Fungal infections in the organ transplant recipient can cause significant morbidity and possible mortality. The most common cause of CNS infection in the organ transplant population is C. Neoformans[3]. The diagnosis of cryptococcal meningitis can be a difficult one as the disease often presents with a sub-acute onset and non specific symptoms and signs. The disease should be suspected in any immunocompromised patient with fever, headache and signs or symptoms referable to the central nervous system (CNS). Our patient presented with fever, headache and bilateral complete ophthalmoplegia. Diagnosis was confirmed by positive CSF cryptococcal indian ink stain and culture and supported by MRI findings.
Cranial neuropathies and ophthalmoplegia are common complications in patients with cryptococcal meningitis, yet bilateral complete ophthalmoplegia is a very rare presentation. Sumit Mohan and colleagues reported a case of cryptococcal meningitis in 2006 with complete loss of vision and hearing as well palsies of the third, sixth and seventh cranial nerves in a sequential manner [4]. Apart from that in our review of the literature we found several references to cases of cryptococcal meningitis with numerous combinations of or isolated second, third, fourth, sixth, seventh and eighth cranial neuropathies. Also there had been reported cases of intranuclear ophthalmoplegia, wall-eyed bilateral internuclear ophthalmoplegia (WEBINO), right Horner's and right hemiparesis syndrome. None of these patients had bilateral complete ophthalmoplegia at presentation or subsequently and there is remarkable paucity of data on bilateral complete ophthalmoplegia in the literature.
MRI of our patient had multiple nodular lesions in basal ganglia and thalamus, but brainstem was spared. These radiological features argue against brainstem pathology as a cause for bilateral complete ophthalmoplegia, which is remarkable. Lesions in basal ganglia and thalamus have been previously reported in cryptococcal meningitis [5, 6]. It is believed that the meningeal infection along the base of the skull may involve the adjacent brain parenchyma, giving rise to cryptococcomas or may extend along the Virchow-Robin spaces. The cryptococcal organisms spread through the Virchow-Robin spaces, dilating these spaces, to ultimately propagate in the basal ganglia, internal capsule, thalamus, and brain stem [5, 6].
Previous reports have described horizontal and vertical gaze palsies in patients with either unilateral or bilateral thalamic vascular lesions (infarction/haemorrhage) [7, 8]. There was no evidence of midbrain involvement in these cases. It has been shown that pathways from the frontal and supplementary eye fields do traverse the medial thalamus. The primate thalamus also has reciprocal inputs to the frontal and supplementary eye fields. This input arises from the internal medullary lamina. The central thalamus is traversed by frontocortical axons, which send collaterals to internal medullary lamina complex neurons. The internal medullary lamina complex also receives afferents from several brain stem populations and the superior colliculus, and it has reciprocal connections with the inferior parietal pole [7]. The possible mechanism of the horizontal gaze disturbances is interruption of the descending fibers from the frontal eye field at the thalamus near the dorsal medial nuclei, internal medullary lamina or medial pulvinar. Vertical gaze dysfunction may result from involvement of the intralaminar and part of the dorsomedial nucleus [8]. Bilateral thalamic involvement may have been a possible mechanism for the ophthalmoplegia without brainstem involvement in our patient. However MRI will not completely exclude coexisting small brainstem lesions.
Cryptococci are thought to physically block the passage of CSF across the arachnoid villi as well as in the subarachnoid spaces. This causes CSF to accumulate causing high intracranial pressure. Increased intracranial pressure leads to compression of the cranial nerves causing neuropathies [4]. Sixth cranial nerve palsy is very common in the setting of raised intracranial pressure as a false localizing sign and it is well reported in cryptococcal meningitis as well [9]. This factor may have contributed to bilateral abductor weakness in our patient. However, ocular palsies seen in this patient solely due to raised intracranial pressure has been poorly described. Inflammation and direct invasion of cranial nerves by the fungus is also thought to be responsible for cranial neuropathies in cryptococcal meningitis [10].
When considering all of these factors, we postulate that bilateral thalamic lesions, inflammation and invasion of the cranial nerves and raised intracranial pressure may have acted individually or in combination to cause bilateral complete ophthalmoplegia in this patient.
Patient’s clinical condition improved with antifungal treatment. Although CSF drainage is recommended as a measure of reducing intracranial pressure in patients with cryptococcal meningitis, it was not done in our patient because CSF pressure was only modestly elevated and as he had clinical improvement with the antifungal agents.
