Myasthenia gravis concurrent with Parkinson's disease in a Spanish cohort. Causation or correlation?

BACKGROUND: Comorbidity between myasthenia gravis (MG) and other autoimmune diseases is well-documented. However, concurrent MG and Parkinson's disease (PD) have rarely been described. This concurrence has mostly been considered coincidental in cases reported to date. MATERIAL/METHODS: We characterized patients with concurrent MG and PD within a cohort of 631 MG patients by gender, age, MGFA class, quantitative MG score at diagnosis, UPDRS score at diagnosis, and the DaTSCAN uptake pattern, to determine the frequency and the phenotype of individuals with these two concurrent entities. Meta-analysis of cases in the literature was used for comparison with our series. RESULTS: Eighteen cases were identified in which the two diseases were concurrent. The major characteristics of the phenotype are male prevalence, late-onset MG, and frequent initial symptoms of dropped head and oculobulbar involvement. DAT confirmed reduced bilateral uptake in eleven patients and reduced unilateral uptake in the others. CONCLUSIONS: To our knowledge, this is the largest reported series of concurrent MG and PD. This concurrence is more common than expected (2.85%). Either MG or PD may appear first. We found no iatrogenic relationship for the order of appearance. The overlapping of symptoms sometimes leads physicians to overlook the second disease, instead viewing it as a deterioration of the first. This study describes patients with well-documented diagnoses of both MG and PD, thus providing further indications of a shared etiology of these two diseases. Prospective studies including genetic, immunological, and environmental analysis are necessary to identify possible common pathogenic mechanisms.

BDNF levels and nigrostriatal degeneration in "drug naïve" Parkinson's disease patients. An "in vivo" study using I-123-FP-CIT SPECT.

INTRODUCTION: Parkinson's Disease (PD) is a common neurodegenerative disorder, characterized by a progressive loss of dopaminergic neurons and whose cause remains unclear. Brain-Derived Neurotrophic factor (BDNF) is a protein involved in dopaminergic cells survival. Previous studies have shown decreased serum BDNF levels in PD patients. AIM AND OBJECTIVES: The aim of the study was to evaluate serum BDNF levels in a group of recently diagnosed non-medicated PD patients and its relationship with the nigrostriatal system degeneration using I-123-FP-CIT. METHODS: 30 recently diagnosed, unmedicated PD patients were included in this study. Serum BDNF levels were measured twice using a sandwich enzyme linked immunoabsorbent assay and compared with levels of 27 unrelated Caucasian healthy adults. A I-123-FP-CIT SPECT was performed in all PD Patients in order to assess the association between serum BDNF levels and I-123-FP CIT uptake in several brain areas using a volumetric semi-automatic method. RESULTS: PD patients showed lower serum BDNF levels (Median = 49.61, IQ range: 43.55 to 61.82) than the controls (Median = 68.82, IQ range: 51.87 to 88.14) (U = 211.00, z = -3.10, p = 0.002). BDNF levels in PD patients correlated with both caudate (Spearman r = 0.58, p = 0.001 for ispilateral and r 0.55, p = 0.002 for contralateral) and putamen (Spearman r = 0.68, p < 0.001 for ipsilateral and r = 0.80, p < 0.001 for contralateral) I-123-FP-CIT uptake ratios. CONCLUSIONS: Serum BDNF levels were lower in recently diagnosed, untreated PD patients compared to controls. These lower levels were significantly correlated with the I-123-FP-CIT uptake ratios.

A comparative study of the target volume definition in radiotherapy with «Slow CT Scan¼ vs. 4D PET/CT Scan in early stages non-small cell lung cancer. / Estudio comparativo en la definición del volumen de tratamiento en radioterapia con «Slow TC Scan¼ vs. 4D PET/TC Scan en estadios iniciales de cáncer de pulmón de célula no pequeña.

OBJECTIVES: To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow¼-CT (CTs) in the radiotherapy planning process. MATERIAL AND METHODS: A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. RESULTS: The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. CONCLUSION: Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer.

Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis.

AIM: To describe the characteristic magnetic resonance imaging (MRI) findings of paraneoplastic autoimmune encephalitis in patients with new-onset status epilepticus. MATERIALS AND METHODS: The neuroimaging and clinical data of five patients with paraneoplastic autoimmune encephalitis debuting as status epilepticus were retrospectively reviewed. All patients met the criteria for definite paraneoplastic syndrome and all underwent brain MRI during the status epilepticus episode or immediately after recovery. RESULTS: All patients showed hyperintense lesions on T2-weighted imaging (WI) involving the limbic structures, specifically the hippocampus. Three of them showed additional extra-limbic areas of signal abnormalities. The areas of T2 hyperintensity were related to the electroclinical onset of the seizures. In three patients, various techniques were used to study cerebral perfusion, such as arterial spin labelling MRI, single photon-emission computed tomography (SPECT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET). Arterial spin labelling showed hyperperfusion overlapping the inflammatory lesions, whereas PET and SPECT disclosed increased perfusion and increased metabolism. The subtraction SPECT co-registered to MRI (SISCOM) demonstrated hypermetabolism outside the areas of encephalitis. After clinical recovery, follow-up MRI revealed the development of atrophy in the initially affected hippocampus. Two patients who had recurrent paraneoplastic autoimmune encephalitis manifesting as status epilepticus showed new T2 lesions involving different structures. CONCLUSION: The presence of limbic and extra-limbic T2 signal abnormalities in new-onset status epilepticus should suggest the diagnosis of a paraneoplastic syndrome, especially when status epilepticus is refractory to treatment. The lesions are consistently seen as hyperintense on T2WI.

[Variables that influence the indication of a second myocardial perfusion gated-SPECT after a normal stress-rest gated SPECT]. / Variables que influyen en la indicación de una segunda gated-SPECT de perfusión miocárdica después una gated-SPECTde estrés-reposo normal.

OBJECTIVE: The objective of this study was to investigate predictor variables at the moment of normal stress-rest myocardial perfusion gated SPECT for indication of a second gated SPECT. MATERIAL AND METHODS: A prospective, single center cohort study was conducted. We evaluated 2326 consecutive patients (age 63.6 ± 13 years, 57.3% females) without perfusion defects and with normal left ventricular ejection fraction on a myocardial perfusion gated SPECT. Clinical and stress test variables were studied to predict indication of a second gated SPECT and presence of reversible perfusion defects in the second gated SPECT. RESULTS: During a mean follow-up of 3.6 ± 2 years a second gated SPECT was performed in 286 patients (12.3%). Independent predictor variables of a second gated SPECT were presence of three or more cardiovascular risk factors (χ(2): 5.510; HR: 1.4; p=0.019), previous acute myocardial infarction (χ(2): 3.867; HR: 1.4; p=0.049), previous coronary revascularization (χ(2): 41.081; HR: 2.5; p<0.001), and a positive stress test (χ(2): 8.713; HR: 1.5; p=0.003). Observation of perfusion defects in the 280 patients in whom a second stress-rest gated SPECT was performed was more likely in male patients (χ(2): 4.322; HR: 1.9; p=0.038) who had a first pure pharmacological gated-SPECT (χ(2): 7.182; HR: 2.6; p=0.007). CONCLUSIONS: In patients with a first normal myocardial perfusion gated SPECT, various clinical factors and variables derived from the stress test affect the indication of a second gated SPECT and the presence of ischemia in the latter.

[Analysis of the diastolic function by myocardial perfusion gated SPECT after coronary revascularization in acute myocardial infarction]. / Análisis de la función diastólica mediante gated-SPECT de perfusión miocárdica tras revascularización coronaria en el infarto agudo de miocardio.

OBJECTIVE: To evaluate the evolutive changes in diastolic function after percutaneous coronary revascularization (PCR) in acute myocardial infarction (AMI), using myocardial perfusion gated SPECT. METHODS: Thirty-two patients (mean 61.9±9.7 years, 7 women) were studied by two at rest gated SPECT: the first gated-SPECT-1 was performed with an injection of a dose of (99m)Tc-tetrofosmin prior to PCR and the second gated-SPECT-2 between the fourth and fifth weeks after AMI. Changes of peak filling rate (PFR) and the time to peak filling rate (TTPF) were assessed between both studies, and were related to the extent of salvaged myocardium (SM), end-diastolic (EDV) and end-systolic (ESV) volumes, and left ventricular ejection fraction (LVEF) changes. RESULTS: An improvement was observed in diastolic function parameters Gated-SPECT-2: PFR increased significantly (P=0.011) while the TTPF decreased without reaching statistical significance (P=0.288). In multivariate analysis, adjusted by clinical and coronary variables, improvement of PFR was significantly associated with percentage of SM (P=0.030), increase in LVEF (P=0.004) and with ESV volume reduction (P=0.005). Improvement of TTPF was only related significantly to the percentage of SM (P=0.046). PFR increased 0.01 EDV/sec. and TTPF decreased 1.14ms for each cm(2) increase of the area of SM. CONCLUSIONS: After PCR in AMI, the myocardial perfusion gated SPECT makes it possible to assess the significant improvement in diastolic function mainly related to the amount of MS.

[Short exercise-rest versus long myocardial perfusion gated SPECT protocols in patients with ischemic cardiomyopathy]. / Protocolo corto esfuerzo reposo frente a protocolo largo en la gated-SPECT de perfusión miocárdica de pacientes con miocardiopatía isquémica.

OBJECTIVE: The purpose of this study was to analyze left systolic ventricular function and myocardial perfusion characteristics between short one day exercise-rest and long two days gated SPECT (Single Photon Emission Computed Tomography) protocols in patients with ischemic cardiomyopathy (ICM). METHODS: A prospective study of 40 patients (59.6±8.9 years, 3 women) with IHD (left ventricular ejection fraction (EF) ≤40%) was performed with myocardial perfusion gated SPECT. From 5 to 10 days after a one-day exercise-rest study (gated SPECT-1), patients were called back for a second rest study (gated SPECT-2) in order to compare EF and differences in perfusion summed rest score (ΔSRS=SRS1-SRS2) and summed difference score (ΔSDS=SDS1-SDS2) between both protocols. RESULTS: Between rest-gated SPECT-1 (short protocol) and rest-gated SPECT-2 (long protocol) EF increased (34% vs 37%, P= 0.008) in 26 patients (65%), and in 11 patients (27.5%) the increase was ≥5%. There were no significant differences in clinical and coronary angiography variables between patients with and without increase of the EF ≥5%. In the multivariate analysis, ΔSRS (95% CI: -1.1 to -29.2) and ΔSDS (0.179-1.236) were predictors for this EF increase between both studies. CONCLUSIONS: Exercise-rest short protocol can underestimate EF in patients with CM. Stunning but also contamination of rest images by previous exercise images in a short protocol could explain these results.

[Quantitative evaluation of 123I-FP-CIT SPECT: validation of a semiautomated method]. / Evaluación cuantitativa del SPET con 123I-FP-CIT: validación de un método semiautomático.

OBJECTIVE: To assess the utility of a quantification of the 123I-FP-CIT uptake by the definition of some reference values, normal range values and interobserver variation. PATIENTS AND METHOD: Fifty patients with a 123I-FP-CIT SPECT: 25 patients had a pathological SPECT with the diagnosis of Parkinson's disease and the remaining had a qualitative normal SPET, with the diagnosis of 14 drug-induced Parkinsonism and 11 with psychogenic Parkinsonism. In the transversal slices, the best central slice that showed the nuclei of the base best was selected and standard ROIs (Region Of Interest) were applied. Specific (caudate and putamen) versus non specific (occipital) and laterality ratios were calculated. A normal statistical analysis for independent quantitative samples was used (mean, standard deviation and range) as well as variation coefficient and correlation coefficient of two observers and the 10th and 90th percentile. RESULTS: The variation coefficient interobserver was 3.24-5.61 and the correlation coefficient was 0.89-0.99. Cut-off values between both populations were established at 2.10 in the right putamen and at 2.05 in the left. Cut-off values definition in caudate were not assessable due to overlapping of ratios of both populations. CONCLUSIONS: This quantification method is highly reproducible. It makes it possible to obtain reference values and to define normal range.