Frontotemporal cognitive function in X-linked spinal and bulbar muscular atrophy (SBMA): a controlled neuropsychological study of 20 patients.

A cross-sectional neuropsychological study of cognitive functions in 20 male patients with genetically proven spinal and bulbar muscular atrophy (SBMA) was performed, with a comparison of their cognitive performance with that of 20 age- and education-matched control subjects. Neuropsychological assessment covered executive functioning, memory, and attentional control. The SBMA patients revealed deficits in verbal and non-verbal fluency as well as concept formation.

Long-term MRI and clinical follow-up of symptomatic and presymptomatic carriers of dysferlin gene mutations.

We report the results of a longitudinal study involving MRI and clinical follow-up in nine siblings from four families with Miyoshi myopathy (MM). All individuals carried pathogenic dysferlin gene (DYSF) mutations with six of them suffering from symptomatic disease and three being presymptomatic. In presymptomatic subjects, MRI was sensitive to detect alterations in muscle tissue years before disease onset.

Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET.

Improving binding potential analysis in [11C]raclopride PET studies using cluster analysis.

To calculate binding potentials (BP) in [11C]raclopride brain PET studies a reference tissue model is widely used. The aim of the present study was to improve the determination of time activity curves (TAC) of reference tissue regions using cluster analysis. In four patients with Huntington disease TACs of a cerebellar reference region were calculated either from manually placed circular ROIs within the cerebellum or by cluster analysis.

Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study.

Objectives: To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM).

Methods: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II).

X-linked bulbospinal neuronopathy: Kennedy disease.

Objective: To characterize the earliest symptoms of X-linked bulbospinal neuronopathy (Kennedy disease [KD]) during the course of the disease, including a definition of the age of onset.

Methods: We describe the earliest symptoms, signs on clinical investigation, electrophysiological and muscle biopsy specimen findings, and creatine kinase levels in 34 patients with KD. Correlations were made among the CAG-repeat length and clinical symptoms, age at onset, and the presence of electrophysiological and laboratory findings.

Proton magnetic resonance spectroscopy with metabolite nulling reveals regional differences of macromolecules in normal human brain.

Purpose: To quantify the macromolecular content in different anatomic brain regions and to evaluate an age dependency of the macromolecular concentrations.

Material And Methods: A short echo time Stimulated Echo Acquisition Mode (STEAM) sequence was used without and with inversion recovery metabolite nulling in 8-12 healthy volunteers. Quantitation was achieved by an extended LCModel, and macromolecular resonances at 0.

Proton MRS in Kennedy disease: absolute metabolite and macromolecular concentrations.

Purpose: To investigate whether glutamine and glutamate (Glx) were elevated in Kennedy Disease (KD), and whether pathological proteins were spectroscopically visible as altered macromolecular (MM) resonances.

Materials And Methods: Ten patients with KD and twelve healthy volunteers were investigated using a stimulated echo acquisition mode (STEAM) spectroscopy sequence with metabolite-nulling.

Results: The concentrations of Glx remained unchanged in KD.

Imaging and neurochemical markers for diagnosis and disease progression in ALS.

Based on the development of a transgenic animal model, an increasing number of experimental strategies have revealed the potential to modify the selective degeneration of motor neurons, a feature unique to motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The translation of this success into therapeutic effects in human diseases is a challenge of the future. For this purpose, tools must be developed which serve as diagnostic and surrogate markers for diagnosis and disease progression.

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis.

Objective: To evaluate proton magnetic resonance spectroscopy for detection and monitoring of upper motoneuron degeneration in patients with amyotrophic lateral sclerosis.

Methods: Seventy patients with amyotrophic lateral sclerosis according to the El Escorial criteria were compared with 48 healthy control subjects. Single-volume proton magnetic resonance spectroscopy (echo time, 272 milliseconds; repetition time, 2000 milliseconds) was performed in both motor cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr.

Proton magnetic resonance spectroscopy in Kennedy syndrome.

Objective: To seek regional metabolite abnormalities in patients with Kennedy disease (KD) using proton magnetic resonance spectroscopy.

Design: Nine patients with KD showing the typical phenotype without clinical signs of upper motor neuron involvement were compared with 17 male, age-matched, healthy control subjects. Relative metabolite concentrations for N-acetyl (NA) groups, choline-containing groups (Cho), phosphocreatine (Cr), and lactate (Lac) were determined in the brainstem and the motor region.

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements.

Objectives: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations.

Materials And Methods: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years.

[31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases].

Purpose: 31P-MR spectroscopy of skeletal muscle under exercise was used to obtain the range of normal variation and comparison was made for different neuromuscular diseases.

Methods: 41 examinations of 24 volunteers and 41 investigations in 35 patients were performed on 1.5 T MR systems (Gyroscan 515 und S15/ACSII, Philips).

ALS.

The cause of ALS is not known but there are four main hypotheses about its etiology. First, an excess of extracellular glutamate in the CNS of patients with ALS resulting from a defect in glutamate reuptake may have excitotoxic effects on motor neurons. Clinical trials suggest the antiglutamate agent riluzole improves survival of patients with the disease.

Muscle phosphofructokinase deficiency in two generations.

Phosphofructokinase (PFK) is the key regulatory enzyme of glycolysis. Patients lacking the muscular isoform of PFK typically present with myopathy and compensated hemolysis (glycogenosis type VII or Tarui's disease). Since 1965 about 30 cases of muscular PFK deficiency have been reported.