Biomedical subjects

Prachi Dubey

Publications and source records attributed to Prachi Dubey.

9 recordsLinked to original sources

PubMed2006

Cognitive evaluation of neurologically asymptomatic boys with X-linked adrenoleukodystrophy.

BACKGROUND: Various studies have demonstrated abnormal neuropsychological function in boys with the childhood cerebral phenotype of X-linked adrenoleukodystrophy. Not much is known about the cognitive function of neurologically asymptomatic boys with X-linked adrenoleukodystrophy who have normal brain magnetic resonance imaging results. OBJECTIVE: To describe the cognitive profile of 52 neurologically asymptomatic boys with X-linked adrenoleukodystrophy (mean +/- SD age, 6.7 +/- 3.6 years). METHODS: Neuropsychological tests included evaluation of IQ (full-scale IQ, verbal IQ, and performance IQ), 5 major cognitive domains (language, visuospatial skills, perception, visuomotor or graphomotor skills, memory, and attention or executive function), adaptive skills, and academic achievement. Standardized z scores relative to age-appropriate published norms were generated. Association between age and cognitive performance was evaluated using nonparametric Spearman rank correlation and robust median regression adjusting for full-scale IQ and socioeconomic status. RESULTS: All but 4 patients had normal cognitive function. There was a negative correlation between age and visual perception as well as age and visuomotor skills after adjustment for full-scale IQ and socioeconomic status. CONCLUSIONS: This study provides, to our knowledge, the first evidence of overall normal cognitive function in neurologically and radiologically normal boys with X-linked adrenoleukodystrophy, indicating no evidence of neurodevelopmental abnormalities despite the inherent ABCD1 mutation. Subtle deterioration with age was observed in some functional domains. This suggests that prevention and timely institution of therapy can potentially preserve cognitive function seen in patients with the cerebral X-linked adrenoleukodystrophy phenotype. X-linked adrenoleukodystrophy should be considered a candidate disorder for neonatal screening.

Adrenoleukodystrophy↗

PubMed2006

Sensorimotor function and axonal integrity in adrenomyeloneuropathy.

BACKGROUND: Gait abnormalities and sensorimotor disturbances are principal defects in adrenomyeloneuropathy (AMN). However, to our knowledge, their association with overall impairment and neuroanatomical changes has not been defined. OBJECTIVES: To understand how sensorimotor impairments create mobility deficits and to analyze how these impairments are related to specific metrics of axonal integrity. DESIGN: Cross-sectional study assessing impairments, including vibration sensation, strength, spasticity, and global measures of walking and balance. Fractional anisotropy was measured to evaluate the integrity of the corresponding brainstem tracts. PARTICIPANTS: Men with AMN and healthy control subjects. RESULTS: Individuals with sensory loss only showed minimal walking deficits. Concomitant strength and sensory loss resulted in slower walking, with abnormal knee control; increased spasticity led to an exaggerated trunk motion and a knee-flexed (crouched) posture. Hip strength was an independent predictor of walking velocity in subjects with AMN. Subjects with sensory loss only had greater sway amplitudes during standing balance testing, which did not worsen with additional impairments. There were significant associations among sway amplitude, great toe vibration sense, and dorsal column fractional anisotropy. Brainstem fractional anisotropy in AMN was significantly negatively correlated with impairment, indicating that overall tract integrity is associated with sensorimotor abnormalities in AMN. CONCLUSIONS: Impairment measures capture specific abnormalities in walking and balance that can be used to direct rehabilitation therapy in AMN. Tract-specific magnetic resonance imaging metrics, such as fractional anisotropy (used herein to evaluate structure-function relationships), significantly reflect disease severity in AMN.

Adrenoleukodystrophy↗

PubMed2006

Developmental dyspraxia is not limited to imitation in children with autism spectrum disorders.

Impaired imitation of skilled gestures is commonly reported in autism. Questions, however, remain as to whether impaired imitation is associated with a more generalized deficit in performance of gestures consistent with a dyspraxia and whether the pattern of errors differs from that observed in typically developing children. To address these questions, praxis in 21 high-functioning children with autism spectrum disorders (ASD) was compared with 24 typically developing controls using a traditional approach in which performance was evaluated through detailed examination of error types. Children with ASD produced significantly fewer correct responses not only during Gesture to Imitation, but also during Gesture to Command and with Tool Use. The pattern of errors in ASD was similar to that of controls with spatial errors being most common in both groups; however, body-part-for-tool errors were more common in children with ASD, suggesting dyspraxia is not entirely attributable to motor deficits. The findings suggest that autism is associated with a generalized praxis deficit, rather than a deficit specific to imitation. In a developmental disorder such as autism, the findings may reflect abnormalities in frontal/parietal-subcortical circuits important for acquisition (i.e., learning) of sensory representations of movement and/or the motor sequence programs necessary to execute them.

Apraxias↗

PubMed2005

Adrenoleukodystrophy: new approaches to a neurodegenerative disease.

X-linked adrenoleukodystrophy (X-ALD), which was first described in 1923, was viewed until 1976 as a rare and inexorably fatal neurodegenerative disorder that affected boys. The genetic defect and biochemical abnormalities have now been defined. Ongoing research has resulted in new findings: (1) there is a wide range of phenotypic expression. At least half of patients with X-ALD are adults with somewhat milder manifestations, and women who are carriers may become symptomatic. X-ALD is often misdiagnosed as attention-deficit/hyperactivity disorder in boys and as multiple sclerosis in men and women, and is not an uncommon cause of Addison disease; (2) the incidence of X-ALD, estimated to be 1:17,000 in all ethnic groups, approximates that of phenylketonuria; (3) noninvasive and presymptomatic diagnosis and prenatal diagnosis are available; family screening and genetic counseling are key to disease prevention; and (4) new therapies, applied early, show promise. Neonatal screening is likely to become available, and a wider awareness of X-ALD and its various modes of presentation permit new proactive approaches to this distressing disorder.

Adrenal Cortex Hormones↗

PubMed2005

Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil.

OBJECTIVES: To identify asymptomatic boys with X-linked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression. METHOD: Eighty-nine boys (mean +/- SD baseline age, 4.7 +/- 4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities. RESULTS: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. Abnormalities occurred only in the 64 patients who were aged 7 years or younger at the time therapy was started. There was significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. (For a 0.1-microg/mL increase in the length-adjusted area under the curve for the hexacosanoic acid level, the hazard ratio for incident MRI abnormalities in the whole group was 1.36; P = .01; 95% confidence interval, 1.07-1.72.) Results for patients aged 7 years or younger were similar (P = .04). CONCLUSIONS: In this single-arm study, hexacosanoic acid reduction by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. We recommend Lorenzo's oil therapy in asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results.

Adrenoleukodystrophy↗

PubMed2005

Diffusion tensor-based imaging reveals occult abnormalities in adrenomyeloneuropathy.

"Pure" adrenomyeloneuropathy (AMN) is the noninflammatory myeloneuropathic variant of X-linked adrenoleukodystrophy, where the disease process appears to be restricted to spinal cord tracts and peripheral nerves. The absence of obvious brain involvement makes it distinct from the inflammatory cerebral phenotypes of X-linked adrenoleukodystrophy. However, some pure AMN patients later experience development of cerebral demyelination, but little is known about the extent of brain involvement in pure AMN patients who have normal brain magnetic resonance imaging. We used diffusion tensor imaging to investigate possible occult cerebral abnormalities in such pure AMN patients. Fractional anisotropy and trace were studied in three-dimensional reconstructions of white matter tracts commonly involved in cerebral phenotypes of X-linked adrenoleukodystrophy. Results demonstrated reduced fractional anisotropy and increased trace in bilateral corticospinal tracts and genu of corpus callosum (p < 0.05). Diffusion tensor imaging-based three-dimensional fiber tracking showed occult tract-specific cerebral microstructural abnormalities in pure AMN patients who had a normal conventional brain magnetic resonance image. Corticospinal tract abnormalities could reflect a centripetal extension of spinal cord long-tract distal axonopathy. Accompanying abnormalities in genu of corpus callosum indicate that the disease pathology in pure AMN may not be limited to spinal cord long tracts alone, although the involvement of the latter is most prominent and severe.

Adrenoleukodystrophy↗

PubMed2005

Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening.

OBJECTIVE: Plasma assay for very long-chain fatty acids has made it possible to perform large-scale screening of at-risk individuals to identify asymptomatic patients with X-linked adrenoleukodystrophy (X-ALD). We evaluated the burden of undiagnosed adrenal insufficiency in 49 such patients (age, 4.5 +/- 3.5 years). STUDY DESIGN: Serum adrenocorticotropic hormone (ACTH) and standard-dose ACTH stimulation test were performed at the baseline and followed prospectively until initiation of adrenal replacement therapy (follow-up, 2 +/- 1.7 years). RESULTS: At baseline, 39 (80%) patients had impaired adrenal function, serum ACTH levels were elevated in 34 (69%) patients, and ACTH stimulation test was abnormal in 21(43%) patients. There was a moderate association between Serum ACTH and age at baseline, ( r = 0.32, P = .05). By the end of follow-up, 86% of patients had borderline or overt adrenal insufficiency (age of onset, 4.8 +/- 3.7 years). CONCLUSIONS: We detected a high prevalence of unrecognized adrenocortical insufficiency in asymptomatic boys with X-ALD. It is known to be a frequent cause of morbidity and can be prevented by careful monitoring, early identification of impaired adrenal reserve, and timely initiation of therapy. It manifests early and before onset of neurologic symptoms, suggesting X-ALD as a candidate disorder for neonatal screening.

Adrenal Insufficiency↗

PubMed2005

X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes.

X-linked adrenoleukodystrophy (X-ALD) in males can present with eight distinct phenotypes, which vary greatly in respect to phenotypic expression, age of onset and rate of progression and therapy. The plasma very long chain fatty acid assay permits precise diagnosis and is already abnormal at birth. The clinical features, molecular biology, pathogenesis, and therapeutic approaches, including the indications for Hematopoietic Stem Cell Transplants (HCT) and dietary therapy are discussed, with emphasis on the asymptomatic, childhood cerebral, and adrenomyeloneuropathy phenotypes. The rationale for neonatal screening and the profound effect that such screening would have on the therapy of X-ALD, including the role of HCT, are discussed.

Adolescent↗

PubMed2004

Progress in X-linked adrenoleukodystrophy.

PURPOSE OF REVIEW: The purpose of this article is to review and evaluate the new information about X-linked adrenoleukodystrophy that has been reported in 2002 and 2003. RECENT FINDINGS: X-linked adrenoleukodystrophy has two distinct neurological phenotypes: adrenomyeloneuropathy, a non-inflammatory axonopathy mostly in adults, and an intensely inflammatory cerebral myelinopathy mostly in children. The two forms often co-occur in the same family. Heterozygous women and the X-linked adrenoleukodystrophy mouse model often have the adrenomyeloneuropathy phenotype. More than 500 distinct mutations in the defective gene (ABCD1) have been identified, and except in one unique family, do not correlate with the phenotype. Bone marrow transplantation is beneficial in patients with early cerebral involvement. A panel of brain neuroimaging studies aids the selection of patients for bone marrow transplantation. Lorenzo's oil administered to neurologically asymptomatic boys who are less than 6 years old and have a normal magnetic resonance imaging scan appears to reduce the probability of developing neurological abnormalities later in life. SUMMARY: Progress has been achieved in the delineation of the phenotypes, pathogenesis, diagnosis and prevention of X-linked adrenoleukodystrophy, and therapies are emerging.

Adrenoleukodystrophy↗