Pooled systematic studies that compare treatment stragegies for post-stroke spasticity prove that Botulinum toxin-A (BoNT-A) has superior efficacy and safety and has become the first line management in tandem with physiotherapy. The natural evolution of spasticity show that, not only are neural mechanisms of muscle hypertonus come into play, but that biomechanical forces may likely set in 3 months after stroke. Uses of BoNT-A have been driven by pre-defined goals in the established stage of spasticity (i.E. > 6 months from onset of stroke), as well as the practice of repeat cycle injections to reduce muscle tone. About 19-33% of patients develop spasticity within 3 months after the ictus. Early intervention with BoNT-A (i.e. < 3 months from onser stroke spasticity) can be aimed at preventing the increasing severity of spasticity and the contracture development. There are two randomiaed double blind placebo-controlled trials, and a one single blind comparator trial with a non-injected group, that have recently been performed as early BoNT-A intervention, in tandem with rehabilitation. All the 3 trials showed benefit in terms of reduction in muscle tone with BoNT-A, and one study showed improvement in function, in subanalysis of severely weak muscles at baseline. In the large double blind placebo controlled study, pain reduction was achieved and muscle tone had sustained reduction over the longitudinal observation of 24 weeks, despite a single cycle injection of BoNT-A. The combination of early nrurorehabilitation and early BoNT-A application is an appealing therapeutic approach for upper limb post-stroke spasticity. Neurorehabilitation by constraint-induced movement therapy, in tandem with BoNT-A have been proven to reduce muscle overactivity and improve motor control, but remains to be established in a setting of early spasticity.

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The objective of the study is to monitor on a wide population base the safety and efficacy of zonisamide in patients with partial, generalized, and combined seizures. This is an open label, descriptive, post-marketing surveillance preliminary report that includes the data obtained from October 2008 to May 2010 of a four-year study. The study included 516 patients allocated to either zonisamide monotherapy or zonisamide add-on therapy, with efficacy and safety assessed monthly for three months. For adult patients, a maximum oral dose of 600 mg per day was allowed while a maximum dose of 12 mg/kg/day of zonisamide was allowed for pediatric patients. Efficacy measures were the proportion of responders and percentage change in seizure frequency from baseline. 321 of the 516 patients were included in the efficacy analysis. The responder rates were 53.27%, 80.37%, and 92.52% after the 1st month, 2nd month, and 3rd month of treatment respectively. The use of zonisamide led to seizure-reduction rates of 45.74%, 68.43%, & 82.85% during the 1st, 2nd, & 3rd month of use respectively. Safety analysis was done on all the 516 subjects. Adverse events were mostly mild and observed in 6.78% of patients. No serious adverse events were encountered. 7 subjects (1.4%) discontinued taking zonisamide because of increased seizure frequency in 4 patients, and 1 patient each due to absence of effect on seizure-control, rashes, and thrombocytopenia. All the rest continued taking zonisamide.

Human ; Male ; Female ; Seizures ; Zonisamide ; Isoxazoles ; Exanthema ; Marketing ; Thrombocytopenia ; Epilepsy

CONTEXT: Pregabalin has shown efficacy in the treatment of multiple chronic pain syndromes.
OBJECTIVES: The objective was to evaluate the overall safety and tolerability of pregabalin in the treatment of a several neuropathic pain syndromes in a naturalistic setting using a flexible dosage regimen.
METHODS: Patients aged >- 18 years with neuropathic pain of various etiologies participated in an open-label, non-comparative study at 95 sites in the Philippines. Treatment included pregabalin for 4 weeks, with upward dosage titration to 600 mg/day at investigator discretion. Efficacy was rated with an 11-point pain visual analog scale (VAS). Physicians and patients rated pregabalin on treatment satisfaction, efficacy and safety using a Clinical Global Impression (CGI) rating scale. Descriptive statistics were used for quantitative variables and categorical frequency counts for qualitative variables.
RESULTS: The efficacy analysis (intent-to-treat) included 1603 patients. Mean VAS pain score improved from baseline (7.2 +- 1.6) to 3.8 +- 1.8 at second visit and 2.3 +- 1.4 at last visit. Physicians' and patients' impression of pregabalin regarding treatment satisfaction, efficacy and safety using a CGI rating scale showed> 75% who gave a rating of excellent at second visit gave the same rating at final visit. Adverse events (AEs) were generally mild to moderate, with dizziness and somnolence most frequently reported.
DISCUSSION: Improvement in mean VAS pain scores as well as physicians' and patients' overall satisfaction with tolerability and efficacy support the usefulness of pregabalin in the treatment of various neuropathic pain syndromes in Asian patients.
WHAT'S KNOWN? Pregabalin is effective for the treatment of chronic pain syndromes, including painful diabetic peripheral neuropathy, postherpetic neuralgia, spinal cord injury and fibromyalgia.
WHAT'S NEW? This open-label, non-comparative study demonstrates safety, tolerability and efficacy for neuropathic pain syndromes in Asian patients.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Adolescent ; Neuralgia, Postherpetic ; Pregabalin ; Dizziness ; Fibromyalgia ; Chronic Pain ; Neuralgia ; Pain Measurement ; Diabetic Neuropathies ; Spinal Cord Injuries

Sulodexide was evaluated in an investigator-initiated, multi-center, randomized, controlled, open-labeled study to determine its safety and tolerability profile, and effect on the neurological recovery and functional outcome of patients with acute ischemic stroke. Sixty-five (65) patients were randomized to Standard care group and 46 to Standard care plus Sulodexide Treatment group. Sulodexide was observed to be safe and well-tolerated among patients included in this study. Although not statistically significant, Modified Rankin Scale Responder Analysis consistently showed higher proportions of functionally improved patients in the Sulodexide group than in the Standard Care group on treatment days 10, 30, and 90 respectively.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Glucuronyl Glucosamine Glycan Sulfate ; Research Personnel ; Stroke ; Glycosaminoglycans

Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Island in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the preva-lence 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.

Human ; Male ; Female ; Aged ; Adult ; Dystonia ; Dystonia Musculorum Deformans ; Dystonic Disorders ; Genetic Diseases, X-linked ; Islands ; Parkinsonian Disorders ; Penetrance

It is now commonly accepted that non-motor symptoms of Parkinson's disease often outweigh and sometimes even antedate the development of motor symptoms of PD. It can prove to be more disabling and more challenging to treat and it clearly impacts quality of life in PD. This article provides a concise review of non-motor features in Parkinson's disease as well as the pathophysiological mechanisms underlying each complication. Currently available management strategies will be outlined as well.

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Targeted for relief of spasms, posturing, pain, impaired function and disfigurement, botulinum toxin type-A (BoNT-A) was injected in dystonias of X-linked dystonia-parkinsonism (XDP). From 1992-2012, focal/ multifocal dystonia combinations were injected in XDP at the following regions: Peri-ocular (21 cases), oromandibular (50 cases), ligual (35 cases), laryngeal (5 cases), cervical (56 cases), truncalaxil (24 cases) upper limbs (13 cases) and lower limbs (18 cases). Pain was frequently reported in 40/50 cases with oromandibular dystonia, 28/56 cases with cervical dystonia, 18/24 cases with truncal-axil dystonia and 16/31 cases with limb dystonia. Outcomes were assessment through the global dystonia rating scale (DRS) at week 4, VAS pain reduction at week 4, duration of BoNT-A effects and safety. Cranial, laryngeal and cervical dystonia showed substantial improvement (DRS median score of 3-4), whereas truncal-axil and limb dystonias showed moderate improvement (DRS median score of 2), following BoNT-A. Pain reduction ranged from 30-100% (VAS), for those dystonias that reported co-morbid pain. BoNT-A effects had a duration ranging from 8-20 weeks. Procedures were generally well tolerated, and the adverse events were most significant in laryngeal injections (voice breathiness, but was eventually followed by a strong voice). The other events were mouth dryness, dysphagia and weekness in oromandibular, cervical and limb dystonias, respectively. Therefore, BoNT-A is a safe and valuable therapeutic option for the dystonias of XDP, especially the disabling and painful dystonias. BoNT-A injection working protocols could be adopted in dystonia that adheres to cost minimization (e.g. lower dose end per selected muscles), yet achieving a substantial benefit, and a reduced adverse event profile. Futhermore, this present study allowed us to recommend a "high potency, low dillution" of BoNT-A in oromandibular, linual, laryngeal, cervical and distal limb dystonias. In dystonias of the abdominal, paraspinal and proximal limb muscles, the "low potency, high dilution" BoNT-A injection protocol could be adopted.

Human ; Botulinum Toxins, Type A ; Deglutition Disorders ; Dystonic Disorders ; Genetic Diseases, X-linked ; Lower Extremity ; Pain ; Spasm ; Torticollis ; Xerostomia

OBJECTIVE: To compare the scores of patients with idiopathic Parkinson's Disease using the Montreal Cognitive Assessment and Mini-Mental State Examination in a tertiary hospital
BACKGROUND: Parkinson's Disease (PD) is a neurodegenerative disorder diagnosed clinically based on the signs of resting tremor bradykinesia, rigidity and loss of postural reflexes. According to Bassett et al, 20% to 40% of PD patients ultimately become demented with an incidence of 10% per year. Cognitive decline is an impotant predictor of dementia in PD. Almost all patients with PD suffer from selective cognitive impairments including difficulties with attention, concentration, planning, sequencing, concept formation, problem solving, set-shifting and memory which are thought ro reflect dysfunction of cortical circuits subserving frontal brain regions. Identification of cognitive impairment in PD is crucial. It predicts future cognitive decline and may eventually be a target for pharmacologic intervention to prevent or delay the development of dementia.
METHODS: A descriptive study. A convenience sampling of 95 patients with idiopathic Patkinson's disease were screened for cognitive impairment.
RESULTS: Mean MMSE and MoCA scores were 26.1 (SD 2.9) and 19.8 (SD 4.28). Based on the published cutoff scores for cognitive impairment for Parkinson's Disease, 72% of the participants scored 26/30 and below on MoCA whereas only 42% scored 26/30 and below on the MMSE. Impairments were seen in numerous cognitive domains including executive function, language, recent semantic memory, visuo-spatial processing and constructional praxis. Predictors of cognitive impairment on the MoCA include low level of education and older age.
CONCLUSIONS: MoCA was able to detect more cognitive impairments in patients with Parkinson's disease than MMSE. Therefore, MoCA is a better screening tool to detect cognitive impairments in PD patients.

Human ; Male ; Female ; Attention ; Brain ; Cognition ; Cognition Disorders ; Cognitive Dysfunction ; Dementia ; Hypokinesia ; Muscle Rigidity ; Neuropsychological Tests ; Parkinson Disease ; Tremor

OBJECTIVE: To determine the prevalence of anxiety and its correlation with the quality of life among cognitively-intact, community dwelling Filipino patients with idiopathic Parkinson disease (PD) seen at the Movement Disorders Clinic of a tertiary hospital.
STUDY DESIGN: Prospective, cross-sectional study.
METHODS: Seventy six (76) Filipino outpatients fulfilling the United Kingdom Parkinson Disease Society Brain Bank Clinical Diagnostic Criteria for PD were included in the study. Demographic data were obtained including: age, sex, onset of disease, disease duration and medication intake. The Mini Mental State Examination (MMSE) was done to exclude significant cognitive impairment. The Hamilton Anxiety scale (HAM-A) was administered to quantify anxiety. The degree of anxiety was correlated with the quality of life instrument, Short form health survey (SF 36); and the functional and motor severity using the Unified Parkinson Disease Rating Scales (UPDRS).
FINDINGS: Our cohort of patients had a mean: age of 61 years (range: 42 - 81 years), and disease duration of 1.3 years (33 months). Out of the 76 patients, 37( 48.6%) probably had significant anxiety symptoms based on the the HAM A. Anxiety greatly impacts scores on SF 36.
CONCLUSION: The prevalence of anxiety among this Filipino cohort of patients is 48.6% which is higher than commonly reported worldwide. The presence of anxiety significantly correlated with poorer quality of life.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Anxiety ; Anxiety Disorders ; Brain ; Cognition Disorders ; Cognitive Dysfunction ; Parkinson Disease ; Quality Of Life

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.

Human ; Abdominal Pain ; Carbidopa ; Dyskinesias ; Dystonia ; Dystonic Disorders ; Headache ; Levodopa ; Nausea ; Parkinsonian Disorders ; Statistics, Nonparametric ; Vomiting