One and a half syndrome
One-and-a-half syndrome is a syndrome caused by horizontal eyeballs movement disorders that is characterized by an ipsilateral conjugate horizontal gaze palsy (the “one”) and an ipsilateral internuclear ophthalmoplegia (INO) (the “half”) 1). The eye ipsilateral to the lesion (ipsilateral paramedian pontine reticular formation [PPRF] or the ipsilateral abducens [6th cranial nerve] nucleus) has limited horizontal motility, and only remaining horizontal movement is the contralateral eye has only one-half of its horizontal motility intact (abduction). Hence the name “one-and-a-half” syndrome. The only horizontal movement that remains is abduction of the contralateral eye, which is usually accompanied by nystagmus. (Figures 1 and 2). The apparent adduction deficits can be overcome with convergence. One-and-a-half syndrome is caused by a lesion that affects the ipisilateral paramedian pontine reticular formation (PPRF) or the ipisilateral abducens nucleus (6th cranial nerve that is responsible for the horizontal gaze palsy) and the ipsilateral medial longitudinal fasciculus (MLF) (responsible for the internuclear ophthalmoplegia – failed adduction of the ipsilateral eye) 2). Along with one-and-a-half syndrome, there are a series of rare and uncommon syndromes that the lesion is closely related with one-and-a-half syndrome called one-and-a-half syndrome spectrum disorders 3). When this lesion also affects the fascicle of the the ipsilateral facial nerve (7th cranial nerve) in the region of the facial colliculus as it wraps around the 6th cranial nerve nucleus, it produces a lower motor neuron pattern of ipsilateral facial weakness. When this occurs, a one-and-a-half syndrome plus a 7th nerve palsy, it is termed an eight-and-a-half syndrome 4).
The diagnoses of one-and-a-half syndrome and its spectrum disorders rely on distinctive clinical symptoms, neuroanatomy, especially imaging technologies 5). Other associated symptoms including visual impairment, impaired swallowing and fine motor deficits may contribute to locating the lesions. The treatment depends on the causes of the syndrome.
Figure 1. One-and-a-half syndrome
Footnote: Diagram showing the mechanism for one-and-a-half syndrome. (A) Pathologic lesion (blue oval shaded area) in the dorsal pontine tegmentum involves both the left ipsilateral paramedian pontine reticular formation (PPRF) (or the left abducens nucleus) causing an ipsilateral complete conjugate horizontal gaze palsy and affecting the left medial longitudinal fasciculus (MLF) causing an ipsilateral internuclear ophthalmoplegia (INO). Only contralateral abduction is spared. (B) Position of eyeballs, with rightward gaze, the left eye has the impaired adduction, while the abduction of the right eye is intact, except for the nystagmus, and with left gaze, both eyes have impaired horizontal movement (abduction of the left eye and adduction of right eye).
Abbreviations: X = interruptions of signal transmission or eye movement that are a result of the lesion; 6th nucl. = abducens nuclei; 6th n = ipsilateral abducens nerve (cranial nerve VI); 3rd nucl. = oculomotor nuclei.[Source 6) ]
Figure 2. One-and-a-half syndrome (orthophoria in primary gaze, total left gaze palsy and limitation of adduction of the left eye in right gaze)
Footnote: A 43-year-old male patient presented with chief complaint of sudden onset, progressively worsening binocular diplopia in the right eye for the preceding 1 month. No history of any trauma or similar complaint was elicited in the past. The patient was found to be adequately built, with vital signs being normal and had no evidence of systemic abnormality. On ocular examination, best-corrected distance visual acuity and near vision in both the eyes were 6/6 and N6, respectively. Anterior and posterior ocular segment evaluation was unremarkable. Although the eyes were aligned in primary position, horizontal gaze palsy was noted with loss of saccades and pursuit movements in levoversion. On attempted dextroversion, the right eye was abducting with associated abduction nystagmus, in the absence of left eye adduction. Both vertical gaze and convergence were normal. Based on ocular findings, the diagnosis of ipsilateral one-and-a-half syndrome was made. Magnetic resonance imaging (MRI) was advised following clinical evaluation, which revealed an irregular complex cystic enhancing space-occupying lesion measuring 42 mm × 39 mm × 35 mm, in the region of fourth ventricle closely abutting the brain stem posteriorly (Figure 3A and B). Multiple small ring and disc enhancing lesions were also seen in the bilateral cerebellar hemispheres and right occipital lobe. Radiological findings suggested brain metastasis. Further evaluation was supplemented with 18F-fludeoxyglucose positron emission tomography/computed tomography (CT) imaging to locate the primary pathology. Abdominal CT scans showed primary neoplastic lesion, arising from the upper pole of the right kidney and another exophytic mass in the lower pole of the left kidney. In addition, metastatic lesions in the right adrenal gland, pancreas, and brain were seen. Based on examination and investigations, diagnosis of Stage 4 renal cell carcinoma (inoperable) with brain metastasis with associated ipsilateral one-and-a-half syndrome was made. The patient was shifted to oncology department and started on palliative radiotherapy after sorting consultation for the same.[Source 7) ]
Figure 3. One and one half syndrome MRI of patient 1
Footnote: Postcontrast T1-weighted image (a) and T2-weighted image (b) show an irregular complex cystic heterogeneously enhancing mass measuring 42 mm × 39 mm × 35 mm in region of fourth ventricle, abutting brain stem.[Source 8) ]
8 and half syndrome
Eight-and-a-half syndrome is characterized by one-and-a-half syndrome with the seventh cranial nerve damage 9). In eight-and-a-half syndrome, patients presented sudden onset of horizontal diplopia and right facial paralysis. The primary eye position was normal. The patient had combination of the right gaze paresis, along with impaired adduction in right eye and abduction with nystagmus in the left eye 10). The vertical movements of two eyes were normal, with right peripheral facial paralysis. It is clear that the eight-and-a-half syndrome lesions are located in the ipsilateral paramedian pontine reticular formation (PPRF), MLF, facial nerve nucleus or nerve bundle. Or the lesions damaged ipsilateral abducens nucleus, medial longitudinal fasciculus (MLF), facial nerve nucleus or nerve bundle. Therefore, the lesion is easily located in the ipsilateral pontine tegmentum.
The head MRI T2-weighted image showed a high signal at the right paramedian pontine tegmentum. According to the patient’s signs and head MRI, the damaged sites were considered in the right abducens nucleus, right medial longitudinal fasciculus (MLF) and right facial nerve (Figure 4A). The paracentral artery occlusion of pons was considered in this case.
Similar to one-and-a-half syndrome, the common cause of eight-and-a-half syndrome is pontine infarction caused by the perforating artery occlusion. The rare causes include infection, tumor, demyelination, or brain stem vasculitis. Eight-and-a-half syndrome is the most common variant of one-and-a-half syndrome spectrum disorder.
Figure 4. 8 and half syndrome
Footnote: Schematic diagram of the lesion of one-and-a-half syndrome spectrum. (A) Eight-and-a-half syndrome; (B-F) nine syndrome; (G) thirteen-and-a-half syndrome; (H) fifteen-and-a-half syndrome; (I) sixteen-and-a-half syndrome.
Abbreviations: Abd. nucl. = abducens nucleus; IV = 4th ventricle; ML = medial lemniscus; MLF = medial longitudinal fascicle; 7th nucl. = facial nerve nucleus; 7th n. = facial nerve; CST = corticospinal tract; PPRF = parapontine reticular formation; ICP = inferior cerebellar peduncle; spinal trigeminal nucl. = spinal trigeminal nucleus; cochlear nucl. = cochlear nucleus.[Source 11) ]
Horizontal eyeballs movement disorder neuroanatomy
Brain structures involving the horizontal movement in eyeballs mainly include paramedian pontine reticular formation (PPRF), abducens nucleus and medial longitudinal fasciculus (MLF) 12). The disorders of horizontal movement in eyeballs resulting from the damage to the above brain structures are divided into three categories 13):
- Horizontal gaze palsy;
- Internuclear ophthalmoplegia (INO);
- One-and-a-half syndrome.
Paramedian pontine reticular formation (PPRF) is the supranuclear center located near the ipsilateral abducens nucleus and the ventral medial longitudinal fasciculus (MLF) that receives the nerve impulses from visual area of the frontal and parietal lobes and controls horizontal conjugate eye movements 14). It is believed that the PPRF includes excitatory neurons and dominates the ipsilateral abducens nucleus 15). The ipsilateral abducens nucleus emits the abducens nerve, which controls the ipsilateral lateral rectus. It also emits MLF, which dominates the contralateral oculomotor subnucleus and then goes to control the contralateral medial rectus resulting in the ipsilateral eyeball abduction and the contralateral eyeball adduction, forming horizontal conjugate movement of eyes. If the isolated side of PPRF is damaged, the eyes could not gaze at the lesion side, presenting the horizontal gaze palsy to the lesion side 16).
The abducens nucleus is located in colliculus facialis, which is in the lower part of the pons and the bottom of the fourth ventricle 17). It contains two functionally distinct cell groups: the abducens motoneurons that innervate the lateral rectus muscle; the internuclear neurons which axons cross the midline and ascend via the contralateral MLF to oculomotor subnucleus and control the medial rectus 18). Therefore, the unilateral lesion of the abducens nucleus will also produce ipsilateral horizontal gaze paralysis.
Medial longitudinal fasciculus (MLF) are the longitudinal nerve fibers that locate on the back of the pons and are close to the front of the fourth ventricle, a part of which relating to horizontal gaze is from the side of the abducens nucleus to the contralateral oculomotor subnucleus 19). The lesion of unilateral pontine tegmentum can damage the ipsilateral MLF, causing the ipsilateral internuclear ophthalmoplegia (INO), and its clinical manifestations show the ipsilateral intraocular muscle paralysis and contralateral horizontal nystagmus when staring at the opposite side. If the damage does not involve the midbrain, the convergence reflex is integrated 20).
One and a half syndrome causes
One-and-a-half syndrome is caused by a lesion of unilateral tegmentum of pons (pontine tegmentum), causing damage to the ipsilateral paramedian pontine reticular formation (PPRF) or ipsilateral abducens nucleus (or both) and medial longitudinal fasciculus (MLF) which causes conjugate gaze palsy 21) (Figure 1). Reported causes for one-and-a-half syndrome include pontine hemorrhage, aneurysms, vascular malformations, pontine infarction secondary to thrombosis or spasm of basilar artery (usually due to occlusion of paramedian perforating branches of the basilar artery) 22), tumors like glioma, metastases [e.g., metastatic breast carcinoma 23), acute myeloid leukemia 24)], demyelinating diseases like multiple sclerosis (MS) or acute demyelinating encephalomyelitis (ADEM), hindbrain anomalies (e.g. Chiari malformation) and infective conditions like tuberculosis (e.g. tuberculoma) 25). In the elderly, infarction tends to be the most common etiology, while tumors and MS should be considered in younger patients 26).
The most common cause of one-and-a-half syndrome was cerebrovascular disease, and usually was brain stem lacunar infarction, followed by the demyelinating etiology (multiple sclerosis), and then the infectious cause including neurocysticercosis and brainstem encephalitis 27). Other uncommon causes were head trauma, brain stem tumor (primary or metastasis), astrocytomas, etc. 28). Therefore, the vast majority of one-and-a-half syndrome companied by other positioning signs is due to the different lesions of brainstem 29). Only a very small number of patients showed isolated one-and-a half syndrome, while the lesions are smaller and localized, such as brainstem cysticercosis 30), brainstem tuberculosis 31), brainstem cavernous hemangioma (cavernomas) 32) and the local hemorrhagic infarction of brainstem 33).
One and a half syndrome symptoms
The most common symptom of one-and-a-half syndrome is diplopia. Further questioning will likely yield a description of binocular, horizontal diplopia that is worse with contralateral gaze. Other complaints include blurred vision, oscillopsia, difficulty looking to the affected side, and a ‘quivering’ eye 34).
One and one half syndrome symptoms:
- Blurred vision
- Difficulty looking to one side
- “Quivering” of eye
- No visual complaints
- During ipsilateral gaze: complete lateral gaze palsy
- During contralateral gaze: internuclear ophthalmoplegia (INO)
- ADduction intact with convergence
Depending on the etiology, size, and location of the lesion, other neurological findings may be noted on physical exam. Inclusion of cranial nerves II, V, VII, VIII, IX, and XII were detected in Wall and Wray’s 1983 case and literature review 35). Other findings included Horner syndrome, weakness or spasticity, sensory deficits, abnormally brisk or asymmetric reflexes, extensor plantar responses, and incoordination 36). Additionally, when the facial motor nucleus is simultaneously affected, a central facial palsy can be seen, and such cases have been deemed “eight-and-a-half syndrome” 37). Other interesting associations with one-and-a-half syndrome include oculopalatal myoclonus 38) and Cheirooral syndrome 39).
One and a half syndrome diagnosis
A full ocular motility exam, including convergence, should be performed. In one-and-a-half syndrome, the apparent adduction deficits can be overcome with convergence. Forced ductions may be helpful to rule out a restrictive palsy. A neurological exam with attention to the cranial nerves may help you further localize a lesion. Consider thyroid function testing, myasthenia gravis antibody testing, or in-office endrophonium testing if thyroid eye disease or myasthenia gravis are a clinical concern. Adduction deficits due to myasthenia gravis cannot be overcome by convergence. Neuro-imaging is indicated, with MRI being the modality of choice.
One and a half syndrome treatment
Treatment, management, and prognosis depend on the underlying cause of the one and one half syndrome. Collaboration with neurology or neurosurgery may be necessary.
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