The role of imaging in staging and monitoring testicular cancer.

The prognosis for testicular cancer is excellent, with a 5-year survival rate greater than 95%. Patients affected can therefore expect to be cured after treatment. Successful treatment requires assessment of the condition at the various stages of its management. Imaging plays a major role in initial analysis of the lymphatic extension and in looking for metastases. It is essential for evaluating the response to treatment and during follow-up after treatment. CT is the most commonly used imaging method in this context, but the role of PET is currently developing. The purpose of this paper is to review the role of the imaging methods commonly used in the management of testicular cancer.

[Contribution of lymphoscintigraphy in the exploration of lymphedema in children]. / Intérêt de la lymphoscintigraphie dans l'exploration des lymphoedèmes de l'enfant.

OBJECTIVES: The objectives of this work were a) to assess the feasibility of lymphoscintigraphy in very young children, and b) to assess its usefulness in understanding the underlying pathophysiology. PATIENTS AND METHODS: Forty-one children (age range 3 months-16 years) with primary lymphedema of the lower and/or upper limbs underwent lymphosinctigraphy using 99mTC-labeled colloid (Nanocis or Nanocol) injected subcutaneous at the foot and/or hand level. Recording time, which depended on the child's age, included at least static images during the thirty minutes following injection and four hours later. RESULTS: Abnormal activity of the lymph collectors, nodes, and interstitial space were analyzed according to age (> or < 2 years). Abnormal findings were classed as simple hypoplasia (n=18) or other type of lymph disease: diffuse lymphatic dysplasia (n=6), mixed vascular dysmorphism (n=5), amniotic bride disease (n=1), and hypoplasia revealed by occurrence of a minor factor (n=11). These observations demonstrate the role of lymphoscintigraphy in the diagnosis and prognostic evaluation of lymphedema in children. CONCLUSION: Lymphoscintigraphy is a useful technique for very young children with lymphedema providing further information contributing to overall exploration.

The value of immunoscintigraphy in the detection of recurrent colorectal cancer.

The aim of this prospective study was to determine whether anti-carcinoembryonic antigen (anti-CEA) scintigraphy is a useful additional technique in the diagnosis recurrence of colorectal cancer. Forty patients with suspected recurrence of colorectal cancer, underwent immunoscintigraphy (IS) and helical computed tomography (CT) in the 2 weeks before surgery. Surgical findings were used to evaluate the performance of the imaging techniques. Suspected areas on IS and CT were systematically explored. Helical CT was found to be superior to IS for the liver, the sensitivity and specificity of CT being 100% and 90%, respectively, vs 53% and 100% for IS. However, IS was better than CT for the detection of extra-hepatic abdominal recurrence: sensitivity and specificity of IS were 100 and 82% respectively vs 33 and 82% for CT. Seven cases of peritoneal carcinomatosis were overlooked by helical CT. Our results indicate that IS improves detection of extra-hepatic abdominal recurrence of colorectal cancer. Immunoscintigraphy is valuable as a guide to the treatment strategy and operative procedures.

Quantitative analysis of striatal dopamine D2 receptors with 123 I-iodolisuride SPECT in degenerative extrapyramidal diseases.

123I-Iodolisuride has high specific affinity for binding on dopamine D2 receptors in the striatum and has been used in a few single photon emission computed tomography (SPECT) studies of extrapyramidal disorders. The diagnosis of Parkinson's disease (PD) is very difficult in the first 5 years of evolution, with 15-25% false positive diagnoses. The aim of this study was therefore to determine the value of iodolisuride SPECT in discriminating Parkinson's from the most frequent Parkinson-plus syndromes (PPS). Seventeen patients with an extrapyramidal syndrome had a SPECT examination 1 h after injection of 180-185 MBq of 123I-iodolisuride. They were followed under dopaminergic treatment for at least 2 years. After 2 years, they were separated in two groups according to specific clinical criteria and sensitivity to dopaminergic treatment: nine patients had PD (age = 59.8+/-8.8 years; Hoehn and Yahr = 1.8+/-0.7; evolution = 4.3+/-3 years) and eight had PPS (age = 71.6+/-7.3 years; Hoehn and Yahr = 2.9+/-2.0; evolution = 4.1+/-1.5 years). The binding potential of iodolisuride in the striatum was assessed by considering the striatum (S)/occipital lobe (O) ratio at the pseudo-equilibrium 1 h after injection. The S/O ratio was statistically different between PD and PPS (1.97+/-0.3 vs. 1.65+/-0.2 (P<0.02)). Iodolisuride SPECT could differentiate both groups with a sensitivity of 88.8% and a specificity of 75%. Iodolisuride is a good specific D2 receptor ligand for SPECT and complements specific clinical criteria for the diagnosis of Parkinson's disease and differentiation between different extrapyramidal disorders.

Characterization of 99mTc-DTPA aerosols for lung permeability studies.

BACKGROUND: The interpretation of 99mTc diethylenetriamine pentaacetate (99mTc DTPA) aerosol clearance is based on the hypothesis that the 99mTc-DTPA complex is not altered by the nebulization process. OBJECTIVES: To characterize (1) the radiochemical purity (RCP) of 99mTc-DTPA and the stability of labeling after jet nebulization, and (2) the particle size distribution of the aerosol. METHODS: RCP and stability--the aerosol was driven by oxygen, captured on filters which were eluted and RCP was checked by thin layer chromatography. Particle size distribution--the aerosol was generated using dry air (50 psi) at three different flow rates, i.e. 3 (1 run), 6 (4 runs) and 9 l x min(-1) (4 runs). The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (sigma(g)) were determined using a cascade impactor from the radioactivity counted on each stage. RESULTS: The RCP was more than 95% in all cases. Mean MMAD (+/-SD) was 0.70 microm (+/-0.07) at 9 l x min(-1), 0.93 microm (+/-0.05) at 6 l x min(-1) (p < 0.05) and 1.50 microm at 3 l x min(-1). Mean sigma(g) (+/-SD) was 2.02 (+/-0.08) at 9 l x min(-1), 2.00 (+/-0.16) at 6 l x min(-1) and 1.90 at 3 l x min(-1). CONCLUSION: This study demonstrates (1) that the high RCP of 99mTc-DTPA is not affected by jet nebulization, even when using oxygen at a high flow rate, and (2) that when using a flow rate between 6 and 9 l x min(-1), the MMAD remains optimal for peripheral lung deposition.

Technetium-99m ECD single photon emission computed tomography in brain trauma: comparison of early scintigraphic findings with long-term neuropsychological outcome.

OBJECTIVE: The aim of this study was to assess the prognostic value of early brain scintigraphy in head injury in relation to long-term neuropsychological behavior. Twenty-four patients underwent technetium-99m (Tc-99m) ethyl cysteinate dimer single photon emission computed tomography (SPECT) within 1 month of the trauma. Scintigraphic abnormalities were evaluated both visually and semiquantitatively using the brain-to-cerebellum ratio method. The clinical neuropsychological investigation was conducted to evaluate abnormalities related to motor deficit, frontal behavior, and memory and language disorders. All patients had abnormalities on SPECT scan. One year after trauma, 14 patients (58%) had neuropsychological sequelae. The brain-to-cerebellum ratios in the left basal ganglia and brain stem were significantly decreased in patients with memory disorders (P = .03 and P = .02, respectively). Moreover, SPECT visual analysis indicated that low uptake in the basal ganglia, thalamus, and brain stem was associated with subsequent motor deficit, frontal behavior, and language and memory disorders. The authors conclude that brain SPECT can be valuable in predicting the neuropsychological behavior of survivors of severe head injury.

D2 receptor imaging in neonates using I-123 iodobenzamide brain SPECT.

PURPOSE: Hypoxic-ischemic injury induces early changes in cerebral energy that later lead to the presence and extension of brain damage and subsequently to severe neurodevelopmental impairments such as the dyskinetic form of cerebral palsy, which is associated with damage to the striatum. The purpose of the current study was to evaluate the viability of D2 receptors in the perinatal period using I-123 iodobenzamide brain SPECT and to correlate this with early neurologic status. METHODS: After obtaining informed parental consent, 12 full-term neonates with hypoxic-ischemic events were included. I-123 iodobenzamide brain SPECT was performed 1 week after birth, corresponding to a gestational age of 39.2+/-1.7 weeks. Images were acquired using a brain-dedicated gamma camera 1 hour after intravenous injection of 30 MBq (0.8 mCi) I-123 iodobenzamide. Magnetic resonance images (T2 weighted sequence: repetition time/echo time: 2,000/30 to 150) of the brains of the same neonates were acquired on the same day. RESULTS: The right and left striatum:cerebellum activity ratios were between 1.28 and 2.25, with the greatest concentration of I-123 iodobenzamide occurring in the striatum area. A tendency of the striatum:cerebellum ratio to decrease was observed as the severity of the perinatal hypoxic-ischemic event increased despite striatal hypersignal on magnetic resonance imaging in only two neonates. CONCLUSIONS: This study, which confirms that I-123 iodobenzamide could be used in the neonatal period, shows the biochemical maturation of D2 receptors as early as 1 week after birth and also suggests the deleterious effect of perinatal hypoxic-ischemic events on D2 receptors.

[Amyotrophic lateral sclerosis manifesting as cognitive disorders. Value of brain perfusion scintigraphic tomography in intensive care]. / Sclérose latérale amyotrophique révélée par des troubles cognitifs. Intérêt de la tomoscintigraphie de perfusion cérébrale en réanimation.

BACKGROUND: Cognitive disorders have been described in amyotrophic lateral sclerosis, but usually after the diagnosis has ben established. CASE REPORT: A 57-year-old man was intubated for acute respiratory distress subsequent to pneumonia and diaphragm palsy. He had a 2-year history of drug-resistant depression and deterioration of cognitive functions. A pyramidal syndrome associated with biopsy-proven chronic neurogenic atrophy led to the diagnosis of amyotrophic lateral sclerosis. The electromyogram did not contribute to diagnosis. Brain MRI only evidenced moderate bilateral frontal-temporal atrophy. Brain SPECT demonstrated major perfusion defects in the frontal lobes. DISCUSSION: This patient had amyotrophic lateral sclerosis and frontal-temporal dementia with an unusually late onset clinical presentation: cognitive disorder was the inaugural sign. Brain SPECT and muscle biopsy enabled us to identify the cortical and peripheral motor neurone involvement in this uncooperative intensive care patient totally dependent on mechanical ventilation.

Effects of the method of drawing regions of interest on the differential diagnosis of extrapyramidal syndromes using 123I-iodolisuride SPET.

Various parameters are currently used for the semi-quantitative assessment of dopamine D2 receptors and differ according to the delineation of the striatal region of interest (ROI) and the choice of the reference ROI. The aim of this study was to assess the value of different ROI approaches in differentiating patients with normal or increased numbers of D2 dopamine receptors (group 1 = Parkinson's disease, n = 8) from patients with decreased dopamine D2 receptors (group 2 = other extrapyramidal syndromes, n = 9) using 123I-iodolisuride SPET (ILIS-SPET). 123I-iodolisuride (190 +/- 31 MBq) and 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) perfusion SPET were performed in the same position, with a dual-headed gamera camera equipped with fan beam collimators. Both a geometric approach (ellipse, circle or rectangle) and an anatomical approach using the CT scan and perfusion SPET as anatomical guides were used to draw striatal and reference ROIs. A total of 33 different parameters were calculated for each patient, indicating the ratio of counts between the striatal and reference ROIs (frontal, occipital cortex or cerebellum) and the asymmetry between the right and left striatum. More significant differences between group 1 and group 2 were found by using geometric ROIs than by using anatomical ROIs. The most discriminant ratios were the caudate/occipital, caudate/frontal and striatum/occipital ratios (P = 0.001, P = 0.002, P = 0.003 respectively). A close correlation was found between the striatum/caudate and striatum/occipital ratios, but not between the striatum/frontal and striatum/occipital ratios or between the striatum/frontal and striatum/caudate ratios. We conclude that the occipital cortex is the best reference for the semi-quantitative evaluation of dopamine D2 receptors as the frontal cortex could include some dopamine D2 receptor-bound radioligand, and that the caudate/occipital ratio is an appropriate parameter for differentiating Parkinson's disease from non-Parkinson extrapyramidal syndrome by 123I-iodolisuride SPET.

[Scintigraphic imaging of stage III non-small-cell bronchial cancer]. / Imagerie scintigraphique du cancer bronchique non à petities cellules de stade III.

Scintigraphic imagery is a functional image based on the difference of the in vivo concentration of injected radio-active traces as a function-of the metabolic characteristics of the tissues. A positive emission tomography (TEP) relies on an injection of substances which reflect the metabolic activity of the tissues and consist of protein renewal with 11C-methionine or glucose metabolism with F18-fluorodeoxyglucose (FTG). The imagery by TEP enables 85-90% of solitary pulmonary nodules to be detected. The degree of capture of the tracer enables some differentiation of a malignant lesion from a benign lesion which fixes less. In the assessment of the degree of extension in the mediastinal nodes of non-small cell Stage III cancers imagery by TEP has a sensitivity ads specificity which appears superior to those of computed tomography (TEM). The interpretation of the image is simplified by carrying out fusion images between TEM and TEP. The application of TEP in the research into thoracic recurrence has shown a cumulated specificity of 81% and a reliability of 91%. The imagery by TEP is only practised in a few centres. It should be developed in pulmonary pathology if the cost of the apparatus diminishes and if FTG is available. Radioscintigraphy is losing ground in the precise domain of non-small cell carcinoma although it shows up well as a technique in neuro-endocrine tumours. Few studies have shown a decisive value in the radioimmunoscintigraphic evaluation of the extension of mediastinal nodes. A gallium 67 scintigraphy has weak specificity and on account of this has been abandoned for the staging of tumours. Another approach has been isotopic imagery of macrophages but is major inconvenience is a lack of specificity. Scintigraphic studies coupled with ventilation/perfusion remains a useful pre-operative test above all in patients with chronic airflow obstruction with gross tumours at the borderline of operability.

Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-m ethylph enyl)nortropane (PE2I).

For the diagnosis and follow-up of neurodegenerative diseases, many cocaine derivatives have been proposed as radioligands to explore the dopamine transporter. As none of them have all the criteria of specificity and kinetics for human use, we have developed a new derivative, (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methy lphenyl)nortropane (PE2I), which displays promising properties. We report the characterization of PE2I in vitro on rat striatal membranes and in vivo in rats and in monkeys. PE2I had a high affinity (Kd = 0.09 +/- 0.01 nM) and high specificity for the dopamine transporter. In rats we observed a high accumulation in the striatum; by contrast, a very low fixation was measured in the cortex. Moreover, a preinjection of a saturating dose of GBR 12909 prevented the striatal accumulation of PE2I by 74%. These results confirmed the specificity of PE2I for the dopamine transporter. In vivo in monkeys, SPECT studies showed a high accumulation in striatum. Moreover, an equilibrium state was obtained 1 h after injection. PE2I seemed to be the most promising ligand for the dopamine transporter exploration by SPECT using a single-day protocol.

Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging.

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3beta-(4-methylphenyl) nortropane ([123I]PE2I) was evaluated as a probe for in vivo dopamine transporter imaging in the human brain. Six healthy subjects were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 1 h after injection. The background radioactivity was low. The volume of distribution in the striatum was 94+/-24 ml/ml. The results were compared with those of [123I]beta-CIT imaging. There was no significant uptake of [123I]PE2I in serotonin-rich regions such as the midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is specific for the dopamine transporter. One main polar metabolite of [123I]PE2I was found in plasma, and the parent plasma concentration decayed rapidly. Radiation exposure to the study subject is 0.022+/-0.004 mSv/MBq (effective dose). The preliminary results suggest that [123I]PE2I is a selective SPET ligand for imaging striatal dopamine transporter density.

A new iodinated tropane derivative (beta-CDIT) for in vivo dopamine transporter exploration: comparison with beta-CIT.

SPECT exploration of the dopamine transporter with tropane derivatives such as beta-CIT has already produced very valuable information in humans. However, the high affinity of this tracer for both dopamine and serotonin transporters and its slow in vivo kinetics provide the best images in humans more than 20 h after injection. In order to improve those properties, we performed structural changes in the tropane structure in the phenyl and nitrogen substituents for higher affinity and specificity and obtained a promising ligand, 2 beta-carbomethoxy-3 beta-(3',4' diclorophenyl)-8-(3-iodoprop-2E-enyl) nortropane (beta-CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with beta-CIT. In vitro competition studies revealed that beta-CIT and beta-CDIT similarly inhibited the binding of [3H]GBR 12935 (Ki = 27.5 and 29.0 nM, respectively). In contrast, competition studies with [3H]paroxetine and [3H]nisoxetine showed that beta-CDIT had a lower affinity for the serotonin transporter than beta-CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than beta-CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] beta-CDIT in the striatum. In addition, preinjection of GBR 12909 prevented accumulation of this ligand in the striatum by 80%, whereas only a 30% decrease was obtained for [125I] beta-CIT. It seems, therefore, that the combination of aromatic and nitrogen substitution improves the properties of tropane derivatives to provide an exclusive dopamine transporter ligand potentially usable in SPECT.

Iodolisuride and iodobenzamide, two ligands for SPECT exploration of the dopaminergic D2 receptors: a comparative study.

Iodobenzamide (IBZM) and iodolisuride (ILIS), which belong to different chemical families, are two radioligands used for SPECT imaging of dopamine D2 receptors. We have compared their cerebral biodistribution in control rats and their ability to detect quantitative modifications of D2 receptors in experimental models. IBZM and ILIS have a similar cerebral distribution in vivo in control rats and permitted the detection of upregulation of striatal dopamine D2 receptors in a model of chronic haloperidol treatment. Moreover, we observed that 1 h after injection of a saturating dose of haloperidol, IBZM uptake was 72% displaced from the striatum, while ILIS uptake was 50% displaced. In an experimental model of excitotoxic striatal lesion, the in vivo accumulation of IBZM was 30% decreased on the lesioned side, in agreement with a decrease in dopamine D2 receptor density. By contrast, the accumulation of ILIS was identical in the lesioned and in the intact striatum. From the results, it appears that IBZM and ILIS, which are both used to image dopamine D2 receptors in vivo, behave differently in pathological experimental models. The ligand for human exploration should then be chosen according to the suspected pathology.

[Pulmonary deposition of colistin aerosols in cystic fibrosis. Comparison of an ultrasonic nebulizer and a pneumatic nebulizer]. / Déposition pulmonaire des aérosols de colistine dans la mucoviscidose. Comparaison d'un nébuliseur ultra sonique et d'un nébuliseur pneumatique.

The objective of this study was to quantify the deposition in the lung of a Colistine aerosol generated using a pneumatic nebuliser (Pari LL(R) equipped with a Pari Master, Pari, Germany) and to compare this with the results obtained with an ultrasonic nebuliser (DP100, DP Medical, France) in four subjects suffering from cystic fibrosis being colonised with Pseudomonas aeruginosa. To quantify the pulmonary deposition of the aerosols we have used an indirect isotopic method which consists in assimilating the kinetics of the molecules studied with a serum albumin tagged with Technetium 99m (Tc99mm) and added to a preparation of Colistine. We have previously verified that the addition of a radioactive tracer does not change the normal distribution or dynamics of the medication within the aerosol and the radioactive counter linked to the tracer reflects the mass of the medicament. The pulmonary deposition was expressed as a percentage of the nebuliser dose. A regional analysis of the deposition (central, peripheral, superior and inferior) was carried out and in central deposition compared to the periphery (C/P) and superior compared to inferior (S/I) were calculated. With the DP100 nebuliser the pulmonary deposition of the aerosol was very reproducible from one patient to another, varying only between 9.5 to 14 percent of the nebuliser dose. With the Pari LL the fraction deposited varied more from one patient to another from 5.6 to 27% of the nebuliser dose. In three of four patients, the pulmonary deposition was superior or equal to that obtained with the ultrasonic nebuliser. The patients whose pulmonary deposition was inferior, using the pneumatic nebuliser, was the youngest in the group and co-ordinately poorly the triggering of the nebuliser with the beginning of inspiration. With the two nebulisers, the pulmonary deposition of Colisitine was very heterogeneous throughout the pulmonary parenchyma. The mean of the ratio C/P and S/I obtained in all four patients was identical (1.35 an 0.86 respectively), indicating a deposition of the aerosol which was predominantly central and inferior but was distributed equally in the peripheral parts of the lung. Pneumatic nebulisers offer a reliable alternative notably for domiciliary treatment for Colistine aerosols in patients suffering from cystic fibrosis. In younger patients who have not yet acquired good motor co-ordination, nebulisers which function continuously or are triggered by inspiration seem to be the preferred choice.

Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

[Tracheal carcinoma infiltrating the thyroid gland and mimicking subacute thyroiditis. Contribution of Doppler to differential diagnosis]. / Carcinome trachéal envahissant la thyroïde et mimant une thyroïdite subaiguë. Apport du Doppler au diagnostic différentiel.

In the present case Color Coded Doppler showed a marked increase in vascularization in the right lobe of the thyroid with high systolic velocities (1 m/s). This sign was only doubtful compared with clinical, biological and isotopic data. Because of dramatic laryngeal dyspnea, surgery was conducted which allowed the final diagnosis of thyroid invasion by tracheal epidermoid carcinoma. This demonstrates the particular role of Color Coded Doppler in the management of inflammatory thyroid diseases.

[Progressive supranuclear paralysis. Quantification of dopamine D2 receptors using radionuclide tomography]. / Paralysies supra-nucléaires progressives. Quantification des récepteurs dopaminergiques D2 par tomoscintigraphie.

Progressive supranuclear palsy (PSP) may sometimes be misdiagnosed as Parkinson's disease in its early stages, hence an early positive diagnosis of PSP based on dopamine D2 receptor density could be extremely valuable. In the present case report, the absence of dopamine D2 receptors was clearly demonstrated in the striatum using 123I-iodobenzamide (IBZM) tomoscintigraphy. This illustrates the potential use of IBZM tomoscintigraphy to identify Parkinson-like's disease presenting with decreased dopamine D2 receptor density; and hence to predict L-Dopa effectiveness. Further studies are needed to evaluate the vaue of IBZM tomoscintigraphy in the different Parkinson's like diseases.