While poorly understood, conjugate eye deviation (CED) is really quite frequent: about 20% of stroke patients, about a third of thrombolyzed patients and roughly half of thrombectomy patients have it.
In this modern era where neurological workup of stroke patients is reduced to the barest minimum for the sake of door-to-needle and door-to-groin time, the door-to-neurologist’s-brain interval and ratio suffers just as much as the patient, inflating the role of the only diagnostic measure that is properly carried out: neuroimaging. Therefore radiological signs of severe impairment gain more attention and conjugate eye deviation is one of the easy and seemingly objective signs (while, say, a Babinski is hard to capture in an image of the brain). In contrast to the rest of the neurological exam you can also find CED on CT (CT-CED) retrospectively, so there are quite a few papers on it.
In the neurological exam one would require the following semiquantitative information:
- Any eye deviation
- Significant eye deviation (> 15°) – increases interrater reliability of CED
- Severe eye deviation (> 30°) – if supratentorial, highly associated with spatial neglect
- With head deviation – usually with severe eye deviation. Note that head-on-trunk deviation cannot be seen on CT as the patient’s head is fixed in the machine.
- Fixed: cannot be overcome by contralateral visual stimulation – this might hint at accompanying spatial/visual neglect or hemianopia
- Supranuclear: can be overcome by VOR/OCR – if not, obviously a brainstem stroke should be suspected
- With nystagmus, usually in the direction of the eye deviation – this is ictal mainly. In theory it could be pontine but I have never observed the combinaton of CED + nystagmus in that case and could not find any case reports.
Since the FEF is quite near to the precentral gyrus and large strokes tend to damage the pyramidal tract as well, we expect a contralateral hemiparesis to accompany the ipsilesional eye deviation in most cases of damage to the frontal eye field.
CT versus clinician?
It is noteworthy that mild forms of conjugate eye deviation may actually only be seen with eyes closed (those of the patient, silly!) – this is much harder to examine clinically than radiologically, although it requires that the CT technician consistently ask patients to keep their eyes closed and that patients be able to follow this command.
This reduces correlation between the clinical examination (as reported in the gaze palsy item of the NIHSS) and the CT finding; e.g. in this 2017 study, a kappa of only 0,34 was achieved, while the interrater reliability of CT-CED was very good (even without a predefined threshold for the degree of eye deviation). UCSD seems to be better at fitting the clinical examination to CT results, achieving a kappa of 0,89 but they have the advantage of having a cool name for CT-CED: the “DEYECOM sign”.
Usually, CED and especially severe and/or fixed CED points to large hemispheric strokes. Still there is a well documented 2002 report of a smaller cortical stroke in the region of the frontal eye field (FEF) that caused ipsilesional CED (see below for comments about the localization of the FEF) and we have seen such ourselves.
Neglect versus CED
A long-standing controversy surrounds the relation between CED and spatial neglect. Obviously a patient that ignores, say, the left world, will have his eyes or even his head turned right. Vice versa, if you cannot turn your eyes to the left, you tend to not see things on the left (although you will still recognize that something is happening on the left – something a real neglect patient would not). So if in some studies only visual cues have been used to diagnose neglect, there should be a strong correlation between the two and the more severe the neglect the worse the eyes (and head) deviate. There are definite cases of CED without neglect and the two phenomena have a different half life, with CED usually subsiding after hours to days, while neglect can take much longer. So there is a relationship but they are not married.
There are some case series and reports on contraversional CED in supratentorial strokes, sometimes called wrong-way deviation. This can be explained by:
- ictal CED – stimulation of the frontal eye field (see below) causes contralesional eye deviation, often with nystagmus (so-called epileptic nystagmus which really is quite specific). If in the setting of acute stroke or intracerebral hemorrhage this requires that the FEF is not in the core but in the border region of the stroke (the outer penumbra, where cells are still viable, semi-functioning but easily excitable), for instance in M2 occlusions of the temporoparietal trunc,
- bilateral stroke – not necessarily recognized in the acute images; can hint at proximal embolic source, vasculitis and much more,
- herniation: the well-known falsely localizing sign of ipsilesional hemiparesis in space-occupying lesians such as malignant MCA stroke or large ICH with transtentorial herniation – compression of the contralateral crus cerebri against the cerebellum through midline shift of the mesencephalon (producing Kernohan’s notch),
- hemorrhage with contralateral lesion,
- parietal stroke: some authors mention that spatial neglect from right parietal stroke can lead to contraversive eye deviation. I have to admit that I don’t understand it, but there you have it.
Where is the FEF is located?
This question has bothered generations of researchers, starting with neurosurgical observations of patients in ancient times, somewhat later primate studies, then human semi-invasive studies (including direct cortical stimulation) and more recently PET, SPECT and fMRI research. The conclusion of this detailled review is that the precise localization depends on the setting of the experiment (which stimulus is used? what is required from the patient to do?), but it should be somewhere between the dorsal third of the midfrontal gyrus, the deeper parts of the precentral sulcus, and maybe the frontal parts of the precentral gyrus around that region.
Finding it on CT/MRI
Remember that one of the various (and not always successful) ways to localize the central sulcus is by walking along the easily recognized superior frontal sulcus from front to back, parallel to the falx, until you hit the precentral gyrus.
Laterally you should find the hand knob (with the Omega sign), more medially and inferiorly the paracentral lobule which closes the ring formed around the central sulcus: precentral gyrus -> paracentral lobule -> postcentral gyrus -> subcentral gyrus and back again. The frontal eye field should be slightly lateral to the corner of the L formed by the superior frontal sulcus and the precentral sulcus (see Image).
Since the FEF is near the precentral gyrus and large strokes tend to injure the pyramidal tract as well, we expect a contralateral hemiparesis to accompany the ipsilesional eye deviation in most cases of damage to the frontal eye field.
Besides the cortical structures the caudate nucleus, thalamus und the subinsular basal ganglia can cause neglect and thereby conjugate eye deviation, thus contradicting the dogma that CED is a strictly cortical sign. But remember that this holds true not only for neglect and CED but also for aphasia. While most of the acute cases with these so-called “cortical deficits” that end up with only a subcortical stroke do have cortical hypoperfusion in the acute phase there are definite (if rare) cases of isolated strokes in either of the three regions with either of the three symptoms. Perhaps we should call them the gray (substance) deficits.
Significance of cortical signs
Why bother? Because cortical signs accompanying a hemiparesis strongly suggest a large vessel occlusion, thus necessitating CT angiography.
As an aside, many strokeologists count visual field disturbances as cortical signs. I hesitate to do so, as most quadrantanopias are probably caused by MCA strokes in the temporal or parietal subcortical visual radiation and then there is also the case of the anterior choroidal artery strokes causing hemianopia.
Differential for acute stroke
If taken as a sign of cortical dysfunction the differential for CED in the acute setting of presumed stroke is narrow: stroke/ICH, postictal (or ictal if ipsilateral to the paresis), dysglycemic. The other classic differentials for acute CNS focal deficit (such as migraine, MELAS, …) have not been reported to cause clinically consistent CED. Remark that if only the radiological sign of CED is used then a lot of false positives (50% in this series) will arise, because patients can and will look around at times during CT.
Ocular eye movements are mediated through various brainstem pathways, nuclei and cranial nerves. Lesions of these structures lead to nystagmus (gaze evoked, upbeat or downbeat), diplopia, internuclear ophthalmoplegia etc. CED is among the more rare signs of brainstem strokes:
- Sometimes pontine lesions to the medial longitudinal fascicle (near median pontine, as in this case report) lead to contraversion of the eyes rather than the more frequent sign of internuclear ophthalmoplegia.
- There are also some reports of medullary strokes (both dorsolateral – aka Wallenberg – and dorsomedial) with CED, in which case malfunction of the olivocerebellar pathways, the nucleus prepositus hypoglossi (taking care of gaze holding) or the MLF have been implicated, with ipsilesional eye deviation.
- A non-systematic study of cerebellar strokes found subclinical (only radiographic) CED in about a third of patients, mostly contraversional.
- In my personal experience, bilateral lesions to the pyramidal tract in the medulla have led to protraced (> 1 year) conjugate eye and head deviation.
Take home messages
- Note eye and gaze position clinically in all your acute stroke patients – it is a sign of badness.
- Note eye and gaze position on CT and try to verify it clinically.
- In gaze deviation think 1) cortical 2) brainstem 3) subcortical 4) contralateral.