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.

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 or 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 hyperintense 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., parkinsonian 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 retrotransposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pathology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to more rational and directed therapies.

Slow improvement of clinically-diagnosed dengue haemorrhagic fever case fatality rates.

Dengue haemorrhagic fever (DHF) is recognized as a leading cause of hospitalization and death among children in many Southeast Asian countries. This study reviews the case fatality rates of DHF cases admitted to a referral hospital in Cebu (Philippines) over the past 5 years. Information on patients 14 years old or younger admitted from 1 January 1997 to 31 December 2001 with the final clinical diagnosis of DHF was collated and analysed. Case fatality rates were compared before and after a standardized management protocol was implemented by the healthcare staff and after introduction of revisions to that protocol. The case fatality rate during the 2-year periods prior and after introduction of the management protocol decreased significantly from 197/2644 (7.45%) to 39/1182 (3.30%) (P < 0.01). Following the introduction of revisions to the protocol, the case fatality was reduced even further to 52/1697 (3.06%) (P = 0.7). In this government hospital the introduction of a standardized management protocol for DHF was associated with a significant improvement in the case fatality rate of hospitalized children with clinically diagnosed DHF. However, compared with reports from hospitals in other dengue-endemic countries, the improvement has been slow. Possible ways to decrease fatality rates further have been identified.