Differences Among Native Hawaiian, Asian, and White Patients with Progressive Supranuclear Palsy.

BACKGROUND: Most studies of progressive supranuclear palsy (PSP) have been conducted in White populations. OBJECTIVE: The objective of this study was to identify whether differences exist for patients with PSP among Whites, East Asians (EAs), and Native Hawaiians/Pacific Islanders (NHPIs) in Hawaii. METHODS: We conducted a single-center, retrospective study of patients meeting Movement Disorder Society probable PSP criteria (2006-2021). Data variables included age of onset and diagnosis, comorbidities, and survival rate. Variables were compared across groups using Fisher's exact test, Kruskal-Wallis rank sum test, and log-rank tests. RESULTS: A total of 94 (59 EAs, 9 NHPIs, 16 Whites, and 10 Others) patients were identified. Mean age ± standard deviation (in years) of symptom onset/diagnosis were both youngest in NHPIs (64.0 ± 7.2/66.3 ± 8.0) followed by Whites (70.8 ± 7.6/73.9 ± 7.8), then EAs (75.9 ± 8.2/79.2 ± 8.3) (P < 0.001). Median survival from diagnosis was significantly lower (P < 0.05) in NHPIs (2 years) compared with EAs (4 years) and Whites (6 years). CONCLUSIONS: There may be racial disparities for PSP, and studies are needed to identify genetic, environmental, and socioeconomic contributions. © 2023 International Parkinson and Movement Disorder Society.

DRPLA: An unusual disease or an underestimated cause of ataxia in Brazil?

BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia caused by pathological expansion of CAG trinucleotide repeats in the ATN1 gene. Most cases were described in patients from Japanese ancestry who presented with adult-onset progressive cerebellar ataxia associated with cognitive impairment, choreoathetosis and other movement disorders. DRPLA has been rarely described in Brazilian patients. METHODS: We performed a retrospective observational multicentric study including six different Neurology Centers in Brazil. All patients with genetically confirmed diagnosis of DRPLA had their medical records evaluated and clinical, genetic and neuroimaging features were analyzed. RESULTS: We describe of eight Brazilian patients (5 male, 3 female) from four nuclear families with genetically confirmed DRPLA. The most common neurological features included cerebellar ataxia (n = 7), dementia (n = 3), chorea (n = 2), psychiatric disturbances (n = 2), progressive myoclonic epilepsy (n = 2) and severe bulbar signs (n = 1). Progressive myoclonic epilepsy was observed in two juvenile-onset cases before 20-year. A large CAG trinucleotide length was observed in the two juvenile-onset cases and genetic anticipation was observed in all cases. Neuroimaging studies disclosed cerebellar atrophy (n = 6), as well as brainstem and cerebellar atrophy (n = 2) and leukoencephalopathy (n = 1). CONCLUSION: The patients described herein reinforce that clinical features of DRPLA are highly influenced by age of onset, genetic anticipation and CAG repetition lengths. There is a large complex spectrum of neurological features associated with DRPLA, varying from pure cerebellar ataxia to dementia associated with other movement disorders (myoclonus, choreoathetosis). DRPLA is an unusual cause of cerebellar ataxia and neurodegeneration in Brazilian patients.

Genetic movement disorders in patients of Jewish ancestry.

IMPORTANCE: Genetic diseases often cluster in different ethnic groups and may present with recognizable unique clinical manifestations. OBJECTIVE: To summarize current knowledge about movement disorders overrepresented among patients of Jewish ancestry. EVIDENCE REVIEW: We searched PubMed and the OMIM and Israeli National Genetic Databases for articles published from 1969 through March 31, 2014, using the search terms Parkinson's disease,movement disorders, ataxia, dystonia, chorea, and Creutzfeldt-Jakob with and Jewish. The final reference list was generated by giving priority to articles directly related to the topic, articles with the latest information, and comprehensive but relevant reviews. FINDINGS: About one-third of patients with sporadic Parkinson disease (PD) and more than 40% of patients with familial PD of Ashkenazi Jewish descent likely carry the G2019S mutation in the LRRK2 gene, a mutation in the glucocerebrosidase (GBA) gene, or both. This finding contrasts with only a 10% frequency of these mutations in patients with PD who are of non-Jewish ancestry. A dystonia due to a TOR1A gene mutation is responsible for most early-onset autosomal dominant dystonia, and 90% of Ashkenazi Jews who develop early-onset disease have TOR1A-related dystonia. Familial Creutzfeldt-Jakob disease and cerebrotendinous xanthomatosis tend to cluster among Jews of North African descent, and Machado-Joseph disease is particularly frequent in Yemenite Jews. CONCLUSIONS AND RELEVANCE: Genetic forms of PD are much more common in patients of Ashkenazi Jewish ancestry with sporadic and familial PD than in the non-Jewish population. The recognition of the particular movement disorder phenotype, coupled with information about the ethnic origin of the patients, may point to specific genetic testing and lead to early and correct diagnosis.

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.

BACKGROUND: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. METHODS: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges' g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. RESULTS: Out of 699 potentially eligible hits, 6 studies (N=1740, mean age=46.0±10.4years; males=73.1%; Asians=80.5%, Caucasians=19.5%; schizophrenia=96.2%) were included in this meta-analysis. Pooling data from all studies, no significant associations were found between BDNF Val66Met polymorphism and TD (p=0.82) or AIMS total scores (p=0.11). However, in studies including only Caucasians (n=339), Met allele carriers had significantly higher AIMS total scores (Hedges' g=0.253, 95% confidence interval=0.030 to 0.476, p=0.026) and non-significantly higher TD occurrence (p=0.127). Conversely, there was no association between BDNF and AIMS scores (p=0.57) or TD (p=0.65) in Asians. CONCLUSION: Although there was no significant association between BDNF Val66Met polymorphism and TD or AIMS scores across all patients, our results suggest that BDNF Val66Met polymorphism affects severity and, possibly, TD development in Caucasians. Since the number of studies and patients was still small, additional data are needed to confirm genotype-racial interactions. Furthermore, BDNF enhancing treatments for TD may require further study, especially in Caucasians.

The interaction of polymorphisms of IL10 and DBH was associated with general symptoms of PANSS with TD in Chinese Han schizophrenic patients.

OBJECTIVE: Tardive dyskinesia (TD) is a human hyperkinetic movement disorder as a result of potentially irreversible long-term chronic first-generation antipsychotic medications. Unfortunately, mechanisms involved in the development of TD have been poorly understood. Previous studies have indicated that some genetic polymorphisms of immune system and dopamine beta-hydroxylase (DBH) genes may be involved in the pathogenesis of TD. Rs1800872 and rs72393728 are located on the promoter of interleukin-10 (IL10) and DBH gene, respectively. The genetic association between the rs1800872 and TD is unclear. Previous studies have indicated that genetic variations of IL 10 and DBH are implicated in the positive and negative symptoms in schizophrenia. However, the interaction of two variations with severity of TD and symptoms of schizophrenic patients with TD has not been reported. The present study investigated whether these variations and their interaction were associated with clinical phenotypes of TD with schizophrenia in a genetically homogeneous northern Chinese Han population. METHODS: Rs1800872 and rs72393728 were genotyped in schizophrenic patients with TD (n = 372) and without TD (NTD; n = 412). The Abnormal Involuntary Movement Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were applied to assess the severity of TD and psychopathology of schizophrenia, respectively. RESULTS: The allele and genotype frequencies of rs1800872 and rs72393728 did not significantly differ between TD and NTD patients (p>0.05). No significant difference was found in the AIMS total score among the genotypes of two loci (p>0.05). Interestingly, the interaction of rs1800872 and rs72393728 showed a significant association with the PANSS general score (p = 0.011), and a trend toward to the PANSS total score (p = 0.055). CONCLUSION: These findings suggest that the interaction of rs1800872 and rs72393728 variants may play a role in psychopathology of the general symptoms on PANSS in schizophrenic patients with TD in a northern Chinese Han population.

Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia.

OBJECTIVE: Schizophrenia is a psychiatric disorder diagnosed by the presence of a number of symptoms with cognitive impairment as a core feature. Long-term antipsychotic treatment is often associated with the emergence of tardive dyskinesia (TD) and the presence of TD is linked to cognitive impairment. This study examined the relationship between TD and cognitive deficits in Chinese patients with schizophrenia. METHODS: We recruited 206 chronic patients with TD (n=102) and without TD (n=104) meeting DSM-IV criteria for schizophrenia and 104 control subjects who were matched on age, gender, and education. All the patients completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Symptom Scale (PANSS), and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: The PANSS total score (p=0.01), N subscore (p=0.006), and AIMS total score (p<0.001) were significantly higher in patients with TD compared to patients without TD. Patients with TD scored lower for visuospatial/constructional, attention, and total index scores (all p<0.001) on the RBANS. AIMS orofacial scores were identified as an independent contributor to RBANS total scores and attention index (p<0.05), whereas AIMS limb and truncal scores were an independent determinant to the visuospatial/constructional index of RBANS (p<0.05). CONCLUSION: TD was associated with greater cognitive impairment in patients with schizophrenia compared to those without TD. The orofacial and limb-trunk TD specifically appeared to be a risk factor or contributor to the different aspects of cognitive deficits in schizophrenia. The association between schizophrenia and TD may be explained in part by oxidative stress.

Association between TNF-α promoter -308A/G polymorphism and tardive dyskinesian Chinese Han patients with schizophrenia.

OBJECTIVE: Previous studies have indicated that the immune may be involved in the pathogenesis of tardive dyskinesia (TD). Some genetic polymorphisms in the human leukocyte antigen (HLA) I and II regions have been associated with TD, and the tumor necrosis factor-α (TNF-α) gene is located in the HLA III region. TNF-α levels in the striatum significantly increased in haloperidol-induced TD in rats. The TNF-α gene -308A/G single nucleotide polymorphism (SNP) has been shown to directly influence TNF-α expression. The genetic association between the TNF-α gene -308A/G SNP and TD is unclear. The present study investigated whether this variation is associated with clinical phenotypes and TD in schizophrenia in a genetically homogeneous northern Chinese Han population. METHODS: We genotyped the TNF-α gene -308A/G SNP in patients with schizophrenia with TD (n=350) and without TD (n=410). The Abnormal Involuntary Movement Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were used to assess the severity of TD and psychopathology of schizophrenia, respectively. RESULTS: The allele and genotype frequencies did not significantly differ between patients with schizophrenia with and without TD (p>0.05). No significant difference was found in the total AIMS score between the genotypes (p>0.05). However, the PANSS negative symptom subscore was associated with risk for TD (p=0.004), and a significant difference was found in total AIMS score between the genotypes in TD patients (p=0.013). CONCLUSION: The TNF-α gene -308A/G polymorphism does not appear to play a major role in the susceptibility to TD in patients with schizophrenia in a northern Chinese Han population. However this polymorphism may play a role in the TD severity.

Clinical and inheritance profiles of hyperekplexia in Jordan.

Hyperekplexia is a rare nonepileptic disorder characterized by excessive startle response to acoustic, visual, or other stimuli. Patients with hyperekplexia are often misdiagnosed as having epilepsy. The presentation modalities, phenotypes, and the modes of inheritance among patients with hyperekplexia from 9 Jordanian families are described. All families were referred with the preliminary diagnosis of uncontrolled seizures with onset of the disease in the neonatal period and with variable and atypical presenting features. The inheritance profile in 4 families was compatible with autosomal recessive and in 1 family with autosomal dominant inheritance. Four families showed sporadic cases of hyperekplexia. This is the first report of a series of patients with hyperekplexia from Jordan. The clinical manifestations show atypical features that have not been previously reported, pointing to the probable broader clinical spectrum of this entity. Recognition of the syndrome allows for prompt proper management and provision of genetic counseling.

Occupational exposures and movement abnormalities among Japanese-American men: the Honolulu-Asia Aging Study.

OBJECTIVE: The authors analyzed data on 1,049 men aged 71-93 years (excluding those with prevalent Parkinson's disease and stroke) from the Honolulu Heart Program (1965-1968) and the Honolulu-Asia Aging Study (1991-1999) to determine whether occupational exposures to pesticides, solvents, metals, manganese, and mercury during middle age were associated with 14 movement abnormalities 25 years later. METHODS: Analyses of variance and multivariate logistic regression were used to assess associations of interest. RESULTS: After adjustment for age, BMI, cognitive functioning, smoking, alcohol drinking, education, and physical activity, there was a positive association between abnormal 'facial expression' and the highest exposure to metals [odds ratio (OR) = 2.62; 95% confidence interval (CI) = 1.35-5.11; trend, p = 0.02], and the highest exposure to mercury (OR = 1.91; 95% CI = 1.04-3.49; trend, p = 0.03). Age was positively associated with all movement abnormalities, and cognitive function, body mass index and physical activity were inversely associated with most movement abnormalities. CONCLUSION: Higher exposure to any metal, and specifically mercury, was associated with abnormal facial expression.

Transcultural comparison of psychogenic movement disorders.

Prompted by the lack of cross-cultural comparative data, and because a better understanding in the different clinical presentations of psychogenic movement disorders (PMDs) is relevant to neurological assessment and interventions, we compared the phenomenology, anatomical distribution, and functional impairment of PMDs in the United States and Spain. Consecutive patients diagnosed with PMD by a movement disorder specialist from one US site and from eight Spanish university centers were included in the study. The two groups were similar in their movement types, anatomical distribution, and functional impairment. PMDs were more prevalent in women than in men and were most common in upper and lower extremities. Gait and speech dysfunctions were distributed similarly in both countries. We found action tremor to be the most frequent PMD in both countries.

The life situation and functional capacity of the elderly with locomotor disability in Sweden and Poland according to a model by Lawton.

A quadripartite concept, the Good Life for older people, was developed by the American psychologist M. P. Lawton and forms the theoretical framework of this study. Ninety Swedish and 93 Polish subjects, aged > or = 60 years who had reported locomotor disturbances in selected samples from the two countries, took part in the study. Interviews were performed using the Philadelphia Geriatric Center Multilevel Assessment Instrument (PGCMAI) and functional testing was done using the Standardized Practical Equipment (SPE). The Polish elderly scored lower in most domains of the PGCMAI, which meant a worse life situation according to the Good Life model. On the SPE, scoring was lower in the Polish group, mainly on items related to balance and mobility. There was a logic convergent validity between the PGCMAI and the SPE in the whole group. The somewhat more complicated life situation for the Polish elderly has to be further analysed.

Interrater and test-retest reliability of the Movement Assessment Battery for Chinese preschool children.

OBJECTIVE: The aim of this paper was to check on the reliability of the Movement Assessment Battery for Children (Movement ABC) in preparation for its standardization in Hong Kong. Interrater and test-retest reliability are reported for Age Band One, designed for use with children ages four to six. METHOD: Interrater reliability of the Movement ABC was estimated using two trained observers with 79 children. Test-retest reliability was assessed using 75 children who were tested twice by the same tester over a 2- to 3-week interval. RESULTS. Agreement between testers was good with a mean intraclass correlation of 0.96 across items. A value of 0.77 was obtained for test-retest reliability. CONCLUSION: These results support the use of this component of the Movement ABC in Hong Kong.

Impaired mobility and impaired working capacity among foreign born people and native born Swedes.

OBJECTIVE: The aim of this study is to analyse the influence of country of birth and attained level of education, on impaired mobility and impaired working capacity adjusted for age, sex, and other background variables. SETTING: Sweden. DESIGN: A random sample of 5798 men and 6072 women ages 55-74 years were interviewed face to face by Statistics Sweden 1986-1993. Dependent variable: impaired mobility and impaired working capacity. INDEPENDENT VARIABLES: sex, age, country of birth (Swedes, Finns, Western countries, south Europeans, and all others), attained level of education, marital status, form of tenure, and social network. This study was designed as a cross sectional study. The data were analysed with unconditional logistic regression in main effect models. The results are shown as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In general, poor health, defined as impaired working capacity or impaired mobility, proved to be more frequent among foreign born people and in all socially disadvantaged groups such as those with a low educational status, people renting a dwelling or with a poor social network. Impaired working capacity and impaired mobility were more frequent among female "all others". The impaired mobility among men and women born in south Europe was high with OR = 2.65 (CI = 1.34, 5.25) and OR = 3.17 (CI = 1.44, 7.00) in the full model. Men and women from Finland and all other countries had high risks for impaired mobility when adjusted for all background variables. Finnish men and south European women had the highest odds ratios for impaired working capacity. There was a clear gradient between educational status and impaired working capacity, with the highest odds ratios for men and women, 2.39 and 1.92, with a low attained level of education, when adjusting for the independent variables. CONCLUSION: Country of birth and educational status are two important independent factors with influence on poor health defined as impaired mobility and impaired working capacity in age 55-74.

Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder that clinically overlaps with Huntington's disease (HD) and manifests combinations of chorea, myoclonus, seizures, ataxia, and dementia. DRPLA is caused by a CAG triplet repeat (CTG-B37) expansion coding for polyglutamine on chromosome 12 and exhibits the genetic phenomenon of anticipation. This neurodegenerative disease has only rarely been reported in non-Japanese pedigrees, and there are only a few neuropathological studies in genetically confirmed patients. We report 10 cases of DRPLA from two North American and two British pedigrees in which CTG-B37 expansions have been demonstrated within each kindred (54-83 repeats), individually in 8 of the 10 cases, and describe the neuropathological findings in 4 cases. Members of DRPLA kindreds have a wide range of clinical phenotypes and markedly variable ages at onset. The neuropathological spectrum is centered around the cerebellifugal and pallidofugal systems, but neurodegenerative changes can be found in many nuclei, tracts, and systems. Evidence of CTG-B37 triplet repeat expansion should be sought in HD-like cases that are negative for expanded triplet repeats within the HD IT15 gene or in autopsy cases with degeneration of the dentatorubral or pallidoluysian systems.

3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome.

Eleven new patients of Iraqi-Jewish origin with bilateral optic atrophy, neurological abnormalities ('optic atrophy plus' syndrome) and 3-methylglutaconic aciduria (type III) are described. Clinical abnormalities in decreasing order of frequency were bilateral optic atrophy, extrapyramidal signs, spasticity, ataxia, dysarthria and cognitive deficit. An association with age was found only for spasticity. Spasticity, extrapyramidal signs and optic atrophy frequently led to major disability, in contrast to ataxia, dysarthria and cognitive deficit. The combined excretion of 3-methylglutaconic and 3-methylglutaric acid ranged between 9 and 187 mmol/mol creatinine. The primary enzymatic defect possibly may reside in the mitochondrial respiratory chain.