Pearls & Oy-sters: Upbeat Nystagmus and Quadriplegia in a Young Girl with Bilateral Medial Medullary Syndrome

Discussion

Our patient presented with abrupt onset of neck pain, quadriplegia, sensory loss, and respiratory failure, which usually indicates a complete high cervical cord transection or vascular pathology involving the brainstem, such as in acute vascular dissection. Brain and cervical spine MRI were performed immediately, but DWI, which could show early changes of an infarct, was missed in the imaging sequence. Spontaneous vessel occlusion leading to ischemia or infarction was not emphasized early, because of the patient's very young age at onset with the absence of common risk factors for stroke.

In this case, the finding of nystagmus in a quadriplegic patient helped to localize the lesion to the brainstem instead of being a purely cervical cord disease. In a medulla oblongata lesion, horizontal gaze-evoked nystagmus is commonly reported in lateral medullary syndrome due to the involvement of the vestibular nuclei and its projection.¹ The neural integrators responsible for horizontal gaze are the medial vestibular nuclei and the nucleus prepositus hypoglossi.² Medullary lesions located in the paramedian region usually manifest as an upbeat nystagmus (UBN).^3,4 UBN beats upward in the primary position and can be aggravated by looking in an upward direction of gaze. Its common etiologies include tumor, stroke, multiple sclerosis, and Wernicke encephalopathy.³

On the other hand, vertical gaze-evoked nystagmus (GEN) can also be prominent in upward or downward direction of gaze, but it disappears in the primary eye position. Vertical GEN occurs primarily in midbrain lesions, where the interstitial nucleus of Cajal serves as the primary neural integrator.² The flocculus and nodulus of the cerebellum also play a role in maintaining an eccentric position of gaze.²

Another type of vertical nystagmus is spontaneous downbeat nystagmus, in which the fast phase beats in a downward direction in the primary eye position.³ It can be aggravated by looking down and to the side while in a prone position. It is mainly due to bilateral disease of the cerebellar flocculus, but has rarely been reported in paramedian medullary lesions.³

MMS is a rare form of posterior circulation stroke that occurs in fewer than 1% of cases.⁵ It occurs even more rarely bilaterally in a young patient without underlying diseases. MMS is more commonly seen in elderly men, and the main mechanism of stroke is atherosclerosis involving the vertebral artery.^5,–,7 Large artery disease is more common than small penetrating arteries occlusion.^6,7 Occlusion of the anterior or posterior spinal arteries can be associated with cervical cord ischemia or infarction, as demonstrated in our case.¹ Clinical presentations of MMS include motor weakness, dysarthria, and hypoglossal nerve palsy.^4,5 Other reported symptoms of bilateral MMS are rapidly progressive quadriplegia, generalized numbness, nystagmus, giddiness or vertigo, and mild impairment of consciousness.^1,4,7,8

The medulla oblongata has a unique arterial supply from the branches of the vertebral artery, namely from the anterior and posterior spinal arteries, in addition to the perforating arteries and the long circumferential artery.⁶ The medulla oblongata is divided into few vascular territories: the anteromedial, anterolateral, lateral, and posterior territories.⁶

The characteristic brain MRI finding of heart appearance in bilateral MMS has been described in multiple case reports.^1,4,8 The heart appearance sign is considered to appear when the infarct occurs in the bilateral anteromedial medulla, which is supplied by branches of vertebral artery and anterior spinal artery and may extend to the anterolateral territory, which is fed by short and long transverse branches of the vertebral artery.¹ Lesions involving the anteromedial vascular territory are common in the rostral part of the medulla oblongata.^1,6,7 Unilateral vertebral artery occlusion may also cause a bilateral infarction, because the rostral median branches of the vertebral artery penetrate the midline to supply the contralateral anteromedial arterial territory.^1,6

We postulated that our patient had MMS with anterior spinal artery (ASA) infarction due to emboli of an unrecognized source, which possibly dislodged to multiple distal branches rather than causing blockage of the main vessels, as evidenced by a normal MRA of the main cerebral vessels. A rare cause of ASA infarction in a young patient is fibrocartilaginous emboli (FCE), due to the migration of the nucleus pulposus material from the intervertebral disc to the nearby vessels and subsequent embolization to the spinal arteries.⁹ In one review of histopathology-confirmed FCE, 6 out of 41 cases presented with an abrupt onset of neck pain and quadriplegia due to ASA infarction involving the medulla oblongata and cervical cord. A total of 40% of deaths in these cases were attributable to respiratory complications.⁹ FCE can occur even with a very minimal or unnoticed injury to the neck and without degenerative spine changes seen on MRI. FCE can only be confirmed by biopsy of the occluded vessels, mostly taken during the autopsy, and no specific treatment was available.⁹

Spinal cord infarction is often mistaken for and treated as acute transverse myelitis. In this case, the clues to support infarction rather than myelitis include very abrupt onset, with maximal neurologic deficit within the first hour, normal CSF examination, distribution of lesion area following vascular territory of ASA (anterior 2/3 of the cord), no contrast enhancement on MRI with relatively normal initial scan, and absence of clinical response to early administration of high-dose methylprednisolone.⁹ In neuromyelitis optica, the long segment lesion is usually located centrally in the gray matter. It enhances with contrast and might also show restricted diffusion on DWI.¹⁰ Other causes of restricted diffusion on brain MRI include immune encephalitis, multiple sclerosis, venous infarction, and brain abscess.¹⁰

Few case reports highlight that early MRI features of MMS might be missed if the MRI is not thoroughly interpreted.^4,8 Similar to our case, a retrospective review of the first MRI, which was initially read as normal, actually showed early changes of infarct in the paramedian region of the medulla, which sometimes can be misinterpreted as midline artifacts. As the prognosis of bilateral MMS is guarded, it is crucial to recognize the early imaging features of MMS, because urgent reperfusion therapy might help to salvage the ischemic area in selected cases.^5,7 In our case, further investigations with conventional cerebral angiography, extended duration of cardiac Holter monitoring, and transesophageal echocardiogram would be helpful to look for the source of emboli in a young patient.