Dieter Emrich

Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration.

The nocturnal myoclonus syndrome (NMS) consists of stereotyped, repetitive jerks of the lower limbs that occur during sleep or wakefulness. NMS is often related with restless-legs syndrome (RLS) and can cause severe sleep disturbances and daytime sleepiness. The efficacy of dopamine agonists in the treatment points to a dopaminergic dysfunction in NMS. We investigated the central dopamine D2-receptor occupancy with [123I] labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) ([123I]IBZM) and single photon emission tomography (SPET) in 20 patients with NMS and in 10 healthy controls. In most of the patients with NMS there was a lower [123I]IBZM binding in the striatal structures compared to controls. The results indicate that NMS is related to a decrease of central D2-receptor occupancy.

Dopamine D2 receptor alteration in patients with periodic movements in sleep (nocturnal myoclonus)

Periodic movements in sleep (PMS) can cause severe sleep disturbances. We investigated the central dopamine D2 receptor density in patients with PMS with123I-IBZM and single photon emission tomography (SPET). In PMS there was a lower123I-IBZMbinding in the basal ganglia compared tothe control group. The results indicate a loss of central D2 receptors in PMS.

Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the course of dopamine replacement therapy in patients with nocturnal myoclonus syndrome (NMS)

Single photon emission tomography (SPET) permits the in vivo measurements of regional cerebral radioactivity in the human brain following the administration of compounds labeled with photon-emitting isotopes. According to our SPET findings of a reduced binding of [123I]labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) to D2 dopamine receptors in striatal structures in untreated patients with nocturnal myoclonus syndrome (NMS) it seemed to be of interest to investigate whether there are changes in D2 receptor binding under dopamine replacement therapy or not. We studied the uptake and distribution of [123I]IBZM before and in the course of dopamine replacement therapy in four patients with severe insomnia caused by a nocturnal myoclonus syndrome (NMS). We found an increase of the IBZM binding to D2 receptors in the course of treatment, which was associated with an improvement of sleep quality. Reasons for this are discussed. The [123I]IBZM SPET technique in conclusion offers an interesting tool for in vivo investigations of functional changes in the dopaminergic neurotransmitter system in longitudinal studies.

AUTONOMY IN EUTHYROID GOITRE: MALADAPTATION TO IODINE DEFICIENCY

The occurrence of negative TRH tests in euthyroid goitre was analysed in 486 patients without scintigraphic evidence of autonomous adenoma from an area of iodine deficiency. After ensuring by various means that methodological errors could be excluded, the following results were obtained.

Determination of the autonomously functioning volume of the thyroid

AbstractThe aim of this work was to determine the autonomously functioning volume in euthyroid and hyperthyroid goitres for prognostic and therapeutic purposes. To this end, various groups of patients were selected: individuals without evidence of thyroid disease, euthyroid patients with diffuse goitre of normal structure and function, euthyroid patients with evidence of autonomy and patients with hyperthyroidism due to autonomy. In all of them the thyroid uptake of technetium-99m was determined under exogenous suppression (TcUs) in the euthyroid state and under endogenous suppression (TcU) in the hyperthyroid state. It was demonstrated that:1.In patients with unifocal autonomy the TcUs and TcU correlated linearly with the autonomous volume delineated and measured by sonography.2.A nearly identical result was obtained if the mean autonomous volume in individuals without thyroid disease of 2.2 ± 1.1 ml calculated by TcUs/TcU x total thyroid volume was used as a basis.3.The critical autonomous volume, i.e. the volume at which hyperthyroidism will occur, was found to be 16 ml at a cumulated sensitivity and specificity of >0.9. The method can be used to select patients for definitive treatment before hyperthyroidism occurs and to measure the autonomously functioning volume independent of its distribution within the thyroid for treatment with radioiodine. The method is easy to perform and is also an example of how a relative parameter of a function can be converted into an absolute parameter of a functioning volume.

Treatment of endemic goitre due to iodine deficiency with iodine, levothyroxine or both: results of a multicentre trial.

Abstract. Preliminary clinical studies and recent in vitro investigations suggest that iodine administration may be an effective alternative in the treatment of the diffuse euthyroid goitre of iodine deficiency. Therefore a 12‐month multicentre study was initiated in which 166 patients were randomly assigned to take either 150 μg levothyroxine day‐1 (group A, n= 61), 400 μg iodine day‐1 (group B, n= 50), or a combination of 75 μg levothyroxine and 200 μg iodine day‐1 (group C, n= 55) for 8 months with follow‐up examinations at 4 and 8 months as well as 4 months after cessation of treatment. Initially, thyroid volume, as determined by ultrasound, was not significantly different in the three groups.

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Cerebrovascular Reactivity to Acetazolamide in (Senile) Dementia of Alzheimer’s Type: Relationship to Disease Severity

Neuropathological reports about denervation and amyloid angiopathy in dementia of Alzheimers type (DAT) as well as signs of selective incomplete white matter infarctions point to a vascular involvement within the degenerative process. In order to investigate potential alterations of cerebrovascular function we performed cerebral blood flow measurements before and after intravenous injection of 1 g acetazolamide using technetium-99m hexamethylpropyleneamine oxime and single photon emission tomography in 12 patients (6 female, 6 male; mean age 70.8 +/- 9.6 years) with probable (senile) dementia of Alzheimers type (SDAT) and 9 controls (7 female, 2 male; mean age 71.2 +/- 8.6 years). SDAT patients revealed significantly reduced cerebrovascular reactivity with lower values with increasing cognitive impairment. We discuss possible underlying mechanisms.

Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody

Immunoscintigraphy with a technetium-99m murine monoclonal IgG1 antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE.

Scintigraphic detection of inflammatory heart disease

Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated.