Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Islands in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the prevalence rate is highest in the province of Capiz, where 1:4000 men suffer from the disorder. There is a high degree of penetrance and generalization. While women often serve as carriers, XDP is not limited to men. An updated XDP Philippine registry (as of January 2010) has identified 505 cases, with 500 males and 5 females. While some report that females may carry a milder form of the disorder, in our experience, both sexes generally follow a similar progressive clinical course.

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132–2.435) and by 1.352 (95% CI 1.042–1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346–2.722), by 1.614 (95% CI 1.260–2.068), and by 1.234 (95% CI 1.089–1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457–2.673) and by 1.831 (95% CI 1.506–2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772–1.179), longer ICU stay (aOR 0.983, 95% CI 0.772–1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947–1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944.

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.

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X-Linked dystonia parkinsonism (XDP) is a rapidly progressive and disabling neurodegenerative disease affecting mainly male Filipinos with origins from Panay Island. We reviewed all the past neurosurgical ablative procedures done for XDP patients listed in the Philippine XDP registry. From 1960 to 1982, six patients had undergone bilateral chemopallidotomies or bilateral thalomotomies staged over time. Half of these patients had significant improvement in their symptoms but five of the six patients (83%) developed postoperative morbidities, mainly speech impairment or hemiparesis. All the five reported GPi deep brain stimulation (DBS) cases for XDP were also reviewed, showing consistently immediate improvement of symptoms (61.5%-88.3% decrease in the Burke-Marsden-Fahn Dystonia Rating Scale) lasting up to a year with no adverse effects noted. We also present the first Philippine case of GPi DBS done in the youngest XDP patient to date. This present case showed dramatic improvement (88.3% decrease of the Burke-Marsden-Fahn Dystonia Rating Scale) of his dystonic symptoms, without incurring any persistent adverse effects. The results of these early cases of pallidal DBS for XDP show that DBS is generally a safe and effective procedure for alleviating the disabling symptoms of XDP in contrast to previous ablative surgeries performed on these patients.

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X-linked dystonia-parkinsonism(XDP) is a neurodegenerative disorder endemic to the Philippines. A rating scale was developed by the authors under the guidance of the Movement Disorder Society of the Philippines (MDSP) to assess XDP severity and progression, functional impact, and response to treatment in future clinical trials. Our main objective was to validate our new scale, the XDP–MDSP scale. The initial validation process included pragmatic testing to XDP patients followed by a modified Delphi procedure with an international advisory panel of dystonia, parkinsonism and scale development experts. Pearson correlation was used to assess construct validity of our new scale versus the assess construct validity of our new scale versus standard dystonia, parkinsonism, non-motor and functional scales; and also to assess divergent validity against behavioral and cognitive scales. The 37-item XDP–MDSP scale has five parts: I-dystonia, II-parkinsonism, III-non-motor features, IV-ADL, and V-global impression. After initial validation, the scale was administered to 204 XDP patients. Inter-domain correlation for the first four parts was acceptable. The correlation between these domains and the global rating was slightly lower. Correlations between Parts I, II, III, and IV versus standard dystonia, parkinsonism, non-motor and functional scales were acceptable with values ranging from 0.323 to 0.428. For divergent validity, a significant correlation was seen with behavioral scales. No significant correlation was noted with the cognitive scale. The proposed XDP–MDSP scale is internally valid but the global rating subscale may need to be modified or eliminated. While there is convergent validity, divergent validation was successful only on cognitive and not behavioral scales. The frequent co-occurrence of anxiety and depression, and its effect on the motor and functional state, may explain this finding.

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