The clinical phenotype of X-linked recessive torsion dystonia was documented in 42 affected individuals from 21 families. In 7 families, there were 9 sibships (core families) with 2 or more affected individuals available for evaluation. The ages of the patients ranged from 29 to 79 years with a mean of 46.2 +/- 10.1 years; the mean age of onset of dystonia was 35.0 +/- 8.0 years with a range of 12 to 48 years; and the mean duration of illness was 11.1 +/- 7.9 years. First manifestations were noted in the lower extremities in 36%, the axial musculature in 29%, the upper extremities in 23%, and in the head in 12% of the cases. The majority of patients displayed gait abnormalities (90%), leg dystonia (79%), oromandibular dystonia (64%), neck dystonia (57%), blepharospasm (57%), and truncal dystonia (52%). The disease generalized in 90% of the cases within 1 to 11 years of onset (median duration, 5 years). Overall, the condition was disabling, but the Fahn-Marsden disability score did not correlate with age of onset, duration of illness, site of onset, rate of generalization, or presence of parkinsonism. Thirty-six percent of the cases displayed at least 1 of the following "parkinsonian symptoms": bradykinesia, tremor, rigidity, loss of postural reflexes and a shuffling gait. Parkinsonism was diagnosed as definite in 14%, probable in 2%, and possible in 19% of the cases. Given this high association of dystonia and parkinsonism, we propose to call the disorder X-linked dystonia-parkinsonism syndrome (XDP).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract Background The current prevalence of X‐linked dystonia parkinsonism is not known. No screening tool for the condition exists. By developing a screening questionnaire, the present study is intended to be the first step in identifying the prevalence of the disease. Aim To develop and validate a simple, easy to use, community‐based, screening questionnaire for the diagnosis of X‐linked dystonia parkinsonism. Methods Community health workers administered an 11‐item yes/no questionnaire in the native Panay island language to 54 genetically‐confirmed X‐linked dystonia parkinsonism patients and 54 healthy controls from the island of Panay. The questionnaire is made up of elements from existing questionnaires on Parkinson's disease and dystonia, and known clinical features of the disease. The participants were partitioned into training ( n = 88) and test ( n = 20) datasets. To select which items were predictive of X‐linked dystonia parkinsonism, the Clinical Utility Index of each item was determined. Afterwards, multivariable binary logistic regression was done to build a predictive model that was run on the test dataset. Results Four items on “sustained twisting,” “jaw opening and closing,” “slowness in movement” and “shuffling steps” were found to be the most predictive of X‐linked dystonia parkinsonism. All had at least a “good” Clinical Utility Index. The questions showed 100% sensitivity and 90% specificity (95% CI 65.6–100%) in identifying cases. Conclusions The resulting four‐item questionnaire was found to be predictive of X‐linked dystonia parkinsonism. The screening instrument can be used to screen for X‐linked dystonia parkinsonism in a prevalence study.
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.
Objectives. To correlate the presence and levels of total mercury (THg) in cord blood and meconium indicating prenatal exposure with developmental milestones at 2 years and to compare these subjects with controls of comparable age using cognitive adaptive test and clinical linguistic auditory milestone scale (CAT/CLAMS). Methods. In 48 of the original Tagum (T) subjects, cord blood and meconium Hg levels, head circumference (HC) at birth, and duration of breastfeeding were correlated with CAT/CLAMS at 2 years. At 2 years, THg levels using cold atomic vapor absorption spectrometry were determined in the hair of 46 T subjects and 88 Saranggani (S) controls; THg levels in blood were tested in 48 T subjects and 45 S controls. These levels were correlated with CAT/CLAMS. Both groups had standard physical and neurologic examinations, hearing screen using transitory evoked otoacoustic emissions, serum glutamate pyruvate transaminase, and routine urinalysis. A prevalidated Socioeconomic Means Test was given to both groups. Results. The Hg level in cord blood was negatively correlated with CAT/CLAMS at 2 years. The HC at birth was negatively correlated with levels of Hg in hair of T subjects 2 years later. HC at birth and 2 years hence were positively correlated with CAT/CLAMS. The following were significantly higher in S controls than in T subjects: expressive language quotient 82.569 ± 2.21 versus 71.57 ± 2.61; CLAMS 87.96 ± 2.43 versus 77.67 ± 2.51; CAT 90.57 ± 2.22 versus 83.15 ± 1.43; and full-scale developmental quotient 89.31 ± 2.14 versus 80.56 ± 1.86. Fifteen percent of T subjects had global delay (full-scale developmental quotient ≤70) versus 5.48% in S controls. Hg levels in hair and blood in both T subjects and S controls at 2 years showed no correlation with CAT/CLAMS. The duration of breastfeeding in both groups likewise showed no correlations with CAT/CLAMS. Conclusion. The study suggests that prenatal Hg exposure is correlated with lower scores in neurodevelopmental screening, but more so in the linguistic pathway. Other confounding factors cannot be eliminated.
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 tried or have been tried on medications typically used for patients with generalized dystonia. These drugs include anticholinergic agents, baclofen, clonazepam and other benzodiazepines, tetrabenazine, and clozapine. Although several articles have shown that these classes of drugs are beneficial for patients with generalized dystonia, none have been systematically studied specifically for XDP patients. We are currently conducting the first randomized, placebo-controlled trial on the use of levodopa for the symptomatic treatment of XDP. This article reviews the data on the various dystonia medications that have been used in XDP.
The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring. Haplotype analysis has confirmed independent mutational events. All individuals share adult-onset, predominantly cerebellar signs and a slowly progressive course. However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His). In this study, we present the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis.
'%3e%3ccircle r='9'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cpath d='m-19 0 1.169 1.169L0 0l-17.831-1.169z'/%3e%3cpath id='a' d='m-.884.116.05.05L0 0z' transform='scale(19.2381)'/%3e%3cuse xlink:href='%23a' transform='scale(1 -1)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(45)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(90)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(180)'/%3e%3cg transform='translate(-2.02)'%3e%3cg id='f' transform='translate(37.962)'%3e%3cpath id='e' d='M5 0 1.618 1.176l-.073 3.58-2.163-2.854-3.427 1.037L-2 0z'/%3e%3cuse xlink:href='%23e' transform='scale(1 -1)'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='rotate(120)'/%3e%3cuse xlink:href='%23f' transform='rotate(-120)'/%3e%3c/g%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
