Psychophysical analysis of contrast processing segregated into magnocellular and parvocellular systems in asymptomatic carriers of 11778 Leber's hereditary optic neuropathy.

We examined achromatic contrast discrimination in asymptomatic carriers of 11778 Leber's hereditary optic neuropathy (LHON 18 controls) and 18 age-match were also tested. To evaluate magnocellular (MC) and Parvocellular (PC) contrast discrimination, we used a version of Pokorny and Smith's (1997) pulsed/steady-pedestal paradigms (PPP/SPP) thought to be detected via PC and MC pathways, respectively. A luminance pedestal (four 1 degree x 1 degree squares) was presented on a 12 cd/m2 surround. The luminance of one of the squares (trial square, TS) was randomly incremented for either 17 or 133 ms. Observers had to detect the TS, in a forced-choice task, at each duration, for three pedestal levels: 7, 12, 19 cd/m2. In the SPP, the pedestal was fixed, and the TS was modulated. For the PPP, all four pedestal squares pulsed for 17 or 133 ms, and the TS was simultaneously incremented or decremented. We found that contrast discrimination thresholds of LHON carriers were significantly higher than controls' in the condition with the highest luminance of both paradigms, implying impaired contrast processing with no evidence of differential sensitivity losses between the two systems. Carriers' thresholds manifested significantly longer temporal integration than controls in the SPP, consistent with slowed MC responses. The SPP and PPP paradigms can identify contrast and temporal processing deficits in asymptomatic LHON carriers, and thus provide an additional tool for early detection and characterization of the disease.

Childhood Leber's hereditary optic neuropathy (ND1/3460) with visual recovery.

The authors report the clinical features and the results of genetic and biochemical studies of a child affected by ND1/3460 Leber's hereditary optic neuropathy, who demonstrates a persistent visual recovery after protracted monitoring. A 10-year-old male suffered from a severe right visual impairment that was incidentally detected. Within 2 months the left eye was also seriously involved, and visual acuity worsened to 20/300 in both eyes, associated with bilateral cecocentral scotomas and dyschromatopsia. During the following months a progressive visual improvement occurred, and 2 years later the visual acuity was 20/20 OU. After 9 years of follow-up the clinical status is unchanged. The mutation at np ND1/3460 was found to be virtually homoplasmic in the proband's mtDNA, which was extracted either from platelets or leukocytes, whereas the mother and the sister tested heteroplasmic for the same mutation. The specific activity of complex I in platelets was reduced in the proband and normal in his relatives. An abnormal resistance of NADH:ubiquinone reductase to the inhibitory effect of rotenone was found in platelet mitochondria from the proband and family members and was consistent with the degree of heteroplasmy. This pattern of biochemical abnormalities suggests a cumulative effect of the increasing percentage of mutated mtDNA on complex I function, which involves the interaction between complex I and its substrate ubiquinone in the heteroplasmic condition (asymptomatic state), and the catalytic function of complex I, as mutated mDNA turns toward the homoplasmic condition (symptomatic state).

Serum angiotensin converting enzyme in diabetic retinopathy.

Serum levels of angiotensin converting enzyme (SACE) were measured in 118 diabetic patients divided into the following four groups: 44 insulin-treated diabetic patients with severe retinopathy, 38 non insulin-treated diabetic patients with severe retinopathy, 18 diabetic patients, including both insulin-treated and non insulin-treated subjects with background retinopathy, 18 diabetic patients, insulin-treated and non insulin-treated without signs of retinopathy. Nineteen retinopathic patients non diabetic were also studied in order to verify whether SACE levels are altered when retinopathy is present independently from diabetes. The control group was composed of 44 normal subjects. When the data from the above six groups of subjects were submitted to statistical tests (one-way ANOVA, T-test of Bonferroni and test of Student-Newman-Keuls), the study yielded the following results: i) a remarkable difference between the SACE levels in healthy subjects and those in the three groups of diabetic retinopathic patients considered; ii) a non statistically significant difference of SACE levels between normal subjects and diabetic patients without retinopathy; iii) a non statistically significant comparison of SACE levels of normal subjects versus non diabetic retinopathic patients. Therefore, we concluded that while primitive diseases of the retina are not associated with an increase of SACE levels, yet when diabetes and retinopathy coexist, the SACE levels increase remarkably (in rather an independent way from the type of diabetes, the age of subjects, the stage of retinal disease and the daily average insulin dose), suggesting that most of the enzyme's increase originates from the endothelium of peripheral vasa, widely involved in most of the retinopathic diabetic patients.

Bilateral striatal necrosis, dystonia and optic atrophy in two siblings.

Two siblings developed a neurological disorder in the first decade characterised by generalised dystonia, hypokinesia, and subacute visual loss. CT and serial MRI examinations showed bilateral lesions of the striatum, mainly in the putamen. The classification of these patients is discussed in relation to infantile bilateral striatal necrosis (IBSN), Leigh's disease, and Leber's optic neuropathy. The literature shows a clinical and aetiopathogenetic overlap between these syndromes. In our cases parental consanguinity and the involvement of a single generation suggest a new clinical condition with autosomal recessive transmission.

Bilateral trochlear nerve palsy associated with cryptococcal meningitis in human immunodeficiency virus infection.

This is the report of a case of bilateral trochlear nerve palsy secondary to cryptococcal meningitis in a 34-year-old woman with acquired immune deficiency syndrome. Based on clinical and neuroradiologic findings, it is concluded that in the present case, a postinflammatory shrinking of the arachnoid has stretched the fourth cranial nerves at their point of emergence from the dorsal surface of the brainstem.

Mitochondrial DNA mutation in an Italian family with Leber hereditary optic neuropathy.

Mitochondrial (mt) DNA from a Southern Italian family with Leber hereditary optic neuropathy was analyzed for the presence of the reported mutation at position 11778 of the ND4 subunit gene. The point mutation was found in mt DNA extracted from peripheral blood in all members of the family with the exclusion of the father, and was present in a homoplasmic fashion, despite the phenotypic heterogeneity of disease presentation among family members.