Quantitation of neuroreceptors: a need for better SPECT imaging.

AIM: Existing methods to determine the binding potential in brain receptor and transporter studies with single-photon emission computed tomography (SPECT) show a marked dependence on the physical performance of the scanner and on the regions of interest (ROIs) drawn. We examined the influence of the physical performance on the binding potential. METHOD: The authors tested three gamma cameras (single-, dual- and triple-head) and two reconstruction techniques (conventional filtered back-projection and iterative reconstruction method) to determine the binding potential in brain receptor studies. Both human and organ-like phantom studies were performed. RESULTS: The binding potential was completely dependent on the imaging resolution, on the reconstruction technique used and on the ROIs drawn. The results of the phantom study revealed that the striatum-to-cerebellum ratio was only 37% of the actual one for the single-head, 63% for the dual-head and 72% for the triple-head gamma camera. CONCLUSION: The multiple head gamma camera with fan-beam collimators and iterative reconstruction with the attenuation based scatter correction is an imaging system of choice which introduces clinically more relevant images and is able to distinguish smaller differences in radioactivity at early stage of disease. However, for quantitative purposes the improvement without the use of the recovery coefficient is not great enough to restore the binding potentials to those of the true ones.

Genetic and environmental factors associated with migraine in schoolchildren.

OBJECTIVE: The aim of this study was to find the prevalence of migraine and headache in schoolchildren in the United Arab Emirates and to determine the genetic and environmental factors associated with these conditions. METHODS: A cross-sectional population study was performed from October 1995 to June 1996. Subjects were selected by a multistage stratified sampling procedure. Data were collected by screening questionnaires followed by clinical interviews. Twelve primary schools and 1400 schoolchildren of United Arab Emirates nationality resident in the Al Ain City, Dubai, and Sharjah emirates were recruited for this study. A total of 1159 (82.7%) schoolchildren gave their consent to the study. RESULTS: The estimated prevalence rates for headache and migraine were 36.9% and 13.7%, respectively. The prevalence of headache is increased with age, the highest prevalence being in 13-year-old children (17.5%). Of the 159 children who fulfilled the diagnostic criteria for migraine, 76 were boys whose mean age (+/- SD) was 10.3 years +/- 2. 8 years, and 83 were girls (mean age 9.9 +/- 2.5 years). Of the children who had migraine, 20 (12.6%) had migraine without aura, and 13 (8.2%) had migraine with aura. The most common migraine symptoms in schoolchildren had been aggravated by physical activity (47.2%) and a positive family history of migraine (46.5%). The most common illnesses were infectious illnesses (41.5%). There was a strong relationship between migraine and the timing of examinations (46.5%). The most common environmental exposure for migraine was found to be playing on a computer (45.9%), followed by loud noise (41.5%), and a hot climate (37.1%). In familial occurrence of headache among immediate relatives, the most frequently affected relative was the mother (17.6%). CONCLUSION: .-Headache and migraine are common in childhood and may be influenced by social, familial, environmental, and psychological factors.

Striatal Dopamine transporter in Parkinson's disease: A Study With a New Radioligand, [(123)I]B-CIT-FP.

Six healthy controls and 12 patients with Parkinson's disease in different disability stages were studied with SPECT using [(123)I]-N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodo-phenyl)-nortropane ([(123)I]beta-CIT-FP), a novel tracer, to label the striatal dopamine transporter. The mean uptake of [(123)I]beta-CIT-FP in the putamen was reduced to 60% of the control mean and to 80% of the average control value in the caudate nucleus. In patients with totally, or predominantly unilateral symptoms the reduction was greater on the side opposite to the predominant symptoms. There was a significant negative correlation between [(123)I]beta-CIT-FP uptake and the Hoehn and Yahr stage both in the putamen (r = - 0.70, p = 0.01) and caudate nucleus (r = - 0.81, p = 0.001). The present results show that SPECT with [(123)I]beta-CIT-FP is a useful method to study the function of presynaptic dopaminergic terminals in PD. Whether [(123)I]beta-CIT-FP provides advantages over widely used [(123)I]beta-CIT other than a shorter scan time and a lower striatal radiation exposure remains to be seen.

Antiplatelet therapy is effective in the prevention of stroke or death in women: subgroup analysis of the European Stroke Prevention Study (ESPS).

Previous stroke prevention studies have suggested that the efficacy of antiplatelet therapy may be less in women than in men. This however, could be due to the small number of women in these trials and the low incidence of cases among female subjects. The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of dipyridamole 75 mg t.i.d and acetylsalicylic acid 330 mg t.i.d. to placebo in the secondary prevention of stroke or death after one or more recent attacks of TIA (transient ischemic attack), RIND (reversible ischemic neurological deficit) or stroke of atherothrombotic origin. From the 2500 patients recruited, 1307 patients were from a single center, Kuopio, East Finland. Forty-five percent of the patients were women. The number of end-point events (stroke or death from any cause) in women was one-third lower than that in men. End-point reduction in the treatment group was about 50% in women and about 40% in men, significantly lower than in the placebo group in both sexes. Thus, in the relatively randomly selected patient population from one Finnish center, a combination of dipyridamole and acetylsalicylic acid is as effective in women as in men in the prevention of stroke or death. It is unclear, however, whether this beneficial effect in both sexes is due to aspirin only or to the combination therapy of aspirin and dipyridamole.

Lysosomal hydrolases in cerebrospinal fluid of multiple sclerosis patients. A follow-up study.

The change in activity of lysosomal hydrolases in the brain tissue of patients with demyelinating disease has been suggested to reflect the demyelination process. In this study we measured neutral proteinase (NP), acid proteinase (AP), and beta-glucuronidase (BG) activities in CSF of 32 patients with multiple sclerosis (MS) (remitting, remitting and relapsing, or chronic progressive course of the disease), 62 controls, and 4 patients with chronic inflammatory disease of central nervous system (ID). Samples from MS patients were taken at different clinical conditions of the disease during the 22-month follow-up. Elevated NP activity was found in patients with relapsing course of MS and also in patients with ID (P less than 0.05). NP activity correlated with the number of leucocytes in CSF of both MS (P less than 0.005, r = 0.50) and control (P less than 0.05, r = 0.21) patients. AP activity decreased in the MS group, especially in patients with remitting or remitting and relapsing courses of the disease (P less than 0.05), but even more in patients with ID (P less than 0.01). During the follow-up the increase in NP activity seemed to be associated with the clinical relapses of MS patients. Other enzymes did not fluctuate with the disease. This study suggests that the change in activity of lysosomal hydrolases is not specific for MS. The increase in NP activity in CSF is associated with clinical relapse of individual MS patients during the follow-up and may indicate immunological activation of the demyelination process in the brain. The large intra- and interindividual variation in enzyme activities in the CSF, however, makes the use of these enzymes difficult for diagnosis of MS and follow-up of MS activity.

The effect of sorbinil treatment on red cell sorbitol levels and clinical and electrophysiological parameters of diabetic neuropathy.

A randomized placebo-controlled double-blind cross-over study was conducted in order to examine the effect of an aldose reductase inhibitor, sorbinil (100 mg daily for 4 weeks), on red cell sorbitol concentration and clinical and electrophysiological parameters of diabetic neuropathy. A total of 31 diabetic patients with either clinically or electrophysiologically verified diabetic neuropathy were studied. Red cell sorbitol levels decreased significantly to the levels reported in non-diabetic subjects, but there were no significant changes in symptoms, signs, vibration perception thresholds or nerve conduction variables. One patient had transient skin rash, fever, myalgia and leucopenia, but no other significant adverse effects were found.

Cholesterol esterase activity in cerebrospinal fluid of multiple sclerosis patients.

Previous studies of brain tissue from multiple sclerosis (MS) patients have shown that the amount of cholesterol esters increases and the level of cholesterol esterase (ChE) activity decreases compared to controls. In this study we present a simple method for measuring ChE activity at pH 7.2 in cerebrospinal fluid (CSF) and CSF-ChE activity during the 18-month follow-up of 32 MS patients in remitting, remitting and relapsing, and chronic progressive courses of the disease. ChE activity in the MS group was compared to the enzyme activity in the CSF of 52 controls and 17 patients suffering from other organic neurological diseases. In the relapse group, ChE activity decreased significantly compared to the chronic progressive group (P less than 0.05) and controls (P less than 0.001). ChE activity was correlated with the Kurtzke points of functional status only in the chronic progressive group of MS patients (P less than 0.05, r = 0.569). During the 18-month follow-up, no significant change was seen in individual levels of ChE among the MS patients. It was concluded that the decrease in pH 7.2 ChE activity in the CSF during the acute phase of MS may reflect the decreased ChE activity in the brains of MS patients. However, the large interindividual variation within patient groups and the slow change at different stages of the disease indicate that measurement of ChE activity in CSF is not suitable for evaluating the clinical diagnosis of MS or for follow-up of the activity of the disease.

Cefaleas crónicas por tensión muscular / Chronic headaches by muscle tension

La tensión nucal es fácil de diagnosticar en la mayoría de los casos, sin embargo, a veces su localización es atípica, por ejemplo, detrás de los ojos o en la región frontal, pasando inadvertida la relación entre el dolor y la contracción muscular. Confirma el diagnóstico un artefacto por contracción muscular en el registro EEG en la misma localización. Además de una vaga sensación de vértigo, suele ser el temor a padecer una enfermedad grave lo que impulsa al paciente a consultar a su médico. En la mayoría de los casos el examen clínico y neurológico permite diferenciar esta afección de otras dolencias. A los pacientes con tensión nucal se los ha de tratar según un esquema bien definido. En primer lugar, se les tiene que explicar la naturaleza de su afección. Luego, suele bastar una medicación durante cierto tiempo y gimnasia en casa. Si los síntomas se deben a condiciones de trabajo desfavorables, pueden estar indicadas sesiones repetidas de fisioterapia. En caso de no responder al tratamiento se requerirán exámenes neurológicos y psicosomáticos.

A method for chromatographic separation and fluorometric quantification of 2',3'-cyclic nucleotide-3'-phosphodiesterase reaction products.

A sensitive method for separation and fluorometric quantification of 2',3'-cyclic nucleotide-3'-phosphodiesterase (EC 3.1.4.37) (CNPase) reaction products with 2',3'-cyclic adenosine monophosphate as substrate is presented. The 2'-AMP product was separated by cellulose thin-layer chromatography in 4 M MgSO4-0.5 M sodium acetate-2-propanol (80:18:2, v/v/v). After reaction with glyoxal dihydrate, the amount of reaction product was determined fluorometrically using excitation at 328 nm and emission at 382 nm. These results correlated well with those obtained using Kurihara and Tsukada's [(1967) J. Neurochem. 14: 1167-1174] paper chromatographic method (r = 0.96). With this fluorometric method, amounts as low as 0.20 nmol of 2'-AMP can be determined, and its sensitivity is comparable to that of the radiochemical method. The method is easy to use and sensitive enough for measuring CNPase activity in tissue with low enzyme activity.

Histamine and histamine-N-methyltransferase in the CSF of patients with multiple sclerosis.

The CSF of twenty-six patients with multiple sclerosis (MS) and of twelve control persons was analysed for histamine and histamine-N-methyltransferase (HMT) activity. Both in patients with remitting and progressive type of disease the histamine level was about 60% higher than in the controls. On the other hand in both groups of patients the HMT activity was significantly lower (32% and 40% respectively) than that of controls. These results suggest an altered histamine metabolism in MS. This might be associated with the immune reaction in MS brain.

Uptake of 5-hydroxytryptamine by blood platelets in Huntington's chorea and Alzheimer type of presenile dementia.

Kinetics of 5-HT uptake by blood platelets was studied om eleven patients with Huntington's chorea and in ten patients with presenile dementia of Alzheimer type. In both groups of patients 5-HT uptake was unchanged in comparison to that of respective controls of the same age. The results do not confirm earlier reports of an increased 5-HT uptake by blood platelets in Huntington's chorea. Platelet 5-HT uptake does not seem to serve as biological test in either disease.

Side effects of sodium valproate during long-term treatment in epilepsy.

Side effects of sodium valproate during long-term treatment have been evaluated retrospectively in 55 patients suffering from refactory epilepsy. The side effects discovered in the study were slight and transient. In three of the 55 patients CNS side effects were noticed. Gastrointestinal symptoms were uncommon. One patient suffered from loss of hair which could have been attributed to sodium valproate. Severe side effects such as abnormal blood counts or organ damage were not discovered. The frequency of side effects was similar to those already reported in the literature except for gastrointestinal symptoms which were more infrequent than previously reported. No direct correlation could be established between the serum concentration of sodium valproate and the side effects.