One And a Half Syndrome

All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.

Article initiated by:

Ahmad Kharsa, Andrew Go Lee, MD, Peter W. Mortensen, MD, Subahari Raviskanthan, MBBS

All contributors:

Osama Al Deyabat, MBBS, Calvin W Wong, Caitlin Makenzie Hackl, Nagham Al-Zubidi, MD, Subahari Raviskanthan, MBBS, Farida Al Belushi MD, Osama Al Deyabat, MBBS, Sanjana Jaiswal

Assigned editor:

Osama Al Deyabat, MBBS

Review:

Assigned status Up to Date

 by Osama Al Deyabat, MBBS on September 19, 2024.

add
Contributing Editors:	add

Disease

In 1967, Charles Miller Fisher described a pattern of ophthalmoplegia in patients with various pontine lesions, known as “one-and-a-half syndrome” (OAHS). OAHS presents with a combination of an ipsilateral conjugate horizontal gaze palsy (referring to the ‘one’ horizontal gaze palsy) and an ipsilateral internuclear ophthalmoplegia (INO) (referring to the ‘half’ of a horizontal gaze palsy) . Importantly, OAHS is distinct from Eight and a Half syndrome by the absence of lower facial palsy (a sign of an upper motor neuron lesion of CN VII).

Etiology

Any disease process causing a dorsal pontine lesion may cause the findings seen inOAHS, including but not limited to vascular, inflammatory, traumatic, infiltrative, demyelinating and neoplastic. Of these, the most commonly reported etiology in adults is vascular, including mainly ischemic brainstem infarction, pontine hemorrhages, basilar artery aneurysms and arteriovenous malformations. Demyelinating lesions (such as multiple sclerosis) and brainstem malignancies (primary or metastatic) including gliomas, metastatic melanoma, ependymoma of the fourth ventricle and astrocytoma of the cerebellum can also cause OAHS. More rarely, infectious causes including neurocysticercosis, brainstem tuberculomas, and brainstem encephalitis have also been reported .

Clinical Presentation

OAHS presents with an ipsilateral conjugate horizontal gaze palsy and limited adduction of the ipsilateral eye (INO). The ipsilateral eye usually remains fixed straight ahead but has diminished or no ability to move in right or left horizontal gaze. The contralateral eye may be exotropic with abduction nystagmus due to the ipsilateral INO . Vertical gaze is preserved in OAHS.

Patients typically present with diplopia, blurred vision and oscillopsia. The neurological exam may show many different patterns of nystagmus including gazed-evoked, upbeat nystagmus, horizontal and rotatory ipsilateral gaze nystagmus, spontaneous contralateral gaze nystagmus. Skew deviation and convergence disorders can also occur . Importantly, convergence is preserved in OAHS.

Physiology

In discussing horizontal eye movements, there are three main structures within the dorsal pontine tegmentum that are relevant, namely the Paramedian Pontine Reticular Formation (PPRF), the internuclear fibers of the Medial Longitudinal Fasciculus (MLF) and the abducens nuclei .

The PPRF and the abducens nuclei act as the final pre-nuclear and nuclear centers for horizontal eye movement after integration of nerve impulses from visual areas of the frontal and parietal lobes, respectively . Therefore, upon the initiation of a horizontal gaze, excitatory neurons within the PPRF project to the ipsilateral abducens nuclei, located within the colliculus facialis at the lower part of the pons . In turn, the abducens nuclei project to two distinct sets of horizontal gaze fibers. First, the ipsilateral abducens nucleus triggers motor fibers that control the ipsilateral lateral rectus muscle. Second, the abducens nuclei also activates the contralateral MLF, which carries a set of excitatory internuclear fibers that decussate at the same topographic level of their parent cell bodies. These fibers ascend to the mid-brain and terminate on neuronal cell bodies at the medial rectus subdivision of the oculomotor nuclear complex .

Pathophysiology

Since the OAHS is a combination of an ipsilateral horizontal gaze palsy and an ipsilateral INO, understanding of the relevant neuroanatomy and potential lesion locations is critical. Given the pathway described earlier, there may be four possible lesion locations to account for the horizontal gaze palsy in the OAHS, including:

(1) damage to both the ipsilateral abducens nuclei and the PPRF,

(2) damage to the ipsilateral abducens nuclei only,

(3) damage to the ipsilateral PPRF only,

(4) damage to the ipsilateral abducens nerve root fiber together with the contralateral MLF in the event of two separate lesions.

In the event of unilateral damage to the PPRF, one of two main findings can be observed, depending on the exact location of the lesion. When the PPRF lesion is located rostrally to the abducens nucleus, ipsilateral paralysis of the horizontal conjugate gaze occurs, including both saccadic and pursuit eye movements. Despite this paralysis, vestibular-induced reflex horizontal eye movements are preserved. In contrast, when the PPRF lesion is at the level of the abducens nucleus, there is loss of all ipsilateral saccadic and pursuit voluntary eye movements along with vestibular-induced reflex horizontal eye movements . Finally, damage to the ipsilateral abducens nucleus results in the arrest of all ipsilateral horizontal eye movements, including voluntary and reflexive movements .

Simultaneously, and in addition to the horizontal gaze palsy, lesions involving the ipsilateral MLF along any segment of its ascending path account for the ipsilateral INO observed in the OAHS. Apart from horizontal movements due to convergence, the internuclear neurons of the MLF are required for any type of conjugated horizontal movement. As such, in the case of an ipsilateral INO, there is paralysis of the ipsilateral eye adduction on attempted contralateral horizontal gaze coupled with a horizontal jerk nystagmus in the contralateral abducting eye . Nevertheless, it is to be noted that convergence, pupillary constrictor reflex activity and vertical eye movements are typically preserved as long as lesions do not involve the midbrain .

Diagnosis

The diagnosis of OAHS is made through a combination of clinical and radiological findings. Clinically, a full ocular motility exam, including assessment of convergence, is performed. In addition, a thorough neurological exam with particular attention to the cranial nerves may further assist in lesion localization. Ocular manifestations of myasthenia gravis (MG) can imitate OAHS (i.e., a pseudo-OAHS), but adduction deficits would not be overcome with attempted convergence in MG. In the case of suspected MG or thyroid disease, MG antibody tests or thyroid function tests can be of clinical consideration respectively.

The diagnosis of OAHS should be made in distinction to other internuclear ophthalmoplegias such as half-and-half syndrome, seven-and-a-half syndrome, and eight-and-a-half syndrome. Importantly, OAHS is distinct from eight-and-half syndrome  seven-and-a-half syndrome in that the ipsilateral eye has both abduction and adduction deficit. Compared to eight-and-a-half syndrome, OAHS lacks the involvement of cranial nerve VII with facial palsy.

Finally, to further elucidate the etiology underlying these symptoms, neuro-imaging is indicated, with MRI being the modality of choice to examine and localize underlying brainstem lesions. Angiography may be indicated if there is suspicion of a vascular etiology of the pontine lesion.

Prognosis

Prognosis of OAHS depends largely on the underlying cause. Some cases have been  reported to resolve spontaneously with a typical recovery period of a few weeks to months. However, in stroke, the prognosis varies from persistent deficit to partial recovery of ocular motility. When associated with demyelinating or inflammatory disease, the prognosis may be more guarded. Ultimately, visual rehabilitation and treatment of the underlying cause can help to improve symptoms and quality of life, but full recovery of eye movements is rare.

Treatment

While the main management of OAHS is directed at the underlying cause, various interventions exist for symptomatic management of disabling diplopia, oscillopsia or blurred vision in unresolved cases. Conservative symptomatic management includes eye patching or single eye occlusion to manage diplopia. Prisms can also be utilized to minimize diplopia with paralytic exotropia. Although unlikely to restore ocular movement, surgical intervention using extraocular muscle recession and adjustable sutures can be considered to improve binocular vision, head posture and cosmesis .

Alternatively, injection of botulinum toxin to selected extraocular muscles has been reported to provide some symptomatic relief in certain cases, specifically those with oscillopsia due to ataxic disconjugate nystagmus. While not a cure, the transient therapeutic effect of the botulinum toxin makes it a suitable option for the management of complex ocular motility problems during the rehabilitation period .