Understanding XDP through imaging,pathology,and genetics

The X-linked dystonia-parkinsonism (XDP) is a severe progressive, adult-onset X-linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third of fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging pathological and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hy-perintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., p[arkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retronsposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudade nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pahtology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to mare rational and directed therapies.

Dry lung syndrome: A distinct clinical entity.

Infants with preterm prolonged rupture of membranes can present with immediate onset of pulmonary insufficiency and need aggressive ventilatory support. Dry lung syndrome remains an under-recognised clinical entity and very few cases are reported in the literature, though a working definition has been previously proposed. The proposed underlying etiopathogenesis for this is functional hypoplasia of the lung where higher than usual ventilatory pressure for initial 1-2 days can improve oxygenation. This study presents two cases which had similar antenatal and immediate postnatal course, but had diametrically opposite outcomes. Strategies to optimise outcomes in the setting of early premature rupture of the membranes should include antenatal assessment of mothers with monitoring of the liquor volume as well as the strength of foetal breathing movements, in-utero transfer with delivery in perinatal centres and attendance by neonatal staff of appropriate experience.