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Presentamos dos casos clínicos ilustrativos con imagen multimodal de síndrome de aumento idiopático de mancha ciega (SAIMC), que debutan con puntos blancos peripapilares en el fondo de ojo. El SAIMC se engloba dentro del complejo de retinopatía zonal aguda oculta externa (AZOOR), solapándose en muchas ocasiones diferentes entidades dentro de este complejo. La hiperautofluorescencia en estos casos es típicamente peripapilar. En el en-facede la angiografía por OCT (A-OCT), a nivel de la capa de los elipsoides, se observan puntos hiperreflectivos peripapilares en ambos casos. En uno de ellos disponemos del campo visual que muestra aumento de mancha ciega reversible. El complejo AZOOR tiene en común la afectación de la retina externa que actualmente podemos demostrar con el OCT estructural. En ambos casos se observa una afectación de las capas externas que se recuperan progresivamente.

To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3gene pathogenic mutation was found.

Cerebral involvement is usually absent in pure adrenomyeloneuropathy (AMN). Recently, nonconventional MR studies have reported brain abnormalities in patients with pure AMN, providing evidence that occult cerebral involvement may occur in this disease. It remains unclear, however, whether these brain abnormalities reflect centripetal extension of spinal cord long-tract axonopathy or can be the expression of a pathologic process largely involving the brain.

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA^Ile gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject.

To characterize the clinical features of a new type of X-linked mental retardation associated with MECP2 mutation in the index family.

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNAIlegene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild‐type clones derived from the same subject.

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to an inherited defect in the metabolic pathway of cholesterol. Early diagnosis of the disease is particularly important as patients benefit from therapy with chenodeoxycholic acid. Although the disease is clinically characterized by the concomitant presence of tendon xanthomas, juvenile cataracts and progressive neurological impairment, clinical features may vary greatly. Neuroradiological studies have suggested that the bilateral abnormality of the dentate nuclei could be typical of this disease. However, this finding has been seen inconsistently on conventional MRI. The dynamic of the CNS pathology in CTX is complex, and whether demyelination or axonopathy has primary importance in the pathogenesis of CTX pathology is not known. To clarify both neuroradiological and pathological issues, we performed combined brain MRI and spectroscopy examinations on 12 CTX patients. On conventional MRIs, bilateral hyperintensities of the dentate nuclei were clearly seen in nine out of 12 patients on T(2) -weighted MRIs, but were evident in all patients using a FLAIR sequence. On proton magnetic resonance (MR) spectroscopy, significant decreases in N: -acetylaspartate resonance intensities (P: <0.0001) and increases in lactate MR signals (P<0.05) were found in the group of CTX patients in large volumes of interest localized above the lateral brain ventricles and in the cerebellar hemispheres. Cerebral values of N -acetylaspartate resonance intensities showed a close correlation with patients' disability (Spearman rank correlation = -0.78, P<0.005). These results suggest that MR abnormalities in the dentate nuclei may be evident consistently in patients with CTX. Proton MR spectroscopy data demonstrated widespread axonal damage (as shown by the decrease in N -acetylaspartate) and diffuse brain mitochondrial dysfunction (as shown by the increase in brain parenchymal lactate) in patients with CTX. The close correlation seen between values of the putative axonal marker N-acetylaspartate and patients' disability scores suggests that proton MR spectroscopy can provide a useful measure of disease outcome in CTX.

Abstract: Muscle biopsy tissue from a patient affected by the juvenile form of neuronal ceroid lipofuscinosis (NCL) was studied immunohistochemically using antibodies to β-amyloid peptide and amyloid precursor protein. Positive reaction in muscle was specifically localized to autophagic vacuoles and blood vessel walls. Increased acid phosphatase reaction suggested enhanced lysosomal activity. We hypothesize that β-amyloid is deposited in NCL muscle by a lysosomal mechanism similar to that proposed in other disorders involving β-amyloid.

Cerebrotendinous xanthomatosis (CTX) is an inherited sterol storage disease associated with the accumulation of cholestanol and cholesterol in various tissues. CTX is caused by a deficiency of sterol-27-hydroxylase, a mitochondrial enzyme that oxidizes the side chain of cholesterol in the pathway leading to the formation of bile acids. In the present study we report two mutations of sterol-27-hydroxylase gene (CYP27 gene) found in Italian CTX patients. Proband T.C. is homozygous for a G–>A transition at the first nucleotide of intron 7. This mutation causes the formation of minute amounts of an abnormal mRNA, in which exon 6 joins directly to exon 8 with the skipping of exon 7. The exon 6-exon 8 junction results in a frame shift, downstream from the codon for Arg362, which generates a string of 28 novel amino acids preceding a premature termination codon. Proband C.U. is homozygous for a G–>C transversion at the last nucleotide of exon 3. This mutation, which changes the consensus sequence of the 5‘ donor splice site, is associated with barely detectable levels of sterol-27-hydroxylase mRNA, of normal size, in proband fibroblasts. As both mutations change the sites for two restriction enzymes, rapid methods were devised for the identification of the healthy carriers among the probands’ family members and for the screening of these mutations in other CTX patients.

The authors describe an infant with vanishing white matter disease with demyelinating peripheral neuropathy. Sequence analysis of EIF2B5gene showed that the patient was a double heterozygote, with novel missense mutation CGA→CAA in codon 269 of exon 6, resulting in the replacement of an arginine residue with glutamine.

Patients with the trisomy 9p syndrome and CNS abnormalities have been poorly assessed. We report a patient with trisomy 9p who showed band heterotopia on MRI. Abnormal neuronal migration is sufficiently frequent in patients with the trisomy 9p syndrome that brain MRI should be routinely considered in all patients with this syndrome.

Marinesco-Sjögren syndrome (MSS) is a rare inherited disease with neurological and ocular manifestations. The latter include bilateral cataracts and, less frequently, nystagmus and strabismus. The authors report here three cases of MSS syndrome, all with optic atrophy, an additional ocular feature not hitherto described in this syndrome.

Decreased olfactory function commonly occurs in idiopathic Parkinson's disease (PD), regardless of stage, treatment, or duration of disease. In the present study, we sought to determine whether different subtypes of PD, categorized according to well-defined clinical criteria, evidence different degrees of olfactory dysfunction. Significantly different scores on the University of Pennsylvania Smell Identification Test (UPSIT) were present between patients with benign PD and malignant PD (respective means [SD] = 22.51 [8.50] and 17.38 [6.29]) and between tremor-predominant PD and postural instability-gait disorder (PIGD)-predominant PD (23.43 [8.18] versus 17.35 [6.00]). No statistically significant differences in UPSIT scores were observed between young-onset and older-onset PD patients. Women outperformed men in most subtypes examined.