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Klaus Seppi

Publications and source records attributed to Klaus Seppi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Progression of parkinsonism in multiple system atrophy.

BACKGROUND: Progression of parkinsonian motor impairment is usually rapid and relentless in multiple system atrophy (MSA). However, it may also be subject to considerable variation. Prospective natural history studies using validated rating scales are required to accurately determine the progression of parkinsonism in MSA. OBJECTIVE: To assess the progression of parkinsonism in patients with the Parkinson variant of MSA. METHODS: Parkinsonian motor impairment was assessed on regular therapy at two time points (mean follow-up 11.8 months, SD 1.4) using the Hoehn and Yahr scale (H&Y), the Schwab and England ADL scale (SES) and the motor examination section of the UPDRS (UPDRS-III) in 38 patients with clinically probable MSA-P. RESULTS: We examined 38 patients with probable MSA-P (mean age 63.2 years, SD 7.4; mean disease duration 4.1 years, SD 3.0). The mean difference of UPDRS-III between baseline and follow-up was 10.8 (95% CI 8.6-12.9), consistent with an average annual 28.3 % increase of UPDRS-III baseline scores. Several variables were associated with faster progression of parkinsonism including low baseline global motor disability as assessed by H&Y and SES, low baseline UPDRS-III score, and short disease duration. UPDRS-III progression was unrelated to gender, age at symptom onset, and age at baseline visit. CONCLUSION: This is the first observational study on UPDRS rates of decline in MSA. The observed 28.6% annual increase of UPDRS-III scores illustrates the rapid progression of motor impairment in MSA. Furthermore, motor progression appeared to be accelerated during the early disease stages. Our data allow sample size calculations that may be helpful for the planning of future therapeutic trials.

Age of Onset↗
PubMed2005

Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study.

BACKGROUND: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. METHODS: As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. FINDINGS: The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.

Age Factors↗
PubMed2005

An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism.

PURPOSE OF REVIEW: The clinical differentiation between Parkinson's disease and atypical parkinsonian disorders (APD) remains a challenge for every neurologist. Conventional magnetic resonance imaging (MRI) and different advanced MRI techniques offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the recent literature on the role of conventional and advanced MRI techniques in the differential diagnosis of neurodegenerative parkinsonian disorders. RECENT FINDINGS: An important role of MRI is the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and different advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and magnetic resonance volumetry (MRV) have been found to show abnormalities in the substantia nigra and basal ganglia, especially in APD. Recent studies using MRV, MTI, DWI and 1H-MRS to discriminate Parkinson's disease from APD are discussed extensively. SUMMARY: Research findings suggest that novel MRI techniques such as MTI, DWI and MRV have superior sensitivity compared to conventional MRI in detecting abnormal features in neurodegenerative parkinsonian disorders. Whether these techniques will emerge as standard investigations in the work-up of patients presenting with parkinsonism requires further prospective magnetic resonance studies during early disease stages.

Diagnosis, Differential↗
PubMed2005

Computerized tremor analysis of valproate-induced tremor: a comparative study of controlled-release versus conventional valproate.

PURPOSE: Valproate (VPA) induces postural tremor in 6-45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. METHODS: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n=10) or CR-VPA (n=8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of >or=8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. RESULTS: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. CONCLUSIONS: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak-trough variation with VPA than with CR-VPA.

Activities of Daily Living↗
PubMed2004

Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population.

AIMS: In diabetic patients, increased urinary albumin excretion (UAE), termed microalbuminuria when in the range between 30 and 300 mg/dL per day, is associated with a higher risk of atherosclerosis and its complications. Whether or not this notion applies to the general population is a matter of ongoing controversy because none of the few previous investigations among non-diabetics strictly represent the general community. METHODS AND RESULTS: Urinary albumin-to-creatinine ratio (uACR), a measure of UAE, was assessed from overnight spot urine samples in a population-based cohort of 684 individuals. The ratio was significantly related to age, gender, blood pressure, diabetes, markers of systemic inflammation, liver enzymes, and parathyroid hormone levels (P<0.001 each). Moreover, uACR emerged as a highly significant risk predictor of carotid and femoral artery atherosclerosis in the general community and the non-diabetic subpopulation alike (age/sex-adjusted P<0.001 each). In multivariable logistic regression analyses, odds ratios (95% CI) of carotid and femoral atherosclerosis amounted to 1.28 (1.01-1.61) and 1.44 (1.15-1.81) for a one unit increase in log(e)-transformed uACR (P=0.040 and 0.002). Corresponding odds ratios in non-diabetic subjects were 1.41 (1.09-1.84) and 1.54 (1.19-1.99) (P=0.010 and 0.001). Multivariable linear regression analyses yielded significant, or near significant, relations with carotid and femoral artery intima-media thickness and atherosclerosis scores (P=0.058-0.001). CONCLUSION: The uACR is significantly and independently associated with the presence and severity of atherosclerosis in the general population. The relation obtained was of a dose-response type and extended to levels far below what is termed microalbuminuria. The novel aspects of our study are its focus on various vascular territories and representivity of the general healthy population.

Aged↗
PubMed2004

Basal forebrain atrophy is a distinctive pattern in dementia with Lewy bodies.

We determined brain atrophy patterns in dementia with Lewy bodies and Alzheimer's disease using voxel-based morphometry, an indirect volumetry. Ten patients with dementia with Lewy bodies, 10 patients with Alzheimer's disease and 10 controls were included. All groups were matched for age; sex and global differences in voxel intensities were included as confounding covariates. We observed basal forebrain atrophy discriminating dementia with Lewy bodies from Alzheimer's disease. Compared to controls, atrophy of lateral prefrontal cortex and left premotor cortex was seen in dementia with Lewy bodies whereas atrophy of the medial temporal cortex, posterior parietal cortex, thalamus and temporo-occipital areas was observed in Alzheimer's disease. Atrophy of insular cortex was found in both patient groups.

Aged↗
PubMed2004

Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study.

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and beta-CIT as well as IBZM. Age-matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of beta-CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.

Adult↗
PubMed2004

Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease.

Both dopamine D2 receptor (D2R) binding single-photon emission computed tomography (SPECT) with [123I]iodobenzamide (IBZM) and diffusion-weighted imaging (DWI) have been shown to contribute to the differential diagnosis of patients with the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). We aimed to compare these two routinely available functional imaging modalities in differentiating patients with MSA-P from PD. For this purpose, results obtained by DWI and IBZM-SPECT were intraindividually compared in a cross-sectional study of 15 MSA-P and 17 PD patients matched for age and disease duration. The activity ratios of striatal to frontal cortex uptake (S/FC ratio) were used as a semiquantitative measure of the relative density of basal ganglia dopamine receptors labeled by IBZM. Regional apparent diffusion coefficients (rADC) were determined in the striatum. MSA-P patients had significantly lower S/FC ratios and significantly higher striatal rADCs than both PD patients and healthy volunteers. There were no significant differences in S/FC ratios and striatal rADC between PD patients and healthy volunteers. Sensitivity of IBZM-SPECT versus DWI for the differentiation of MSA-P from PD was 80% versus 93%, specificity 71% versus 100%, the predictive accuracy 75% versus 97%, the positive predictive value 71% versus 100%, and the negative predictive value 80% versus 94%. Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM-SPECT in the differential diagnosis of MSA-P versus PD.

Basal Ganglia↗
PubMed2004

Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS).

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale-UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-I (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k(w) = 0.6-0.8) to excellent (k(w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.

Activities of Daily Living↗
PubMed2004

Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease.

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinson's disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.

Aged↗
PubMed2003

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.

Aged↗
PubMed2003

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.

Aged↗
PubMed2003

Auditory startle response in cervical dystonia.

The excitability of brainstem neurons is abnormally enhanced in patients with cervical dystonia (CD), but the extend of such abnormality is not known. We examined whether patients with CD showed abnormalities in the auditory startle response (ASR), a brainstem reflex elicited by an unexpected loud stimulus. Thirteen patients with CD were investigated 3 months after botulinum toxin treatment. Thirteen healthy volunteers served as controls. ASRs were elicited by binaural high-intensity auditory stimuli. Reflex electromyographic (EMG) activity was recorded simultaneously with surface electrodes bilaterally from masseter, orbicularis oculi, sternocleidomastoid, and biceps brachii muscles. We found that ASR onset latencies were similar for patients and controls. CD patients had significantly lower ASR probabilities than controls (P = 0.007). ASR area under the curve was significantly smaller in CD patients (P = 0.017). Similar to controls, patients showed a significant habituation of ASR (P < 0.001, each); however, CD patients showed a prolonged tonic or phasic EMG activity after the initial ASR that was not observed in controls. Normal latencies and recruitment pattern indicate a preserved organization of intrinsic neural pathways mediating ASR in CD. Reduced ASR probability and magnitude as well as prolonged EMG activity after the proper startle response corroborate and extend previous findings on brainstem dysfunction in CD.

Adult↗
PubMed2003

Serial contrast-enhanced magnetic resonance imaging and spectroscopic imaging of acute multiple sclerosis lesions under high-dose methylprednisolone therapy.

To evaluate biochemical changes in contrast-enhancing multiple sclerosis (MS) lesions, we examined 14 patients with relapsing-remitting MS at acute clinical exacerbation with the help of contrast-enhanced magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopic imaging (1H MRSI). Using a 1.5-tesla MR system (Magnetom Vision, Siemens, Germany), we followed 29 contrast-enhancing and 24 nonenhancing MS lesions as well as normal-appearing white matter (NAWM) before and during high-dose methylprednisolone (HDMP) therapy. Metabolite ratios of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) were calculated. A transient decrease in contrast enhancement under HDMP therapy was observed. Both groups of MS lesions showed significantly decreased NAA to Cr ratios compared to NAWM with no changes in time. Baseline 1H MRSI revealed significantly increased Cho to Cr ratios in the contrast-enhancing MS lesions (1.13 +/- 0.25) compared to the nonenhancing MS lesions (0.85 +/- 0.26, P < 0.001) and NAWM (0.97 +/- 0.22, P = 0.015). Both the contrast-enhancing and the nonenhancing MS lesions exhibited a significant increase in Cho to Cr ratios from the second to the third 1H MRSI. We identified resonances of lactate in both groups of MS lesions and NAWM without any significant group differences or changes over time. 1H MRSI provides additional information that help to estimate macrophages' activity, cell membrane activation, and neuronal impairment within MS lesions. We believe that combined contrast-enhanced MRI and 1H MRSI may help to further investigate inflammatory processes within active MS lesions and should be employed more frequently to the research on therapy effects in MS.

Acute Disease↗
PubMed2003

Exaggerated auditory startle responses in multiple system atrophy: a comparative study of parkinson and cerebellar subtypes.

OBJECTIVE: Auditory startle responses (ASRs) have recently been reported to be exaggerated in cranial and peripheral nerve supplied muscles of patients with multiple system atrophy (MSA). ASRs displayed increased probability, amplitude and duration, shorter onset latency, and reduced habituation in comparison with healthy subjects. In order to investigate whether certain ASR features may differentiate MSA subtypes, the authors studied ASRs in 21 MSA patients (olivopontocerebellar type, MSA-C: n = 8, striatonigral type, MSA-P: n = 13), and 17 age-matched normal controls. METHODS: ASRs were elicited by binaural high-intensity auditory stimuli which differed randomly in tonal frequency and intensity (250 Hz, 90 db; 500 Hz, 105 db; 750 Hz, 105 db; 1000 Hz, 110 db normal hearing level), presented through tubal insert phones. Reflex electromyographic activity was simultaneously recorded with surface electrodes from masseter, orbicularis oculi, sternocleidomastoid, biceps brachii, abductor pollicis brevis, rectus femoris, tibialis anterior, and soleus muscles. RESULTS: Eighteen MSA patients (86%) had exaggerated ASRs as compared to normal subjects. At group level, indices of ASR disinhibition including increased ASR probability (in extremity muscles), shortened onset latency, and enlarged response magnitude were significantly more marked in MSA-P as compared to MSA-C patients. ASR probability showed habituation in normal subjects, less in MSA-P. and none in MSA-C patients. Three MSA-patients had no ASRs except in orbicularis oculi muscle. CONCLUSIONS: Although absent ASRs may occur in some MSA patients, most of them exhibit exaggerated ASRs. This finding may reflect disinhibition of lower brainstem nuclei due to the degenerative disorder. ASRs were significantly more disinhibited in MSA-P versus MSA-C. suggesting involvement of different neural structures in the two MSA-subtypes.

Acoustic Stimulation↗