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Klinika Neurologii Instytutu Neurologii
Collegium Medicum Uniwersytetu Jagiellonskiego ul. Botaniczna
3, 31-503 Krakow.
Autonomic dysfunction in idiopathic
Parkinson's disease (IPD) is common and occurs in 70% of
patients. The aim of the study was to evaluate autonomic
mechanisms regulating cardiovascular system during tilt
up test in IPD patients. The examination was performed in
35 patients with IPD (26 male and 9 female, mean age 60
+/- 9) and matched with gender and age 35 controls subjects
(healthy volunteers, mean age 59 +/- 9). Patients were divided
into two groups: group I--early stage of disease (n = 20)
and group II--advanced stage of the disease (n = 15). The
tilt test in IPD patients and in the control group lasted
3 minutes. In both groups tilt test was performed with a
head-up tilt position of 60 degrees (tilt table Manumed,
Netherlands). In both groups 30:15 ratio were lower than
in the control group 1.03 +/- 0.08, 0.97 +/- 0.09 v 1.23
+/- 0.1 respectively (p = 0.001). In the second group the
heart-rate variability after the tilt test was lower 6.2
+/- 4/min than in the control group 10.2 +/- +/- 1.9/min
and group I 8.8 +/- 4/min (p = 0.01). The decrease of the
systolic pressure in response to the tilt test was the highest
in group II (16 +/- 14 mmHg), in the control group 4 +/-
7 mmHg, in group I 13 +/- 11 mmHg (p = 0.001). Ortostatic
hypotension in IPD occurs in 36% of patients in an early
stage and in 47% of patients in an advanced stage of the
disease. The use of the tilt test enables the early diagnosis
of cardiovascular disturbances in IPD.
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Nervenklinik und Poliklinik,Neurologie,
Universitatskliniken des Saarlandes,Homburg/Saar.
Patients with idiopathic Parkinson's
disease display a 60% degeneration of the nigrostriatal
neurons before motor symptoms have progressed enough to
allow clinical diagnosis. It is clear that any neuroprotective
therapy starting at such a late stage can have no substantial
effect on the disease progression. Therefore, earlier diagnosis
must be the goal of future research,when at most mild motor
or non-motor symptoms are present or when only risk factors
can be identified. Evidence of various gene mutations associated
with idiopathic Parkinsonism raise the hope that these or
other biological markers will allow earlier identification
of patients at risk. A possibly significant vulnerability
factor for developing Parkinson's disease can also be demonstrated
by means of transcranial sonography. Since the individual
tests are not sufficiently specific or sensitive, a gradual,
precise, and inexpensive battery of tests needs to be developed
for the successful identification of a risk group for this
disease. The extent of damage to the dopaminergic system
in these patients can be quantified using nuclear techniques.
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Divisione di Medicina Interna, Ospedale
di Circolo, Universita dell'Insubria, Viale Borri 57, 21100
Varese, Italy.
BACKGROUND: Different coagulation
abnormalities according to stroke subtypes have been reported.
We have assessed the clinical utility of D-dimer, a product
of fibrin degradation, in the early diagnosis of stroke
subtypes. METHODS: Patients hospitalized after an acute
ischemic cerebrovascular event underwent D-dimer assay (STA
Liatest D-Dimer) (reference level, <0.50 micro g/mL)
on days 1, 6 +/- 1, and 12 +/- 1 and were studied to identify
stroke subtypes. RESULTS: We included 126 patients (mean
age, 75.5 years) and 63 age-matched control subjects. Stroke
subtypes were cardioembolic in 34 patients (27%), atherothrombotic
in 34 (27%), lacunar in 31 (25%), and unknown in 27 (21%).
At all 3 measurements, D-dimer levels were significantly
higher in the cardioembolic group (mean +/- SEM, 2.96 +/-
0.51, 2.58 +/- 0.40, and 3.79 +/- 0.30 micro g/mL, respectively)
than in the atherothrombotic (1.34 +/- 0.21, 1.53 +/- 0.26,
and 2.91 +/- 0.23 micro g/mL, respectively) (P<.05) and
lacunar (0.67 +/- 0.08, 0.72 +/- 0.15, and 0.64 +/- 0.06
micro g/mL, respectively) groups (P<.01). The difference
was also significant between the latter 2 groups (P<.01).
We found no difference between the lacunar group and controls
(0.53 +/- 0.14 micro g/mL). According to day 1 measurements,
the optimal cutoff point for predicting cardioembolic stroke
was 2.00 micro g/mL, resulting in a specificity of 93.2%
and in a sensitivity of 59.3%. For predicting lacunar stroke,
the cutoff point was 0.54 micro g/mL, with a specificity
of 96.2% and a sensitivity of 61.3%. CONCLUSION: The increasing
use of the D-dimer assay in clinical practice could be extended
to patients presenting with acute cerebrovascular ischemic
events to help predict stroke subtype.
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Research Institute Neurosciences Vrije
Universiteit, Department of Neurology, Vrije Universiteit
Medical Center, Amsterdam, The Netherlands.
Olfactory dysfunction is a common
finding in patients with Parkinson's disease (PD). As most
studies reported on odor identification in more advanced
and treated PD, we administered an odor detection, discrimination,
and identification test to a heterogeneous, partly de novo,
group of patients. Forty-one non-demented PD patients, 24
of whom had untreated early PD, and 18 healthy controls,
were examined. Odor identification and discrimination data
were corrected for odor detection scores. PD patients scored
significantly lower on all olfactory tests. Interestingly,
the subgroup of de novo patients with early PD also showed
significant olfactory disturbances compared with healthy
subjects. Within the PD group, using multiple regression
analysis, we found a significant, negative correlation between
odor discrimination measures and disease The present study
is the first to describe decreased performance of PD patients
on odor discrimination, in addition to the already well-established
deficits in odor detection and identification. Furthermore,
odor discrimination measures were related to disease severity,
possibly indicating that at least some aspects of olfactory
dysfunction in PD may be secondary to ongoing degenerative
processes in PD. As significant olfactory impairments were
found in early, de novo PD, olfactory tests may be useful
in the early diagnosis of PD.
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Department of Neurology, University
of Saarland, Gebaude 90, 66421 Homburg/Saar, Germany.
In idiopathic Parkinson's disease
(IPD) approximately 60 % of the nigrostriatal neurons of
the substantia nigra (SN) are degenerated before neurologists
can establish the diagnosis according to the widely accepted
clinical diagnostic criteria. It is conceivable that neuroprotective
therapy starting at such an 'advanced stage' of the disease
will fail to stop the degenerative process. Therefore, the
identification of patients at risk and at earlier stages
of the disease appears to be essential for any successful
neuroprotection. The discovery of several genetic mutations
associated with IPD raises the possibility that these, or
other biomarkers, of the disease may help to identify persons
at risk of IPD. Transcranial ultrasound have shown susceptibility
factors for IPD related to an increased iron load of the
substantia nigra. In the early clinical phase, a number
of motor and particularly non-motor signs emerge, which
can be identified by the patients and physicians years before
the diagnosis is made, notably olfactory dysfunction, depression,
or 'soft' motor signs such as changes in handwriting, speech
or reduced ambulatory arm motion. These signs of the early,
prediagnostic phase of IPD can be detected by inexpensive
and easy-to-administer tests. As one single instrument will
not be sensitive enough, a battery of tests has to be composed
measuring independent parameters of the incipient disease.
Subjects with abnormal findings in this test battery should
than be submitted to nuclear medicine examinations to quantify
the extent of dopaminergic injury and to reach the goal
of a reliable, early diagnosis.
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MRC Cyclotron Unit, Hammersmith Hospitals,
London, United Kingdom.
Current accepted clinical criteria
for the diagnosis of Parkinson's disease (PD) provide high
sensitivity for detecting parkinsonism but generally show
poor specificity for identifying brainstem Lewy body disease.
Biochemical markers that can be used to reliably diagnose
clinical and preclinical PD have thus far been sought unsuccessfully.
It is now known that some PD kindreds have a mutation of
the alpha-synuclein gene, but this cannot be used as a genetic
marker for most familial and sporadic cases. Functional
imaging provides a means of discriminating typical from
atypical PD, revealing characteristic patterns of loss of
dopaminergic function. In addition, PET and SPECT show preserved
levels of striatal metabolism and dopamine receptor binding
in PD, whereas levels are reduced in the atypical variants.
[18F]Dopa PET can also detect preclinical PD. In one series
there was a reported 40% prevalence of preclinical dopaminergic
dysfunction in asymptomatic adult relatives of familial
PD patients. Finally, PET and SPECT can both be used to
follow PD progression objectively. Such studies suggest
an annual 4 to 12% loss of dopamine terminal function in
early PD and a preclinical disease window of only a few
years. In the future, functional imaging is likely to play
an increasingly important role in assessing the efficacy
of putative neuroprotective agents.
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Department of Neurology, North Shore
University Hospital/Cornell University Medical College,
Manhasset, NY 11030, USA.
Early-stage Parkinson's disease (EPD)
is often clinically asymmetric. We used 18F-fluorodeoxyglucose
(FDG) and PET to assess whether EPD can be detected by a
characteristic pattern of regional metabolic asymmetry.
To identify this pattern, we studied 10 EPD (Hoehn and Yahr
stage I) patients (mean age 61.1 +/- 11.1 years) using 18F-FDG
and PET to calculate regional metabolic rates for glucose.
The scaled subprofile model (SSM) was applied to metabolic
asymmetry measurements for the combined group of EPD patients
and normal subjects to identify a specific covariation pattern
that discriminated EPD patients from normal subjects. To
determine whether this pattern could be used diagnostically,
we studied a subsequent group of five presumptive EPD patients
(mean age 50.9 +/- 18.3), five normal subjects (mean age
44.6 +/- 15.3), and nine patients with atypical drug-resistant
early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0).
In each member of this prospective cohort, we calculated
the expression of the EPD-related covariation pattern (subject
scores) on a case-by-case basis. We also studied 11 of the
EPD patients, five patients with APD, and 10 normal subjects
with 18F-fluorodopa (FDOPA) and PET to measure presynaptic
nigrostriatal dopaminergic function, and we assessed the
accuracy of differential diagnosis with both PET methods
using discrimination analysis. SSM analysis disclosed a
significant topographic contrast profile characterized by
covariate basal ganglia and thalamic asymmetries. Subject
scores for this profile accurately discriminated EPD patients
from normal subjects and APD patients (p < 0.0001). Group
assignments into the normal or parkinsonian categories with
FDG/PET were comparable to those achieved with FDOPA/PET,
although APD and EPD patients were not differentiable by
the latter method. Metabolic brain imaging with FDG/PET
may be useful in the differential diagnosis of EPD.
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MRC Cyclotron Unit, Hammersmith Hospital,
London, U.K.
A number of neurodegenerative diseases
can manifest as parkinsonian disorders. Structural imaging,
such as CT and MRI, is of limited value for differentiating
these diseases. PET can demonstrate the selective patterns
of disruption of regional cerebral metabolism and neurotransmitter
systems associated with subcortical degenerations, such
as Parkinson's disease, striatonigral degeneration, progressive
supranuclear palsy, and corticobasal degeneration. It can
also determine, where underlying Parkinson's disease may
be suspected, whether nigral dysfunction is present in patients
with isolated tremor or drug-associated rigidity. Finally,
PET can detect the presence of subclinical disruption of
the dopaminergic system in at-risk subjects, such as relatives
of patients with Parkinson's disease, or subjects exposed
to nigral toxins, such as MPTP. With the advent of putative
neuroprotective agents for Parkinson's disease, PET can
help identify patients with early disease who might benefit
from therapy with these agents and monitor their disease
progression.
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Department of Pharmacology, University
of Gothenburg, Sweden.
This paper is a preliminary report
of work aiming to elucidate the possible use of 5-S-cysteinyl
metabolites of catechols in the cerebrospinal fluid as markers
in the early diagnosis of Parkinson's disease (PD). The
rationale for this approach is the hypothesis that this
disorder is caused by a failure of antioxidative mechanisms
to prevent the excessive autoxidation of dopamine and other
catechols that yields highly reactive and cytotoxic semiquinones
and quinones. 5-S-cysteinyl adducts of these quinones have
been detected in human brains, analyzed postmortem, and
appear to be formed at an increased rate in elderly individuals,
who show an increased loss of dopaminergic neurons.
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Gertrudis-Klinik Biskirchen, Parkinson-Zentrum.
Parkinson's disease is a chronic-progressive
neuro-degenerative syndrome, which should be diagnosed as
early as possible because of the therapeutic success in
the beginning. Knowing the initial symptoms and using modern
technical devices like SPECT and PET we shall be able to
influence the course and the prognosis of the disease positively.
The application of a current combined drug-therapy and in
addition physiotherapy, speech-therapy and psychotherapy
enable us to provide quality of life or to restore it. Repeated
treatments in Parkinson medical centers intensify the efficacy
of therapeutic efforts. Nevertheless even in early stages
patients and physicians can be confronted with social medical
problems like defining the degree of disability or the time
for receiving a pension. The knowledge of specific disease-related
findings will help to judge all these problems in accordance
with the needs of the patients.
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