Atypical Blepharospasm with Oromandibular Dystonia Associated with Cerebral Amyloid Angiopathy

ABSTRACT

A case of atypical blepharospasm with oromandibular dystonia is presented in a patient found to have cerebral amyloid angiopathy on magnetic resonance imaging and a shared mechanism is discussed.

Introduction

Benign essential blepharospasm and its related disorder, blepharospasm with oromandibular dystonia (also known as Meige’s syndrome) are dystonic disorders of the facial nerves marked by tonic-clonic spasms of the facial muscles.¹ The pathophysiology of the conditions is thought to be related in large part to dysfunction of the thalamus and the basal ganglia, including the globus pallidus, striatum, and the substantia nigra.¹ The thalamus normally stimulates the motor cortex to produce normal movements, whereas the globus pallidus normally inhibits the thalamus to prevent unwanted movements, and the striatum normally inhibits the globus pallidus so that the globus pallidus will not cause excessive inhibition of the thalamus. Finally, the substantia nigra normally stimulates the striatum by releasing dopamine. If the substantia nigra stops exciting the striatum, the striatum stops inhibiting the globus pallidus, and the globus pallidus stops inhibiting the thalamus. Loss of inhibition of the thalamus results in unwanted movements in various parts of the body, including the face, neck, and throat.² Despite laboratory evidence for this mechanism in patients with essential blepharospasm and Meige’s syndrome, neuroimaging studies of these regions in patients with these conditions typically show no structural lesions.³ We report the first case of blepharospasm associated with cerebral amyloid angiopathy (CAA). The imaging findings in this case support the above mechanism and emphasises the importance of obtaining appropriate magnetic resonance imaging (MRI) sequences in patients with blepharospasm, particularly when there are atypical features.

Case report

A 64-year-old man presented with a 3 week history of facial spasms for which he initially presented to a local emergency department where he underwent non-contrast MRI that was said to show no abnormalities. He was subsequently evaluated by a neurologist who prescribed lorazepam and valproic acid without relief. The patient’s past medical history was significant for mild cognitive impairment, well-controlled hypertension, dyslipidaemia, type 2 diabetes mellitus, chronic kidney disease, uncontrolled migraine with vestibular features, benign postural paroxysmal vertigo and vestibular neuritis, an L3 spinal schwannoma for which he had undergone surgery 38 years prior, and a history of head trauma and neck fracture from diving into a swimming pool 46 years earlier, requiring a C5–C7 fusion. He denied tremors, limb rigidity, trouble writing, or shuffling gait. His ocular history was significant for recurrent corneal erosions in the left eye after trauma from a hairbrush. Relevant medications include gabapentin, venlafaxine, magnesium-oxide, and aspirin 81 mg; he had previously failed nortriptyline and had some improvement with occipital nerve blocks. His family history was positive for an aunt with excessive blinking but negative for dementia, Parkinson’s disease, or intracranial haemorrhage.

On examination, the patient had intermittent bilateral symmetrical eyelid and brow spasms as well as pursed lips with rightward deviation from cheek spasms (Figure 1 and Supplemental video). The spasms were more tonic than clonic. The patient reported that the spasms would occur 10–20 times per day, were worse when he reclined or was supine, and occasionally woke him from sleep. He was diagnosed with atypical blepharospasm with oromandibular dystonia due to asymmetry in the lower face with deviation of the pursed lips to the right.

Figure 1.

External colour photograph of patient with tonic facial spasm involving orbicularis oculi and orbicularis oralis bilaterally and right zygomaticus muscles.

Given the asymmetrical cheek involvement, MRI of his brain with and without contrast using an internal auditory canal protocol was ordered to rule out microvascular compression or mass compressing the facial nerve. The MRI was negative for compressive lesions; however, the susceptibility weighted imaging (SWI) sequences showed scattered lesions throughout the cortex as well as bilateral involvement of the globus pallidus confirmed with phase imaging (Figure 2). These features were considered consistent with CAA.

Figure 2.

Magnetic resonance image showing (a) scattered punctate foci of susceptibility in the peripheral parenchyma at the level of the pons (arrowheads); (b) bilateral globus pallidi on susceptibility weighted imaging (white arrows); (c) confirmed on phase imaging (black arrows).

He was treated with onabotulinumtoxin A (Botox®) to the areas of spastic muscle contraction, including the right forehead, right brow, bilateral procerus and glabella, bilateral pretarsal orbicularis oculi of the upper and lower eyelids, right lateral periorbital orbicularis oculi, right levator labi superioris muscle just lateral to the nares, bilateral orbicularis oris muscles just superior and inferior to the angle of the lips, right risoris muscle just lateral to the angle of the lips, and the right platysma just inferior to the angle of the jaw. He has subsequently been treated about every 3 months with marked improvement in spasms and improved sleep.

Discussion

CAA is caused by beta-amyloid deposition in the walls of medium-sized cerebral and meningeal arteries.⁴ Patients may be asymptomatic, develop intracranial haemorrhages, or dementia. It can be sporadic, associated with Alzheimer’s disease, Parkinson’s disease, or Lewy body dementia;⁵ or familial, with the familial form associated with a mutation in one of three genes: APP (most common): CST3, or ITM2B.⁴ There has been one reported case of blepharospasm in a patient with familial early onset Alzheimer’s dementia associated with a pathologic APP variant; however, the report did not mention the presence of CAA in the patient or blepharospasm in other family members,⁶ and no other cases of CAA and blepharospasm have been reported. APP mutations are rare in sporadic CAA, and are estimated to occur in only 0–8% of cases, and therefore genetic testing is not recommended without a family history of dementia or spontaneous cerebral haemorrhages.⁷

Although no pathological cause or localisation has been identified in the majority of patients with blepharospasm, the masked facies of Parkinsonism and increased co-occurrence with multi-system atrophy, Lewy body disease, and progressive supranuclear palsy suggest that these conditions share a common mechanism involving dysregulation of the basal ganglia and thalamic dopaminergic pathways.^8,9 Some authors have hypothesised that blepharospasm is characterised by a combination of dopamine and acetylcholine excess, whereas rigid hypokinetic disorders, such as Parkinsonism are associated with dopamine deficiency and acetylcholine excess; and hyperkinetic disorders such as Huntington’s disease and tic disorders are associated with dopamine excess and acetylcholine deficiency.¹⁰

This case is the first to report a novel association between CAA and blepharospasm. We hypothesise that the microhaemorrhages in the globus pallidi in this case led to the dysregulation of the patient’s thalamo-striatal system and the consequent facial spasms. The patient had undergone MRI brain 1 month and 1 year earlier, both without SWI or other sequences for chronic haemorrhage such as gradient echo (GRE) and, thus, the pathology in this case was not identified.

GRE depends on the T2 signal loss during proton relaxation that occurs from paramagnetic (deoxyhaemoglobin, ferritin, haemosiderin), diamagnetic (calcium), and ferromagnetic particles.^11,12 GRE only assesses the signal intensity (T2 loss) of these particles; however, SWI sequences (magnitude, filtered phase, combined magnitude and phase, and minimum intensity projection) integrate the inherent magnetic phase information and, thus, increase the sensitivity of the imaging for microbleeds.¹¹ GRE software is available from a number of manufacturers including Phillips, Siemens, General Electric, Hitachi, and Toshiba, although it may be referred to by different initials, such as “FFE, GRE, GE, or FE”.^11,13 SWI software is available on magnets with at least 1.5 T strength and on multiple platforms, including Siemens, Philips, General Electrical (called SWAN), Hitachi (called BSI), and Cannon (called Flow Sensitive Black Blood).^14,15 Physicians should discuss with their local radiology facilities what platforms and technologies are available at the specific locations. SWI has been shown to be particularly helpful in identifying microbleeds in CAA and in distinguishing CAA from hypertensive cerebral angiopathy; as well as identifying haemorrhagic diffuse axonal injury from brain trauma; central nervous system vascular malformations; arterial strokes; neurodegenerative diseases; and brain tumours.¹⁴

SWI and GRE sequences may not be included in standard MRI sequences ordered for essential blepharospasm and related disorders.¹¹ Thus, CAA may be an under-recognised cause of facial dystonias in some patients. We recommend that providers ordering MRI in such patients should request that SWI or GRE sequences be part of the protocol, with special attention paid to the thalami and basal ganglia. Diagnosis of CAA is important as it may affect the use of antiplatelet/anticoagulant therapy and also may help identify patients who or at risk or may already have early dementia and who may benefit from lifestyle changes or pharmacotherapy.

Declaration of interest statement

Andrew R. Carey: expert witness fees, consulting fees for US Nutraceuticals (not conflicting with the contents of this manuscript), consulting fees for Horizon Therapeutics. Neil R. Miller: expert witness fees, consulting fees from Quark Pharmaceutical Company (not conflicting with the contents of this manuscript).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01658107.2021.1958871.