title: Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis.
abstract: Although subclinical involvement of sensory neurons in amyotrophic lateral sclerosis (ALS) has been previously demonstrated, corneal small fiber sensory neuropathy has not been reported to-date. We examined a group of sporadic ALS patients with corneal confocal microscopy, a recently developed imaging technique allowing in vivo observation of corneal small sensory fibers. Corneal confocal microscopy (CCM) examination revealed a reduction of corneal small fiber sensory nerve number and branching in ALS patients. Quantitative analysis demonstrated an increase in tortuosity and reduction in length and fractal dimension of ALS patients' corneal nerve fibers compared to age-matched controls. Moreover, bulbar function disability scores were significantly related to measures of corneal nerve fibers anatomical damage. Our study demonstrates for the first time a corneal small fiber sensory neuropathy in ALS patients. This finding further suggests a link between sporadic ALS and facial-onset sensory and motor neuronopathy (FOSMN) syndrome, a rare condition characterized by early sensory symptoms (with trigeminal nerve distribution), followed by wasting and weakness of bulbar and upper limb muscles. In addition, the finding supports a model of neurodegeneration in ALS as a focally advancing process.
authors.affiliation: Cornea and Ocular Surface Disease Unit, Eye Repair Lab, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Information Engineering, University of Padova Padova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Grisan
authors.affiliation: Department of Information Engineering, University of Padova Padova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Scarpa
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fazio
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Comola
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy ; Vita e Salute San Raffaele University Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Cornea and Ocular Surface Disease Unit, Eye Repair Lab, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rama
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute Milan, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
keywords: ALS; cornea; facial-onset sensory and motor neuronopathy; motor neuron disease; neuromuscular; neuroophthalmology; neuropathy