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PubMed2002

Noradrenergic receptors and in vitro respiratory rhythm: possible interspecies differences between mouse and rat neonates.

Similar in vitro experiments were performed on brainstem-spinal cord preparations from mouse and rat neonates to compare the noradrenergic regulations of the respiratory network. In preparations retaining the pons, rhythmic phrenic bursts occurred in rats but not in mice. Transection of the pons, electrolytic lesions and noradrenaline applications showed that the pontine noradrenergic A5 group inhibited the respiratory rhythm generator in both species but the inhibition was especially potent in mice. After pons elimination, noradrenaline applications to the medulla decreased the respiratory frequency in rats but increased it in mice. Noradrenergic agent applications revealed that the frequency changes implicated medullary alpha 1 and alpha 2 noradrenergic receptors in mice and rats, respectively. Thus, interspecies differences seem to exist in the noradrenergic regulations of the rat and mouse medullary respiratory networks.

Action Potentials↗
PubMed2002

Nonverbal social perception and symptomatology in schizophrenia.

This study examined the relationship between nonverbal social perception and symptomatology in schizophrenia. Schizophrenic patients (n=28) and normal controls (n=28) were given the profile of nonverbal sensitivity test (PONS). Patients' symptoms were rated with the brief psychiatric rating scale (BPRS). Schizophrenic subjects performed significantly more poorly than normal subjects in their ability to decode nonverbal cues. In addition, normal subjects improved their accuracy significantly more than patients when provided with additional cues per scene to decode. The patients' total PONS score was not significantly correlated with the BPRS summary scores for positive or negative symptoms, but was significantly correlated with the individual positive symptom of conceptual disorganization. Subjects classified as having paranoid schizophrenia (n=11) on the basis of chart diagnoses performed significantly better on the PONS than did undifferentiated schizophrenic subjects (n=13). The discussion reviews how these results contribute to our understanding of social deficits in schizophrenia.

Adult↗
PubMed1999

Poor perception of nonverbal social-emotional cues in relatives of schizophrenic patients.

The present study compared nonverbal social perception in relatives of schizophrenic patients (n = 21) with that of normal controls (n= 19). We hypothesized that relatives would display deficits in social perception and we sought to determine the skills that are associated with this deficit. Relatives performed significantly worse than controls on the Profile of Nonverbal Sensitivity Test (PONS), despite comparable performance on skills hypothesized to be related to nonverbal social perception: visual perception, nonverbal problem solving, facial recognition, facial affect recognition, naming, social judgment, and vigilance. To further explore the relationships among these skills, we calculated correlations between the PONS score and associated skills separately within both the relative and control groups and assessed whether the values of these correlations differed between groups. Correlations that differed significantly indicated a greater association, within relatives, between slower reaction times on vigilance tasks and poor PONS performance. Further research is needed to clarify the nature of this relationship, to better characterize social perception deficits in relatives, and to determine whether these perceptual deficits are part of the genetic diathesis to schizophrenia.

Adult↗
PubMed1998

DNA binding properties of the ecdysteroid receptor in the salivary gland of the female ixodid tick, Amblyomma hebraeum.

Salivary gland degeneration in the female tick, Amblyomma hebraeum Koch (Acari: Ixodidae) is controlled by an ecdysteroid hormone. In an earlier study (Mao, H., McBlain, W.A., Kaufman, W.R., 1995. Some properties of the ecdysteroid receptor in the salivary gland of the ixodid tick, Amblyomma hebraeum. Gen. Comp. Endocrinol. 99, 340-348), we demonstrated that a protein component of a salivary gland extract binds to ponasterone A (Pon A) with high affinity (Kd-1 nM), suggesting a tick ecdysteroid receptor (EcR). In this study, the Pon A binding protein bound to calf thymus DNA; this binding could be dissociated by Drosophila hsp27 EcRE. The binding protein shifted the [32P]hsp27 EcRE band on a gel mobility shift assay; formation of the complex with hsp27 EcRE required KCl (optimal concentration was approximately 75 mM). A number of physiologically effective ecdysteroids enhanced the binding with the following order of potency: Pon A > Mur A > Mak A > 20E > ecdysone, whereas vertebrate steroids (estradiol, cholesterol, corticosterone, progesterone, testosterone) had no such effect. Using monoclonal antibodies against Drosophila EcR and USP, we found that AG 10.2 recognized three bands (90.5, 87.3 and 84 kDa for EcR) and AB11 recognized at least two major bands (50.3 and 47.1 kDa for USP) in the salivary gland extract by western blot analysis. In addition, AB11 supershifted the tick EcR-hsp27 EcRE band on a gel mobility shift assay, indicating that the tick EcR heterodimerized with a USP-like protein for DNA binding. Furthermore, selective mutations to the 15-basepair palindrome of hsp27 EcRE at positions-5, + 2, or adding a base to the spacer, resulted in considerably reduced affinity to the tick EcR/USP. We thus propose a sequence similarity of EcREs between A. hebraeum and its insect counterpart.

Animals↗
PubMed2003

Event-related potentials during visual S1-S2 paradigm in multiple system atrophy: relation to morphologic changes on brain MRI measurement.

Although mild cognitive deficits in multiple system atrophy (MSA) have been proved on neuropsychological testing, the cognitive function in MSA has not been investigated sufficiently from an electrophysiological view point. We performed a visual Event-related potential (ERP) examination and quantitative magnetic resonance imaging (MRI) measurements on 24 MSA patients and 18 normal subjects, and investigated the relationship between the ERP abnormalities and the morphological changes of the brain in MSA patients. To elicit ERPs, we used S1-S2 task which needs frontal lobe function for execution. We found significant prolongation of P3 latency and reaction time and significant attenuation of P3 amplitude in MSA, compared with normal control values. We performed the square and linear MRI measurements on MSA and normal subjects. The cerebellum, the pons, the perisylvian cerebral area and the deep cerebral gray matter in MSA were significantly smaller than those in normal subjects. The mean value in MSA was significantly increased for the bicaudate index and Huckman number compared with those in normal subjects. In MSA, we found significant correlation between P3 latency and atrophy of the cerebellum and the pons, while we found no correlation between ERP abnormalities and quantitative MRI measurements of any other regions. Our results showed that the prolongation of visual P3 latency during S1-S2 task was significantly associated with atrophy of the cerebellum and the pons.

Aged↗
PubMed2001

Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study.

OBJECTIVE: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). METHODS: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). RESULTS: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent findings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. CONCLUSIONS: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage.

Adult↗
PubMed2005

Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase.

PON1 is the best-studied member of a family of enzymes called serum paraoxonases, or PONs, identified in mammals (including humans) and other vertebrates as well as in invertebrates. PONs exhibit a range of important activities, including drug metabolism and detoxification of organophosphates such as nerve agents. PON1 resides on HDL (the "good cholesterol") and is also involved in the prevention of atherosclerosis. Despite this wealth of activities, the identity of PON1's native substrate, namely, the substrate for which this enzyme and other enzymes from the PON family evolved, remains unknown. To elucidate the substrate preference and other details of PON1 mechanism of catalysis, structure-activity studies were performed with three groups of substrates that are known to be hydrolyzed by PON1: phosphotriesters, esters, and lactones. We found that the hydrolysis of aryl esters is governed primarily by steric factors and not the pK(a) of the leaving group. The rates of hydrolysis of aliphatic esters are much slower and show a similar dependence on the pK(a) of the leaving group to that of the nonenzymatic reactions in solution, while the aryl phosphotriesters show much higher dependence than the respective nonenzymatic reaction. PON1-catalyzed lactone hydrolysis shows almost no dependence on the pK(a) of the leaving group, and unlike all other substrates, lactones seem to differ in their K(M) rather than k(cat) values. These, and the relatively high rates measured with several lactone substrates (k(cat)/K(M) approximately 10(6) M(-)(1) s(-)(1)) imply that PON1 is in fact a lactonase.

Animals↗
PubMed2001

Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division.

Cell-fate diversity is generated in part by the unequal segregation of cell-fate determinants during asymmetric cell divisions. In the Drosophila pupa, the pI sense organ precursor cell is polarized along the anterior-posterior axis of the fly and divides asymmetrically to generate a posterior pIIa cell and an anterior pIIb cell. The anterior pIIb cell specifically inherits the determinant Numb and the adaptor protein Partner of Numb (Pon). By labelling both the Pon crescent and the microtubules in living pupae, we show that determinants localize at the anterior cortex before mitotic-spindle formation, and that the spindle forms with random orientation and rotates to line up with the Pon crescent. By imaging living frizzled (fz) mutant pupae we show that Fz regulates the orientation of the polarity axis of pI, the initiation of spindle rotation and the unequal partitioning of determinants. We conclude that Fz participates in establishing the polarity of pI.

Animals↗
PubMed1993

The molecular basis of the human serum paraoxonase activity polymorphism.

The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.

Aryldialkylphosphatase↗
PubMed1996

Brain MRI in children with migraine: a controlled morphometric study.

Sixteen children and adolescents, aged 5-17 years, with migraine and 24 migraine-free age-matched healthy volunteers underwent brain MRI (1.0 T). Signal intensities of the brain, midsagittal and coronal diameters of the brainstem were quantitatively measured. General signal intensities did not differ between the groups. Compared to controls (17%), more migraine patients (50%) had high-signal foci on T2-weighted images. The diameters of the pons were greater in the migraine group (p = 0.016), although within the normal range. The diameters of the mesencephalon and the medulla oblongata did not differ between the groups, perhaps because they reach the adult size in early childhood in contrast to the pons, which continues to grow. Childhood migraine may be associated with slightly more than average growth of the pons. As the pathophysiology of migraine is still unclear, it might be worth studying with new MR methods.

Adolescent↗
PubMed1995

Distribution of branch point prenyltransferases in regions of bovine brain.

Bovine brains contain large amounts of isoprenoid compounds and the enzymes involved in their biosynthesis were investigated. Ten different regions were dissected from fresh bovine brains and, in addition, fractions from cerebellum, spinal cord, and hypophysis were obtained. The cholesterol concentration was found to be approximately 8 mg/g in the cortex regions and three times higher in the pons, medulla oblongata, and white matter. Dolichol concentration varied between 8 and 40 micrograms/g in the different tissues, and ubiquinone was found at a lower level, which varied between 3 and 25 micrograms/g. Farnesylpyrophosphate synthase activity in cytosolic fractions from various regions exhibited only a twofold variation, whereas geranylgeranyl pyrophosphate synthase displayed larger differences, being particularly rich in the pons, medulla oblongata, white matter, and spinal cord. Squalene synthase activity was lowest in the thalamus and threefold higher in the pons. Determination of specific activity based on cholesterol content revealed that enzyme activities in various regions are not related to the actual lipid amount present. Both cis- and trans-prenyltransferases exhibited similarities in their regional distribution showing up to 20-fold differences in activity. Thus, it appears that the mevalonate pathway lipids and the various branch point enzymes involved in their syntheses vary greatly in different brain regions and are subjected to separate regulation.

Animals↗
PubMed2000

Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes.

Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polymorphisms of the PON1 gene and investigated PON1 enzyme activities as paraoxonase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 concentration in 106 patients with type 2 diabetes and 161 control subjects. All 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no difference in serum PON1 concentration between the patient and control groups. The specific activities of PON, ARYL, and DIAZ in patients were 6.82 +/- 3.14 nmol x min(-1) x U(-1) (mean +/- SD, U; unit for serum PON1 concentration), 4.77 +/- 0.17 micromol x min(-1) x U(-1), and 193 +/- 92 nmol x min(-1) x U(-1), respectively, whereas those in controls were 9.33 +/- 3.92 nmol x min(-1) x U(-1), 5.36 +/- 0.14 micromol x min(-1) x U(-1), and 242 +/- 103 nmol x min(-1) x U(-1), respectively. There was no significant difference in the allelic frequencies of -108C/T, 55L/M, or 192Q/R between the patient and control groups. When each enzyme activity was compared between the patient and control groups in each genotype subgroup, all activities were lower in the patient group. The PON and ARYL activities were lower in patients with retinopathy or nephropathy than in those without such complications, and the ARYL activity was also lower in patients with neuropathy. In conclusion, all specific enzyme activities of PON1 were lower in patients with type 2 diabetes independent of the -108C/T, 55L/M, or 192Q/R polymorphism, and this impaired PON1 function may be involved in development of diabetic microangiopathy.

Aged↗
PubMed1997

Cranial MR findings in Wilson's disease.

PURPOSE: To define various cranial MR appearances in Wilson's disease (WD). MATERIAL AND METHODS: MR examinations of 30 patients (9-44 years old) with WD were retrospectively reviewed. Six patients were asymptomatic siblings. Three other patients had isolated hepatic involvement, one with no symptoms. The remaining 21 patients had neurological involvement, 7 of whom had the mixed form of the disease. Nine patients had hepatic dysfunction, the 3 with isolated hepatic involvement and 6 of the 7 with the mixed form. RESULTS: All symptomatic patients (n = 23) had abnormal MR examinations, Atrophy was present in the majority of them. The most frequently involved sites were putamen (18/21) and pons (18/21) in patients with neurological abnormality. The putaminal lesions showed a consistent pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity. Putaminal lesions were lacking in only 3 patients with neurological involvement, all of whom were relatively old and had had the disease for a longer duration. Most of the patients with hepatic dysfunction (8/9) had increased T1 signal intensity in the basal ganglia, particularly in the globus pallidus. Pontine involvement always included the dorsal aspect of the pons, however, in some cases the central portion of pons was also affected but ventrolateral longitudinal fibers were spared. Midbrain (16/21), thalamic (10/21) and caudate nucleus lesions (9/21) were also encountered. In a few patients cortical and subcortical white matter lesions were present with a predilection to the frontal lobe, particularly the precentral region. In one patient, a hemorrhagic focus was identified within the white matter lesion. CONCLUSION: On T2-weighted images, WD is suggested by: atrophy; putaminal lesions with a pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity; and the involvement of the pars compacta of the substantia nigra, periaqueductal gray matter, the pontine tegmentum and the thalamus. The hepatic component of WD may cause increased T1 signal intensity in basal ganglia. In the adult age group, the basal ganglia lesions may be different from those in the pediatric group; the putaminal lesions may not be present; the globus pallidus and substantia nigra may show increased hypointensity on T2-weighted images. Cortical and subcortical lesions may also be present with a predilection to the frontal lobe.

Adolescent↗
PubMed2004

Corticospinal tract degeneration and possible pathogenesis in ALS evaluated by MR diffusion tensor imaging.

BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to investigate the neuronal and axonal fibre distribution in the human brain. Changes in diffusion characteristics of water molecules in the white matter can be estimated as the apparent diffusion coefficient (ADC) and the fractional anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different levels in the corticospinal tract (CST) (corona radiata, internal capsule and pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or retrograde axonal degeneration. METHODS: We studied eight ALS patients with clinical signs of upper motor neuron involvement. The patients were compared with 11 healthy age-matched controls. RESULTS: ADC was significantly increased in the CST in ALS patients at the level of the internal capsule and also increased in the pons, but without statistical significance. ADC was unchanged at the level of the corona radiata. FA was significantly reduced at the lowest level (pons), only tended to be reduced in the internal capsule, but was also unchanged in the corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports the hypothesis of a 'dying back' mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS.

Adult↗
PubMed1998

DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease.

A common polymorphism at codon 192 in the human paraoxonase (PON) 1 gene has been shown to be associated with increased risk for coronary heart disease (CHD) in Caucasian populations. However, these findings have not been reported consistently in all Caucasian and non-Caucasian populations, suggesting that this is not a functional mutation but may mark a functional mutation present in either PON1 or a nearby gene. Recently, two other PON-like genes, designated "PON2" and "PON3," have been identified, and they are linked with the known PON1 gene on chromosome 7. Identification of additional polymorphisms in the PON-gene cluster may help to locate the functional polymorphism. In this report, we describe the existence of a common polymorphism at codon 311 (Cys-->Ser; PON2*S) in the PON2 gene, as well as its association with CHD alone and in combination with the PON1 codon 192 polymorphism in Asian Indians. The frequency of the PON2*S allele was significantly higher in cases than in controls (.71 vs. .61; P=.016). The age- and sex-adjusted odds ratio (OR) was 2.5 (95% confidence interval &sqbl0;95% CI&sqbr0;=1.8-3.1; P=.0090) for the PON2*S allele carriers. Further stratification of the PON2*S association, on the basis of the presence or absence of the PON1*B allele, showed that the CHD risk associated with the PON2*S allele was confined to PON1*B-allele carriers. Likewise, the PON1*B-allele risk was present only among PON2*S carriers. Age- and sex-adjusted ORs for the PON2*S and PON1*B were 3.6 (95% CI=2.6-4.6; P=.011) and 2.9 (95% CI=2.4-3.5; P=.0002) among the PON1*B and PON2*S carriers, respectively. Our data indicate that both polymorphisms synergistically contribute to the CHD risk in this sample and that this genetic risk is independent of the conventional plasma lipid profile.

Adult↗
PubMed2002

Association between the severity of angiographic coronary artery disease and paraoxonase gene polymorphisms in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

Paraoxonase (PON), a high-density lipoprotein-associated enzyme, is believed to protect against low-density lipoprotein oxidation and thus affects the risk of coronary artery disease (CAD). Three polymorphisms in the PON1 (Leu55Met and Gln192Arg) and PON2 (Ser311Cys) genes have been shown to be associated with the risk of CAD in several European or European-derived populations. In the present study, we examined the associations between these three markers and the severity of CAD as determined by the number of diseased coronary artery vessels in 711 subjects (589 whites and 122 blacks) from the Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a National Heart, Lung, and Blood Institute-sponsored multicenter study designed to address issues related to ischemic-heart-disease recognition and diagnosis in women. Subjects were classified as having normal/minimal CAD (<20% stenosis), mild CAD (20%-49% stenosis), and significant CAD (>/=50% stenosis). The women who had >/=50% stenosis were further classified into groups with one-, two-, or three-vessel disease if any of the three coronary arteries had diameter stenosis >/=50%. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON1 codon 192 Arg/Arg genotype was significantly higher in the group with three-vessel disease than in the other groups (those with one-vessel and two-vessel disease) combined (17.02% vs. 4.58%; P=.0066). Similarly, the frequency of the PON2 codon 311 Cys/Cys genotype was significantly higher in the group with three-vessel disease than in the other groups combined (15.22% vs. 4.61%; P=.018). The adjusted odds ratios for the development of three-vessel disease were 2.80 (95% confidence interval 1.06-7.37; P=.038) for PON1 codon 192 Arg/Arg and 3.68 (95% confidence interval 1.26-10.68; P=.017) for PON2 codon 311 Cys/Cys. Our data indicate that the severity of CAD, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster, on chromosome 7.

Adult↗
PubMed2004

Polygonatum rhizoma affects antioxidant defense systems without changing mRNA expression in diet-induced hypercholesterolemic rabbits.

This study was conducted to determine the antioxidant effects of a Polygonatum extract compared with the major antioxidant, vitamin E, in rabbits fed a high-cholesterol diet. Rabbits were given a high-cholesterol (0.5%, wt/wt) diet with vitamin E (0.03%, wt/wt) or a Polygonatum extract (0.05%, wt/wt) for 8 weeks. The body weight gain (g/week) was only significantly increased only in the high-cholesterol-fed control group, yet the relative liver weight was significantly lower in the Polygonatum group compared with the other groups. The supplementation of vitamin E and Polygonatum extract led to an increase in the hepatic catalase (CAT) activity without any change in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Hepatic total glutathione content was significantly higher in the Polygonatum group than in the other groups. The level of hepatic mitochondrial H(2)O(2) was significantly lower in the two supplemented groups compared with the control group, whereas the level of cytosolic H(2)O(2) was only significantly lower in the Polygonatum group than in the control group. The level of plasma thiobarbituric acid-reactive substances (TBARS) was only significantly lower in the vitamin E group, whereas the level of hepatic TBARS was slightly lower in the Polygonatum group than in the other groups. In the case of the high-density lipoprotein-related antioxidant enzyme, vitamin E supplementation produced the highest plasma paraoxonase (PON) activity compared with the other groups, although there was no difference in the hepatic PON activity among the groups. Meanwhile, the plasma vitamin E concentration was significantly higher in the vitamin E and Polygonatum groups than in the control group; however, plasma vitamin A concentration did not differ significantly between the groups. As regards the mRNA expressions of hepatic antioxidant enzymes, the vitamin E and Polygonatum extract supplementation had no effect on the SOD, CAT, GSH-Px, and PON mRNA expression. Accordingly, these results indicate that the Polygonatum extract had a positive effect on the antioxidant defense system based on decreasing the content of hepatic TBARS and hydrogen peroxide, increasing the CAT activity and total glutathione level in the liver, and sparing the plasma vitamin E. Thus, further studies on the functional components in Polygonatum extract and their biological efficacies are needed.

Animals↗
PubMed2003

Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study.

Electrical stimulation of primary sensory afferents is known to have an antinociceptive effect. Animal and functional imaging studies suggest a role for supraspinal structures in this response. Eight patients with chronic migraine (> or =15 days per month of attacks of migraine without aura), who had shown a marked beneficial response to implanted bilateral suboccipital stimulators, were studied. Stimulation evoked local paraesthesia, the presence of which was a criterion of pain relief. On stimulation, the headache began to improve instantaneously and was completely suppressed within 30 min. On switching off the stimulation, the headache recurred instantly and peaked within 20 min. PET scans were performed using regional cerebral blood flow (rCBF) as a marker of neuronal activity. Each patient was scanned in the following three states: (1) stimulator at optimum settings: patient pain-free but with paraesthesia; (2) stimulator off: patient in pain and no paraesthesia; (3) stimulator partially activated: patient with intermediate levels of pain and paraesthesia. All scans were processed and analysed using Statistical Parametric Mapping (SPM) 99. There were significant changes in rCBF in the dorsal rostral pons, anterior cingulate cortex (ACC) and cuneus, correlated to pain scores, and in the ACC and left pulvinar, correlated to stimulation-induced paraesthesia scores. The activation pattern in the dorsal rostral pons is highly suggestive of a role for this structure in the pathophysiology of chronic migraine. The localization and persistence of activity during stimulation is exactly consistent with a region activated in episodic migraine, and with the persistence of activation of that area after successful treatment. The dorsal rostral pons may be a locus of neuromodulation by suboccipital stimulation. In addition, suboccipital stimulation modulated activity in the left pulvinar.

Adult↗