Periodic alternating nystagmus consists of involuntary oscillations of the eyes with cyclical changes of nystagmus direction. It can occur during infancy (e.g. idiopathic infantile periodic alternating nystagmus) or later in life. Acquired forms are often associated with cerebellar dysfunction arising due to instability of the optokinetic-vestibular systems. Idiopathic infantile periodic alternating nystagmus can be familial or occur in isolation; however, very little is known about the clinical characteristics, genetic aetiology and neural substrates involved. Five loci (NYS1-5) have been identified for idiopathic infantile nystagmus; three are autosomal (NYS2, NYS3 and NYS4) and two are X-chromosomal (NYS1 and NYS5). We previously identified the FRMD7 gene on chromosome Xq26 (NYS1 locus); mutations of FRMD7 are causative of idiopathic infantile nystagmus influencing neuronal outgrowth and development. It is unclear whether the periodic alternating nystagmus phenotype is linked to NYS1, NYS5 (Xp11.4-p11.3) or a separate locus. From a cohort of 31 X-linked families and 14 singletons (70 patients) with idiopathic infantile nystagmus we identified 10 families and one singleton (21 patients) with periodic alternating nystagmus of which we describe clinical phenotype, genetic aetiology and neural substrates involved. Periodic alternating nystagmus was not detected clinically but only on eye movement recordings. The cycle duration varied from 90 to 280 s. Optokinetic reflex was not detectable horizontally. Mutations of the FRMD7 gene were found in all 10 families and the singleton (including three novel mutations). Periodic alternating nystagmus was predominantly associated with missense mutations within the FERM domain. There was significant sibship clustering of the phenotype although in some families not all affected members had periodic alternating nystagmus. In situ hybridization studies during mid-late human embryonic stages in normal tissue showed restricted FRMD7 expression in neuronal tissue with strong hybridization signals within the afferent arms of the vestibulo-ocular reflex consisting of the otic vesicle, cranial nerve VIII and vestibular ganglia. Similarly within the afferent arm of the optokinetic reflex we showed expression in the developing neural retina and ventricular zone of the optic stalk. Strong FRMD7 expression was seen in rhombomeres 1 to 4, which give rise to the cerebellum and the common integrator site for both these reflexes (vestibular nuclei). Based on the expression and phenotypic data, we hypothesize that periodic alternating nystagmus arises from instability of the optokinetic-vestibular systems. This study shows for the first time that mutations in FRMD7 can cause idiopathic infantile periodic alternating nystagmus and may affect neuronal circuits that have been implicated in acquired forms.
We describe a 20 months old boy with neuro-fibromatosis type 1 (NF-1) who presented with diencephalic syndrome due to a large hypothalamic tumour and developed massive necrosis after chemotherapy associated with severe encephalopathy.
We report this case because of rapid progression of presenting symptoms, the rare association with diencephalic syndrome in NF-1, chemotherapy induction of “tumour lysis” associated with encephalopathy, reduced toxicity and sustained improvement with vinblastine, the therapeutic benefit of tumour drainage signs of resolution of diencephalic syndrome and then restoration of visual movements and function associated with developmental recovery. The presentation of tumour in this case highlights the importance for parents and doctor to known and recognize the precocious symptoms, and justifies sharing these features as an indicator with parents and GP’s to justify early / urgent specialist review, particularly in the first two years of life. Early recognition could offer a reduced risk of brain injury.
Nystagmus can be a manifestation of various ocular and systemic disorders. However, it may represent a separate disease entity by itself, as in idiopathic infantile nystagmus. In this chapter we will attempt to classify nystagmus, paying particular attention to various infantile nystagmus forms. We will highlight the major features of associated malformation and inherited systemic diseases and will describe in detail the genetics of inherited idiopathic infantile nystagmus. Where appropriate we will insert the MIM number (Online Mendelian Inheritance in Man) of inherited disorders. The reader is referred to those entries for additional information.Nystagmus consists of repetitive to-and-fro movements of the eye(s). The term “nystagmus” arises from the Greek word ‘νυσαγμόζ’(nystagmos), which is used to describe the head movements of a person in a drowsy state, typically a slow downward drift followed by a corrective quick upward movement. Nystagmus is described as pendular when it consists of sinusoidal slow-phase oscillations. If the slow phases are followed by corrective quick phases, then it is called jerk nystagmus.
Introduction: Smoking cannabis has been described to reduce acquired pendular nystagmus in MS, but its effect on congenital nystagmus is not known. Purpose: To report the effect of smoking cannabis in a case of congenital nystagmus. Methods: A 19-year-old male with congenital horizontal nystagmus presented to the clinic after smoking 10 mg of cannabis. He claimed that the main reason for smoking cannabis was to improve his vision. At the next clinic appointment, he had not smoked cannabis for 3weeks. Full ophthalmologic examination and eye movement recordings were performed at each visit. Results: Visual acuity improved by 3 logMar lines in the left eye and by 2 logMar lines in the right eye after smoking cannabis. The nystagmus intensities were reduced by 30% in primary position and 44%, 11%, 10% and 40% at 20-degree eccentricity to the right, left, elevation and depression, respectively, after smoking cannabis. Conclusion: Cannabis may be beneficial in the treatment of congenital idiopathic nystagmus (CIN). Further research to clarify the safety and efficacy of cannabis in patients with CIN, administered for example by capsules or spray, would be important.
Background: Pharmacological treatment has been successful in some forms of acquired neurological nystagmus. However, drugs are not known to be effective in idiopathic infantile nystagmus or nystagmus associated with ocular diseases. Methods: The authors retrospectively analysed Snellen visual acuity (VA), subjective visual function, and eye movement recordings of 23 patients with nystagmus (13 secondary to multiple sclerosis, three associated with other neurological diseases, two idiopathic infantile, and five with associated ocular diseases) treated with gabapentin or memantine. Results: With gabapentin, 10 of 13 patients with nystagmus secondary to multiple sclerosis (MS) showed some improvement. Memantine improved the VA in all three patients with MS who did not improve on gabapentin. There was no change of nystagmus in other neurological disorders. Patients with congenital nystagmus showed reduction of nystagmus and their VA changes depended on the ocular pathology. Conclusion: Gabapentin and memantine may be effective in acquired nystagmus secondary to MS. To the authors' knowledge this is the first series of patients showing that gabapentin is effective in improving nystagmus in congenital nystagmus/nystagmus associated with ocular pathology. Memantine may be useful as an alternative drug in treating patients with nystagmus.
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