Central pontine myelinolysis presenting as isolated sixth nerve palsy in third trimester of pregnancy.

A 30-year-old primigravida presented with isolated left sixth nerve palsy at 38 weeks gestation. Her MRI showed a lesion consistent with central pontine myelinolysis (CPM). Extensive investigations did not reveal any secondary cause for the CPM. She recovered spontaneously in 2 weeks with complete resolution of her MRI changes. To our knowledge, this is the first report of CPM occurring in third trimester in the absence of identifiable secondary causes and of CPM presenting as an isolated sixth nerve palsy. We discuss the reported causes of CPM in pregnancy, possible pathophysiologic mechanisms involved and the anatomic basis of the unique clinical presentation of sixth nerve palsy in our case.

Case Report

At 38-weeks gestation a 31-year-old primigravida presented with diplopia on left gaze of 1- day duration. The diplopia was worse for far objects. She had unilateral throbbing headache similar to her previous migraines for 3 days prior to admission, associated with two to three episodes of vomitting per day, which were similar to her previous migraine attacks. There was no history of fever, photophobia or phonophobia.

She had an uneventful follow-up in antenatal clinic throughout the pregnancy. Her blood pressure was normal at the 13 week, 20 week and 33 week follow up visits. Her urinalysis was normal and she was not diabetic. There was no significant past medical or family history. She was non-smoker, non-alcoholic and there was no history of substance abuse. Preeclampsia was ruled out and she was referred to neurology with above history on the same day of admission.

On examination, she was alert and oriented. Her blood pressure was 106/65. There was complete paralysis of the left lateral rectus muscle. She had hyper-reflexia in all four limbs (Deep tendon reflexes were 3+). Rest of the neurologic examination was normal. MRI brain showed a non-enhancing, central, symmetrical, pontine T2 hyper-intensity which also showed evidence of restricted diffusion [Figure 1a and b] consistent with central pontine myelinolysis (CPM). The MRI of orbits, MR angiogram and MR venogram were unremarkable.

Figure 1

(a and b) Diffusion-weighted image showing central pontine hyperintensity. Corresponding area on ADC mapping shows hypointensity, suggesting a diffusion restriction in the central pons. (c) Sagittal T2-weighted image showing a hyperintensity in the central pons. (d) Axial T2-weighted image showing a triangular area of hyperintensity in the central pons. The arrow represents the proposed site of VI nerve fascicle injury

Blood investigations including full blood count, ESR, renal, liver and thyroid function tests, folate, Vitamin B12, calcium and phosphate were normal. Serial daily electrolytes did not reveal any derangement. Toxicology and autoimmune workup included were negative.

Lumbar puncture opening pressure was normal and CSF was unremarkable. (WBC = 0; Proteins = 0.24g/; Glucose normal; Gram stain, bacterial culture, fungal smear and culture, TB-PCR and TB-culture negative, oligoclonal bands negative).

Patient underwent Caesarean section. A healthy baby weighing 3180 g was delivered. Considering the diagnosis of CPM due to typical lesion, absence of obvious secondary cause and mild symptoms and signs, she was observed without any specific treatment. She gradually improved and the left eye abduction movement had recovered to about 50% at the time of discharge 4 days after the delivery. At 2-week follow-up after discharge, she was asymptomatic and her VI nerve palsy had fully recovered. A repeated MRI at this time showed complete resolution of the previous changes. [Figure 2]

Figure 2

Two consecutive axial T2-weighted cuts of pons after 2 weeks of MRI in Figure 1. Note the complete resolution of the pontine hyperintensity

Discussion

There are two attributes of our case which make it unique. First is the occurrence of CPM in third trimester of pregnancy in the absence of any identifiable secondary cause and second is the presentation of CPM with an isolated VI nerve palsy.

In pregnancy, central pontine myelinolysis is seen in the first trimester, in the context of hyperemesis gravidarum.[1] The rapid fluctuations in blood osmolality due to acute hyponatremia and/or its rapid correction are commonly implicated factors. In pregnancy, hypokalemia and thiamine deficiency[2] (also associated with hyperemesis in first trimester), salt restricted diet[3] and lithium toxicity in 2nd trimester,[4] gestational diabetes in third trimester,[5] and magnesium sulfate in immediate postpartum period[6] have been associated with pregnancy-related CPM. However, all these patients had hyponatremia (except one who had hypokalemia) of variable severity secondary to the underlying conditions described. Our case is unique in the sense that she did not have any identifiable secondary cause.

To our knowledge, our case is the first description of CPM in third trimester of pregnancy in the absence of secondary causes. Our patient's sodium level on admission was normal and it remained normal throughout the week of her admission. Whether pregnancy itself makes brain susceptible to myelinolysis due to minor osmotic imbalances is a hypothesis arising out of our observation. In our patient, vomiting, although mild, could have been the minor trigger responsible.

CPM has a broad clinical spectrum with asymptomatic cases[7] at one end and florid cases with quadriparesis, locked-in state and coma[1] at the other end of spectrum. Presentation of CPM as isolated VI nerve palsy is unusual and not reported earlier to our knowledge.

In our patient, the MRI lesion does correlate anatomically to the location of VI nerve fascicle. After its origin at VI nerve nucleus in pons, the VI nerve fascicle passes anteriorly through the substance of pons. In our case, the left posterior angle of the central pontine triangular lesion was perhaps the site where the fascicle was involved [Figure 1d arrow]. This location is just posterior to the pyramidal tract and anterior to the medial lemniscus. These two structures were spared clinically. With the pontine lesion, and temporal relation of clinical recovery to radiologic resolution, it is hard to attribute the VI nerve palsy to other causes than the pontine lesion itself.

Cases of pre-eclampsia and hypertension presenting as VI nerve palsy in pregnancy have been described.[8] But these patients did not have CPM like brain lesions and our patient did not have any evidence of pre-eclampsia or hypertension.

There were no signs of raised ICP in our patient. Also, the MRI did not show any evidence of edema in the extrapontine region to explain raised ICP as the cause. In our patient, one might argue for other causes of transient pontine edema resulting from conditions like posterior reversible encephalopathy syndrome (PRES). However, our patient had no risk factors for the same and the MRI did not show even subtle changes suggestive of PRES.

MRI differentials for central pontine lesions described in our patient include infarct, metastasis, glioma, multiple sclerosis, encephalitis, and radiation or chemotherapy-induced changes.[9] Thus, such changes are not specific to CPM. The benign clinical course and complete resolution of MRI changes in short span of 2 weeks without any specific treatment makes alternative diagnoses unlikely in our case.

Conclusion

Occurrence of CPM in third trimester of pregnancy without obvious secondary causes and spontaneous resolution after delivery makes us postulate as to whether pregnancy itself, due to its hormones predisposes to this condition. Isolated VI nerve palsy could be another presenting manifestation of central pontine myelinolysis.