Apraxia of Eyelid Opening Improved by Pallidal Stimulation in Progressive Supranuclear Palsy

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Apraxia of eyelid opening (AEO) was described as involuntary eyelid closure (IEC) without observable contraction of the orbicularis oculi (OO). ¹ Physiologic studies reveal that AEO rarely involves isolated inhibition of the levator palpebrae (LP). More often, contraction of the orbicularis oculi (OO) or co‐contraction of the LP and OO is involved. ² , ³ , ⁴

AEO is often a complication of neurodegenerative disease. In Parkinson's disease (PD), deep brain stimulation (DBS) can cause or relieve AEO. ⁵ The effects of subthalamic nucleus (STN) DBS on AEO are being elucidated. How DBS affects AEO in other locations or diseases is largely unreported. We report on a case of AEO improving after pallidal DBS in a patient with progressive supranuclear palsy (PSP). This case expands the spectrum of neurodegenerative disorders in which AEO is affected by DBS.

Case Report

A 71‐year‐old male presented with micrographia and IEC. The IEC worsened in bright light and there was no sensory trick. He developed early falls. Exam revealed paralysis of upgaze and slowed vertical saccades. Carbidopa/Levodopa (1000 mg/day) and Ropinirole (1.5 mg/day) did not improve IEC or balance problems. AEO was diagnosed and the patient received botulinum toxin A injections with partial benefit (35 units orbicularis oculi bilaterally—preseptal, pretarsal, orbicular). Eye crutches, myectomy of the upper eyelids, and frontalis sling were ineffective.

Four years later, he came to our clinic for an evaluation for DBS. He indicated his AEO was intolerable. He described himself as a “prisoner” in his body and “essentially blind.” He was desperate for DBS. His exam showed complete vertical and moderate horizontal gaze paresis, slowed horizontal saccades, limb bradykinesia, hypomimia, hypophonia, rigidity, and retropulsion. An MRI of the brain revealed midbrain atrophy (Fig. 1).

FIG 1.

A: MRI brain images of patient in sagittal (top) and axial (bottom) views. Midbrain atrophy is evident. B: Coronal (top) and axial (bottom) three‐dimensional lead reconstructions based on segmentation of basal ganglia structures using the pre‐operative magnetic resonance imaging and post‐operative computerized tomographic scan. Dark brown structures are globus pallidus pars externa and lighter brown structures are globus pallidus pars interna. In the axes, S = superior, R = right, A = anterior. The leads are Medtronic 3389 with left electrode contacts numbered 0 to 3 inferior to superior, whereas the right contacts are numbered from 8 to 11 inferior to superior. Active contacts are highlighted in red. Lead position is localized in globus pallidus pars interna.

Our university's multidisciplinary DBS conference reviewed the patient's situation. The patient was offered surgery with an indication of dystonia after extensive counseling. Bilateral globus pallidus internus (GPi) DBS was selected. Implantation of bilateral Medtronic 3389 leads was uneventful; left electrode contacts numbered 0 to 3 and the right electrode contacts numbered 8 to 11. Post‐operative reconstruction demonstrated that the left lead was located in the posterolateral region of GPi, whereas the right lead was slightly more anterior (Fig. 1). Botulinum toxin treatment was discontinued. The patient reported a 75% improvement in his AEO. He described himself as “alive again” resuming social events/cinema and playing with his grandchildren.

One year after implantation, his eyes were open 50% of the time. Reprogramming improved him with these parameters: left GPi, bipolar setting using contact 2 anode and 3 cathode; amplitude 5.3 V; pulse width 60 ms; frequency 130 Hz; and right GPi, double monopolar setting using Case anode and 9 and 10 cathodes; amplitude 4.7 V; pulse width 60 ms; and frequency 130 Hz. Bipolar settings were used on the left to avoid dysarthria and double monopolar stimulation on the right may have compensated for the anterior lead location. (Fig. 1) Botulinum toxin treatment was resumed. He recovered 90% benefit. Two years after implantation, the patient manifested increased Parkinsonism, backward falls, and complete paralysis of eye movements. A diagnosis of probable PSP was made based on Movement Disorders Society's criteria. ⁶ DBS benefit on AEO was sustained (Video S1).

Discussion

AEO was first described as “a defect in the voluntary initiation of lid opening” without paralysis or blepharospasm. ¹ AEO is associated with neurological disorders, including frontotemporal lesions, PD, Huntington's disease, multiple system atrophy, and especially PSP. ³ Our patient met criteria for probable PSP with Richardson's syndrome. ⁶ In PSP with blinking abnormalities, MRI volumetric studies implicate pathology in a network involving the middle frontal gyrus, supplementary motor area, basal ganglia, and white matter of the brainstem. ⁷

Electromyographic studies demonstrate that varied physiology underlies AEO. Simultaneous EMG recordings of the OO and LP revealed that only 14% of AEO patients have isolated inhibition of the LP. ² Most patients exhibit associated contraction of the orbicularis oculi and dystonic co‐contraction of the LP and OO may be observed. ² , ⁴

In PD, STN DBS may cause or improve AEO. ⁵ STN DBS disrupts normal blink synergy in PD and complicating AEO occurs at high stimulation intensities suggesting current spread to eyelid control pathways. ⁸ AEO improves with low intensity STN DBS suggesting repair of a dopaminergic deficit. ⁹ One report of DBS in another location described a PD patient in whom pallidal DBS improved gait freezing and completely alleviated AEO. ¹⁰ Our case extends the observations of DBS in AEO to PSP. Improvement in AEO cannot be attributed to repair of dopaminergic pathways in this patient with levodopa unresponsiveness. Likely, pallidal DBS in our case lessened LP‐OO dystonia, a hypothesis that would need confirmation by physiologic analysis.

Although our exceptional case expands the observations on AEO and pallidal stimulation to include success in a patient with PSP, we are not proposing isolated AEO as an indication for DBS.

Authors Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.

T.O.: 1A, 1B, 1C, 3A, 3B

J.V.: 1A, 1B, 1C, 3B

R.P.: 1B, 1C, 3B

N.H.: 1B, 1C, 3B

J.M.: 1A, 1B, 1C, 3A, 3B

Disclosures

Ethical Compliance Statement: Informed consent was obtained from the patient and his wife for the case report publication. Our institutional review board reviewed and approved this case report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: N.H. and R.P. receive funding under P50 NS098753, R01 NS113746, and R01 NS081118. J.V. receives funding from the Engdahl Family Foundation and The Kurt B. Seydow Dystonia Foundation. The authors note no conflicts of interest.

Financial Disclosures for Previous 12 Months: J.V. reports consulting activity for LivaNova, Adamas, InsighTec, Surgical Information Sciences, Boston Scientific, Abbott/St. Jude Medical, and Medtronic.

Supporting information

Video S1. Video of patient with deep brain stimulation turned off and on without his awareness of stimulator state. The patient is instructed to keep his eyes open. With stimulation off eyelids are closed at baseline and can be opened only for brief periods. When stimulation is turned on his eyes are continuously open.