There is a paucity of published literature on the different oral medications tried for X-linked dystonia parkinsonism (XDP). In practice, most XDP patients are tired on medication typically used for patients with generalized dystonia. These drugs include anticholinergic agents, baclofen, clonazepam and other ben-zodiazepines, tetrabenazine, and clozapine. Although several articles have shown that these classess of drugs are beneficial for patients with generalized dystonia, none been systematically studied specifically for XDP patients. We are currently conducting the first randomized, placebo-controlled trial on the medications that have been used in XDP.

BACKGROUND AND OBJECTIVE: X-linked dystonia parkinsonism (XDP, DYT3, MIM #314250) is a neurodegenerative movement disorder found endemically in the Philippines. An SVA retrotransposon insertion mutation has been described in patients with XDP, which requires Southern analysis for detection. However, this method is costly and time-consuming. Hence we developed a PCR-based method and validated it among our local population.

METHODS AND RESULTS: A total of 58 samples from 58 patients with a clinical diagnosis of XDP were collected. Other samples were from an obligate female carrier, two unaffected male relatives, and two patients with typical Parkinson’s disease. Primers designed to amplify the SVA retrotransposon found in the DYT3-TAF1 gene (NCBI Accession Number AB191243) were used. All patients were positive for the expected 3229-bp product after PCR amplification. The normal control showed a 599-bp product, while the female carrier showed both the 3229 and 599-bp product. Subsequent RFLP analysis using BamHI verified the presence of the SVA retrotransposon insertion mutation. CONCLUSION: Our results show that large-scale PCR-based testing to screen for genetic diseases with a relatively high prevalence such as XDP is possible in our setting. When followed by RFLP analysis, this can provide genetic confirmation of the diagnosis of XDP and facilitate proper genetic counselling and therapy.
Dystonia 3, Torsion, X-Linked

OBJECTIVES: Transcranial sonography of the substantia nigra for diagnosing premotor stages of Parkinson disease has been attracting increasing interest. Standard reference values defining an abnormal increased echogenic size (hyperechogenicity) of the substantia nigra have been established in several populations using high-end stationary ultrasound systems. It is unknown whether a portable ultrasound system can be appropriately used and how the Filipino population would compare with the well-studied white population.
METHODS: We prospectively studied substantia nigra echogenic sizes and third ventricle widths in 71 healthy adult German participants and 30 age- and sex-matched Filipino participants using both a well-established stationary ultrasound system (in the German cohort) and a recently distributed portable ultrasound system (in both ethnic cohorts).
RESULTS: Mean substantia nigra echogenic sizes, cutoff values defining abnormal hyperechogenicity, and intra-rater reliability were similar with both systems and in both ethnic cohorts studied. The Filipino and German participants did not differ with respect to the frequency of insufficient insonation conditions (each 3%) and substantia nigra hyperechogenicity (10% versus 9%; P = .80). However, third ventricle widths were smaller in the Filipino than the German participants (mean ± SD, 1.6 ± 1.1 versus 2.4 ± 1.0 mm; P = .004).
CONCLUSIONS: The frequency of substantia nigra hyperechogenicity appears to be homogeneous in white and Asian populations. Screening for this feature may well be performed with a present-day portable ultrasound system.

BACKGROUND: Anti-N-Methyl-D-Aspartate receptor (anti-NMDAR) Encephalitis is the most common type of autoimmune encephalitis that affects children, adolescents and young adults. Since its discovery in 2007, there is still a paucity of data on the disease and factors affecting its outcome. OBJECTIVES: To describe the clinical characteristics of children and adolescents with anti-NMDAR encephalitis and to analyze factors that may affect its outcome. METHODS: Forty-three patient records of diagnosed anti-NMDAR Encephalitis were included. The outcome was evaluated using the modified Rankin Scale (mRS), and Clinical Assessment Scale for autoimmune Encephalitis (CASE). RESULTS: Ages ranged from 2 years to 18 years old, majority in the 12-18 years age range. Sixty percent were female. First line treatment using immunotherapy was given to all patients: 37% as monotherapy and 84% combination therapy (MPT only 23%, IVIg only 4%, MPT + IVIg or TPE 21-26%, and MPT + IVIg + TPE 16%). Clinical outcomes on discharge and on follow-up were assessed using the mRS and CASE. On discharge the proportion of the patients who had mild impairment (mRS<2, CASE<9) was more than 50%. On median duration follow-up of 31 weeks (range 24-40 weeks), 96.8% had significant improvement (mRS<2, CASE<9). Among the possible factors that were assessed to affect outcome, only severity of the illness at the start of the treatment influenced clinical outcome. CONCLUSION Early diagnosis and initiation of treatment before the progression of the disease will promote faster recovery and more optimal clinical outcome. CASE may be used as an additional tool in assessing response to treatment.

BACKGROUND: XDP is an X-linked recessive disorder characterized by parkinsonism and dystonia described among Filipinos. Oral medications are frequently ineffective. Lately, DBS have been promising. However these are not generally available or affordable for the vast majority of patients. We then decided to evaluate the effectiveness of levodopa-carbidopa for XDP.
OBJECTIVE: To compare the efficacy, safety and tolerability of levodopa-carbidopa vs. placebo in XDP patients.
METHODS: After informed consent and randomization, the BFM and the UPDRS parts III and IV were performed at baseline and monthly up to 6 months. Patients were randomized to receive either levodopa-carbidopa at a starting dose of 125 mg levodopa/ day in 2 divided doses or corresponding placebo. Gradual uptitration was done to a maximum of 1000 mg levodopa/ day or until side effects appeared.
Homogeneity of the characteristics of patients in the 2 groups was determined using Independent t-test and Chi-square test. To determine the significance of changes in the efficacy parameters within each group, Wilcoxon Matched Pairs Signed Ranks Test was used. To compare the scores of the different efficacy parameters of the 2 groups, Mann Whitney U Test was applied to the data. A p?0.050 was considered significant.
RESULTS: A total of 107 patients were recruited. There were 13 screen failures, and 94 were subsequently enrolled. The baseline characteristics (age, duration of illness, baseline BFM and UPDRS (motor) scores were not significant between levodopa and placebo (age in years: 47 + 9.35 vs. 50 + 9.51; duration of illness in years 6.3 + 7 vs. 6.2 + 5.2; BFM score: 32.8 + 24.5 vs. 28.4 + 26.5; UPDRS score 29.9 + 20.7 vs. 34.8 + 26.8).
There was a decrease in BFM scores from baseline to all follow-up periods in patients given levodopa but were statistically significant only on visit 2 and visit 9. In the placebo group, decrease in scores was also observed in some observation periods but no statistical significance was shown. A comparison of the 2 groups showed that the magnitude of decrease in the levodopa group was statistically greater than the placebo group on the second visit. There were no significant differences observed in all other follow-up periods. Both groups showed a decrease in UPDRS scores but significant decrease was observed in visits 2, 5, 6, 7, 9 of the levodopa group. While in the placebo group, a significant decrease was observed only on visit 2. Comparison of the 2 groups did not show any significant differences.
There were 17 patients from the levodopa group who reported adverse events (most common: increased involuntary movements, nausea/ vomiting/ dizziness, headache, and generalized weakness. In the placebo group, there were 11 patients (most common: increased involuntary movements, abdominal pain). There were 9 patients who dropped out (levodopa: 4, placebo: 5).
CONCLUSION: There was a significant decrease in the BFM and UPDRS scores in XDP patients given levodopa compared to placebo. Levodopa is a safe and effective drug that may be considered in patients with XDP.
NOTE: This study was supported by an unrestricted grant by Torrent Pharma Philippines, Inc.

X-linked dystonia parkinsonism (XDP) is a rapidly progressive and disabling neurodegenerative disease affecting mainly male Filiponos 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 stage 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 Dystonia Rating Scale) lasting up to a year with effects noted. We also present the first Philippine case of GPi DBS done in the youngest XDP patients to date. This present case showed dramatic improvement(83.3% desrease 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 on these patient

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.