Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences.

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course.

Newborn screening for adrenoleukodystrophy: International experiences and challenges.

X-linked adrenoleukodystrophy (XALD) is the most common leukodystrophy. It has an estimated incidence of around 1/17.000, and a variable phenotype.

Allogenic hematopoietic stem cell transplantation in two siblings with adult metachromatic leukodystrophy and a systematic literature review.

Two siblings were diagnosed with adult metachromatic leukodystrophy (MLD) and treated with hematopoietic stem cell transplantation (HSCT). While the older sibling was symptomatic at the time of diagnosis, her younger brother was diagnosed and transplanted at the presymptomatic state. We describe patients' clinical, biochemical, and genetic features, as well as neuropsychological and neurophysiological test results, and brain magnetic resonance imaging from pretransplantation and posttransplantation assessments.

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist.

Background: The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia.

Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin.

Background: Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the external and internal environment of the cardiovascular system as compared to the healthy situation.

Methods: Here we tested the hypothesis that the cardiovascular system in healthy rats and rats resuscitated from a cardiac arrest may be differentially affected by a transient receptor potential vanilloid type 1 agonist, by continuous intravenous infusion of dihydrocapsaicin (DHC).

[123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: implications for the use of cerebellum as a reference region.

The low density of cerebellar dopamine D(2)/D(3) receptors provides the basis for using the cerebellum as a representation of free- and non-specifically bound radioligand in positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies. With the development of ultra high-affinity dopamine D(2)/D(3) ligands like [(123)I]epidepride, [(18)F]fallypride, and [(11)C]FLB-457, quantification of extrastriatal low density receptor populations including the cerebellum is possible with important implications for calculation of binding parameters. [(123)I]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9).

Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender.

Background: The aim of the study was to examine extrastriatal dopamine D(2/3) receptor binding and psychopathology in schizophrenic patients, and to relate binding potential (BP) values to psychopathology.

Methods: Twenty-five drug-naive schizophrenic patients and 20 healthy controls were examined with single-photon emission computerized tomography (SPECT) using the D(2/3)-receptor ligand [123I]epidepride.

Results: In the hitherto largest study on extrastriatal D(2/3) receptors we detected a significant correlation between frontal D(2/3) BP values and positive schizophrenic symptoms in the larger group of male schizophrenic patients, higher frontal BP values in male (n = 17) compared to female (n = 8) patients, and - in accordance with this - significantly fewer positive schizophrenic symptoms in the female patients.

Imaging of dopamine transporters and D2 receptors in patients with Parkinson's disease and multiple system atrophy.

Purpose: The aim of this study was to ascertain whether combined presynaptic and postsynaptic dopaminergic single-photon emission computed tomography (SPECT) scanning is useful for differentiation between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy of the striatonigral type (MSA) and healthy subjects.

Methods: SPECT measurements of the dopamine transporter (DAT) were done with 123I-beta-CIT, while for determination of the dopamine D2-like receptors (D2), 123I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight patients with MSA and 11 healthy age-matched control subjects.

Quantification of [(123)I]PE2I binding to dopamine transporters with SPET.

The iodinated cocaine derivative [(123)I]PE2I is a new selective ligand for in vivo studies of the dopamine transporter (DAT) with single-photon emission tomography (SPET). The aim of the present study was to describe a method for accurate quantification of binding data following a bolus injection of [(123)I]PE2I. Six healthy subjects (age 51+/-24 years) underwent xenon-133 SPET for quantification of regional CBF and [(123)I]PE2I SPET for quantification of DAT binding.

Benzodiazepine receptor quantification in Huntington's disease with [(123)I]omazenil and SPECT.

Objectives: Increasing evidence suggests that metabolic changes predate neuronal death in Huntington's disease and emission tomography methods (PET and SPECT) have shown changes in glucose consumption and receptor function in early and possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor complex (BZR) is expressed on virtually all cerebral neurons BZR density images may be used to detect neuronal death. In this study the regional cerebral [(123)I]iomazenil binding to BZR was determined in patients with Huntington's disease and normal controls by a steady state method and SPECT.

In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography.

This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled haloperidol (0.

SPECT tracer [(123)I]IBZM has similar affinity to dopamine D2 and D3 receptors.

Emission tomography investigations of the pathophysiological involvement of the cerebral dopaminergic transmitter system in the living human brain relies heavily on a careful selection of the most suitable radioligand. In recent years, many clinical studies have employed [(123)I]IBZM in SPECT studies. The aim of the present study was to characterize the binding of IBZM to dopaminergic receptor subtypes as a means of elucidating which receptor subtypes are visualized and examined by [(123)I]IBZM.

Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample.

No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.

The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transport and cerebral metabolism (CMRglc) was studied using the intravenous double-indicator method and positron emission tomography using [18F]fluorodeoxyglucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/- 4 years old) were studied twice during a euglycemic and a euglycemic-hyperinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose.

Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies.

The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique.

Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria.

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied.

Neuroreceptor quantification in vivo by the steady state principle and [123I]iomazenil in rats.

A steady state method for neuroreceptor quantification in vivo in small laboratory animals is described, using [123I]iomazenil as tracer for the benzodiazepine receptor. The method was used for determination of the receptor equilibrium constant for a non-radioactive ligand, flumazenil, in rats and involved measurement of the nonspecific binding of [123I]iomazenil. Thirty-five animals were intravenously infused for 2 h with [123I]iomazenil and flumazenil in different proportions to obtain occupancies of the benzodiazepine receptor from close to 0 to about 99%.

Tomographic cerebral blood flow measurement during carotid surgery.

Objectives: The aim of the study was to depict regional cerebral blood flow (rCBF) during carotid cross clamping using 99mTechnetium-hexamethylpropylene amine oxime (TcHMPAO). This tracer rapidly passes the blood-brain barrier and is retained for hours in the brain tissue. Injecting TcHMPAO during surgery and performing single photon emission computer tomography (SPECT) scanning shortly after the operation thereby pictures rCBF at the time of injection.

Brain extraction and distribution of 99mTc-bicisate in humans and in rats.

Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cystein diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using 24Na+ as an intravascular cotracer.

Benzodiazepine receptor equilibrium constants for flumazenil and midazolam determined in humans with the single photon emission computer tomography tracer [123I]iomazenil.

This study is based on the steady state method for the calculation of Kd values recently described by Lassen (J. Cereb. Blood Flow Metab.

Thrombolytic therapy in acute ischemic stroke. A Danish pilot study.

Background And Purpose: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow.

Methods: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms.

The effect of tirilazad mesylate (U74006F) on cerebral oxygen consumption, and reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.

Background: The 21-aminosteroids are a series of compounds designed to inhibit lipid peroxidation in the cell, and, as such, may have cerebral protective effects. The current study was performed to evaluate the effect of a 21-aminosteroid, tirilazad mesylate (U74006F), on cerebral blood flow, metabolism, and carbon dioxide reactivity.

Methods: Using a double-blind study design, eight volunteers received tirilazad mesylate, and eight others received only vehicle.

Regional cerebral blood-flow measured by HMPAO and SPECT in a 5-year-old boy with Landau-Kleffner syndrome.

We present a 5-year-old boy with Landau-Kleffner syndrome, whose clinical manifestations were very similar to cases previously reported in the literature. CT and MRI scan failed to document any morphological abnormalities of his brain. However, high resolution rCBF imaging by HMPAO and SPECT demonstrated relatively low-flow areas in the left middle frontal gyrus and the right mesiotemporal/hippocampal region corresponding to the localization of EEG changes.

The effect of ketanserin on cerebral blood flow and cerebrovascular CO2 reactivity in healthy volunteers.

The effect of the anti-hypertensive agent ketanserin on the cerebral blood flow (CBF) and the cerebrovascular CO2 reactivity was examined in 10 healthy volunteers. Ketanserin was administered as an intravenous bolus of 10 mg followed by an infusion of 6 mg/h. Before administration CBF was measured by single photon emission computerized tomography (SPECT) of inhaled 133Xenon.