Axonal degeneration and inflammation in acute optic neuritis

Aims: To investigate whether plasma biomarkers for axonal injury and inflammation are related to loss and recovery of visual function in acute optic neuritis (ON).Methods: Eighteen patients with ON and 14 controls were investigated in a longitudinal, prospective study. Plasma phosphorylated neurofilament heavy chain ( NfH(SMI35); a surrogate marker of axonal injury), nitric oxide metabolites (NOx), and citrulline ( surrogate markers of inflammation) were measured.Results: Patients with ON had higher median plasma NfH(SMI35) values than controls (0.17 versus 0.005 ng/ml; p< 0.05) and higher NOx values (49 versus 35.5 mu M; p< 0.001). Plasma NfH(SMI35) values correlated inversely with visual acuity at presentation ( R = -0.67; p = 0.01). NfH(SMI35) was higher in patients with poor recovery of visual acuity than in those with good recovery (0.25 ng/ml versus 0.09 ng/ml; p< 0.05). Three of four patients with high NfH(SMI35) and high NOx values experienced a poor recovery as opposed to only one of five with high NOx but normal NfH(SMI35) values.Conclusions: NfH(SMI35), a surrogate marker for axonal damage, is a prognostic indicator and should be considered in the design of neuroprotective treatment strategies

The diagnostic and prognostic value of neurofilament heavy chain levels in immune-mediated optic neuropathies

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79 ± 1.51 ng/mL) compared to patients with CRION (0.13 ± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions

The Use of Serum Glial Fibrillary Acidic Protein Measurements in the Diagnosis of Neuromyelitis Optica Spectrum Optic Neuritis

Background: Glial fibrillary acidic protein (GFAP) is a specific intermediate filament of the cytoskeleton of the astrocyte and may be used as a specific marker for astrocytic damage. It is detectable in the cerebrospinal fluid following a relapse caused by Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) spectrum disease. Higher levels are found following an NMO-related relapse. It is not known if GFAP is also detectable in the serum following such relapses. In particular, it is not known if lesions limited to the optic nerve release GFAP in sufficient quantities to be detectable within the serum. The aim of this study was to ascertain the extent to which serum GFAP levels can distinguish between an episode of optic neuritis (ON) related to NMO spectrum disease and ON from other causes.Methodology/Principal Findings: Out of 150 patients consecutively presenting to our eye hospital over the period March 2009 until July 2010, we were able to collect a serum sample from 12 patients who had presented with MS-related ON and from 10 patients who had presented with NMO spectrum disease-related ON. We also identified 8 patients with recurrent isolated ON and 8 patients with a corticosteroid-dependent optic neuropathy in the absence of any identified aetiology. GFAP was detectable in the serum of all but three patients (two patients with MS-related ON and one with recurrent optic neuritis). The median serum GFAP level in the patient group with NMO spectrum disease was 4.63 pg/mL whereas in all other cases combined together, this was 2.14 pg/mL. The difference was statistically significant (P = 0.01). A similar statistically significant difference was found when cases with pathology limited to the optic nerve were compared (P = 0.03).Conclusions: Glial pathology in NMO related optic neuritis is reflected in elevated serum GFAP levels independently of whether or not there is extra-optic nerve disease

Photophobia in migraine: A symptom cluster?

Photophobia is one of the most common symptoms in migraine, and the underlying mechanism is uncertain. The discovery of the intrinsically-photosensitive retinal ganglion cells which signal the intensity of light on the retina has led to discussion of their role in the pathogenesis of photophobia. In the current review, we discuss the relationship between pain and discomfort leading to light aversion (traditional photophobia) and discomfort from flicker, patterns, and colour that are also common in migraine and cannot be explained solely by the activity of intrinsically-photosensitive retinal ganglion cells. We argue that, at least in migraine, a cortical mechanism provides a parsimonious explanation for discomfort from all forms of visual stimulation, and that the traditional definition of photophobia as pain in response to light may be too restrictive. Future investigation that directly compares the retinal and cortical contributions to photophobia in migraine with that in other conditions may offer better specificity in identifying biomarkers and possible mechanisms to target for treatment

Recurrent ptosis in an adult due to isolated paresis of the levator palpebrae superioris and Muller's muscle of unknown aetiology

We report on the case of a middle-aged woman who suffers from recurrent right-sided ptosis. The ptosis is always complete with preserved ocular motility. Full recovery is the rule. The involvement of both the Muller's muscle and levator palpebrae superioris is demonstrated clinically, pharmacologically, and by high-resolution magnetic resonance imaging. The results presented point towards a local pathology of the lid surface anatomy; the etiology, however, remains unknown