MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.

PURPOSE Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Background: Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. Results: We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. One of the patients presented also variants in mitochondrial DNA that may have contributed to the peculiar phenotype. The deleterious effect of the identified missense changes was experimentally validated in yeast model. OPA1 level was reduced in available patients\u2019 biological samples, and a clearly fragmented mitochondrial network was observed in patients\u2019 fibroblasts. Conclusions: This report provides evidence that bi-allelic OPA1 mutations may lead to complex and severe multi-system recessive mitochondrial disorders, where optic atrophy might not represent the main feature

Prognostic Value of Contrast Enhanced MRI in Acute Isolated Optic Neuritis: A Short Term Follow Up Study

To correlate optic nerve Magnetic Resonance Imaging (MRI) findings with visual function in acute isolated optic neuritis at presentation and to define its predictive value on visual outcome

Diagnostica differenziale oftalmoscopica tra edema e pseudoedema della papilla ottica

L'edema del disco ottico (ODE: Optic Disc Edema) è un segno clinico allarmante data la sua possibile associazione con patologie che possono portare a cecità o addirittura minacciare la vita del paziente; per esempio, l'edema bilaterale della papilla ottica (papilledema) è segno di Ipertensione Intracranica, spesso dovuta alla presenza di una neoplasia intracranica in espansione. Esistono tuttavia delle condizioni oculari benigne (varianti anatomiche) che mimano un edema della papilla; tali condizioni sono responsabili di uno pseudo edema della papilla ottica (PODE). La diagnosi differenziale tra un vero edema e uno pseudoedema della testa del nervo ottico può essere difficile e problematica con misdiagnosi allarmanti che capitano frequentemente nella pratica clinica, dovute alla sovrapposizione di aspetti morfologici similari tra l'ODE e la PODE. Sottostimare un vero edema papillare in fase acuta con ritardo nella diagnosi può essere molto pericoloso per il paziente, così come una misdiagnosi a fronte di uno pseudoedema può portare ad un percorso diagnostico-terapeutico errato con costi sociali elevati, ospedalizzazione ed esami invasivi potenzialmente pericolosi e ingiustificati. Anche se l'OCT viene oggi ampliamente utilizzato in ambito specialistico, l'esame di prima esecuzione per valutare la presenza di un edema resta l'oftalmoscopia indiretta del nervo ottico.L'alterazione del flusso assonico produce delle alterazioni morfologiche sia di tipo meccanico che di tipo vascolare. Tali alterazioni rappresentano i 10 segni oftalmoscopici dell'edema della testa dell'ottico. Tuttavia, alcuni di questi segni possono essere presenti nel caso di un PODE, rendendo difficile una diagnostica differenziale, soprattutto se la valutazione oftalmoscopica viene effettuata da personale medico che non sia un neuroftalmologo, ovvero poco familiare con l'osservazione della papilla ottica. Scopo di questa relazione è quello di illustrare le laterazioni tipiche dell'ODE oltre che verificare la minima combinazione di segni oftalmoscopici necessari a garantire una accuratezza elevata per una diagnosi corretta di ODE

Accuracy of Funduscopy to Identify True Edema versus Pseudoedema of the Optic Disc.

Purpose: Differential diagnosis between acute optic disc edema (ODE) and optic disc pseudo-edema (PODE) may be a clinical challenge even for well-trained ophthalmologists. Funduscopy remains the first-line investigation. The aim of this study was to assess the accuracy, sensitivity, and specificity of funduscopy in differentiating ODE from PODE. Methods: Observational, cross-sectional, two-center study of subjects referred for presumed acute ODE. During funduscopy each observer completed a form concerning the presence/absence of the ten conventional signs of ODE. 74 patients with ODE and 48 subjects with PODE were included in the analysis. Accuracy, sensitivity, and specificity from all possible combinations of signs were calculated by Support Vector Machine (SVM) analysis. Results: As a single sign, the swelling of the peripapillary retinal nerve fiber layer had the highest accuracy (0.92; 95% CI: 0.82–0.97). Little variation was observed when more than fours signs were present; the best four-sign combination was: SWELLING, HEMORRHAGES, papilla ELEVATION, and CONGESTION of peripapillary vessels (accuracy = 0.93, 95% CI: 0.83–0.98; sensitivity = 0.95; and specificity = 0.89). The presence of retinal and/or choroidal folds appeared to be a pathognomonic sign of true ODE (100% of sensitivity), but with a low rate of presentation (23%). Conclusions: The presence of at least four ophthalmoscopic signs (with the sign “swelling” included) gives the highest accuracy. Furthermore, peripapillary retinal folds seem to be related exclusively to ODE, since they were never observed in our PODE group. These data may be useful for clinicians when evaluating patients referred for presumed optic disc edema in the acute phase