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.

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.

[Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use]. / Neuroimagen funcional en el diagnóstico de pacientes con síndrome parkinsoniano: actualización y recomendaciones para el uso clínico.

Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression.

[Functional neuroimaging with SPECT in Parkinson's disease and Parkinsonisms]. / Neuroimagen funcional mediante SPECT en la enfermedad de Parkinson y los parkinsonismos.

INTRODUCTION: The diagnosis of Parkinson's disease and the different Parkinsonian syndromes is currently determined by applying established clinical criteria. Today, different neuroimaging techniques, such as positron emission tomography and single-photon emission computerised tomography (SPECT), are a valuable aid to further our understanding of both the pathophysiology and the diagnosis of the different Parkinsonian pictures. AIM. To examine the usefulness of the different tools utilised to assess the integrity of the nigrostriatal system by visualising the pre-synaptic dopamine transporters and post-synaptic D2 receptors using SPECT techniques; we also sought to determine the role played by the alteration of the cardiac sympathetic innervation using meta-iodobenzylguanidine. DEVELOPMENT: We review the usefulness of the different nuclear medicine techniques for the diagnosis and differential diagnosis of the distinct clinical pictures that are accompanied by Parkinsonian symptoms, and we also discuss the possible future perspectives of said techniques. CONCLUSIONS: A combination of the different nuclear medicine techniques that have been reviewed here is useful in the study and characterisation of Parkinsonian syndromes. In the future they could be used to detect subjects who are possibly at risk of developing Parkinsonism and to be able to assess the effect of therapies that may have a potential modifying effect on the disease.

[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.

[Adrenal cortex scintigraphy with and without dexamethasone suppression in the study of primary aldosteronism]. / Gammagrafía suprarrenal cortical con frenación y supresión de la frenación con dexametasona en el estudio del hiperaldosteronismo primario.

AIM OF THE STUDY: To evaluate the diagnostic performance and efficacy of adrenal scintigraphy in primary aldosteronism following the protocol that combines adrenal suppression scintigraphy plus non-suppression study. METHODS AND PROCEDURES: 20 patients referred to our service with the suspicion of primary aldosteronism were studied by combined scintigraphy. Thirteen men and 7 women, mean age of 52 years, aged from 31 to 73 years, were included. Uptake of free iodine by the thyroid was inhibited by oral Lugol 5 % administration. Dexamethasone 4 mg per day was administered from day 7 to the third day of detection, when administration was stopped. Adrenal scintigraphy was performed after intravenous injection of I-131-norcolesterol (37 MBq). Images were taken at 24 and/or 48 hours and on the third day. Afterwards, dexamethasone administration was stopped and late images on 5th and/or 7th days were obtained. The scintigraphic result was confirmed with the final clinical evaluation (FCE) of the patient. RESULTS: 11 patients presented pathological studies, 9 adenomas (8TP + 1FP) and 2 bilateral adrenal hyperplasia (2TP); 7 normal scintigraphies (6TN and 1 non-conclusive FCE) and 2 non-conclusive scintigraphies (1 incidentaloma and 1 non-conclusive FCE). Normal adrenal glands were visualized in all cases on the 5th and/or 7th day scintigraphy. CONCLUSION: The study of adrenal functionalism by the combined protocol of adrenal suppression study plus later non-suppression study made it possible to identify with high precision primary aldosteronism and to confirm the function of normal adrenal glands.