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Biomedical subjects

Linda A Heier

Publications and source records attributed to Linda A Heier.

9 recordsLinked to original sources

Possible axonal regrowth in late recovery from the minimally conscious state.

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patient's DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference.

Adolescent↗

Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group.

PURPOSE: To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. PATIENTS AND METHODS: Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. RESULTS: Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. CONCLUSION: Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders.

Genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. Inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. The purpose of this paper is to help define these complex issues relevant to the use of genetic medicines and to describe the strategy we have used to confront these issues in a phase I trial of adeno-associated virus-mediated gene transfer to the central nervous system of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal lysosomal storage disease associated with progressive neurodegeneration and death by mid-childhood. Our approach to these challenges should provide a useful paradigm for investigators initiating other genetic medicine- based studies to treat inevitably fatal diseases.

Clinical Trials, Phase I as Topic↗

MR quantitation of volume and diffusion changes in the developing brain.

BACKGROUND AND PURPOSE: Brain volume and diffusion change during maturation. Quantitation of these changes may be helpful in understanding normal brain development. We used diffusion-weighted imaging to characterize the volumetric and diffusion changes in vivo. METHODS: We recruited 30 pediatric volunteers (aged 1 month-17 years; 14 male, 16 female). Diffusion was measured in three orthogonal directions with a b value of 1000 s/mm2. The diffusion parameters from the entire brain were calculated and fitted to a triple gaussian model. In addition, region-of-interest measurements were made in caudate, thalamus, genu and splenium of the corpus callosum, and periventricular white matter (PVWM). The brain volume was measured by counting pixels and by using the model. RESULTS: Water diffusion of the whole brain, caudate, thalamus, genu and splenium of the corpus callosum, and PVWM decreased during maturation, with the most significant change within the first 2 years. Robust negative correlations were found between age and the measured average diffusion constant (Dav) values in each of the measured locations (P <.005). Volumes of different cerebral compartments and the total intracranial volume (ICV) increased rapidly during the first 2 years of life and then had a slower growth process through adolescence. Age was correlated with the ICV and the volume of each brain compartment (P <.005). CONCLUSION: Brain diffusion decreases and brain volume increases during maturation, with the most significant changes occurring within the first 2 years of life. The brain model used in this study provides a good estimate of the increasing brain volume.

Adolescent↗

Safety and feasibility of using a central venous catheter for rapid contrast injection rates.

OBJECTIVE: Our aim was to determine the safety and feasibility of using a central venous catheter for rapid contrast injections during CT. MATERIALS AND METHODS: An in vitro experiment was performed using a 7-French Arrow-Howes multilumen central venous catheter. Each catheter port was tested by varying contrast agent flow rates delivered by a power injector. Contrast media specifications were kept similar to routine clinical practice. The in vivo experiment included 104 cases in which rapid contrast injections, 3.0-5.0 mL/sec, were delivered through a central venous catheter for dynamic CT examinations. Patient monitoring for early complications of contrast extravasation, cardiac arrhythmia, and allergic reactions was performed. Contrast injections were monitored for pressure limitation, automatic flow-rate adjustment, and catheter injury. Chart review was performed for delayed complications of mediastinal hematoma, infection, or catheter malfunction. RESULTS: During the in vitro experiment, all desired flow rates, 3.0-9.9 mL/sec, could be delivered through the central venous catheter with no catheter injury. No immediate or early patient or catheter complications were observed during the in vivo experiment. Follow-up evaluation revealed that 18 blood cultures and one catheter culture were positive for bacterial growth. In a subgroup of 43 patients, five contrast injections were pressure-limited by the power injector, and only one had the flow rate automatically adjusted to 3.6 mL/sec from 4.0 mL/sec. CONCLUSION: Rapid contrast injection rates, at 3.0-5.0 mL/sec, through the Arrow-Howes multilumen central venous catheter are feasible and safe in the clinical setting. However, a strict protocol should be followed to avoid possible serious complications.

Adult↗

Diffusion-tensor MR imaging in children with developmental delay: preliminary findings.

PURPOSE: To determine whether diffusion-tensor magnetic resonance (MR) imaging can depict abnormalities in patients with a diagnosis of developmental delay but structurally normal brain MR imaging results. MATERIALS AND METHODS: Twenty pediatric patients who received a diagnosis of developmental delay underwent brain MR examinations, including diffusion-tensor MR imaging. The MR findings in these patients were compared with those in 10 age-matched neurodevelopmentally healthy children. Diffusion constant (Dav) and anisotropy were measured bilaterally in regions of interest in the centrum semiovale, corona radiata, internal capsule, corpus callosum, and subcortical white matter of the frontal and parieto-occipital lobes. By using a one-tailed Student t test in the positive direction for Dav and in the negative direction for anisotropy and P <.05 to indicate a significant difference, the Dav and anisotropy values for children with developmental delay were compared with those for children who were neurodevelopmentally healthy. RESULTS: The children with developmental delay had significant increases in Dav in all measured structures (P, <.001 to <.03). Significant decreases in anisotropy were detected in all white matter fiber tracts studied (P, <.001 to <.03) except the posterior limb of the internal capsule. CONCLUSION: In the children with developmental delay, diffusion-tensor MR imaging depicted decreases in anisotropy and increases in Dav in the white matter fiber tracts, which appeared to be normal at conventional MR imaging.

Anisotropy↗

Developmental delay in children: assessment with proton MR spectroscopy.

BACKGROUND AND PURPOSE: The cause of developmental delay frequently is unknown, and clinicians and families can be frustrated by the lack of neuroimaging correlation especially when considering therapeutic options and long-term prognosis. We sought to determine if proton MR spectroscopy can depict abnormalities in patients with developmental delay who have structurally normal brain MR images. METHODS: Children with developmental delay who were older than 2 years (mean age, 5.0 years; range, 3.0-10.0 years) and those aged 2 years or younger (mean age, 1.5 years; range, 0.5-2.0 years) and age-matched control subjects for each patient group underwent brain MR imaging and proton MR spectroscopy. A point-resolved spectroscopy sequence (2000/144 [TR/TE]) was used. Voxels (8 cm(3)) were placed in the subcortical white matter of the frontal and parieto-occipital lobes bilaterally. N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were assessed. RESULTS: All patients had normal brain MR images. In children with developmental delay who were aged 2 years or younger, no statistically significant differences were detected in the NAA/Cr or Cho/Cr ratios compared with those of the control subjects. In children with developmental delay who were older than 2 years, decreases in the NAA/Cr ratio were observed in frontal (P <.001) and parieto-occipital (P <.017) subcortical white matter, and elevations in the Cho/Cr ratio were detected in the frontal (P <.24) and parieto-occipital (P <.002) subcortical white matter compared with age-matched control subjects. CONCLUSIONS: In children with developmental delay who are older than 2 years, proton MR spectroscopy depicted abnormalities in the NAA/Cr and Cho/Cr ratios. Proton MR spectroscopy should be performed as part of the neuroimaging evaluation of developmental delay. Further studies will be needed to determine if abnormalities detected with proton MR spectroscopy can be used as a diagnostic tool and neuroimaging marker to assess long-term functional outcome.

Aging↗

Evidence of cerebral reorganization following perinatal stroke demonstrated with fMRI and DTI tractography.

A 44-year-old man with a left perinatal stroke and recurrent refractory epilepsy underwent functional MRI (fMRI) for motor and language mapping to determine if further epilepsy surgery could be performed without loss of language. Language was activated excessively in the right hemisphere, with only small areas of left hemisphere activation. This suggests bilateral language dominance acquired secondary to the perinatal stroke with the right hemisphere activation resulting from neonatal neuronal reorganization. Functional data were overlaid onto 3D diffusion tensor tractography, providing a unique image of the right hemisphere language recruitment.

Adult↗