Current State of Stroke Care in the Philippines.

Stroke remains the leading cause of disability and death in the Philippines. Evaluating the current state of stroke care, the needed resources, and the gaps in health policies and programs is crucial to decrease stroke-related mortality and morbidity effectively. This paper aims to characterize the Philippines' stroke system of care and network using the World Health Organization health system building blocks framework. To integrate existing national laws and policies governing stroke and its risk factors dispersed across many general policies, the Philippine Department of Health (DOH) institutionalized a national policy framework for preventing and managing stroke. Despite policy reforms, government financing coverage remains limited. In terms of access to medicines, the government launched its stroke medicine access program (MAP) in 2016, providing more than 1,000 vials of recombinant tissue plasminogen activator (rTPA) or alteplase subsidized to selected government hospitals across the country. However, DOH discontinued the program due to the lack of neuroimaging machines and organized system of care to support the provision of the said medicine. Despite limited resources, stroke diagnostics and treatment facilities are more concentrated in urban settings, mostly in private hospitals, where out-of-pocket expenditures prevail. These barriers to access are also reflective of the current state of human resource on stroke where medical specialists (e.g., neurologists) serve in the few tertiary and training hospitals situated in urban settings. Meanwhile, there is no established unified national stroke registry thus, determining the local burden of stroke remains a challenge. The lack of centralization and fragmentation of the stroke cases reporting system leads to reliance on data from hospital records or community-based stroke surveys, which may inaccurately depict the country's actual stroke incidence and prevalence. Based on these gaps, specific recommendations geared toward systems approach - governance, financing, information system, human resources for health, and medicines were identified.

Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression.

BACKGROUND AND PURPOSE: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. METHODS: Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. RESULTS: All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. CONCLUSIONS: This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

OBJECTIVE: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. RESULTS: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. CONCLUSIONS: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Incidence of Parkinson's disease in Singapore.

To investigate the incidence of Parkinson's disease (PD) in Singapore, a parkinsonism-free cohort of 14,835 participants was followed-up and incident cases of PD identified through phone interviews, medical record reviews and a hospital's database. A movement disorders specialist subsequently verified the diagnosis through a medical records review. The age and sex-adjusted (US 1990 population) incidence rate was 32 per 100,000 person years for individuals aged 50 years and above. The rates differed between Chinese, Malays and Indians (p=0.03). The difference in inter-racial rates needs to be interpreted with caution in view of the small numbers. The incidence of PD in Singapore is comparable with that in Western countries.

A 9-year review of dystonia from a movement disorders clinic in Singapore.

The clinical features of dystonia have not been evaluated in Southeast Asia. We therefore investigated the clinical spectrum and characteristics of dystonia in Singapore, a multi-ethnic Southeast Asian country comprising 77% Chinese, 14% Malays, and 8% Indians. We identified all dystonia patients from the Movement Disorders database and Botulinum Toxin clinic between 1995 and November 2004. Their medical records were reviewed to verify the diagnosis of dystonia and obtain demographic and clinical data using a standardized data collection form. A total of 119 (73%) patients had primary dystonia whilst 45 (27%) had secondary dystonia. There were 77% Chinese, 9% Malays, and 8% Indians. The most common focal dystonia were cervical dystonia (47%), writer's cramp (32%), and blepharospasm (11%). There was no significant difference in the distribution of dystonia between the different races. Males were noted to have earlier onset of dystonia overall. There was a significant male predominance in primary dystonia overall (M:F 1.6:1, P=0.008) and in the subgroup of focal dystonia (M:F 1.6:1, P=0.037). This contrasts with previous studies that found a female predominance. The role of genetic, hormonal, and environmental factors and their interactions need to be investigated to better understand the gender differences in the occurrence of dystonia.

Clinical characteristics of patients with multiple system atrophy in Singapore.

INTRODUCTION: Our study aimed to describe the clinical features of multiple system atrophy (MSA) in Singapore and verify its diagnosis using the consensus statement in the diagnosis of MSA. MATERIALS AND METHODS: All patients suspected to have MSA between 1995 and March 2005 were identified from the Movement Disorders database and the autonomic function testing results. The medical records were reviewed using a standardised data collection form. The diagnosis of MSA was verified using the consensus statement. Disease progression was evaluated using 2 pre-determined events: aid-requiring walking and wheelchair use. RESULTS: Seventy-two per cent (33/46) fulfilled the consensus statement. There were 85% Chinese, 9% Malays, and 6% Indians. The mean age at onset of the disease was 60 +/- 10 years. We found a predominance of males (M:F = 1.5:1) as well as MSA-C cases (67%). The most common initial presenting features were parkinsonism and cerebellar signs (27% each). Abnormal neuroimaging was seen in 29 patients (91%). Autonomic function testing was abnormal in 58% (7/12). The risk for aid-requiring walking and wheelchair use at 3 years from onset of the disease was 31% and 17%, respectively. By 5 years, this had increased to 45% and 30%, respectively. There was no difference in the events rate between MSA subtypes. CONCLUSIONS: The clinical characteristics of MSA in Singapore are presented. Our study revealed a predominance of MSA-C patients as well as a later age at onset of disease and longer median time to aid-requiring walking and wheelchair use compared to Japanese patients.

Analysis of LRRK2 functional domains in nondominant Parkinson disease.

A comprehensive sequence analysis of 29 exons that code for the functional domains of LRRK2 in 160 nondominant Parkinson disease (PD) patients was performed. Novel variant screening in a further 470 sporadic PD patients and 630 controls revealed two novel variants (R1067Q and IVS33 + 6 T>A), which are likely to be pathogenic in five patients. One patient presented initially with a typical essential tremor phenotype, expanding the phenotypic spectrum of LRRK2 mutations.

The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.