Oculomotor nerve palsy as an extraintestinal manifestation of Crohn’s disease

Abstract

Patients with inflammatory bowel disease (IBD) may present with extraintestinal manifestations. Neurological symptoms associated with IBD are infrequent. Thus, any unexplained neurological symptom that occurs in patients with IBD should raise the suspicion of a link between the two disorders. We report a case of a man in his 60s, who was diagnosed with Crohn’s disease and developed ptosis and diplopia. Neurological examination revealed oculomotor nerve palsy, sparing the pupil. MRI and magnetic resonance angiography of the brain were insignificant and no other cause was determined. He was treated with oral corticosteroids and symptoms gradually subsided. Cranial nerve palsies associated with IBD have been rarely reported. They usually involve the optic and acoustic nerve and are attributed to a common dysimmune base. This is the first reported case of oculomotor nerve palsy (III cranial nerve) associated with IBD. Clinicians treating patients with IBD should be alert for unusual neurological complications and treat them appropriately.

Background

Crohn’s disease (CD) and ulcerative colitis, the two main types of inflammatory bowel disease (IBD), are common causes of gastrointestinal morbidity with a worldwide distribution. IBDs are multisystemic diseases affecting other organs outside the gastrointestinal tract, most commonly the skin, joints, eyes and blood. These extraintestinal manifestations are not rare, occurring in 20%–40% of patients, and sometimes precede the onset of gastrointestinal symptoms by many years or may appear simultaneously.¹ Nervous system may also be affected during the course of IBD, but the actual incidence is not known due to the poor literature available, consisting mostly of case reports and case series. In one large review, neurological manifestations were estimated to occur in 3% of patients with IBD.² IBD can affect both the central and peripheral nervous system. In the central nervous system, it manifests most commonly as cerebrovascular or demyelinating disease.³ Peripheral neuropathy, either axonal or demyelinating, is the most frequent manifestation of peripheral nervous system involvement and might be attributed either to IBD or to treatment with metronidazole, ciclosporin, sulfasalazine and biological agents. The fact that peripheral neuropathy responds to steroid therapy supports the idea that peripheral neuropathy in IBD may be autoimmune induced, in addition to the effects of neurotoxic drugs.⁴

Cranial nerve palsies associated with IBD have been rarely reported, and are restricted to the II (optic nerve), VII (facial nerve) and VIII (acoustic nerve). Regarding oculomotor nerves, there is only one report of VI (abducens) nerve palsy, resulting in horizontal diplopia.⁴

Case presentation

We report a case of acute III (oculomotor nerve) palsy in a man in his late 60s. The patient had a known medical history of CD since 2000, currently treated with mesalazine 1000 mg three times a day, and being in a stable condition without exacerbation in the last 5 years. During the course of the disease, he has suffered a few episodes of iridocyclitis, treated with steroid eye drops. The rest of his medical history was unremarkable. The patient felt retro-orbital pain on the right, and 3 days later, he developed complete ptosis. When his eyelid was manually elevated, he experienced diplopia in all gaze directions, except to the right. Pupils were equal and responded to light, directly and indirectly. Symptoms were stable and did not fluctuate during the day. Visual acuity was unaffected. The rest of the neurological examination was normal. The clinical presentation was compatible with III nerve palsy, sparing the pupil.

Investigations

The patient underwent imaging testing, brain MRI and magnetic resonance angiography with gadolinium-enhanced views, to exclude intracranial masses compressing III (neoplasms, infarcts, aneurysms, demyelination and pituitary adenomas or apoplexy), and full laboratory testing to exclude non-suppressive causes of III palsy (complete blood count, haemoglobin A1C, serum sedimentation rate, C reactive protein, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, antibodies against acetylcholine receptors and anti-MuSK antibodies, creatine kinase, serum lactate, connective tissue screen). All the above investigations brought normal results.

Differential diagnosis

Morbidity and mortality are strongly linked to the aetiology causing oculomotor nerve palsy. Therefore, it is urgent to diagnose and rule out those causes that, if left untreated, may have an unpleasant outcome. Compressive lesions are more likely to involve the pupil, but this is not mandatory. In this case, although the pupil was unaffected, a comprehensive imaging study was performed to rule out neoplasms, aneurysms, pituitary adenomas, cavernous sinus thrombosis, stroke or meningeal infiltration. Since there was no history of trauma or neurosurgical procedure, those possible diagnoses were also rejected. All other non-compressive causes of III nerve palsy, such as diabetes mellitus, thyroid disease and giant cell arteritis, were excluded following suitable laboratory testing. Other conditions that may mimic III palsy are myasthenia gravis and myositis, and these were also excluded after testing for specific antibodies and imaging of the orbital cavity. Since no other specific cause could be identified, III palsy was attributed to vasculitis-induced nerve ischaemia, reflecting the higher predilection for microvascular ischaemic third nerve cranial nerve palsies in older versus younger adults.⁵

Treatment

The mechanism underlying neurological complications of IBD is not clear. Nutritional deficiencies, infections, thromboembolism and toxic effects of drugs used to treat IBD have all been equally suggested.⁴ Moreover, immunological abnormalities affecting cell-mediated and humoral immunity may be involved in the development of neurological complications.² Since there has been no previous similar case to rely on, it was decided to start the patient on oral corticosteroids, a treatment recommended in other similar cases of cranial nerve involvement, such as in cases of facial palsy,⁶ optic neuritis with optic disc swelling⁷ and sensorineural hearing loss.⁸ Furthermore, in similar reported cases of ischaemic vasculitis damaging nerves, such as in cases of Churg-Strauss syndrome and microscopic polyangiitis, the vasculitis affecting vasa nervorum was complicated by oculomotor nerve palsy that gradually improved with corticosteroid treatment.^{9 10}

Outcome and follow-up

The patient experienced immediate relief of retro-orbital pain after the initiation of corticosteroids and gradually observed improvement first in eyelid elevation. One month later, he is still experiencing diplopia, but with a tendency for symptomatology to subside. He has returned to his normal daily activities and feels confident that all symptoms will gradually subside.

Discussion

To the best of our knowledge, this is the first case report describing isolated III nerve palsy associated with CD causing ptosis, diplopia and retro-orbital pain.

Ptosis and diplopia, the main symptoms presented in this case, could also be related to neuromuscular junction diseases or myositis. Myasthenia gravis, an autoimmune disease affecting neuromuscular junction, is often associated with other autoimmune diseases, including IBD.^{1 4 8} Myasthenia causes ptosis and diplopia, which are typically characterised by fluctuations over time. Orbital myositis is a non-specific, localised orbital inflammatory process, in which one or more extraocular muscles are involved. This condition can present with almost similar symptoms, that is, retro-orbital pain aggravated by eye movements, diplopia and ptosis due to eyelid swelling.^11–14 In our case, both conditions were thoroughly investigated and ruled out through appropriate tests; therefore, III nerve palsy was the only plausible examination for this clinical picture.

Cranial nerve palsies associated with IBD have been rarely reported, mostly in the form of case reports. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, and this is supported by the fact that they respond to steroid treatment. In addition, other mechanisms such as brain–gut axis dysfunction, thromboembolism, infections and nutritional deficiencies may contribute to the pathogenesis of neurological complications. Vasculitis is also reported as a rare factor leading to nerve palsy by affecting vasa nervorum, causing either demyelination or axonal damage to peripheral nerves.¹⁵

Ischaemic optic neuropathy has been commonly reported.^{7 16–19} Most authors attribute the nerve injury to optic disc ischaemia due to local vasculitis or hypercoagulopathy, peripapillary inflammation or intracranial hypertension. In some cases, optic neuropathy is attributed to neurotoxic effects of drugs (infliximab, ciclosporin A).⁸ Bell’s palsy has also been reported in the course of CD, but mostly was related to toxic effects of treatment, adalimumab and methotrexate.^{6 20} Recurrent facial nerve palsy occurring in Melkersson-Rosenthal syndrome has been reported in association with CD.^{21 22} Sensorineural hearing loss is the most commonly described cranial nerve palsy in patients with IBD.^23–29 The pathogenesis is not clear, but the clinical response to steroid and immunosuppressive therapy suggests that immune mechanisms might been implicated. Vestibular dysfunction may accompany auditory symptoms as well. Regarding oculomotor nerves, only one case report describes abducens nerve palsy. The patient presented with sudden onset of diplopia in lateral gaze and retro-orbital pain. Abducens palsy was attributed to microvascular ischaemic demyelination that gradually remyelinated, and full recovery was observed after 3 months. We believe that both cases of oculomotor nerve palsies associated with IBD might share common pathogenetic mechanisms. No other report of isolated palsy of oculomotor nerves has been reported.

IBDs are systematic diseases, often affecting extraintestinal systems. The nervous system may also be involved, although rarely. Reporting cases of otherwise unexplained neurological symptoms in patients with IBD will raise awareness among physicians regarding their recognition and appropriate treatment.

Patient’s perspective.

Translated by the author

Αt first I felt a sharp pain behind my eye, but I was not alarmed, for I thought it was another attack of iridocyclitis, even though no redness in my eye was noticed. So, I started the steroid eyedrops on my own, as I usually do in similar instances. Then suddenly, after a couple of days, and for no reason, at all I woke up in the morning to find that I couldn’t open my right eye. This was new for me and certainly did not remind me of iridocyclitis. I visited my ophthalmologist, that confirmed that it was not iridocyclitis and urged me to see a neurologist, because probably I had a problem in my head. At that moment, I was horrified, because I knew it wasn’t the same old story of iridocyclitis I was used to, and knew it will eventually go away. After the first brain imaging was done and was negative, I was reassured that it was just an inflammation of a nerve and the prognosis would be favorable.

Learning points.

• Although extraintestinal manifestations of inflammatory bowel disease (IBD) are common, neurological complications are under-reported and their actual incidence is unknown.

• Isolated cranial nerve palsies have been only rarely reported in patients with IBD.

• The pathogenetic mechanism underlying cranial nerve palsy is not clear, but inflammation and/or ischaemia are considered as possible factors related to altered immunity.

• In most cases of cranial nerve involvement, steroid treatment favoured outcome, supporting the idea of immune dysregulation resulting in nerve palsy.

• Early recognition and treatment of neurological complications are crucial for preventing major morbidity.

Ethics statements

Patient consent for publication

Obtained.