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Albert C Ludolph

Publications and source records attributed to Albert C Ludolph.

At least 19 recordsLinked to original sources
PubMed2006

Amygdala size in amyotrophic lateral sclerosis without dementia: an in vivo study using MRI volumetry.

BACKGROUND: Evidence for extra-motor involvement in non-demented patients with amyotrophic lateral sclerosis (ALS) has been provided by multiple studies, in particular neuropathological studies have demonstrated neuronal loss in the amygdala. The aim of this study was to investigate possible alterations of amygdala volumes in vivo. METHODS: Twenty-two moderately disabled patients with definite ALS without cognitive or behavioural deficits and 22 age-matched healthy controls were included. Amygdala and total brain volumes were measured by region-of-interest-based volumetry in 3-D MRI. RESULTS: A trend was observed with reduced amygdala size in the ALS group, since mean absolute and brain size-corrected amygdala volumes were 6.9% and 7.6% lower in the patient group compared to those in normal controls (P = 0.086 and P = 0.110), respectively. CONCLUSION: Volumetrically identifiable alterations of the amygdala can be mapped in vivo and may be associated with psychopathological findings in later stages of ALS.

Amygdala↗
PubMed2006

In vivo quantification of spinal and bulbar motor neuron degeneration in the G93A-SOD1 transgenic mouse model of ALS by T2 relaxation time and apparent diffusion coefficient.

Magnetic resonance imaging (MRI) has provided important information in characterizing amyotrophic lateral sclerosis (ALS) in humans and in animal models. A frequently used animal model to study mechanisms of pathogenesis and the efficacy of drugs in ALS is a transgenic mouse over-expressing the human mutated G93A-superoxide dismutase 1 (G93A-SOD1). In our study, we applied MRI to find suitable progression markers, which can be used to monitor the development of ALS and to evaluate therapeutic approaches at early stages of the disease. Therefore, we generated parameter maps of the spin-spin relaxation time (T2) and the apparent diffusion coefficient (ADC) starting at day 70 after birth, i.e., before motor scores decline around day 90. Depending on the progression of the disease, G93A-SOD1 mice showed significantly increased values of T2 in the brain stem motor nuclei Nc. V (trigeminal nucleus), VII (facial nucleus), and XII (hypoglossal nucleus), and spinal cord compared to non-transgenic wild-type mice and transgenic mice over-expressing the non-mutated wild-type human SOD1 (tg-SOD1). Similar effects in these motor nuclei were revealed by ADC mapping. Furthermore, in the upper spinal cord, a dorsal-ventral difference with significantly higher T2 values in the ventral part was demonstrated by T2 mapping. While both T2 and ADC might prove useful as progression markers and enable the longitudinal non-invasive evaluation of ALS in G93A-SOD1 mice, the potential is limited by age-dependent effects in case of ADC mapping.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Tau isoforms expression in transgenic mouse model of amyotrophic lateral sclerosis.

Tau is a protein involved in regulation of microtubule stability, axonal differentiation and transport. Alteration of retrograde transport may lead to motor neuron degeneration. Thus alternative mRNA splicing and expression of tau isoforms were studied in a transgenic mouse model harboring the human SOD1 G93A mutation. The studies were performed on cortex, hippocampus and spinal cord of 64- and 120-day-old animals (presymptomatic and symptomatic stage) and wild type controls. Exon 10 was found in all studied tissues. The 2N isoform containing exons 2 and 3 (+2+3) and the 1N (+2-3) predominated over the 0N (-2-3) in brain regions of the studied mice. The 2N expression was significantly lower in cortex and hippocampus of symptomatic animals compared to analogue control tissues. The decrease in 2N expression resulted in lower levels of total tau mRNA and tau protein. No changes in tau expression were observed in spinal cord of studied animals.

Alternative Splicing↗
PubMed2006

Primary progressive aphasia accompanied by environmental sound agnosia: a neuropsychological, MRI and PET study.

As part of the frontotemporal dementias, primary progressive aphasia (PPA) is typically characterized by nonfluent speech with paraphasias, but there is growing evidence that also a fluent variant of PPA exists. We describe a patient suffering from PPA who adds to the broad clinical spectrum of this disorder. Moreover, we report for the first time that PPA may be associated with severe impairment in meaningful nonverbal sound recognition (environmental sound agnosia). These neuropsychological findings were found to be associated with distinct focal alterations in functional and structural neuroimaging.

Aged↗
PubMed2006

Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice.

OBJECTIVE: The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD). METHODS: We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice. RESULTS: Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 microm Ca2+ than wild-type mitochondria. INTERPRETATION: Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.

Animals↗
PubMed2006

Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes.

We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each). They were also significantly higher in MSA than in PD and controls (P < 0.05 each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory-supported differential diagnosis of atypical parkinsonian syndromes.

Adult↗
PubMed2006

Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry.

The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

Adolescent↗
PubMed2005

Only subtle cognitive deficits in non-bulbar amyotrophic lateral sclerosis patients.

Neuropsychological investigations of amyotrophic sclerosis (ALS) patients revealed considerable discrepancies regarding neurocognitive functions. Some, but not all studies have suggested executive dysfunctioning and memory impairment, and there is a wide range of applied neuropsychological tests and results. In this study, we investigated the neuropsychological performance of 15 non-bulbar ALS patients, 14 patients with neuromuscular symptoms, and 15 healthy controls. To avoid confounding effects of motor disability, performance was assessed using exclusively motor-free tests of frontal lobe functioning (specific memory functions, conditional-associative learning, attention, and executive functions). ALS patients exhibited poorer performance in two conditions (semantic and alternating condition, respectively) of the Verbal Fluency Test, suggesting a subtle executive deficit. No deficits were found in tests of memory, conditional-associative learning, or attention. Assessed mood status was not related to neuropsychological performance. Verbal memory (CVLT) and verbal fluency (lexical condition) were positively associated with duration of disease. Our results support the view that there are only subtle cognitive deficits in ALS patients and we assume a possible effect of practice on cognitive tasks following reduced daily motor activity.

Aged↗
PubMed2005

Spastin related hereditary spastic paraplegia with dysplastic corpus callosum.

Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.

Adenosine Triphosphatases↗
PubMed2005

Frequency of a tau genotype in amyotrophic lateral sclerosis.

We investigated the susceptibility of the dinucleotide polymorphism A0 in the tau gene to amyotrophic lateral sclerosis (ALS). In 416 unrelated patients with ALS and 242 control subjects the A0/A0 genotype was not associated with the pooled sample of ALS cases. Subgroup analysis revealed that in sporadic ALS the A0 polymorphism was significantly overrepresented. There was no association of the A0/A0 genotype with the age and site of disease onset or the presence of dementia. The studied tau genotype may contribute to the multifactorial genetic background of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Emotional responding in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease, leaving the patient in a partially or completely deafferented state. In an explorative study, we investigated responses to visual socio-emotional stimuli in ALS patients. Pictures from the International Affective Picture System (IAPS) were verbally judged by 12 moderately affected ALS patients with a spinal onset and a slow progression and 18 age-matched controls, and data were compared with psychophysiological responses. Verbal emotional judgments of patients were more positive than ratings of controls. Regarding arousal, patients neutralized extreme pictures, in that they rated calm pictures as more exciting than controls and exciting pictures as more calm. These changes of emotional processing were unrelated to depression or frontal lobe dysfunction. There were no major differences between patients and controls concerning physiological responses to emotional stimuli. We conclude that emotional responses of ALS patients tend to be altered towards positive valence and towards a more balanced arousal state in early stages of the disease. These findings contradict assumptions of a generally negative impact of the disease on the emotional disposition and may indicate compensatory cognitive or neuroplastic changes.

Aged↗
PubMed2005

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit.

Amyotrophic lateral sclerosis (ALS) is a devastating disorder of the central nervous system in middle and old age that leads to progressive loss of spinal motoneurons. Transgenic mice overexpressing mutated human Cu(2+)/Zn(2+) superoxide dismutase 1 (SOD1) reproduce clinical features of the familial form of ALS. However, changes in SOD1 activity do not correlate with severity of motor decline in sporadic cases, indicating that targets unrelated to superoxide metabolism contribute to the pathogenesis of the disease. We show here that transgenic expression in mice of GluR-B(N)-containing L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptors with increased Ca(2+) permeability leads to late-onset degeneration of neurons in the spinal cord and decline of motor functions. Neuronal death progresses over the entire lifespan but manifests clinically in late adulthood, resembling the course of a slow neurodegenerative disorder. Additional transgenic expression of mutated human SOD1 accelerates disease progression, aggravates the severity of motor decline, and decreases survival. These observations link persistently elevated Ca(2+) influx through AMPA channels with progressive motor decline and late-onset degeneration of spinal motoneurons, indicating that functionally altered AMPA channels may be causally related to pathogenesis of sporadic ALS in humans.

Amyotrophic Lateral Sclerosis↗
PubMed2005

MR-pathologic comparison of the upper spinal cord in different motor neuron diseases.

This MRI study was performed to evaluate in vivo alterations of the spinal cord in defined subgroups of motor neuron diseases. Standard MRI examinations of the cervical and thoracic spinal cord in sporadic amyotrophic lateral sclerosis (ALS; n = 39), sporadic lower motor neuron disease (LMND; n = 19), Kennedy's disease (KD; n = 19) and a control group (n = 96) were analyzed with respect to spinal cord signal changes and the thickness of the spinal cord. No significant changes in thickness or signal alterations were observed when comparing ALS, LMND and control groups with one another. However, in KD patients significant upper spinal cord atrophy was detected at the cervical level as compared with all other groups. At the thoracic level, KD patients had significant upper cord atrophy as compared with controls and LMND. Marked atrophy of the upper spinal cord seems to be a feature of the KD-associated central-peripheral distal axonopathy.

Age of Onset↗
PubMed2005

Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD.

A heterozygous R1101K mutation of the p150 subunit of dynactin (DCTN1) is reported in a family with amyotrophic lateral sclerosis (ALS) and co-occurrence of frontotemporal dementia (FTD). Two members of our kindred were affected with motor neuron disease and two with dementia in an autosomal dominant pattern of inheritance. We excluded the involvement of the ALS and FTD-linked genes for copper/zinc superoxide dismutase (SOD1) and tau. The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis.

We present a 32-year-old Turkish male with juvenile amyotrophic lateral sclerosis 2 and a previously unrecognized homozygous deletion in exon 4 of the ALS2 gene (553delA). Disease progression is more rapid than in the ALS2 phenotype cases described to date. The patient's consanguineous parents carry the mutation in the heterozygous state as do his two unaffected brothers.

Adult↗
PubMed2005

On the decline and etiology of high-incidence motor system disease in West Papua (southwest New Guinea).

The etiology of a high-incidence focus of amyotrophic lateral sclerosis and parkinsonism-dementia (ALS/P-D) in south West Papua (Irian Jaya, Indonesia), first described in the 1960s and 1970s, has been attributed to mineral deficiencies, hyperparathyroidism, and metal neurotoxicity arising from reliance on drinking water obtained from springs and shallow wells. More recent visits (1987 and 1990) to the south West Papua focus of neurodegenerative disease cast doubt on this explanation by revealing changes in disease prevalence in communities with an unchanged water supply. These communities have experienced a dramatic decline in ALS and a reversal in the relative prevalence of ALS and parkinsonism. The extrapyramidal disorder can be distinguished from Parkinson disease by pyramidal features (and dementia) reminiscent of Guam P-D. Topical use of cycad seed (termed kurru) gametophyte to treat large skin lesions is advanced as a plausible but unproven etiologic factor. Medicinal use of untreated cycad seed (Cycas sp.) has also been linked with ALS foci in Japan (oral use) and Guam (topical use), with the additional consumption on Guam of food items prepared from Cycas sp. seed or animals that consume cycad seed components.

Amyotrophic Lateral Sclerosis↗