Günther Dr. Platsch

Differentiation of Parkinson's disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT

BACKGROUND Differential diagnosis between idiopathic Parkinsons disease (PD) and multiple system atrophy (MSA) is often difficult in early disease stages. Since MSA is misdiagnosed as PD in more than 20% of the early stages, there is need for methods refining the differentiation of the two disease entities. In PD postganglionic involvement of the autonomic nervous system (ANS) predominates whereas in MSA the ANS is mainly affected in its preganglionic structures. The functional integrity of postganglionic cardiac sympathetic neurons can be investigated using I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT). OBJECTIVES We investigated whether I-123-MIBG-SPECT allows to differentiate between early stages of PD and MSA in patients not yet requiring L-dopa therapy. METHODS Thirty patients (10 PD and 20 MSA patients) underwent MIBG-SPECT and evaluation of heart rate variability (HRV). Patients on any medication interfering with MIBG-accumulation were excluded from the study. Cardiac perfusion was evaluated by myocardial scintigraphy. RESULTS The median cardiac MIBG uptake was significantly decreased in PD as well as MSA patients compared to controls (P<0.001). However, in the PD group MIBG uptake was significantly lower than in MSA (P=0.03). Even in PD patients without clinical signs of autonomic failure, MIBG uptake was significantly lower than in MSA patients (P=0.03). Analysis of heart rate parameters did not differentiate between PD and MSA patients. The median coefficient of variation was significantly smaller in PD and MSA patients compared to control subjects. CONCLUSIONS Our study shows that MIBG-SPECT identifies autonomic cardiac dysfunction in very early stages of both, PD and MSA. More importantly, the technique facilitates differentiation of MSA and PD in the early stages. The different pathology with prominent peripheral, postganglionic sympathetic dysfunction in PD and primarily central and preganglionic lesions in MSA accounts for a lower MIBG uptake in PD compared to MSA patients.

Ictal Pleasant Sensations: Cerebral Localization and Lateralization

Summary:  Ictal pleasant feelings are a rare sign of focal epilepsies. The most popular description was performed by Dostojevskij, who reported an aura by Myshken in one of his books. No convincing evidence has been published concerning the cerebral localization of ictal happiness. In this study, the findings of 11 patients with ictal pleasant feelings are described. In eight patients, the origin of the focal epileptic activity was found in the temporal lobe (most often temporal inferior basal); in three patients, frontal or parietal lobe in addition to temporal lobe involvement was found. According to our findings ictal happiness is a localizing sign pointing to the ictal involvement of temporal mesiobasal areas. Lateralization to the right temporal lobe was found in seven and to the left temporal lobe in four patients.

Outcome of epilepsy surgery correlates with sympathetic modulation and neuroimaging of the heart.

Temporal lobe epilepsy (TLE) is frequently associated with sympathetic over-activity. Single photon emission computed tomography (SPECT) with 123iodine-meta-iodobenzylguanidine (MIBG), a norepinephrine analogue, showed reduced tracer uptake in cardiac sympathetic nerve endings, indicating myocardial catecholamine disturbance. We investigated whether outcome of epilepsy surgery correlates with cardiac autonomic function in TLE patients. We studied 16 TLE patients before and after epilepsy surgery. We recorded heart rate (HR) and determined sympathetic and parasympathetic cardiac modulation as powers of low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) heart rate oscillations. The LF/HF-ratio was calculated as index of sympathovagal balance. Cardiac MIBG uptake was assessed with MIBG-SPECT and compared to control data. After surgery, eight patients were seizure-free and eight had persistent seizures. Sympathetic LF-power and LF/HF-ratio were higher in patients who had persistent seizures than in patients who became seizure-free. After surgery, both parameters decreased in seizure-free patients but increased in patients with persistent seizures. MIBG uptake was lower in patients than controls and even lower in the patient subgroup who had persistent seizures. In this subgroup, MIBG uptake further decreased after surgery (P<0.05). Sympathetic cardiac modulation decreased in TLE patients after successful surgery, but further increased if seizures persisted. Reduction of cardiac MIBG uptake progressed after surgery in patients with persistent seizures. Interference of epileptogenic discharges with autonomic neuronal transmission might account for sympathetic cardiac over-stimulation and reduced MIBG uptake. Both findings are possible risk factors for sudden unexplained death and might be relevant for risk stratification in epilepsy patients.

IKTUALE SYNKOPEN : KARDIALE SYMPATHISCHE INNERVATIONSSTORUNG ALS URSACHE ?

ZusammenfassungWir berichten über 3 Patienten mit iktualer Asystolie. Alle Patienten litten an einer Temporallappenepilepsie (TLE). Die Anfälle wurden im Rahmen der prächirurgischen Epilepsiediagnostik mit simultaner Video-EEG-Ableitung aufgezeichnet. Bei einer Patientin mit kortikaler Heterotopie, die häufig und besonders lang an Synkopen litt, konnte eine nahezu fehlende kardiale sympathische Innervation im MIBG-SPECT (Meta-Iodid-Benzyl-Guanidin-Single-Photon-Emissions-Computer-Tomographie) des Herzens nachgewiesen werden. Eine kardiologische Untersuchung, inkl. Langzeit-EKG und Echokardiographie, hatte normale Befunde gezeigt. Nach einem epilepsiechirurgischen Eingriff verschwanden die synkopalen Ereignisse bei allen Patienten. Ein epileptogen hervorgerufener dominanter parasympathischer Stimulus nach Erregung der Formatio reticularis wird als Ursache der iktualen Bradykardie und Asystolie diskutiert. Eine sympathische Innervationsstörung des Herzen, möglicherweise als Fehlbildung im Zusammenhang mit kortikalen Migrationsstörungen auftretend, die eine reflektorische Autoregulation unmöglich macht, wird als mögliche Ursache für eine besonders lang andauernde Asystolie und damit auch als Ursache des plötzlichen Herztodes während eines epileptischen Anfalls erörtert.SummaryWe report 3 cases of an ictal sinus arrest. All patients suffered from temporal lobe epilepsy (TLE). Seizures were monitored with simultaneaous video-eeg during preoperative epilepsy diagnosis. One patient with cortical dysplasia, who frequently suffered from long lasting syncopes, had a nearly completely missing cardiac sympathetic innervation in MIBG-SPECT (=Meta-Iodide-Benzyle-Guanidine-single-photon-emission tomography). Cardiac investigation including long-term ECG and echocardiography had shown normal findings. After epilepsy surgery the syncopal events in all patients disappeared. A dominant parasympathetic ictal stimulus following excitation of the reticular formation might cause the ictal bradycardia and sinus arrest. A missing sympathetic innervation, possibly occurring as fehlbildung together with cortical dysplasia, which makes autoregulation impossible, might then be the explanation for sudden cardiac ictal death.

Cardiac sympathetic denervation in Ross syndrome demonstrated by MIBG-SPECT

We investigated cardiac sympathetic innervation by metaiodobenzylguanidine (MIBG) imaging in a patient with tonic pupils, loss of tendon reflexes, and segmental anhidrosis (Ross syndrome). Despite normal cardiovascular reflex tests, we observed a reduced global myocardial MIBG uptake as well as a regional uptake defect over the posterolateral cardiac territory indicating left ventricular peripheral sympathetic denervation. MIBG imaging seems to be a useful noninvasive diagnostic method for detection of early--possibly subclinical--cardiac autonomic impairment in Ross syndrome and provides further evidence of injury to postganglionic autonomic neurons as the underlying pathological mechanism of the disease.

Electrocardiographic characteristics indicating a risk of irreversibly impaired myocardial function in chronic aortic regurgitation

In order to define which of selected ECG variables could indicate irreversibly impaired myocardial function in chronic aortic regurgitation 54 patients were stratified according to normal (> or = 50%; Group A, n = 41) or subnormal radionuclide left ventricular ejection fraction (LVEF < 50%; Group B, n = 13) late after aortic valve replacement. Preoperatively, Group B patients had a significantly greater QRS duration, greater R-peak time (RPT) prolongation in I, V5 or V6, greater RPT relative to the S-peak time of the maximum S in V1, V2 or V3 (R-peak delay) and a greater negative T-wave in I or V6, as compared with Group A. These ECG variables together with preoperative angiocardiographic LVEF and end-systolic volume index were subjected to stepwise linear discriminant analysis. The maximum RPT, angio-LVEF and the maximum RPT relative to the S-peak time of the maximum S in V1, V2 or V3 emerged as the most promising variables. Of of Group A patients 82.9% and 84.6% of Group B patients were correctly classified by the three variables. If applied separately, APT prolongation or the presence of the R-peak delay in the left-sided leads, although less sensitive, have reasonably high specificity as risk indicators of irreversibly impaired chamber function, their positive predictive value being 60 and 62.5%, respectively. In conjunction with preoperative LVEF the diagnostic contribution of the two ECG variables amounts to the greatest overall separation of postoperatively preserved from irreversibly impaired systolic function.

R peak time prolongation and R peak delay in leads I, V5, or V6. Diagnostic values as signs of myocardial dysfunction in chronic mitral incompetence.

On the assumption that maximum R peak time prolongation in the left-sided leads I, V5, or V6 and its time relationship to the S peak time of the maximum S amplitude in leads V1, V2, or V3 (representing dorsally directed forces of ventricular depolarization) could indicate the extent of left ventricular volume overloading and possibly left ventricular systolic function, these variables and the preoperative findings of angiocardiography were compared between patients with chronic mitral incompetence who, late after corrective valve surgery, had either well-preserved radionuclide left ventricular ejection fraction (group 1, n = 36) or radionuclide left ventricular ejection fraction below 50% (group 2, n = 30). Before surgery, group 2 patients had a highly significant lower mean left ventricular ejection fraction, a highly significant greater mean end-systolic volume index, a significantly greater mean end-diastolic volume index, a significantly greater mean maximum R peak time in leads I, V5, or V6, and a significantly greater prolongation of the maximum R peak time above the S peak time in the right precordial leads, as compared with group 1. R peak times greater than 50 ms or the presence of R peak delay (maximum R peak time greater than the S peak time of the maximum right precordial S amplitude) yields less sensitive but highly reliable results in predicting radionuclide left ventricular ejection fraction below 50% with both specificity and positive predictive values of 100%. Thus, in chronic mitral regurgitation surgery should not be delayed if patients present these signs because they are specific markers of irreversibly impaired chamber function.