Recovery of the brain choline level in treated Cushing’s patients as monitored by proton magnetic resonance spectroscopy

In a previous study from our group [A. Khiat, C. Bard, A. Lacroix, J. Rousseau, Y. Boulanger, Brain metabolic alterations in Cushing’s syndrome as monitored by proton magnetic resonance spectroscopy, NMR Biomed. 12 (1999) 357–363], proton magnetic resonance spectroscopy (¹H MRS) was used to evaluate changes in cerebral metabolites in patients with Cushing’s syndrome as compared to normal subjects. Data recorded in the frontal, thalamic and temporal areas demonstrated statistically significant decreases of the Cho/Cr ratios in the frontal and thalamic areas but not in the temporal area for Cushing’s syndrome patients. No statistically significant changes in the NAA/Cr ratios were measured in any of the areas studied. In this follow-up study, MRS data are reported for ten patients after correction of hypercortisolism which demonstrate a statistically significant recovery of the choline levels in the frontal and thalamic areas. No variation in the NAA, Cr and mI metabolite ratios relative to H₂O could be measured. Results are interpreted as an inhibition of the phosphatidylcholine degrading phospholipases by glucocorticoids which disappears after correction of hypercortisolism.     

Long-term brain metabolic alterations in exogenous Cushing's syndrome as monitored by proton magnetic resonance spectroscopy

The effects of exogenous Cushing's syndrome on the brain metabolism were investigated by proton magnetic resonance spectroscopy (MRS). Thirteen patients having been treated for 2 to 22 years with prednisone were recruited. On the average, none of the metabolites (NAA, Cr, Cho and mI) were significantly different from those of 40 normal subjects in any of the three regions studied: frontal area, thalamus and temporal area. However, the Cho/H(2)O ratios were found to decrease significantly in the thalamic area as a function of treatment period (-1.3%/year). In the frontal and temporal areas, decreases of the Cho/H(2)O ratios were measured with treatment period but they did not reach statistical significance. Effects on Cho levels can be related to those observed for patients with endogenous Cushing's syndrome and suggest an impairment at the membrane level. The Cho/H(2)O reductions were not found to be dose- or age-dependent. Other metabolite ratios did not vary with treatment period, dose or age.     

Recovery of the brain choline level in treated Cushing's patients as monitored by proton magnetic resonance spectroscopy

In a previous study from our group [A. Khiat, C. Bard, A. Lacroix, J. Rousseau, Y. Boulanger, Brain metabolic alterations in Cushing's syndrome as monitored by proton magnetic resonance spectroscopy, NMR Biomed. 12 (1999) 357-363], proton magnetic resonance spectroscopy (1H MRS) was used to evaluate changes in cerebral metabolites in patients with Cushing's syndrome as compared to normal subjects. Data recorded in the frontal, thalamic and temporal areas demonstrated statistically significant decreases of the Cho/Cr ratios in the frontal and thalamic areas but not in the temporal area for Cushing's syndrome patients. No statistically significant changes in the NAA/Cr ratios were measured in any of the areas studied. In this follow-up study, MRS data are reported for ten patients after correction of hypercortisolism which demonstrate a statistically significant recovery of the choline levels in the frontal and thalamic areas. No variation in the NAA, Cr and mI metabolite ratios relative to H(2)O could be measured. Results are interpreted as an inhibition of the phosphatidylcholine degrading phospholipases by glucocorticoids which disappears after correction of hypercortisolism.     

1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study

BACKGROUND—In vivo magnetic resonancespectroscopy (MRS) has been widely used to assess biochemical changeswhich occur in demyelinating lesions in white matter of patients withmultiple sclerosis. It has been suggested that metabolic variationsevidenced by MRS are sensitive indicators of the effects ofimmunomodulatory treatments in this disease.
Given the recent finding of an increase in the diseaseactivity in patients with multiple sclerosis treated with interferon (IFN) β-1a in the first period of treatment,¹H MRS wasused to investigate further the modification in brain metabolicindices, particularly in the first phase of IFN βtreatment.
METHODS—A ¹H MRS study wasperformed on five patients with relapsing-remitting multiple sclerosiswho were being treated with intramuscular IFN β-1a (6 millionunits/week) for six months and on five untreated patients. The meanage, duration of the disease, and expanded disability status scores(EDSS) of the two groups were similar. Patients were evaluated at thebeginning of the study and in the first, third, and sixth months of treatment.
RESULTS—In the multiple sclerosis whitematter lesions, N-acetylaspartate (NAA), choline (Cho), inositol (Ins),and creatine (Cr) peaks did not vary significantly over the entireperiod of the study in the untreated group.
In the treated group there was a significant increase in theCho peak area at the first month compared with the pretreatment period,and this increase continued in the third and sixth months (p<0.001). Aslight but not significant rise in the Cho peak was also found innormal appearing white matter in the patient group undergoing treatmentwith IFN β-1a. The increase in Cho and the lack of significantchanges in Cr and NAA peaks induced a significant rise in Cho/Cr andCho/NAA ratios over the entire period of treatment compared with thoseat the beginning of the study (p<0.02 and p<0.005 respectively).
In the treated group there was a slight but significantincrease in the Ins peak in the first month (p<0.05) but in the third and sixth months of treatment the Ins values returned to thepretreatment range.
CONCLUSIONS—IFN β-1a has an impact onmetabolite concentrations in multiple sclerosis lesions measured byproton MRS. The increase in Cho, Cho/NAA, and Cho/Cr ratios in multiplesclerosis lesions reinforces the view that they are an index of activeor recent demyelination and could support the clinical,neuroradiological and immunological evidence showing an increase indisease activity during the first period of treatment with IFN β-1a.On the other hand, the increase in the Cho peak could be indicative ofa rise in membrane turnover in multiple sclerosis lesions or aremodelling of plaques which is not necessarily due to a de novo immunemediated demyelination.

     

Brain metabolic differences as a function of hemisphere, writing hand preference, and gender

A total of 35 university-educated normal men (24 right handwriters and 11 left handwriters) and 36 age- and education-matched women (25 right handwriters and 11 left handwriters) underwent a proton magnetic resonance spectroscopy examination in seven 8 cm(3) voxels including the right and left frontal lobe tips, the right and left mid-temporal lobes, the right and left thalami, and the hypothalamus. Dependent measures were N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine/phosphocreatine (Cr) metabolite peak area ratios relative to total H(2)O. As expected, thalamic grey matter contained higher NAA ratios than telencephalic voxels (containing white and grey matter) (p < .001). The thalamic Cr/ H(2)O ratio was higher on the right, but the opposite asymmetry was observed for the temporal lobe (p < .05). Women had a higher left frontal NAA/ H(2)O ratio than men, but men had a higher hypothalamic NAA/ H(2)O ratio than women. Right-handers had a higher temporal lobe NAA/H(2)O ratio than left-handers, particularly in the left hemisphere. In addition, several significant 2- and 3-way interactions between writing hand preference, gender, and hemisphere were observed, but only in the frontal lobe.     

Brain metabolic differences as a function of hemisphere,writing hand preference,and gender

A total of 35 university-educated normal men (24 right handwriters and 11 left handwriters) and 36 age- and education-matched women (25 right handwriters and 11 left handwriters) underwent a proton magnetic resonance spectroscopy examination in seven 8 cm 3 voxels including the right and left frontal lobe tips, the right and left mid-temporal lobes, the right and left thalami, and the hypothalamus. Dependent measures were N -acetylaspartate (NAA), choline-containing compounds (Cho) and creatine/phosphocreatine (Cr) metabolite peak area ratios relative to total H 2 O. As expected, thalamic grey matter contained higher NAA ratios than telencephalic voxels (containing white and grey matter) (p < .001). The thalamic Cr/ H 2 O ratio was higher on the right, but the opposite asymmetry was observed for the temporal lobe (p < .05). Women had a higher left frontal NAA/ H 2 O ratio than men, but men had a higher hypothalamic NAA/ H 2 O ratio than women. Right-handers had a higher temporal lobe NAA/H 2 O ratio than left-handers, particularly in the left hemisphere. In addition, several significant 2- and 3-way interactions between writing hand preference, gender, and hemisphere were observed, but only in the frontal lobe.     

Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean poor seizure control?

BACKGROUND—Proton magnetic resonance spectroscopy(¹H-MRS) is a potentially useful tool in the in vivoinvestigation of brain metabolites in intractable temporal lobeepilepsy (TLE). Focal N-acetylaspartatate (NAA) reductions have beencorrelated with mesial temporal sclerosis (MTS) in surgically resectedepileptogenic foci.
OBJECTIVE—To evaluate the abnormalities in themetabolites NAA, creatine+ phosphocreatine (Cr), and cholinecontaining compounds (Cho) in the temporal lobe of medically refractorypatients with temporal lobe epilepsy, seizure free patients withtemporal lobe epilepsy, and normal controls.
PATIENTS AND METHODS—Ten refractory patients, 12 seizure free patients with temporal lobe epilepsy, and 10 age matchednormal controls were studied by ¹H-magnetic resonancespectroscopy. All patients had consistently unilateral temporal EEGabnormalities and a normal brain MRI. Proton MR spectra were obtainedfrom an 8 ml volume in the medial temporal lobes in patients withtemporal lobe epilepsy (ipsilateral to EEG foci) and the normalcontrols. The signals measured were expressed in terms of NAA/Cr,NAA/Cho, and Cho/Cr.
RESULTS—When compared with seizure free patientswith temporal lobe epilepsy and normal controls, the 10 refractorypatients with temporal lobe epilepsy had a lower mean (SEM) NAA/Crratio (1.65(0.53) v 2.62 (0.60), and 2.66 (0.73);p<0.002 and p<0.006) and a lower mean NAA/Cho ratio (1.59 (0.79)v 2.83 (1.33) and 2.58(0.67); p<0.02 andp<0.007).Furthermore, the two patients showing the lowest NAA/Cr ratios (1.47 and 1.73) in the seizure free group had had a past period of poorseizure control.
CONCLUSIONS—There were reduced temporal NAA/Cr andNAA/Cho ratios, suggesting neuronal loss or damage, associated withpast or present poor seizure control in the patients with temporal lobeepilepsy, but it does not exclude the possibility of a future completeseizure control (seizure free patients with temporal lobe epilepsy at the time of ¹H-MRS). This study warrants further¹H-MRS investigation with a larger series of patients withtemporal lobe epilepsy.

     

Proton magnetic resonance spectroscopy of normal appearing white matter in familial and sporadic multiple sclerosis

Objective To assess metabolite levels in normal–appearing white matter in sporadic and familial multiple sclerosis (MS). Methods Using H–MRS and applying one voxel measure we assessed NAA/Cho,NAA/Cr and Cho/Cr ratios in 26 patients with sporadic and in 25 with familial MS and compared them with healthy subjects. Results In both MS groups NAA/Cho and NAA/Cr ratio were significantly lower than in healthy individuals whereas Cho/Cr ratio was higher in MS patients. In sporadic MS patients NAA/Cho and NAA/Cr ratios were lower, although not significantly, than in familial cases. The Cho/Cr ratio was similar in both MS groups. Conclusion These results suggest that subtle differences in H–MRS measures corresponding to axonal rather than to myelin pathology might occur in sporadic and familial MS.     

A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea

Background and purpose: Repeated episodes of hypoxia, hypercapnia and transient blood pressure elevation in obstructive sleep apnea syndrome (OSAS) may damage neutral structures and induce cerebral metabolic impairment. This study aimed to determine the impact of OSAS on cerebral metabolites measured by ¹H magnetic resonance spectroscopy (¹H ‐MRS). Methods: Twenty OSAS patients underwent standard overnight polysomnography and ¹H‐MRS separately. Proton volumes of interest (VOIs) were placed in frontal and midtemporal regions bilaterally. Results: Significantly lower values of the N‐acetylaspartate (NAA)/creatine (Cr) ratio were found in frontal regions (P < 0.004) compared with 20 age‐matched control subjects. A significant increase in the myo‐inositol (Ins)/Cr ratio was evident bilaterally in temporal and frontal regions (P < 0.00002 and P < 0.04). Choline (Cho)/Cr ratio values were also significantly greater in temporal regions (P < 0.00001). A significant negative correlation (r = ?0.51, P < 0.03) was found between the apnea‐hypopnea index (AHI) and NAA/Cr ratio in the frontal regions of OSAS patients. Conclusions: Reduction in the NAA/Cr ratio in frontal regions of OSAS patients could be related to neural loss. Increase in the Cho/Cr ratio in temporal regions and Ins/Cr ratio in both frontal and temporal regions could be interpreted as evidence of membrane breakdown and reactive gliosis, respectively, consequent to repeated episodes of hypoxia in OSAS.     

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.     

Preliminary findings of proton magnetic resonance spectroscopy in occipital cortex during sleep deprivation

Proton magnetic resonance spectroscopy ((1)H MRS) has revealed biochemical alterations in various psychiatric disorders. Changes in brain metabolites may be caused not only by the disease's progression or response to treatment, but also by physiological variability. The aim of this study was to use (1)H MRS to assess the effects of specific short-term physiological states on major metabolites. Eight healthy women underwent (1)H MRS at the beginning and end of a 40-h period of sleep deprivation. The ratios of N-acetyl-aspartate (NAA), total creatine (tCr), and choline-containing compounds (Cho) to water (H(2)O) were determined from the occipital cortex during both baseline and photic stimulation conditions. During sleep deprivation, NAA/H(2)O decreased by 7% and Cho/H(2)O by 12%. Photic stimulation had no effect on the measured metabolites in the alert state, but in the sleep-deprived state the level of Cho/H(2)O increased during neuronal activation. The results suggest that NAA/H(2)O and Cho/H(2)O may depend on the state of alertness.     

Combined application of MRS and DWI can effectively predict cell proliferation and assess the grade of glioma: A prospective study

In order to assess combined application of MRS and DWI for prediction cell proliferation and grade diagnosis of glioma, We prospectively collected the Cho/Cr, Cho/NAA, Cr/NAA of MRS and tumor parenchyma ADC (ADC_T), contralateral mirror brain tissue ADC (ADC_H), rADC (rADC = ADC_T/ADC_H). According to postoperative pathology, the patients were divided into two groups: LGG group and HGG group, compared differences of age, gender, Ki67, MRS, DWI between two groups. Next, we analyzed the correlation between MRS, DWI and Ki67. On this basis, the sensitivity and specificity of MRS, DWI and MRS combined with DWI (MRS + DWI) in diagnosis of glioma grade were evaluated. The differences of Ki67, Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC between LGG group and HGG group were statistically significant (p = 0.000, 0.000, 0.000, 0.008, 0.000, and 0.000 respectively). From ROC curve, area under the curve (AUC), sensitivity and specificity of Cho/Cr, Cho/NAA, Cr/NAA, ADC_T, rADC, PRE (MRS + DWI) were (0.901, 86.7%, 85.7%), (0.876, 80.0%, 82.1%), (0.704, 63.3%, 71.4%), (0.862, 82.1%, 83.3%), (0.820, 75.0%, 76.7%), (0.920, 86.7%, 89.3%), respectively. Fisher's linear discriminant functions results suggest: Y₁ = -20.447 + 3.46•X₁ + 17.141•X₂ (LGG), Y₂ = -19.415 + 4.828•X₁ + 14.543•X₂ (HGG). Our study suggested that MRS and DWI can effectively predict cell proliferation preoperative. MRS combined with DWI can further improve sensitivity and specificity in assessing the grade of glioma.     

Positron emission tomographic measurement of cerebral blood flow and temporal lobectomy

We used positron emission tomography (PET) and bolus injection of H₂¹⁵O to measure interictal cerebral blood flow (CBF) in 32 patients who had temporal lobectomy for uncontrolled complex partial seizures. Seizure focus localization was confirmed by ictal video–electroencephalographic (video-EEG) telemetry, and patients who had imaging findings suggesting the presence of a tumor were excluded. PET-CBF studies were interpreted using a standard template by raters blinded to EEG and clinical data, and were not used in surgical planning. After surgery, patients were followed for 32 ± 18 months. Twenty-six patients were seizure free and 6 had persistent seizures. Mean lateral temporal hypoperfusion was 8 ± 14% in patients who became seizure free and 9 ± 6% in patients with persistent seizures. Fourteen patients had at least 15%, and 11 at least 20% hypoperfusion, but were not more likely to be seizure free. Three additional patients had 15 to 20% hypoperfusion in the temporal lobe contralateral to their EEG focus. PET measurement of CBF using bolus H₂¹⁵O should not be used to help select patients for temporal lobectomy.     

Short echo time 1 H magnetic resonance spectroscopy of childhood brain tumours

Aims To explore short echo time (30 ms) 1 H magnetic resonance spectroscopy (MRS) in children with brain tumours and determine the contributions to the characterization of these tumours of the metabolites inositol/myoinositol and glutamate/glutamine, which are not visible at long echo times (135 or 270 ms). Methods Over a 12-month period 86 single-voxel MRS investigations were performed on 59 children with various brain tumours on a Siemens Symphony 1.5-T Magnetom using point-resolved spectroscopy and echo time of 30 ms. Results The procedure was well tolerated, and good-quality data were obtained. N-Acetyl aspartate (NAA)/Choline (Cho) and creatine (Cr)/Cho concentration ratios were significantly (p<0.001) lower in tumour (0.95 and 1.63, respectively) compared with non-involved brain (3.68 and 3.98, respectively) in all histological types. Inositol/Myoinositol (Inos)/Cho ratios were significantly (p<0.05) lower in untreated tumours (1.91) than in treated tumours (3.93) and in non-involved brain (3.32). Inos/Cho ratios were high in diffuse pontine gliomas and low in medulloblastomas and supratentorial primitive neuroectodermal tumours (p<0.01). Glutamate/Glutamine (Glut)/Cho ratios were high in grade 1 astrocytomas (6.4) and unbiopsied optic gliomas (9.84) but low in diffuse pontine gliomas (2.44). Lipids and macromolecules were present in most tumours but in low quantities in non-involved brain. Conclusion Good-quality short echo time MRS data can be collected routinely on children with brain tumours. Inos and Glut levels show greater variability between tumour types than NAA, Cho and Cr present at long echo times, providing improved tumour characterization. Inos/Cho levels differ between untreated and treated tumours and may be useful for treatment monitoring.     

Effect of cerebrospinal fluid shunts on intracranial pressure and on cerebrospinal fluid dynamics: 2. A new technique of pressure measurements: results and concepts1 3.A concept of hydrocephalus

Part 2 describes measurements of intracranial cerebrospinal fluid (CSF) pressure in 18 adult patients with CSF shunts, all pressure measurements being referred to a horizontal plane close to the foramina of Monro. All 18 patients had normal CSF pressure by lumbar puncture; however, in one patient an intracranial pressure of +280 mm was subsequently measured after pneumoencephalography. Twelve patients had pre-shunt CSF pressures measured intracranially: 11 ranged from +20 to +180 mm H₂O and one was +280 mm H₂O in the supine position. In the upright posture nine patients had values of −10 to −140 mm H₂O, while three others were +60, +70, and +280 mm H₂O. After CSF shunting in these 18 patients the pressures were −30 to +30 mm H₂O in the supine position and −210 to −370 mm in the upright position. The effect of posture on the siphoning action of these longer shunts in the erect, adult patient is a major uncontrollable variable in maintenance of intracranial pressure after shunting. Other significant variables are reviewed. In Part 3 a concept of the hydrocephalus phenomenon is described. Emphasis is placed on the pressure differential (P_d) and force differential (F_d) causing pre-shunt ventricular enlargement and post-shunt ventricular size reduction. The site of P_d, which must be very small and not to be confused with measured ventricular pressure, P, must be at the ventricular wall.     

Detection of metabolites in the white matter of frontal lobes and hippocampus with proton in first-episode treatment-naïve schizophrenia patients

Aim: This study aimed to investigate the changes of the metabolites in the white matter of frontal lobes and hippocampus in schizophrenia by using proton magnetic resonance spectroscopy (¹H‐MRS). Methods: Sixty‐three first‐episode treatment‐naïve schizophrenia (FES) patients and 63 age‐, gender‐ and education level‐matched healthy controls were recruited. The relative levels of metabolites including N‐acetylaspartate (NAA), choline‐containing compounds (Cho), (Cr) and myo‐inositol (MI) were detected with ¹H‐MRS, and the laterality index (Li) was calculated. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale. Results: Compared with controls, FES patients did not show significant differences in all metabolites. The severity of positive symptoms was negatively correlated with the NAA/Cho in the white matter of the left frontal lobe and positively correlated with the Cho/Cr in the right white matter of frontal lobes. A negative correlation was observed between the severity of negative symptoms and the NAA/Cr in the white matter of bilateral frontal lobes. No difference was shown in the Li of metabolites between FES patients and controls. Conclusions: The metabolites such as NAA, Cho and MI in white matter of frontal lobes and hippocampus were not significantly altered in FES patients. The lower axonal integrity/number (NAA concentration) may be associated with more severe negative symptoms, and dysmetabolism in process of myelination in the white matter of frontal lobes associated with more severe positive symptoms.     

Age-related changes in muscarinic cholinergic receptors in the living brain: a PET study using N-[C]methyl-4-piperidyl benzilate combined with cerebral blood flow measurement in conscious monkeys

The effects of changes in regional cerebral blood flow (rCBF) with aging on muscarinic cholinergic receptor binding were evaluated with [¹⁵O]H₂O and N-[¹¹C]methyl-4-piperidyl benzilate (4-MPB) in the living brains of young (5.9±1.8 years old) and aged (19.0±3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo with [¹¹C]4-MPB, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and graphical Patlak plot analysis was applied. In addition, two-compartment model analysis using the radioactivity curve in the cerebellum as an input function (reference analysis) was also applied to determine the distribution volume (DV=K₁/k₂′) for [¹¹C]4-MPB. With metabolite-corrected arterial input, Patlak plot analysis of [¹¹C]4-MPB indicated a regionally specific decrease in muscarinic cholinergic receptor binding in vivo in the frontal and temporal cortices as well as the striatum in aged compared with young animals, showing no correlation with the degree of reduced rCBF. In contrast, on the reference analysis with cerebellar input of [¹¹C]4-MPB, all regions assayed except the pons showed a significant age-related decrease of DV, and the degree of reduction of DV was correlated with that of rCBF. These results demonstrated the usefulness of kinetic analysis of [¹¹C]4-MPB with metabolite-corrected arterial input, not with reference region’s input, as an indicator of the aging process of cortical muscarinic cholinergic receptors in vivo measured by PET with less blood flow dependency.     

Areas of interictal spiking are associated with metabolic dysfunction in MRI-negative temporal lobe epilepsy

PURPOSE: The objective of our study was to determine noninvasively whether metabolic dysfunction is present in focal areas of interictal electrophysiologic abnormality and whether metabolic dysfunction correlates with frequency of spiking. METHODS: We used a prospective, power analysis-driven, age-matched design to study 20 subjects with nonlesional temporal lobe epilepsy by using magnetoencephalography (MEG) and proton magnetic resonance spectroscopy (1H-MRS). MEG was used to localize the source area of interictal spikes. 1H-MRS measured integrated peak areas for N-acetyl compounds (NAA) and choline-containing compounds (Cho) in both hippocampi, the MEG spike zone, and the region contralateral to the MEG spike zone in all subjects. 1H-MRS was performed in seven controls. RESULTS: Fifteen of 20 subjects had a lower NAA/Cho ratio in the MEG spike zone compared with the contralateral homologous region. NAA/Cho was significantly decreased in the MEG spike zone (p < 0.01). NAA/Cho ratios were not significantly different between the hippocampus ipsilateral and contralateral to the spike activity, or from control hippocampi. NAA/Cho ratios did not correlate with spike frequency. CONCLUSIONS: Metabolic dysfunction is present in focal areas of interictal spiking in nonlesional temporal lobe epilepsy. These findings confirm that functional abnormalities can be detected in vivo in radiographically normal-appearing cortex exhibiting abnormal excitability.     

急性脑梗死后血管性认知障碍的磁共振波谱研究

目的应用质子磁共振波谱(1 H-MRS)技术,探讨急性脑梗死后血管性认知障碍(VCI)患者的颅内物质代谢变化与认知损害的关系。方法对86例脑梗死患者(脑梗死组)及21名健康对照者(对照组)进行简易精神状态检查量表(MMSE)和蒙特利尔认知评分量表(MoCA)评分,并计算其视空间及执行功能评分。根据认知评分结果,将脑梗死组分为脑梗死后认知功能正常组(NCI)、脑梗死后VCI非痴呆组(VCIND)、脑梗死后痴呆组。对脑梗死组及健康对照进行1 H-MRS检查,测定右额叶、左颞叶、左丘脑及顶枕叶交界处N-乙酰天冬氨酸(NAA)/肌酸(Cr)、肌醇(mI)/Cr及胆碱复合物(Cho)/Cr比值,并分析脑梗死组物质代谢比值与认知评分(MoCA评分、视空间及执行功能)间的相关性。结果 (1)与对照组(左颞叶及左丘脑NAA/Cr 1.53±0.08、1.52±0.10)相比,VCIND组左颞叶及左丘脑NAA/Cr(1.46±0.07、1.47±0.07)降低(P=0.001、P=0.006);与VCIND组右额叶1.46±0.10比较,梗死后痴呆组右额叶、左颞叶及左丘脑NAA/Cr(1.38±0.14、1.39±0.06、1.42±0.09)降低(分别P<0.001、P<0.001、P=0.003)。对照组及NCI组间的各区域物质代谢比值无统计学差异(均P>0.05)。(2)所有脑梗死患者中,除右额叶Cho/Cr外,余各感兴趣区物质代谢比值与MoCA评分间均相关,其中以左颞叶、左丘脑NAA/Cr值与MoCA评分的相关性为著(分别r=0.566,P<0.001;r=0.485,P<0.001);除右额叶、丘脑及顶枕叶交界处Cho/Cr外,余各物质代谢比值与视空间及执行功能评分间相关,其中亦以左颞叶及左丘脑NAA/Cr值的相关性为著(分别NAA/Cr为r=0.591,P<0.001;r=0.491,P<0.001)。结论左丘脑及左颞叶代谢异常可能为VCI患者认知损害的早期关键环节之一,随着VCI病变进展可能整个皮质及皮质下环路区域都将出现代谢异常。     

Long-term treatment with clonidine and α-receptors in the brain of Normotensive rats

The aim of the present study was to investigate whether or not changes in rat brain α-adrenoceptors take place during chronic treatment with a low dose of clonidine. Male Wistar normotensive rats were treated with clonidine (0.1 mg/kg) i.p. twice daily for 12 days. This treatment caused a significant increase in [³H]clonidine and in [³H]WB4101 binding, respectively, to α₂- and to α₂-adrenoceptors of the frontal cortex; the levels were 30% for [³H]clonidine and 20% for [³H]WB4101. The Scatchard analysis of data obtained in binding studies indicated that the enhanced binding of two ligands to membranes prepared from chronically clonidine-treated animals, was due to an apparent increase in the number of binding sites. These changes were seen 4 h after administration of the last treatment, before the appearance of the withdrawal syndrome. However, noradrenergic α₂-autoreceptors of synaptosomes, from the frontal cortex and hypothalamus of treated animals, were sensitive to the regulatory action of clonidine or of noradrenaline on the [³H]noradrenaline overflow elicited by high K⁺ as well as on the control animals. On the contrary, the α₂-receptors on the serotoninergic nerve terminals from the frontal cortex of treated animals were more sensitive than those of control animals to the action of clonidine or of noradrenaline in counteracting the [³H]5-hydroxytryptamine overflow elicited by high K⁺. These results suggests that during treatment with clonidine no autoreceptor hyposensitivity to the regulatory action of clonidine or noradrenaline on [³H]noradrenaline overflow elicited by high K⁺ takes place, but, as a consequence of the diminished noradrenaline availability at the synaptic cleft, the binding of [³H]WBA101 to α₁-receptors and of [³H]clonidine to pre- and postsynaptic α₂-receptors were significantly elevated in the frontal cortex, a brain areas where the α-₂-receptors are mainly postsynaptic. Thus, the neurotransmitter concentration in the synaptic cleft may be responsible for the trans-synpatic modulation of the α₂-adrenoceptor postsynaptic population. In fact, the α₂-adrenoceptors which are presynaptically located on the serotoninergic terminals, but are postsynaptic in relation to the noradrenergic neurons, also show increased sensitivity after chronic clonidine treatment.