A qualitative and quantitative magnetic resonance diffusion study investigating the pathogenesis of cryptococcal-induced visual loss.
Date
2013
Authors
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Abstract
Background: Cryptococcal induced visual loss is common and increasingly becoming a
debilitating consequence in survivors of cryptococcal meningitis (CM). Conflicting reports of
the optic neuritis and papilloedema models of visual loss have delayed the introduction of
effective interventional strategies for prevention and treatment of visual loss in CM.
Qualitative and quantitative diffusion-weighted imaging (DWI) and diffusion tensor imaging
(DTI) of the optic nerves have proven useful in the examination of the microstructure of the
optic nerve especially in optic neuritis. Its application has been extrapolated to other optic
nerve disorders such as ischaemic optic neuropathy and glaucoma. The aim of this study is to
elucidate the pathogenesis of cryptococcal-induced visual loss using diffusion imaging of the
optic nerve as an investigational tool.
Method: Full ethical approval was obtained from the Greys Hospital, Department of Health
and University of KwaZulu Natal Ethics Committees. Reliable and reproducible optic nerve
diffusion techniques were first developed and optimized on 29 healthy volunteers at Greys
Hospital, Neurology and Radiology departments using a Philips 1.5 Tesla Gyroscan.
Informed consent was also obtained from 95 patients suffering from CM (≥18 yrs. of age), 14
patients with papilloedema and 14 patients with optic neuritis from other causes, recruited
from Greys and Edendale Hospitals. Patients underwent full neuro-ophthalmological
assessments, CSF examination, haematological workup, CD4 count, (viral load for some),
electrophysiological assessment of vision [Visual evoked potential (VEP) and Humphreys
visual fields (HVF)], Magnetic Resonance Imaging (MRI) scan of the brain and orbits and
DWI and DTI of the optic nerves.
Results and Discussion: Visual loss is common in CM, occurring in 34.6-48%. Optic
neuritis was uncommon as evidenced by a lack of signal change and lack of enhancement
within the optic nerve in all patients scanned. The peri-optic CSF space was not dilated and
the optic nerve diameter was not increased regardless of CSF pressure and visual status.
Swollen optic discs occurred in only 25% of patients whereas raised intracranial pressure (>
20cmCSF) was demonstrated in 69-71% of patients. Therefore visual loss could not be
explained by papilloedema alone. The VEP P100 latency was shown to be a useful screening
test for subclinical optic nerve disease in CM, but HVF was not.
The optic nerve diffusion imaging used was reliable and reproducible and produced diffusion
parameters equivalent to other investigators in the field. Neither optic nerve movement nor
the CSF signal was demonstrated to impact significantly on optic nerve diffusion parameters.
Optic nerve diffusion imaging did not demonstrate similarities between CM and
papilloedema or optic neuritis regardless of CSF pressure or vision.
Conclusion: The rarity of optic neuritis in CM and the disparity between papilloedema and
visual loss together with the lack of support from diffusion studies suggest a 3rd mechanism
of visual loss viz. the optic nerve compartment syndrome. Good clinical support is provided
by a case report for this hypothesis that shows re-opening of the peri-optic CSF space and
return of the peri-optic CSF signal on MRI with lowering of intracranial pressure and
antifungal treatment.
Description
Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.
Keywords
Neuroopthalmology., Optic nerve--Diseases., Optic neuritis., Cryptococcus neoformans., Theses--Neurology.