Challenges in ADHD care for ethnic minority children: A review of the current literature.

While attention deficit hyperactivity disorder (ADHD) has been extensively studied in the past decades, the role of social and cultural practices in its assessment, diagnosis, and treatment has been often overlooked. This selective review provides an overview of research that explores social and cultural influences on help-seeking behavior in ethnic minority children with ADHD. Studies were selected that address cultural diversity in three areas of ADHD help-seeking: problem recognition, access to mental health services, and treatment. Special attention was given to studies of treatment selection and adherence in minority groups. Findings suggested that cultural disparities in ADHD care among ethnic minority children occur in the early stages of problem recognition, through service selection, and in the quality of treatment. Ethnic minority children were less likely than their nonminority counterparts to be diagnosed with ADHD and its comorbid conditions and less likely to be prescribed and adhere to stimulant drug treatment. These differences reflect cultural diversity in norms and attitudes towards mental health issues (e.g., fear of social stigma) as well as limited access to qualified health care. Paradoxically, cultural, racial, and language bias may also lead to the overidentification of ethnic minority children as disabled and to higher ratings of ADHD symptoms. This review highlights the importance of sociocultural factors in understanding developmental psychopathology and help-seeking behavior. In addition, it further supports calls for increasing cultural competence in communications during clinical assessment, diagnosis, and treatment in minority communities. Clinical, theoretical, and methodological considerations for future research are discussed.

ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia.

OBJECTIVE: To identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP). METHODS: Clinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP. RESULTS: A homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia. CONCLUSIONS: Our findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP.

Variable PARK2 Mutations Cause Early-Onset Parkinson's Disease in a Small Restricted Population.

Early-onset Parkinson's disease (EOPD) is less common than the typical adult-onset PD and may be associated with a genetic etiology. Mutations in several genes are known to cause autosomal recessive (AR) PD. This study aimed to detect the etiology of EOPD in consanguineous families or families living in a specific small geographic region in Israel. Six families with EOPD affecting more than a single individual were recruited. Homozygous mapping analysis using a single-nucleotide polymorphism-based array was performed in all families, followed by Sanger sequencing of related genes based on the mapping results. In addition, all families underwent PARK2 sequencing and testing for large deletions and duplications in PD-associated genes. Different truncating mutations were detected in the PARK2 gene among affected individuals of three families: c.996C>A (p.Cys332X) and c.101delA in either homozygous or compound heterozygous fashion. Exon 4 deletion was detected in a heterozygous manner in a late-onset PD and in homozygous state in early-onset disease in the same family. No disease-causing mutations were detected in any other tested genes. In total, mutations in the PARK2 gene were detected in four of the six tested families with a history of EOPD. These results further demonstrate the role of PARK2 in AR PD. We recommend genetic analysis for the PARK2 gene when AR PD is suspected.

Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.

OBJECTIVE: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. METHODS: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. RESULTS: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. CONCLUSION: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies.

The prevalence of Parkinson's disease in an Arab population, Wadi Ara, Israel.

BACKGROUND: The prevalence of Parkinson's disease varies among ethnic and geographic groups around the world, being very low in China and high in Argentina. While the main etiology of the disease has yet to be determined, environmental, occupational and genetic factors seem to play important roles. OBJECTIVES: To estimate the prevalence of PD in an Arab Muslim population in Israel, using the drug tracer approach. METHODS: We studied a Muslim Arab population living in a well-defined geographic area in Israel, with the majority located in two towns and two large villages. Of the approximately 115,000 residents, about 38% are under the age of 15 and 7.75% are older than 65. Drug tracer methodology was applied in this study. All those who were on anti-PD medication were identified and examined by a neurologist to confirm the diagnosis. RESULTS: The overall crude prevalence of PD in this population was low, 43.24/100,000, while the prevalence in the age group above 65 years was 477.32/100,000. Below this age, the prevalence was very low, 12.29/100,000. PD prevalence was higher in males than in females (ratio 1.17); 63% of male patients smoked cigarettes. The prevalence was found to be twice as high among the residents of rural areas, where most inhabitants work in agriculture. CONCLUSIONS: The prevalence of PD among the Arab population in Israel is considered low and comparable to that reported in other Arab countries.

Onset of late posttraumatic seizure after dehydroepiandrosterone treatment.

OBJECTIVE: To describe the first reported case of a seizure in a patient using the dietary supplement DHEA in an attempt to improve ovarian oocyte production. DESIGN: Case report. SETTING: University-affiliated teaching hospital, neurologic department. PATIENT(S): A 30-year-old woman with fragile X syndrome and no history of any convulsive disorder who was receiving IVF treatment. INTERVENTION(S): Daily treatment with the dietary supplement DHEA. MAIN OUTCOME MEASURE(S): Generalized seizure. RESULT(S): After 1 month of DHEA treatment, the patient was admitted with a generalized seizure. CONCLUSION(S): A generalized seizure, associated with concurrent intake of DHEA.

Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration.

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.

Membrane-permeable and -impermeable sensors of the Zinpyr family and their application to imaging of hippocampal zinc in vivo.

Esterification of fluorescent biosensors is a common strategy used to trap probes within the cell. Zinpyr-1 (ZP1) is a fluorescein-based bright fluorescent sensor for divalent zinc that is cell permeable without prior modification. We describe here the synthesis and characterization of ZP1 sensors containing a carboxylic acid or ethyl ester functionality at the 5 or 6 position of the fluorescein. The presence of an electronegative carboxylate decreases the proton-induced background fluorescence of the probe by lowering the pKa of the benzylic amines responsible for fluorescence quenching. The charged species ZP1(6-CO2-) is membrane-impermeant, whereas the permeability of the neutral ZP1(5/6-CO2Et) is similar to that of the parent sensor. Intracranial microinfusion of ZP1(6-CO2Et) into rat hippocampus produces reduced staining of vesicular zinc in neuropil and very clear delineation of zinc-positive injured neuronal somata and dendrites as compared with ZP1.

Brachioradial pruritus: a symptom of neuropathy.

BACKGROUND: Brachioradial pruritus (BRP) is a localized pruritus of the dorsolateral aspect of the arm. BRP is an enigmatic condition with a controversial cause; some authors consider BRP to be a photodermatosis whereas other authors attribute BRP to compression of cervical nerve roots. OBJECTIVE: We sought to investigate the presence of neuropathy in patients with BRP. METHODS: We performed electrophysiologic studies of the median, ulnar, and radial nerves in consecutive patients with BRP, including measurement of sensory and motor distal latency, conduction velocity and F responses of the median and ulnar nerves, and sensory distal latency of the radial nerves in both upper limbs. RESULTS: Included in the study were 7 patients, 5 men and 2 women, with an average age of 58.3 years (range: 42-72 years). Of the patients, 4 (57%) had abnormal F responses that were diagnostic for cervical radiculopathy, and 3 of these patients had prolonged distal latencies of the nerves tested, which may be interpreted as sensory motor neuropathy secondary to chronic radiculopathy. The fourth patient had polyneuropathy secondary to diabetes mellitus. CONCLUSION: BRP may be attributed to a neuropathy, such as chronic cervical radiculopathy. The possibility of an underlying neuropathy should be considered in the evaluation and treatment of all patients with BRP.