Cerebrospinal fluid hypovolemia syndrome mimicking ocular myasthenia gravis: A case report

Abstract

Purpose

Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis.

Observeations

A 29-year-old man exhibited fluctuating left ptosis and diplopia after a traffic accident. Although he was suspected of having myasthenia gravis and was treated using oral pyridostigmine bromide, his symptoms did not improve. He also had orthostatic headaches and malaise after the accident. His symptoms were suspected to be associated with traumatic cerebrospinal fluid hypovolemia. After 1000-mL fluid replacement, his diplopia and ptosis improved, and orbital T2-weghted MRI detected a high-signal zone around the optic nerve. We diagnosed him with oculomotor nerve paresis associated with cerebrospinal fluid hypovolemia. The symptoms, including ptosis, diplopia, orthostatic headaches, and malaise, disappeared after epidural blood patch therapy.

Conclusions and Importance

When treating patients with fluctuating ocular symptoms, such as diplopia and ptosis, who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.

1. Introduction

Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage.1, 2, 3 The symptoms may be preceded by trauma, and patients often present with postural headaches as the main symptom and/or nausea, vomiting, and occasionally ocular manifestations, including blurred vision, photophobia, double vision, visual field defects, and abnormal eye movements.4, 5, 6, 7, 8, 9, 10 However, the mechanisms underlying these ocular manifestations are not well understood.

We report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis.

2. Case report

A 29-year-old man exhibited left ptosis and diplopia, and was referred to our neuro-ophthalmology clinic. Six months ago, his car crashed into a roadside tree. He developed orthostatic headaches and malaise after the accident. It was difficult for him to open his eyes, and the out-of-focus feeling gradually worsened over time after waking up and recovered after lying down. Although his previous doctor suspected myasthenia gravis and he was treated using oral pyridostigmine bromide, his symptoms did not improve.

On examination at the first visit, his best-corrected decimal visual acuity was 1.5 in both eyes. The pupillary light reflex was prompt in both eyes. Although no notable limitation in extraocular muscle movement was found in either eye, on alternate prism cover testing, 8 prism diopters of left exotropia and 4 prism diopters of right exotropia were noted at distance. His left ptosis is shown in Fig. 1A. Slit lamp and fundus examinations yielded normal findings in both eyes. Blood test results were unremarkable. The anti-acetylcholine receptor antibody and edrophonium tests were also negative.

Fig. 1.

(A) Face photograph before fluid replacement. Exotropia of the right eye (yellow arrow) and ptosis of the left eye (red arrow) were observed. Photographs after fluid replacement (B) and after epidural blood patch (EBP) therapy (C). Improvement in right exotropia and left ptosis is shown in both B and C. The dashed lines represent the center of both pupils in the orthophoric position. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Based on his history of trauma, we suspected that his symptoms were not associated with myasthenia gravis, but with traumatic CHS. We then laid the patient on the bed in the Trendelenburg position (head lower than feet) and performed 1000 mL (500 mL of lactated Ringer's solution and 500 mL of maintenance transfusion) of rapid intravenous fluid replacement within 2 hours in order to increase the intracranial CSF volume (fluid replacement test), and observed whether these symptoms improved.

Immediately after fluid replacement, his headache and malaise improved. Diplopia and ptosis also improved. The photo after fluid replacement is shown in Fig. 1B. His eye position became orthophoric and left ptosis improved.

Orbital MRI was performed before and after fluid replacement to evaluate the change in CSF with reference to the previous report.¹¹ The images shown in Fig. 2 were taken 15 mm posterior to the eyeball, including the optic nerve and optic nerve sheath. The CSF between them was detected as a circular hyper-intensity. After fluid replacement, the high-signal zone around the optic nerve increased.

Fig. 2.

Orbital MRI (fat saturated T2-weighted). The images were taken 15 mm posterior to the eyeball, including the optic nerve and optic nerve sheath. The right and left optic nerves were imaged individually in the coronal-oblique plane to ensure the slices were orthogonal to the longitudinal axis. The cerebrospinal fluid (CSF) between them was detected as a circular hyper-intensity. The MR images around the optic nerve before and after fluid replacement are shown. After fluid replacement, the high-signal zone around the optic nerve indicating CSF increased.

Next, MR myelography (MRM) was performed for the CSF leakage test. Although no notable CSF leak was detected on the first MRM (Fig. 3A), epidural blood patch (EBP) therapy was performed for the clinical diagnosis and at the patient's request. The temporary improvement in symptoms after fluid replacement became permanent after EBP, and all symptoms, such as orthostatic headaches, malaise, diplopia, and left ptosis, disappeared. On comparison of the MRM images before and after EBP, the hyper-intensity along the nerve roots that was observed before the treatment (Fig. 3A; yellow arrows) decreased or disappeared after the treatment (Fig. 3B).

Fig. 3.

Lumbar MR myelography (MRM) before and after EBP therapy. CSF space expansions at multiple nerve root sleeves with high-intensity signals were identified in the lumbar sacral region on MRM before EBP therapy (A). After EBP, these hyper-intensities decreased or disappeared.

3. Discussion

Traffic accidents can cause CSF leakage, termed “spontaneous intracranial hypotension (SIH)”. Zada et al.⁴ reviewed the ocular manifestations in SIH, which included blurred vision, photophobia, double vision, and visual field defects. Mokri et al. reported that 7 of 40 patients (17.5%) with SIH had a normal CSF pressure. They found that the core pathogenetic factor was a decreased volume of CSF rather than its pressure in SIH.¹² Therefore, the term “cerebrospinal fluid hypovolemia (CFH)” was proposed instead of “spontaneous intracranial hypotension”.¹³ Transient third cranial nerve palsy due to CFH was previously reported.6, 7, 8, 9 We considered the diplopia and ptosis with diurnal fluctuation in our patient to have been caused by oculomotor nerve paresis associated with CFH.

The pathophysiology of cranial nerve palsy in CFH is not fully understood, and potential causes include traction on cranial nerves due to downward displacement of cerebral structures and cranial nerve compression.^9,13 The symptoms in CFH patients worsen within 2 hours of standing or sitting up and can be temporarily relieved by lying in a supine or recumbent position.¹⁴

Variable ptosis and diplopia are the most common manifestations of myasthenia gravis because ocular muscles are more commonly affected due to twitch fibers in ocular muscles developing tension faster and having a higher frequency of synaptic firing than limb muscles.^15,16

The orthostatic change in CFH may be confused with diurnal fluctuation in myasthenia gravis because both symptoms become exacerbated after waking up and recover after lying down. The history of trauma and orthostatic headaches were important for the differential diagnosis, including anti-acetylcholine receptor antibody in the serum and the edrophonium test. Fluid replacement improved his symptoms, and orbital MRI before and after fluid replacement detected an increase in CSF around the optic nerve, which suggested a decrease in the overall volume of CSF.¹⁷

EBP therapy for CHS¹⁸ may have improved these conditions by stopping CSF leakage. MRM was useful for identifying CSF leakage and confirming the effectiveness of EBP, as in previous reports.¹⁹ However, it was difficult to detect CSF leakage by pretreatment MRM alone and the diagnosis of CSF hypovolemia was only confirmed by comparison with post-EBP MRM in this case.

4. Conclusions

We reported a case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with diurnal fluctuation mimicking ocular myasthenia gravis. The fluid replacement test was useful for the differential diagnosis and an increase in CSF after fluid replacement was detected on orbital MRI. EBP therapy was effective for the ocular symptoms and postural headaches. When treating patients with fluctuating diplopia or ptosis who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.

Patient consent

We received written consent from the patient to publish this report. The protocol for the fluid replacement test with orbital MRI was reviewed and approved by the institutional review board of Hokkaido University Hospital for clinical research.

Funding

No funding or grant support.

Authorship

All authors attest that they meet the current ICMJE criteria for authorship.

Declaration of competing interest

Nil.