence of NVC and involved structures, and are all, occasions.
therefore essential in patients who are candidates
for surgery if conservative treatment failed.
TREATMENT
Various treatment options are available for HFS, includ-
DIFFERENTIAL DIAGNOSIS
ing oral pharmacologic therapies, surgery (microvas-
Involuntary facial movements are surprisingly fre- cular decompression of the facial nerve), and local
quent in the general population. Common conditions injections of botulinum neurotoxin (BoNT). Conven-
that can be mistaken clinically for HFS are blepharo- tional medical treatment consists of anticonvulsants
spasm (BSP), tardive dyskinesias (TD), motor tics, (such as carbamazepine, clonazepam, or other benzo-
focal cortical seizures involving the facial muscles, diazepines) or GABAergic drugs (baclofen, gabapentin,
and aberrant regeneration after facial nerve injury. pregabalin). Despite isolated reports that these drugs
Distinguishing between HFS and BSP or TD is rela- relieve spasms, there are no controlled studies and oral
tively easy. BSP involves the face bilaterally, often with medication is unlikely to be helpful because it suffers
spreading to the oromandibular region, whereas HFS is major limitations due to side-effects (sedation).
almost always unilateral. In the rare cases of bilateral The most common surgical procedure is microvascu-
HFS, the contractions of both facial muscles are very lar decompression of the facial nerve, based on the sepa-
often independent and asymmetric, whereas in patients ration of the offending vessel from the nerve. This
with BSP the contractions of both orbicularis oculi achieves marked improvement in HFS in the majority
muscles manifest at the same time. In addition, in of patients (> 90%), although some reports describe a
patients with BSP, spasms of eye closure are associated recurrence rate up to 20% (Tan et al., 2002). Microvascu-
with lowering of the eyebrow beneath the superior lar decompression is a highly invasive procedure and
orbital rim (Charcots sign), whereas patients with complications (hearing loss, cerebellar injury, cerebrospi-
HFS may manifest the so-called other Babinski sign, nal fluid leakage) are not uncommon (McLaughlin et al.,
(i.e., the eyebrow raising caused by contraction of the 1999), but may be reduced by the routine use of intrao-
frontalis muscle ipsilateral to the facial spasm), a phe- perative evoked potential monitoring. Nevertheless, the
nomenon never observed in patients with BSP. Patients introduction of treatment with BoNT has markedly
with TD have been exposed to neuroleptic agents or reduced the number of patients undergoing surgery.
dopaminergic antagonists and present with stereotypi- BoNT is a potent neurotoxin that blocks the calcium-
cal movements often affecting not only the face, but mediated release of acetylcholine at the synaptic junc-
also the neck, trunk, and limbs. At variance with tion, resulting in local chemodenervation with target
HFS, motor tics are brief, rapid, and nonrhythmic muscle atrophy and functional reversible paralysis. The
movements that can be wilfully suppressed for varying serotype A is the most commonly used in clinical prac-
periods and may be accompanied by other features of tice. Several large, open case-control studies showed that
Tourette syndrome. Partial seizures due to discharges local injections with BoNT cause a benefit rate between
in the motor cortex may present as unilateral clonic 76 and 100% (Defazio et al., 2002; Costa et al., 2005).
movements of the face, head, and neck, resembling Because of its safety and efficacy BoNT is the preferred
those seen in HFS. Continuous, repetitive, stereotyped symptomatic treatment for primary HFS.
movements of the face and head may occur in focal BoNT type A is injected subcutaneously in the orbi-
epilepsy as manifestations of nonconvulsive status cularis oculi muscle or lower facial muscles (Brin
epilepticus, a disorder that may be particularly difficult et al., 2003). The toxin, diluted to a minimal concentra-
to distinguish from HFS. A useful clue is that these tion to minimize diffusion, is injected (using a 30-gauge
movements disappear during sleep, and respond well needle) in several sites (46) of the palpebral and orbital
to antiepileptic drugs; electroencephalography may portions of the orbicularis oculi muscle, most commonly
provide other useful diagnostic clues. Facial myoclonus in the proximity of the pretarsal region. The injection
in Whipple disease is rhythmic and usually bilateral. sites are selected according to observation of the invol-
Aberrant regeneration after facial nerve injury (or untary twitches and it is generally recommended to start
postparalytic synkinesias) differs from HFS because with low doses. Injection in the upper face is often
 HEMIFACIAL SPASM
sufficient to reduce the spasms of the lower part of the
face. The toxin can be injected in the lower facial mus-
cles (orbicularis oris, levator angularis, depressor anguli
oris, and buccinator) when intense spasms persist. How-
ever, injection in these muscles is usually poorly toler-
ated because of weakness and distorted facial
expression.
The clinical benefit is partially dose-dependent; the
improvement begins 36 days after the treatment and
lasts a mean of 2.8 months. Transient adverse effects
occur in approximately 20% of the patients and include
ptosis, mild facial weakness, bruising and, more rarely,
diplopia, excessive tearing, and headache. Because
HFS rarely remits spontaneously, most patients need to
continue the treatment for many years, if not throughout
life. The long-term efficacy and safety of BoNT were
documented by a multicenter study in a series of 65
patients with primary HFS treated for at least 10 years
(Defazio et al., 2002). Treatment effectiveness (as
measured by the response rate and average duration of
improvement) as well as the average BoNT dose
remained unchanged in the first to 10th years. The rate
of local adverse effects (including upper-lid ptosis,
facial weakness, and diplopia) diminished significantly
in the 10th year of treatment. A recent evidence-based
review (Simpson et al., 2008) concluded that, although
the evidence supporting BoNT use in HFS spasm is
suboptimal because of few properly controlled clinical
trials, BoNT is effective for the treatment of HFS and
induces minimal side-effects (one class II and one class
III study).
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