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Disease Entity

Plus Minus Lid Syndrome, or Plus Minus Syndrome, is an acquired neurologic defect which includes a constellation of eye findings of unilateral ptosis and contralateral eyelid retraction.1 It was first described by Bertrand Gaymard and colleagues in a 1992 case report.1

General Pathology

Damage to the nucleus of the posterior commissure causes bilateral supranuclear lid retraction (Collier lid retraction sign), however if the lesion also affects the oculomotor fascicle – the lid retraction on one side could be masked by ptosis due to an associated fascicular oculomotor nerve palsy2 causing the plus minus syndrome. Imaging usually reveals unilateral lesions dorsal and rostral to the red nucleus in the region of nucleus of posterior commissure which extends ventrally to include the oculomotor nerve fascicle on the ptotic side2.

Pathophysiology

The nucleus of the posterior commissure normally sends inhibitory projections to the levator palpebrae superioris nucleus.3,4 The levator palpebrae superioris nucleus is a single central caudate nucleus that innervates both levator palpebrae superioris muscles.3,4 A lesion that damages the nucleus of the posterior commissure within the dorsal mesencephalon results in bilateral lid retraction, which is known as Collier sign.1,2 Collier sign is often associated with other signs of dorsal mesencephalic dysfunction such as deficiency of upward gaze, convergence-retraction nystagmus, and pupillary light-near dissociation as part of dorsal mesencephalic syndrome, also known as Parinaud syndrome.2 A lesion that also damages one of the oculomotor nerve fascicles produces a ptosis on the side with the fascicular damage1,2 causing the constellation of finding for plus minus syndrome.

Diagnosis

Physical examination

Observation of one eyelid with ptosis and the other eyelid with retraction. In the true plus minus lid sign if the ptotic eyelid is manually raised then the contralateral retracted eyelid does not fall.5 This is in contrast with pseudo-Plus Minus Syndrome (e.g., ocular myasthenia gravis) where passive opening of the ptotic eyelid causes relaxation of the retracted eyelid.6 Some patients with the true plus minus sign have a dorsal midbrain lesion (plus minus syndrome) but other patients with a true plus minus sign might have lid retraction from one cause (e.g., thyroid eye disease) but ptosis in the fellow eye (e.g., concomitant myasthenia gravis in the same patient).

Signs and Symptoms

Patients will display the characteristic physical findings of ptosis of one eyelid and retraction of the opposite lid.1,2,4,5 Patients may have additional signs and symptoms depending on the neurologic structures impacted by the infarct including ataxia and cerebellar signs.1,4,5,7

Clinical diagnosis

The diagnosis of Plus Minus Lid Syndrome is largely clinical.4,7 It involves observation of ptosis of one lid and retraction of the opposite lid.1 A CT scan or MRI demonstrating an infarct in the paramedian mesencephalon involving the ptotic lid’s levator palpebrae fascicle may aid in the diagnosis.1,4,7

Differential diagnosis

· Myasthenia Gravis

· Thyroid Eye Disease

· Dorsal Midbrain Syndrome

· Aberrant Regeneration of Oculomotor nerve

· Facial nerve palsy – with unopposed action of the levator

· Iatrogenic – post operative, Botox, contact lens use

· Trauma – blow out fractures causing enophthalmos of one eye with pseudoptosis.

Management

General treatment

Case reports discuss possible improvement of symptoms over time.1,4,7 Treatment should be directed at the underlying etiology (e.g., secondary stroke evaluation and prevention for ischemic infarct). 4

Medical follow up

Since Plus Minus Syndrome is due to cerebrovascular infarcts, secondary prevention is important.4 There is no known treatment that will reverse the effects of the stroke, but it is important to follow up with patients to monitor for improvement.1,4

References

1. Gaymard B, Lafitte C, Gelot A, de Toffol B. Plus-minus lid syndrome. J Neurol Neurosurg Psychiatry. 1992;55:846-848.

2. Skarf B. Normal and abnormal eyelid function. In: Miller N, Newman N, eds. Walsh & hoyt's clinical neuro-ophthalmology. 6th ed. Lippincot Williams & Witkins; 2005.

3. Kim S, Oh S, Chang M, K S. Oculomotor neuromyotonia with lid ptosis on abduction. J AAPOS. 2013;17(1):97-99.

4. Kotwal V, Shenoy W, Joshi S, et al. Plus minus lid syndrome with ataxia. J Assoc Physicians India. 2005;53:908-909.

5. Porta-Etessam J, Benito-Leon J, Berbel A, Martinez A. Plus minus lid syndrome without ophthalmoplegia. Eur J Neurol. 1999;6:107.

6. Bandini F. Pseudo plus-minus lid syndrome. Arch Neurol. 2009;66(5):668-669.

7. Alsherbini K, Kapadia K, Sattin J. A rare midbrain infarction presenting with plus minus lid syndrome with ataxia: A case report. Journal of Medical Case Reports. 2011;5:525.

8. Bartley GB. The differential diagnosis and classification of eyelid retraction. Trans Am Ophthalmol Soc. 1995;93:371–389.