Georgios Farmakis

Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson's disease

In idiopathic Parkinsons disease (PD), different clinical subtypes are distinguished due to predominant motor symptoms: a tremor‐dominant type (TDT), an akinetic rigid type (ART), and a mixed type (MT). We compared myocardial sympathetic innervation, measured by MIBG scintigraphy, in different subtypes of PD at early and advanced stages of PD. We applied MIBG scintigraphy in 102 patients with PD. About 57 patients were at Hoehn and Yahr (H&Y) stage 1, 22 at H&Y stage 2, and 23 at H&Y stages 3 and 4. For quantification of myocardial MIBG uptake, the heart‐to‐mediastinum (H/M) count‐ratio was calculated. At all H&Y stages, myocardial MIBG uptake was significantly higher in TDT patients than in ART or MT patients (P < 0.05; ANOVA). Furthermore, at each H&Y stage, myocardial MIBG uptake correlated significantly with severity of hypokinesia (P < 0.05; Spearmans correlation) and rigidity (P < 0.05), but not with severity of resting or postural tremor. The significant correlation between myocardial sympathetic degeneration and severity of hypokinesia and rigidity suggests that myocardial sympathetic degeneration and hypokinetic‐rigid symptoms develop in a closely coupled manner in early as well as advanced PD. No such correlation can be found between myocardial sympathetic degeneration and parkinsonian tremor.

Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson's Disease.

In idiopathic Parkinson’s disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [123I]FP-CIT SPECT – to quantify cerebral nigrostriatal dopaminergic degeneration – and myocardial [123I]MIBG scintigraphy – to quantify extracranial myocardial sympathetic degeneration – were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function.

Myocardial MIBG scintigraphy may predict the course of motor symptoms in Parkinson’s disease

BACKGROUNDnThe metaiodobenzylguanidine (MIBG) scintigraphy is a well established nuclear medicine method to support the clinical diagnosis of Parkinsons disease. In this study we examined the predictive value of the MIBG scintigraphy concerning the severity and progression of the parkinsonian motor symptoms.nnnPATIENTS AND METHODSnThis study included 40 patients with idiopathic Parkinsons disease (age 56 ± 9 years, Hoehn and Yahr stage 1.4 ± 0.7, mean ± standard deviation). All patients underwent a baseline visit and a follow-up visit 3-8 years (5.3 ± 1.6 years) after the baseline visit. (123)I-MIBG scintigraphy was performed only once at the baseline visit. At both visits the motor symptoms bradykinesia, rigidity, resting tremor, postural tremor and axial symptoms were quantified by means of the motor part of the Unified Parkinsons disease rating scale.nnnRESULTSnThe myocardial MIBG uptake correlated significantly with the annual progress of rigidity (r=-0.41, p<0.05; Pearsons correlation) and axial symptoms (r=-0.49, p<0.01). There was no significant correlation (p>0.05) between the initial myocardial MIBG uptake and the annual progress of the other motor symptoms.nnnCONCLUSIONnThe MIBG scintigraphy may predict the velocity of progress of rigidity and axial symptoms in the following 3-8 years. Such a prediction is not possible for the other motor symptoms resting tremor, postural tremor and bradykinesia.

FP-CIT SPECT Does Not Predict the Progression of Motor Symptoms in Parkinson’s Disease

Background/Aims: FP-CIT (fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl-nortroptane) SPECT is a well-established nuclear medicine method to support the clinical diagnosis of Parkinson’s disease (PD). In this study, we examined the prognostic value of FP-CIT SPECT concerning the PD motor symptoms. Methods: All 38 PD patients (age 57 ± 7 years, Hoehn & Yahr stage 1.6 ± 0.8, mean ± SD) underwent a baseline visit and a follow-up visit 3–7 years (5.2 ± 1.3 years) after the baseline visit. Cerebral [123I]FP-CIT SPECT was performed only once at the baseline visit. At both visits the motor symptoms bradykinesia, rigidity, resting tremor, postural tremor and axial symptoms were quantified by means of the UPDRS motor scale. Results: There was no significant correlation between the initial striatal FP-CIT uptake and the annual progress of any motor symptom (= difference [(motor symptom at follow-up visit) – (motor symptom at baseline visit)]/time (in years) between assessments). Conclusion: The initial striatal FP-CIT SPECT does not predict the velocity of progress of PD motor symptoms within an interval of 3–7 years.

Evaluation of transcranial sonographic findings and MIBG cardiac scintigraphy in the diagnosis of idiopathic Parkinson's disease

The diagnosis of idiopathic Parkinsons disease (IPD) is based on clinical criteria. In the last two decades several neuroimaging methods using transcranial sonography (TCS) or radiolabelled tracers such as the myocardial MIBG scintigraphy were applied to support diagnosis of IPD. They have been used independently of each other and their interrelation is not yet clear. In the present study we analyzed the relation between findings of TCS, MIBG scintigraphy, and clinical presentation in 42 patients with IPD who were clinically diagnosed and underwent clinical follow-up over ≥3 years in order to confirm IPD diagnosis throughout the clinical course. The extent of substantia nigra hyperechogenicity (SN+) contralateral to the clinically more affected body side (SN(contra)) was compared to myocardial (123)I-MIBG uptake. SN(contra) did not correlate with the myocardial MIBG uptake (r = -0.10; p = 0.52). Both myocardial MIBG uptake and TCS did not correlate significantly with Hoehn and Yahr stage (r = -0.03; p = 0.87 and r = -0.10; p = 0.54, respectively). Sensitivity of TCS in the diagnosis of IPD was 79%, of MIBG scintigraphy 81%. The combination of both measurements reached a sensitivity of 95%. TCS and MIBG scintigraphy may disclose complementary aspects of IPD. The combined use of both neuroimaging methods might improve the diagnostic sensitivity regarding IPD.

Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma

PurposeThe differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[123I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions.MethodsThis prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250xa0MBq IPA intravenously after overnight fasting. SPECT images at 30xa0min and 3xa0h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging.ResultsTwenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%).ConclusionIn patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed.

PET imaging with p-[I-124]iodo-l-phenylalanine as a new tool for diagnosis and postoperative control in patients with glioma.

Imaging protein metabolism by means of radiolabeled amino acids is an established method in the diagnosis of brain tumors. I-123 iodo-L-phenylalanine is a novel iodinated amino acid currently used for brain tumor imaging with single photon emission computed tomography. Radiolabeling of L-phenylalanine with iodine-124 allows in vivo studies of brain tumors by positron emission tomography, improving image quality. In this report, we evaluate the preand postoperative status in a 73-yearold patient with a glioma after one single injection of I-124 IPA using PET. A single administration of I-124 p-iodo-L-phenylalanine approved both an accurate diagnosis and a postoperative control in this same patient with a glioma.

Splenosis mimicking hepatic adenoma.

Hepatocellular adenomas are rare benign liver tumors that, if not smaller than 5xa0cm and asymptomatic, do, in general, not require surgical intervention.1 However, larger tumors should be resected since there is a risk of hemorrhage or malignant transformation.1 We present here a case of abdominal and hepatic splenosis mimicking hepatocellular adenoma.