Findings that shed new light on the possible pathogenesis of a disease or an adverse effect

Case report

Stroke-induced resolution of primary blepharospasm:
evidence for the lenticular nucleus as a
control candidate
John Christopher Bladen,1 Jasdeep Singh Gill,2 Katherine Miszkiel,3
Daniel George Ezra1
1

Department of Oculoplastics,
Moorfields Eye Hospital, London,
UK
2
Development, Ageing and
Disease, UCL Institute of
Ophthalmology, London, UK
3
Victor Horsley Department
of Neurosurgery, National
Hospital for Neurology and
Neurosurgery, London, UK
Correspondence to
John Christopher Bladen,
​john.​bladen1@​nhs.​net
Accepted 26 June 2018

Summary
Primary blepharospasm is an adult-onset focal dystonia
characterised by involuntary contractions of the
orbicularis oculi, leading to bilateral spasmodic closure
of the eyelids. While spasms of this muscle constitute
the hallmark of disease, other motor manifestations
include increased spontaneous blinking and apraxia of
eyelid opening. Originally misdiagnosed as a psychiatric
condition, blepharospasm is now well established as
being of neurological origin although questions remain
as to its pathophysiological mechanisms.
We report a 66-year-old woman who had a 14-year
history of primary blepharospasm which completely
resolved following a left medial cerebral artery
thromboembolic infarct of the lenticular nucleus. This
report provides supporting evidence of the lenticular
nucleus as a key structure mediating the disease which
can lead to functional blindness.

Background

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Primary (essential) blepharospasm is a focal
dystonia characterised by involuntary contractions
of the orbicularis oculi (OO), triggering bilateral
spasmodic closure of the eyelids.1 Although classically associated with OO spasms, it also constitutes
other motor manifestations including increased
spontaneous blink rate and apraxia of eyelid
opening; the latter is a relatively rarer manifestation
more commonly associated with extrapyramidal
disease.2 3 Clinical characteristics include a female
preponderance, age of onset between the fifth and
seventh decade and a propensity for spread to adjacent muscle groups.4 5 Most cases of primary blepharospasm occur sporadically, however, up to 25%
of patients have at least one family member affected
by dystonia, implicating a genetic component in its
aetiology.6 7
With a greater frequency of psychiatric disturbances occurring in patients, such as depression and
anxiety, blepharospasm was long misdiagnosed as
a psychiatric condition.8 9 Its neurological origin
is now well established with neurotoxic agents
rendering it a curable condition, although questions
remain regarding its pathophysiology.10 11
Both neurophysiological and structural/functional neuroimaging studies have implicated
dysfunction of basal ganglia circuitry in disease aetiology. Electromyogram (EMG) activity in the OO

of blepharospasm patients is significantly greater
than healthy subjects,12 with a case reporting associated increased single-cell firing in the internal
globus pallidus.13 Anatomically, MRI has shown
volumetric increase in putamen grey matter in
patients,14 15 with functional MRI (fMRI) demonstrating its corresponding activation.16 Execution of
motor function is ascribed to the putamen through
multiple connections with other components of
the basal ganglia. Modulation of motor response is
expected to have a contributory role, thus making
the lenticular nucleus a likely candidate area for
the initiation of primary blepharospasm. In view of
the significant effect of blepharospasm on patient
quality of life, it is of great importance to further
elucidate its aetiology to guide prevention.17 18

Case presentation

A 66-year-old woman had suffered from a 14-year
history of primary blepharospasm. The frequency
of blinking episodes increased with time, becoming
almost constant in nature and impacting on her
ability to drive. Subsequently, she was referred to
the Botulinum Toxin Clinic for periorbital injections at 4 monthly intervals, which temporarily
resolved the symptoms to good effect. Her medical
history included hypercholesterolaemia treated
with simvastatin, while her social history included
being an ex-smoker and stopping 3 years prior.
She awoke with sudden onset of right-sided
hemiparesis involving the hand, leg and face, associated with slurred speech. She was taken to the local
hyper-acute stroke unit for an urgent CT brain,
which demonstrated a cerebral infarct secondary to
a left medial cerebral artery thrombus (see figure 1),
so was thrombolysed within 3 hours of onset. She
made excellent progress with recovery of most of
her neurological deficit over the following few
days. Notably, her symptoms of blepharospasm had
completely resolved from the time of the stroke.

Outcome and follow-up

On examination 3 months after the event, she had
normal visual acuity, normal visual fields and full
ocular movements. There was mild residual weakness of her right facial and accessory nerves (cranial
nerves VII and XI, respectively). The ocular surface
was normal, as was the rest of the ophthalmic
examination. Importantly, no blepharospasm

Bladen JC, et al. BMJ Case Rep 2018. doi:10.1136/bcr-2018-224339

1

Findings that shed new light on the possible pathogenesis of a disease or an adverse effect
internal globus pallidus infarction led to the development of
functional neurosurgery.27 The proposed mechanism of resolution is either the loss of a dominant excitatory signal that was
inducing blepharospasm, or stimulation of a dominant control
centre that suppresses the blepharospasm by the infarct. In the
case of the latter, this may be within the internal globus pallidus
as identified by the aforementioned deep brain stimulation study.
In contrast to our stroke-induced resolution of blepharospasm,
other stroke cases report its secondary induction including after
unilateral hemispheric cerebral infarction,28 bilateral thalamic
infarction,29 30 unilateral striatal infarction31 and unilateral parietotemporal infarction.32 This supports accumulating evidence
for several brain regions, not just the basal ganglia, in causation
of blepharospasm, thus implicating it as a network disorder
resulting from dysfunction of one particular component.33 This
hypothesis also rationalises the heterogeneity seen in its clinical
presentation, including frequent non-motor manifestations such
as ocular sensory symptoms and cognitive disturbance.34 35
A limitation of this case is that no MRI was performed as this
could have localised the infarct to the putamen or medial/lateral
basal ganglia. We can postulate, however, that the loss of control
leading to the primary blepharospasm in this individual originated in the left lenticular nucleus.
Figure 1 CT brain within 3 hours of stroke symptoms. A thrombus is
lodged in the left medial cerebral artery (MCA); reduced attenuation is
seen in the left lenticular nucleus with subtle loss of grey/white matter
differentiation in the left precentral gyrus, consistent with acute left
MCA ischaemia.
was observed over a continuous period of 1 hour, which was
confirmed by video recording. Review at 12 months demonstrated continued resolution of the primary blepharospasm
despite full recovery of the hemiparesis.

Discussion

The aetiology of primary blepharospasm is unknown but likely
to be multifactorial, involving central control mechanisms with
the added possibility of individual variation. Triggers such as
pain (including ocular surface irritation), light, stress or emotion
can also induce the spasm. Treatment is thus partly directed
to reducing these triggers, including lubricants, tinted glasses
and behaviour modification.19 20 Paralysis of the spasmodic
muscles using botulinum toxin remains the mainstay of treatment, however, can exacerbate ocular surface dryness and cause
diplopia or blepharoptosis.21
The role of the lentiform nucleus in primary blepharospasm is
supported by microstructural abnormalities found by Yang et al
in structural neuroimaging,22 23 while functional studies demonstrate its overactivity alongside the cerebellum and supplementary motor regions.24 More recently, resting-state fMRI revealed
dysfunctional neural fluctuations at the bilateral striatum, which
correlated with clinical symptoms of blepharospasm.25 Moreover, subthalamic nucleus induction of blepharospasm during
deep brain stimulation can be ablated by stimulation of the
internal globus pallidus, thus highlighting an area of control
within the basal ganglia.26
We report the first case of definitive resolution of blepharospasm following infarction to an area encompassing the left
lenticular nucleus. Moreover, the unilateral infarct gave bilateral
resolution and, importantly, there was no return of the blepharospasm despite recovery of the hemiparesis. This bears similarity to parkinsonian tremor, the resolution of which following
2

Learning points
►► Primary blepharospasm is a focal dystonia characterised by

involuntary contractions of the orbicularis oculi.

►► Blepharospasm is a neurological condition, although often

misdiagnosed as psychiatric, and is eminently treatable with
neurotoxic agents.
►► Aetiology of primary blepharospasm is likely multifactorial,
involving central control mechanisms and individual variation.
►► Neurophysiological and neuroimaging studies both support a
role of the basal ganglia in blepharospasm.
►► Resolution of primary blepharospasm in this patient who
had a stroke with an infarct encompassing the left lenticular
nucleus implicates this as a key structure in pathogenesis.
Contributors JB carried out the planning, acquisition of data, data analysis and
wrote the paper. JSG carried out data analysis and wrote the paper. KM carried out
acquisition of data, analysis of data and wrote the paper. DE carried out the design
of the study, data analysis and wrote the paper.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

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