[18F]FDG-PET and whole-scalp MEG localization of epileptogenic cortex.

PURPOSE: To evaluate combined [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 122-channel whole-scalp magnetoencephalography (MEG) in lateralizing the epileptogenic cortex in patients whose routine presurgical evaluations gave discordant results about the location of the epileptic focus. METHODS: Nine patients (five women, four men) aged 13-40 years were studied. Subdural EEG (SEEG) was recorded from eight patients. Six patients were operated on. RESULTS: In seven of nine patients, PET and MEG agreed in localizing the epileptogenic cortex. When PET and MEG were in congruence, SEEG agreed with the findings. In five of six operated-on patients, PET and MEG results were congruent, and the outcome of the operation was successful. Two patients had discordant PET and MEG results. In one patient, PET showed bitemporal hypometabolism, whereas MEG showed epileptiform activity in the right parietal lobe. The surgical outcome of the palliative temporal lobectomy was poor. Another patient had unilateral temporal hypometabolism in PET and bitemporal activity in MEG. She was not operated on. CONCLUSIONS: In most patients, PET and MEG were congruent in locating the epileptogenic cortex. Thus the combination of these techniques may provide useful support for the localization of the seizure onset and reduce the need for invasive procedures.

Comparison of [18F]FDG-PET, [99mTc]-HMPAO-SPECT, and [123I]-iomazenil-SPECT in localising the epileptogenic cortex.

OBJECTIVES: Firstly, to compare the findings of interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and of single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene-amine-oxime (HMPAO) and 123I-iomazenil in localising the epileptogenic cortex in patients who were candidates for epilepsy surgery, but in whom clinical findings, video EEG monitoring (V-EEG), MRI, and neuropsychological evaluations did not give any definite localisation of the seizure onset. Secondly, to assess the ability of these functional methods to help in the decision about the epilepsy surgery. METHODS: Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT. HMPAO-SPECT was performed in 11 of these 18 patients. Two references for localisation was used--ictal subdural EEG recordings (S-EEG) and the operated region. RESULTS: Fifteen of 18 patients had localising findings in S-EEG. FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients. HMPAO-SPECT visualised the focus less accurately than the two other methods. In three patients S-EEG showed independent bitemporal seizure onset. In these patients FDG-PET showed no lateralisation. However, iomazenil-SPECT showed temporal lobe lateralisation in two of them. CONCLUSION: FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy.

De novo aneurysms: special multiple intracranial aneurysms.

Very few patients develop completely new intracranial aneurysms during long-term follow-up after successfully treated subarachnoid hemorrhages. Aneurysms appearing after therapeutic ligation of proximal major vessels or failed surgery and the growth of previously noticed infundibular widenings or small aneurysms must be excluded to find true de novo aneurysms. Twenty-nine true cases of de novo aneurysms were reported in the literature, and 13 additional cases of our own are described. The incidence of de novo aneurysm formation and rupture is 63 per 100,000 per year in patients known to have a subarachnoid hemorrhage. Young patients could benefit from long-term neuroradiological follow-up.

Chemical neurotransmission in the parkinsonian brain.

In Parkinson's disease the progressive loss of nigrostriatal dopamine neurons leads to striatal dopamine deficiency and correlates with the severity of parkinsonian disability. The findings concerning dopamine receptors both in vitro and in vivo are not consistent, possibly reflecting differences in patient populations, but the presynaptic defect in dopaminergic neurotransmission is greater than that seen in postsynaptic receptor binding studies. The cholinergic neurons in the extrapyramidal nuclei are relatively well preserved, but subcortico-cortical and -hippocampal cholinergic neurons degenerate in relation to the degree of dementia. The decreased GABA receptor binding in the parkinsonian substantia nigra possibly reflects the loss of nigral dopamine neurons, since nigral GABA receptors are located on these neurons. Of the various neuropeptides, the concentration of met- and leu-enkephalin seems to be reduced in the striatum. In the substantia nigra the concentration of substance P decreases, together with the met-enkephalin and cholecystokinin levels. The concentration of somatostatin decreases in the frontal cortex and hippocampus of demented patients. With the exception of the association between cortical somatostatin deficiency and intellectual deterioration, the role of the neuropeptides in the pathophysiology and clinical features of Parkinson's disease are not yet fully understood.

Dopamine D-1 receptors in the parkinsonian brain.

Dopamine D-1 receptors were analyzed in the caudate nucleus, putamen, pallidum, substantia nigra and nucleus accumbens in 20 patients with Parkinson's disease and in 18 age-matched controls by the binding of [3H]flupenthixol. The binding was decreased in the substantia nigra in those parkinsonian patients who were not treated with levodopa. A significantly increased number of D-1 receptors was found in the putamen of patients with Parkinson's disease, especially in those who were treated with levodopa. The increased binding of [3H]flupenthixol was most prominent in those six parkinsonian patients who still had therapeutic response to levodopa. In addition, orofacial dyskinesias were seen in three of these patients. The results of this study indicate that there may be denervation supersensitivity of striatal neurons and also a loss of striatonigral neurons in Parkinson's disease.

Brain muscarinic receptors in senile dementia.

Muscarinic receptors were analyzed in various post-mortem brain samples of 39 patients with different types of dementia and of 30 age-matched controls by the specific binding of [3H]QNB. The diagnoses were verified neuropathologically. The binding of [3H]QNB was significantly decreased in the hippocampus, amygdala and nucleus accumbens in patients with Alzheimer's disease (AD) and with combined type of dementia (CD), whereas in patients with multi-infarct dementia (MID) the binding was not significantly decreased in the limbic areas but only in the caudate nucleus. Of the clinical variables, orofacial dyskinesias in patients with AD but not with MID correlated with low brain weight and with the decreased [3H]QNB binding in the striatum and frontal cortex. The results reveal some differences between AD and MID. Changes in muscarinic receptor binding show that the cholinergic neurons in the limbic system are especially vulnerable in patients with AD and CD.

Brain neurotransmitters and neuropeptides in Parkinson's disease.

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.

Brain neurotransmitters and neuropeptides in Parkinsons disease.

Parkinsons disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.

Brain enkephalin receptors in Parkinson's disease.

Brain enkephalin receptors were studied in post-mortem brain samples of 27 patients with Parkinson's disease and of 26 control subjects without extrapyramidal disorders by the radioligand-binding technique using 3H-leu-enkephalin, 3H-met-enkephalin and 3H-naloxone. The specific binding of both 3H-leu- and 3H-met-enkephalins was significantly increased in the caudate nucleus, putamen, nucleus accumbens, limbic cortex and hippocampus. Scatchard analysis showed that there was an increase in the receptor number, but no significant changes in the mean dissociation constant. Levodopa treatment did not have any significant effect on the enkephalin bindings. A significantly decreased binding of 3H-naloxone was found in the parkinsonian caudate nucleus. Thus there is a supersensitivity of a population of enkephalin receptors in the striatum and limbic system, as well as a loss of other opiate receptors in the striatum, suggesting the involvement of certain brain enkephalin neurons in the pathophysiological process of Parkinson's disease.

Brain receptor changes in Parkinson's disease in relation to the disease process and treatment.

With regard to the behaviour of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either an increase or a decrease in the number of D-2 receptors was found. Dyskinesias, daily fluctuations in performance, and psychotic episodes together with neuroleptic medication, were associated with an increase in the number of striatal D-2 receptors. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. In agreement with post-mortem brain studies, increased responses of prolactin secretion to TRH in vivo also suggested a decreased D-2 receptor function in parkinsonian patients with recent onset and supersensitivity in patients with on-off phenomena. D-3 receptor binding sites had decreased in the parkinsonian striatum. In contrast to D-2 receptors, the D-3 sites seem to be less sensitive to treatment with neuroleptic drugs. Changes in the binding of 3H-enkephalins indicated that there is a supersensitivity of a population of enkephalin receptors (delta) in the striatum and limbic system. Treatment with levodopa did not have any significant effect on the binding of 3H-enkephalins. The binding of 3H-naloxone decreased in the parkinsonian caudate nucleus, suggesting that a population of opiate receptors (mu) is located on the dopamine nerve terminals in the striatum. Thus there are multiple neuronal disturbances in the parkinsonian brain, although those of nigrostriatal dopamine neurons seem to be greater and more closely related to the parkinsonian clinical features and to treatment responses.