Assessment of substantia nigra echogenicity in German and Filipino populations using a portable ultrasound system

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.

Botulinum toxin therapy in established post-stroke upper limb spasticity

Amongst stroke patients, more than a third will develop spasticity, especially those that involve the paretic upper limbs. Despite establish intensive rehabilitaion programs in place, spasticity still affect a post-stroke patient's quality of life and create significant economic and caregiver burdens. The rationale for botulinum toxin type A (BoNT-A) use in spasticity is hinged on the toxin's ability to reduce muscle overactivity via a dual cholinergic blockede of extrafusal and intrafusal muscle. Efficacy and safety of BoNT-A in established post-stroke spasticity have been widely published, effectively establishing robustness of data and first line recommendation. Consensus guidelines and algorithms on the clinical use of BoNT-A for symptomatic upper limb spasticity are now also available. While BoNT-A has been universally shown to reduce muscle tone in spasticity, optimizing therapy requires judicious use of the toxin, while raising one's consciousness of adverse event, including muscle weakness, unwanted or desired in therapy. BoNT-A should not be administered alone in post-stroke spasticity, and its effects are best optimized in concert with a comprehensive neurorehabilitation program.

The promise of deep brain stimulation in X-linked dystonia parkinsonism

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

Anxiety symptoms among cognitively-intact, community dwelling Filipino patients with Parkinson disease

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.

Botulinum toxin-A targeted for focal/ multifocal dystonias- An open- label application in X-linked Dystonia-Parkinsonism

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.

The unique phenomenology of sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag")

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.

Botulinum toxin therapy as early intervention in post-stroke upper limb spasticity

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.

SigN-PQ neuropathic pain questionnaire development and validation in English and Filipino languages

OBJECTIVES: This study aimed to develop and validate a simple questionnaire for chronic neuropathic pain that can be administered as a screening tool by general practitioners and internists in order to help them identify patients with probable neuropathic pain. METHODS: Following a development phase and a pilot study, the revised version of the screening tool which included eleven descriptors associated with neuropathic pain both in English and Filipino languages was validated on 120 consecutive patients with any type of pain except psychogenic pain, recruited in the out-patient clinics of six hospitals. The questionnaire was validated by assessing the sensitivity, specificity, positive and negative predictive value of each item and the overall questionnaire. The internal consistency of the questionnaire items was assessed using the Kuder-Richardson formula 20. RESULTS: Overall, the internal consistency of the SigN-PQ using the Kuder-Richardson formula 20 was 0.7837; the sensitivity was 91.89% with specificity of 80.22%, PV (+) was 65.38% and PV(-) was 96.0%. For the English version, the descriptors with the highest scores were burning (Sensitivity: 100%, Specificity: 93%) and electricity-like (Sensitivity: 100%, Specificity: 93%). For the Filipino version, mainit (burning) has the highest sensitivity of 88% with specificity of 82.6%, followed by gumagapang (tingling) with sensitivity of 86.96% and specificity of 85.42%. The sensation of saksak (stabbing) and hiwa (lancinating) have the lowest sensitivity, 60% and 54% respectively, although their specificity scores are high. Since this study is a validation of a screening tool for neuropathic pain, the investigators decided to choose descriptors with higher sensitivity. Thus, in the final version of the SignN-PQ, the descriptors saksak and hiwa were removed. CONCLUSION: The SigN-PQ Neuropathic Pain Questionnaire has a high overall sensitivity of 91.89% and specificity of 80.22%. The pain descriptors in the questionnaire are consistent with the descriptors cited in the literature. It is a valid screening instrument for neuropathic pain that can be easily incorporated in the daily practice of general practitioners and internists.

Four cases of Kennedy's disease in three families earlier diagnosed as amyotrophic lateral sclerosis

Kennedys disease (KD) is a rare, slowly progressive neurodegenerative disorder of motor neurons in the spinal cord and brain stem. Most of the cases of KD in clinical practice are misdiagnosed. The knowledge of the initial presentation, the range of age within which the disease would manifest and the clinical course of the disease would be very helpful to better manage and anticipate the outcome of such cases. This report highlights the typical earliest presentation of KD and the clearcut clinical picture of KD that differentiates it from other motor neuron diseases of grave scenario and prognosis We report clinical details of 4 male patients with KD seen in our center. Diagnosis of these four patients were based on their clinical picture the time they were first seen. Common features in their history and presentation were the onset of prolonged and intermittent muscle cramps followed by weakness and atrophy of the muscles involved. All of them developed gynecomastia. Three of them have concomitant diabetes, and one has thyroid problem. All of them were initially diagnosed as Amyotrophic lateral Sclerosis.

Detection of subclinical diabetic neuropathy: Potential factors affecting electrodiagnostic parameters

OBJECTIVES: To identify the factors that can potentially affect the ability of electrodiagnostic tests such as sural/radial amplitude ratio or SRAR and the presence of carpal tunnel syndrome or CTS to detect early subclinical neuropathy in diabetes mellitus (DM). Likewise, to investigate the likelihood of developing subclinical neuropathy that can be detected by a positive CTS or SRAR abnormalities, because of the presence of anthropometric factors and sugar levels, in addition to DM duration METHODOLOGY: A retrospective cohort study was undertaken among 144 DM type 2 patients with confirmed subclinical neuropathy. Demographic data such as age, height and age, body mass index (BMI) and blood glucose profiles were obtained. Nerve conduction findings (SRAR and CTS protocols) were statistically analyzed using two sample t-test and multiple logistic regression ratios RESULTS: Patients who were positive in the CTS protocols were taller and had lower BMI. They had shorter duration of DM but with extreme elevations in blood glucose. Variables that are independently associated with a (+) CTS are duration of DM, FBS, BMI, height and weight. Patients with SRAR abnormalities were older and obese, with longer duration of DM and less marked elevations in blood glucose. Variables that are independently associated with SRAR abnormalities are age, duration of DM, weight and BMI CONCLUSION: Factors such as age, duration of DM, weight and height, BMI as well as glucose control can potentially affect the ability of various electrodiagnostic tests (SRAR and the presence of CTS) to detect early subclinical neuropathy. Since confounding factors was different between CTS and SRAR, the pathogenesis of these conditions may be different. The likelihood of developing subclinical neuropathy that can be detected by a (+) CTS or SRAR abnormalities because of the presence of certain factors, were documented.

A pilot study on the effect of statins, fibrates and its combination in rat nerves

OBJECTIVE: To determine the histopathological effect of statins, fibrates and its combination in rat nervesMETHODOLOGY: This is a pilot experimental study. Four male albino rats were used in this study. Each rat was given therapeutic doses of simvastatin alone, gemfibrozil alone, gemfibrozil and simvastatin combination and placebo. On day 21, the sciatic nerve was harvested for histopathologic examinationRESULTS: Although not marked, the combination of simvastatin and gemfibrozil produced more axonal degeneration than did simvastatin alone or gemfibrozil alone. Axonal degeneration was documented on teased nerve fibers and epon cross sectionsCONCLUSION: The use of lipid lowering agents may induce peripheral neuropathy Recommendation: This pilot study serves as rationale to proceed with an experiment not only to document neuropathy but also correlate the possible association of the pathomechanism of myotoxicity and neurotoxicity of lipid lowering agents.