Oculomotor Cranial Neuropathies: Diagnosis and Management

Abstract

Ocular nerve palsies are among the most common cranial neuropathies in neurological practice. Nerves can get affected anywhere along their path from the brainstem to the orbit. There can be isolated involvement of multiple cranial nerves together. The etiologies differ according to the type of presentation. The steps toward the diagnosis need to be strategically planned and must be based on clinical localization. It is crucial to make proper localization to plan further investigations and thus treatment of the etiology. This review covers the approach toward the diagnosis, etiologies involved, and management of ocular cranial neuropathies.

Keywords: Abducens palsy; diplopia; ocular nerve palsy; oculomotor palsy; trochlear palsy.

Figure 1

A 15-year-old girl presented with acute onset binocular horizontal diplopia with drooping of the left eyelid (a–i). She had a history of acute onset weakness of the right upper and lower limb which was treated with aspirin at another center after an MRI showed an acute infarct in the left ventral medulla (DWI: j and ADC: k). She was worked up for etiologies of stroke with normal complete blood count, renal and liver function tests, thyroid function tests, procoagulant workup including APLA, vasculitic workup, echocardiography, and angiography of intracranial and extracranial neck vessels. When she presented to us, her examination revealed left ptosis with restriction of left MR, IR, IO, and bilateral SR with normal pupils, and brisk deep tendon reflexes in the right upper and lower limb. Surprisingly, her visual acuity was 6/60 in the right eye and finger-counting at 3 feet in the left eye with a pale disc bilaterally (fundus photography: p). She also revealed her difficulty in looking at the board in her class because of which she started sitting in the front row. What will be the approach to this patient? Because of the involvement of the anterior visual pathway in her, one can get confused about localization. Another confusing point is brisk reflexes on the right side of the body which can be possible if we consider the lesion at the level of the left cerebral peduncle leading to ipsilateral oculomotor palsy and contralateral corticospinal signs. However, the point to note here is bilateral SR restriction which takes us more toward lesion at the nucleus rather than fascicle. Brisk reflexes were likely because of an old insult (left medullary infarct). Repeat MRI showed diffusion restriction in the left side of the midbrain (DWI: l, m, and ADC: n) supporting the localization. We considered a strong possibility of mitochondrial cytopathy because of young age, recurrent stroke-like presentations, and optic atrophy. Muscle biopsy revealed red ragged fibers which were COX deficient on enzyme stain. DWI: Diffusion weighted image, ADC: Apparent diffusion coefficient, APLA: Antiphospholipid antibodies

Figure 2

A 35-year-old female got admitted for evaluation of fever, anorexia, and weight loss for 2 months. She was evaluated outside and started on antitubercular drugs because of probable pulmonary tuberculosis. However, she has recently developed drooping of both upper eyelids (e). On examination, she had complete ptosis bilaterally with asymmetrical oculomotor palsy with pupillary involvement and left LR restriction (a–i). The localization in this patient could be nuclear as she has bilateral third CN palsy (ptosis and SR restriction are bilateral). Gadolinium-enhanced MRI revealed no involvement of the midbrain but there were dense exudates (yellow arrows in j–l, TIW) entrapping oculomotor nerves at their exit in the interpeduncular fossa and course further in subarachnoid space also abutting optic nerves (red arrow in k) and chiasma. MRI spine showed evidence of Pott's spine at D5 and D6 (yellow circle, m). She was started on dexamethasone with the continuation of antitubercular treatment

Figure 3

A 15-year-old male presented with a history of acute onset drooping of left eye with a deviation of left eyeball laterally and headache since morning. There was no history of headaches in the past. Examination revealed dilated left pupil (e) with sluggish light reflex and left SR, IR, IO, MR restriction with ptosis. Because of painful III CN palsy with pupillary involvement in a young male, the possibility of an aneurysm was considered and gadolinium-enhanced MRI brain and orbit along with constructive interference in steady state with MR angiography was performed. Imaging was unremarkable. CT angiography was done to look out for any aneurysm which might have been missed; however, it was normal. The other routine and serological workup along with cerebrospinal fluid (CSF) pressure and CSF workup were completely normal. He started improving spontaneously. The final diagnosis of ophthalmoplegic migraine was made and he was started on propranolol. He gradually recovered

Figure 4

A 32-year-old female with a history of drooping of upper eyelids for 2 months. It was bilateral, asymmetrical (left > right) without diplopia, but had fluctuations in the symptoms. Examination showed fatiguability on upgaze, no restriction of extraocular movements, and normal pupils. The case can be easily confused with the last case; however, pupillary sparing will lead us to consider the possibility of the neuromuscular junction or muscle disease. The neostigmine test was positive (b), which confirmed the diagnosis of ocular myasthenia. Acetylcholine antibody test came positive

Figure 5

A 40-year-old male with a history of hypertension presented with weakness of the right upper and lower limb along with diplopia and severe ataxia. Examination showed left VI and VII CN palsy with impairment of left horizontal gaze (c: unable to look in left lateral gaze) along with severe gait and stance ataxia, cerebellar speech with oculopalatal myoclonus. MRI brain showed pontine bleed (red arrows in f: FLAIR and g: susceptibility-weighted image)

Figure 6

A 32-year-old male presented with acute onset weakness of the left upper and lower limb with dysarthria and ataxia. Examination revealed bilateral horizontal gaze palsy, right facial palsy (LMN) with stance, and gait ataxia. Noncontrast-enhanced CT head showed hyperintensity in pons likely of acute hemorrhage. MRI brain FLAIR (i) and T2 (j) sequences showed a hypodense lesion in the dorsal aspect of the pons, which showed blooming in the susceptibility-weighted image. Considering the young age of the patient without a history of vascular risk factors, the high possibility of cavernoma was kept

Figure 7

A 38-year-old female with a history of rheumatoid arthritis, on methotrexate and intermittent steroids, presented with a history of headache and recurrent diplopia which improves completely on taking steroids. She had two episodes in the last 4 months. She presented with the third episode because of diplopia on tapering steroids, cushingoid habitus, and increased frequency of headache. On examination, she had right VI (d) and right XII CN palsy (Fig. 7j). Because of a combination of VI and XII CN palsy, the lesion around the clivus was suspected with the possibility of inflammatory etiology (IgG4 disease, sarcoidosis) in view of steroid responsiveness. Neoplastic etiology was also considered because of the high incidence of nasopharyngeal carcinoma in the localization suspected. Contrast-enhanced MRI brain and base of the skull was done, which suggested soft tissue mass lesion in the right skull base region (yellow arrows and circle) with bony erosion of the right petrous apex, basi-occiput, and sphenoid. The lesion was seen extending into carotid space, prevertebral, and nasopharyngeal space causing effacement of the fossa of Rosenmuller inferiorly and clivus posterio-superiorly. Evaluation revealed raised serum IgG4 levels (994 mg/dL normal <800 mg/dL). A tissue biopsy was deferred by an otorhinologist because of the difficult approach at the site of the lesion. FDG-PET scan showed FDG avid lesion and bone scan using TcMDP three-phase study showed increased perfusion and osteoblastic activity in the right petrous apex with subtle erosive changes in clivus. She was restarted on steroids with a cover of injectable antibiotics. She showed mild improvement and is on close follow-up

Figure 8

A 68-year-old female with lung carcinoma presented with dysarthria (more to linguals) in the last 3 months which has been static since then. She had no other significant history. On further examination, she had right abducens palsy (a) and right hemi tongue atrophy with deviation to the right side (c). Localizing her symptoms to right VI CN and right XII CN without any headache or any other long tract signs, we consider the possibility of the lesion at the clivus (Godtfredsen syndrome) or nearby subarachnoid space. Contrast-enhanced MRI of the brain and base of the skull was done to confirm the hyperostotic clival metastasis (d and e) which was further confirmed on FDG-PET CT scan which shows increased uptake (f-h)

Figure 9

A 42-year-old female presented with headache for the past one-and-a-half month and visual loss for 20 days, and left followed by right binocular diplopia. A clinical picture suggested raised intracranial pressure but the etiology seems to be fulminant. The possibility of carcinomatous meningitis, secondary CNS lymphoma was kept initially. Examination showed severe anemia, bilateral grade V papilledema with peripapillary hemorrhages and tortuous vessels (e and f) and multiple cranial nerves palsies (bilateral VI, CN left partial III CN, right VII CN, bilateral IX and X CN, right XII CN). Contrast-enhanced MRI brain was unremarkable except for minimal tortuosity of optic nerves. However, MR venography revealed thrombosis of the right transverse and sigmoid sinuses. Lumbar puncture showed raised ICP of 31 cm H₂O. Cerebrospinal fluid showed malignant epithelial cells of epithelial origin. Ultrasonography (USG) abdomen and pelvis revealed a bilateral adnexal mass with both solid and cystic components confirmed by MRI pelvis (g). USG-guided fine-needle aspiration cytology of adnexal mass confirmed carcinoma. FDG-PET reported FDG avid lesion in the right adnexa with variably FDG avid skeletal lesions (i). She also had hypercalcemia of malignancy which was managed with intravenous hydration and anti-hypercalcemic measures. She was planned for radiotherapy; however, relatives were not ready for further treatment when counseled regarding the disease

Figure 10

A 38-year-old male presented with right frontal headache, throbbing character, pain relieved transiently with oral analgesics. He noticed 10–12 days later a binocular double vision in horizontal gaze. His headache and double vision spontaneously resolved over 20–25 days after the intake of oral analgesics. However, he further developed drooping of the right upper lid associated with redness, tearing, swelling, and pain. On evaluation, he had only a perception of light in the right eye with complete ophthalmoplegia and proptosis (a–i). Keeping clinical localization as superior orbital fissure because of III, IV, VI, and II CN involvement, differentials thought were fungal infection (mucormycosis, aspergillosis) and inflammatory disorders (sarcoid, IgG4 disease). Contrast-enhanced MRI brain showed contrast enhancement and thickening of the right cavernous sinus (yellow arrows in j-l) extending to the right orbital apex. Sinuses were normal in MRI as well as in dedicated CT for paranasal sinuses. One week later, the lesion extended to encase cavernous ICA and into the sellar fossa and right sphenoid sinus. He was started on empirical liposomal Amphotericin (5 mg/kg), and trans sphenoidal biopsy of soft tissue lesion was done. The patient showed improvement with a decrease in eyelid swelling, and ophthalmoplegia but the vision did not improve. Workup for etiology revealed a negative fungal profile, normal serum galactomannan, high serum IgG levels, and normal cerebrospinal fluid workup. Biopsy revealed non-specific inflammation. Whole-body FDG-PET showed increased uptake in the right cavernous sinus, bilateral salivary glands, pancreas, and renal cortices. Hence, the possibility of IgG4 disease was strong. The plan was to start steroids for salvaging the vision; however, he tested positive for both hepatitis C and B. Owing to chronic active hepatitis C, he was started on Sofosbuvir + Daclatasvir and Tenofovir was started for chronic hepatitis B. Because of active viral replication, steroids were started later on

Figure 11

A 22-year-old gentleman presented with acute onset painless horizontal binocular diplopia with no history of diurnal variation or fatiguability since 3 weeks. The next day he had also developed right-sided ptosis and had noticed that he was not able to move his right eyeball in any direction completely. History was suggestive of right-sided LMN facial palsy 2 years back with aberrant regeneration which had persisted till date. At the time of presentation, he had bilateral upper eyelid swelling more on the lateral aspect with restriction of eye movements in all directions in the right eye with pupillary sparing and right LMN facial palsy with the rest of the neurological and systemic examination being normal. Hence, evaluation was done for the syndrome of acute onset painless external ophthalmoparesis with an old history of LMN facial nerve paresis which did not reveal any evidence of neuromuscular junction disorder. Gadolinium-enhanced MRI of the brain and orbit showed an ill-defined lesion in the right cavernous sinus and orbital apex which showed mild contrast enhancement (k). The lesion was FDG avid in FDG-PET of the whole body, with FDG avid enlarged mediastinal and paratracheal lymph nodes (fig. 0-r). The possibility of sarcoidosis was kept which was further confirmed by raised serum ACE levels of 90.1 (normal values: 8–63). Endobronchial ultrasound-guided transbronchial needle aspiration showing epithelioid cell granulomas. Ziehl–Neelsen stain and Bactec culture was negative. The patient was started on oral steroids and azathioprine. He was asymptomatic at 6 months follow-up