ABSTRACT To delineate possibly distinct cognitive impairment in patients with multiple system atr... more ABSTRACT To delineate possibly distinct cognitive impairment in patients with multiple system atrophy (MSA) of cerebellar (MSA-C) and striatonigral (MSA-P) predominance, we employed two experimental tasks sensitive to striatal lesions: the Weather-Prediction Task (WPT) and the Object Alternation Task (OAT). Only MSA-P (n = 10) patients showed reduced learning in the WPT and were impaired at maintaining the alternation rule in the OAT, compared to MSA-C (n = 10) and matched controls (n = 26). Both MSA-groups were impaired regarding digit span and verbal fluency.This distinct pattern of cognitive impairment reflects the prevailing involvement of striato-thalamo-cortical circuits in MSA-P patients and of cerebellar-prefrontal circuits in MSA-C patients. The specific cognitive impairments correspond to the type of motor predominance in MSA.
Apoptotic neuronal death is a key mechanism that regulates the elimination of neuronal precursor ... more Apoptotic neuronal death is a key mechanism that regulates the elimination of neuronal precursor cells during the development of the mammalian brain. The principal action of neurotrophins such as nerve growth factor is probably the suppression of the preexistent machinery of programmed cell death that is readily activated in neurons deprived of neurotrophins. Potassium-mediated neuronal depolarization prolongs neuronal survival in vitro and has become a major model of examining neuronal apoptosis. Apoptosis induced by potassium deprivation triggers a lethal cascade of events that includes specific RNA and protein synthesis, induction of interleukin 1-converting enzyme-like protease activity, and generation of free radicals. Neuronal susceptibility to apoptosis is also regulated by the expression of bcl-2 family proteins. Current research focuses on the significance of these findings for the premature death of adult neurons in human neurodegenerative diseases.
Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and re... more Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and rehabilitation. We examined the effect of stochastic WBV on ataxia in spinocerebellar ataxia types 1, 2, 3, and 6 (SCA 1, 2, 3 and 6) in a single-center double-blind sham-controlled study. Stochastic WBV was applied on four sequent days, each treatment consisting of five stimulus trains of 60-s duration at a frequency of 6.5 Hz and 60-s resting time between stimuli (n = 17). Patients allocated to the sham group received the same treatment with 1 Hz (n = 15). All patients were rated at baseline and after the last treatment using clinical scores (SARA, SCAFI, and INAS). After treatment, we found significant improvements of gait, posture, and speed of speech in the verum group while limb kinetics and ataxia of speech did not respond. Stochastic WBV might act on proprioceptive mechanisms and could also stimulate non-cerebellar/compensatory mechanisms. But at present, the involved cellular mechanism and the presumed neuronal loops cannot be deciphered. Thus, future work is needed to understand the mechanisms of whole body vibration. Finally, the use of stochastic WBV could provide a supplementation to treat ataxia in SCA and can be combined with physiotherapeutical motor training.
A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor... more A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor (ET) has been postulated. Recently, an association between the dopamine D(3) receptor (DRD3) Ser9Gly polymorphism and ET has been reported. We studied whether PD tremor is influenced by Ser9Gly in a genetic association study based on the gene bank of the German Competence Network on Parkinson's disease. The study included analyses of motor predominance (mixed, hypokinetic, and tremor), and tremor type (resting, postural, and action). We did not identify any effect of DRD3 Ser9Gly on tremor in PD, even when regarding various symptom combinations to avoid missing a weak effect on the phenotype. Additional studies incorporating symptoms at disease onset, and grading of tremor response to dopaminergic therapy, are warranted.
The action of d-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB re... more The action of d-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB receptor agonist, was investigated in two experimental models: (1) the pathologically increased muscle tone of the gastrocnemius muscle in spastic mutant Han-Wistar rats and (2) the Hoffmann (H)-reflex recorded from plantar foot muscles after electrical stimulation of the tibial nerve in barbiturate (60 mg/kg) anaesthetized
OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA)... more OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. DESIGN--Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. SETTING--Referral center. PATIENTS--Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. RESULTS--Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. CONCLUSIONS--Data suggest that LOFA may also result from mutation within the FRDA locus.
ABSTRACT To delineate possibly distinct cognitive impairment in patients with multiple system atr... more ABSTRACT To delineate possibly distinct cognitive impairment in patients with multiple system atrophy (MSA) of cerebellar (MSA-C) and striatonigral (MSA-P) predominance, we employed two experimental tasks sensitive to striatal lesions: the Weather-Prediction Task (WPT) and the Object Alternation Task (OAT). Only MSA-P (n = 10) patients showed reduced learning in the WPT and were impaired at maintaining the alternation rule in the OAT, compared to MSA-C (n = 10) and matched controls (n = 26). Both MSA-groups were impaired regarding digit span and verbal fluency.This distinct pattern of cognitive impairment reflects the prevailing involvement of striato-thalamo-cortical circuits in MSA-P patients and of cerebellar-prefrontal circuits in MSA-C patients. The specific cognitive impairments correspond to the type of motor predominance in MSA.
Apoptotic neuronal death is a key mechanism that regulates the elimination of neuronal precursor ... more Apoptotic neuronal death is a key mechanism that regulates the elimination of neuronal precursor cells during the development of the mammalian brain. The principal action of neurotrophins such as nerve growth factor is probably the suppression of the preexistent machinery of programmed cell death that is readily activated in neurons deprived of neurotrophins. Potassium-mediated neuronal depolarization prolongs neuronal survival in vitro and has become a major model of examining neuronal apoptosis. Apoptosis induced by potassium deprivation triggers a lethal cascade of events that includes specific RNA and protein synthesis, induction of interleukin 1-converting enzyme-like protease activity, and generation of free radicals. Neuronal susceptibility to apoptosis is also regulated by the expression of bcl-2 family proteins. Current research focuses on the significance of these findings for the premature death of adult neurons in human neurodegenerative diseases.
Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and re... more Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and rehabilitation. We examined the effect of stochastic WBV on ataxia in spinocerebellar ataxia types 1, 2, 3, and 6 (SCA 1, 2, 3 and 6) in a single-center double-blind sham-controlled study. Stochastic WBV was applied on four sequent days, each treatment consisting of five stimulus trains of 60-s duration at a frequency of 6.5 Hz and 60-s resting time between stimuli (n = 17). Patients allocated to the sham group received the same treatment with 1 Hz (n = 15). All patients were rated at baseline and after the last treatment using clinical scores (SARA, SCAFI, and INAS). After treatment, we found significant improvements of gait, posture, and speed of speech in the verum group while limb kinetics and ataxia of speech did not respond. Stochastic WBV might act on proprioceptive mechanisms and could also stimulate non-cerebellar/compensatory mechanisms. But at present, the involved cellular mechanism and the presumed neuronal loops cannot be deciphered. Thus, future work is needed to understand the mechanisms of whole body vibration. Finally, the use of stochastic WBV could provide a supplementation to treat ataxia in SCA and can be combined with physiotherapeutical motor training.
A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor... more A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor (ET) has been postulated. Recently, an association between the dopamine D(3) receptor (DRD3) Ser9Gly polymorphism and ET has been reported. We studied whether PD tremor is influenced by Ser9Gly in a genetic association study based on the gene bank of the German Competence Network on Parkinson's disease. The study included analyses of motor predominance (mixed, hypokinetic, and tremor), and tremor type (resting, postural, and action). We did not identify any effect of DRD3 Ser9Gly on tremor in PD, even when regarding various symptom combinations to avoid missing a weak effect on the phenotype. Additional studies incorporating symptoms at disease onset, and grading of tremor response to dopaminergic therapy, are warranted.
The action of d-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB re... more The action of d-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB receptor agonist, was investigated in two experimental models: (1) the pathologically increased muscle tone of the gastrocnemius muscle in spastic mutant Han-Wistar rats and (2) the Hoffmann (H)-reflex recorded from plantar foot muscles after electrical stimulation of the tibial nerve in barbiturate (60 mg/kg) anaesthetized
OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA)... more OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. DESIGN--Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. SETTING--Referral center. PATIENTS--Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. RESULTS--Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. CONCLUSIONS--Data suggest that LOFA may also result from mutation within the FRDA locus.
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