Medial prefrontal cortex pathology in schizophrenia as revealed by convergent findings from multimodal imaging.

Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P=0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders.

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects.

The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.

Creatine transporter deficiency in two adult patients with static encephalopathy.

Creatine transporter deficiency is a recently identified X-linked inborn error of metabolism. The natural course of the disease is not well delineated since clinical data from adult patients have scarcely been reported. A progressive course of the disease has been noted in a few described cases. We report the first two Spanish adult patients with creatine transporter deficiency and compare their clinical phenotype and the evolution of the disease with those of other published cases. The two brothers were identified in a study of a cohort of 610 mentally handicapped male patients. The disease was detected by biochemical studies and confirmed by DNA studies. The most significant clinical features were mental retardation, epilepsy and autistic behaviour, and these symptoms did not worsen, in contrast to other reports. They did not present gastrointestinal problems or movement disorders. Creatine transporter deficiency could be an underdiagnosed metabolic disorder and should be considered in adult patients with mental retardation. Clinical presentation of this disorder showed marked differences among adult patients and the course of the disease was static in our cases. Detection of additional adult patients might allow better understanding of the phenotypic outcome at a later age.

[Renal dynamics: comparison between diuretic renogram and magnetic resonance imaging]. / Dimámica renal: comparación entre el renograma diurético y la resonancia magnética.

OBJECTIVE: This study aimed to establish a comparison between the data obtained in the renal functional study through magnetic resonance using gadolinium with diuretic (furosemide) charge (MR-Gd/F), on the one hand, and the parameters obtained with the classical diuretic renogram (DR) (differential renal function -DRF- and renographic curve -RC-), on the other hand. MATERIAL AND METHOD: 10 patients were studied, 6 male and 4 female, aged between 1 month and 6 year-old. All the patients were submitted to a MR-Gd/F and a DR. In both cases, furosemide was used as overload. The pathologies observed included syndrome of the pyeloureteral junction, polar vessel, ureter valve, ectopic ureter, duplex kidney, renal dysplasia, renal ectasy, pelvic kidney and horseshoe kidney. The percentage of gadolinium uptake was compared versus the DRF, and the MR curve was compared versus the RC. Surgical treatment was required in 5 cases and an expectancy behaviour was taken in 3 cases. Among the operated patients, the diagnosis accurry was confirmed by the surgery and the pathological study. RESULTS: A 80% consistency was found between the gadolinium uptake and the DRF. There was a 90% correlation between the MR-Gd/F curve and the RC. In two cases, the MR-Gd/F required to modify the surgical criterion -previously based on the DR- and an expectancy behaviour was taken. In 90% of the operated cases, the diagnostic assumption obtained through the MR-Gd/F coincided with the surgical and pathological findings, whereas there was a coincidence in just 60% of the cases studied through the DR (p > 0.0008). CONCLUSIONS: The MR offers a real time study: anatomical, vascular and functional. Good correlation between DR and MR with respect to: (% DRF,%Gd MR and diuretic curve). The MR demonstrates greater precision in diagnosis.The MR allows recognition of non obstructive polar vessels that can then be conservatively managed.

Early and late complications among 15 victims exposed to indoor fire and smoke inhalation.

AIM: To evaluate early and late complications among victims exposed to indoor fire and smoke inhalation. METHOD: An observational, descriptive and prospective longitudinal study of 15 victims of smoke inhalation admitted to the intensive care unit. RESULTS: Although without significant burns, 13 of the victims were unconscious, with airway injury, abnormal temperature and hypokalaemia, and underwent mechanical ventilation. Initial carbon monoxide concentration averaged 20.4+/-8.3%, dropping to 3.9+/-3.3% 4h later. On the 1st day, two victims recovered and were transferred, and another two died. Creatine kinase levels (2594+/-2455 U/l) correlated with duration of intensive care. Of the remaining 11 patients, 10 had early pneumonia. Steroid treatment was initiated for four patients receiving prolonged mechanical ventilation, because of persistent fever and dry cough without evidence of infection. CONCLUSIONS: Mortality and systemic involvement were related to burn of the upper airway and contact with combustion products. Initial creatine kinase levels emerged as a prognostic marker of injury severity. Bronchoscopy was useful in grading airway injury and obtaining bronchoalveolar culture. Corticosteroids were effective, after the acute phase, in treating non-infectious pulmonary complications.

Stage 1B cervical cancer in a pregnant woman at 25 weeks of gestation.

Cervical cancer associated with pregnancy is rare (0.05%), although it is the most frequently diagnosed malignancy in pregnant women. We present the case of a 28-year-old woman at 25 weeks of gestation diagnosed with Stage 1B cervical cancer. Treatment was delayed until fetal maturity, and an elective cesarean section was performed at 33 weeks' gestation, followed by a total hysterectomy preserving the ovaries, and a pelvic lymphadenectomy. A review of the literature on the treatment of cervical cancer during pregnancy relevant to the case described is also presented.

[Comparison between MRI and the techniques traditionally used in the study of uropathies in children]. / Análisis prospectivo y comparativo entre la resonancia magnética y las exploraciones tradicionales utilizadas en el estudio de las uropatías con afectación funcional del niño.

BACKGROUND: To correlate the anatomical and functional information obtained using MRI in comparison to the techniques traditionally used in the study of uropathies, and to compare their physical and socioeconomic impacts. METHODS: For a period of eleven months we carried out a prospective study of 22 patients of both sexes ranging in age from 1 to 180 months. All suffered from one or another uropathy. Fifty-five percent of the patients were from external consultation while 45% had been diagnosed prenatally. The imaging techniques compared with MRI were as follows: echography, renogram, renal DMSA scan, urography and cystography. For the MRI gadolinium was used, as well as general anesthesia in some cases. RESULTS: There was a significant correlation (r = 0.942 p < 0.01) between MRI and the traditional explorations for the diagnosis of hydronephrosis, horseshoe kidney, kidney duplication, kidney hypoplasia and hypertrophy, multicystic kidney, ureterocele, pyeloureteral stenosis, vesicoureteral stenosis, atrophy of the renal artery, and missing kidney. It was not useful for reflux. Comparing to renal function differential on renogram there was an 86% agreement between the results. The average number of visits was 5.7 and missed workdays 4.1. The cost as a result of MRI was less than that for other explorations (Chi2 = 27,909 p < 0.001). CONCLUSIONS: MRI provides the same information, both morphological and concerning functional quality, as well as vascular, as that obtained through traditional explorations. Irradiation with MRI is nil. At times it requires anesthesia. Its practice reduces costs, visits, missed workdays, and travel time. In the future it could probably be possible to carry out cystography and hydric/diuretic overload testing at the same time, the efficacy will be increased.

A decade of the Catalonian Arthroplasty Register (RACat): Variability, exhaustivity, and survival of prostheses between 2005 and 2014. / Una década del Registro de Artroplastias de Cataluña (RACat): exhaustividad, variabilidad y supervivencia de las prótesis entre 2005 y 2014.

BACKGROUND AND AIM: The Catalonian Arthroplasty Register (RACat) is a public health-based population register used to analyse and evaluate hip and knee replacements in Catalonia. The aim of this study is to present the outcomes after 10 years in operation (January 2005-December 2014). METHODOLOGY: Using the information from the RACat and the minimum basic data set at hospital discharge, an analysis was made of the quality and exhaustivity of the data, as well as a descriptive analysis of the patients, prostheses, and care process. Survival was also analysed by calculating the accumulated incidence of revisions (according to the cause of intervention in hip replacements and conservation or sacrifice of the posterior cruciate ligament in knee replacement). The relationship between revision risk and the fixation technique of the prosthesis is also analysed, using competitive risk models adjusted for gender, age, and comorbidities. RESULTS: The main reason for the primary hip and knee replacement surgery was arthrosis. The accumulated incidence of revisions at 10 years was 3.9% in hip replacements caused by arthrosis, and 2.3% in those caused by fracture. Conservation of the posterior cruciate ligament was achieved in 4.4% of knee replacements, with sacrifice in 5.1%. DISCUSSION: The RACat is consolidated as a tool for the evaluation of joint replacements, with great potential in the analysis of medium and long-term efficacy, the study of the variability in clinical practice, and post-marketing surveillance.

Functional magnetic resonance imaging study of frontal lobe activation during word generation in obsessive-compulsive disorder.

BACKGROUND: Functional imaging studies have demonstrated abnormal patterns of brain activity in obsessive-compulsive disorder, which consistently suggest the alteration of frontal lobe functioning. We performed a brain activation study in obsessive-compulsive disorder using a cognitive task involving the frontal lobes. METHODS: Twenty patients and 20 healthy control subjects were assessed with functional magnetic resonance imaging during a phonologically guided word generation task. The study analysis was based on the comparison of group average time-course functional changes occurring at the site of largest frontal cortex activation during alternating rest and task periods. RESULTS: In terms of relative signal changes, patients showed a significantly greater activation during word generation and a defective suppression of this activation during the following rest period. Both abnormal imaging findings significantly correlated with the severity of the clinical process assessed by the Yale-Brown Obsessive-Compulsive Scale. CONCLUSIONS: The results indicate that functional magnetic resonance imaging during cognitive challenge may be useful to reveal distinctive features of latent brain dysfunction in obsessive-compulsive disorder.

Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study.

OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions. METHOD: Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition. RESULTS: No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders. CONCLUSIONS: Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics.

Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine.

BACKGROUND: Although plasma total homocysteine has been identified as an independent risk factor for vascular disease in a multitude of studies, there is a considerable overlap in values between patients at risk and control subjects. The difference in values can be used to distinguish statistically between the 2 groups, provided each group is large enough; however, discriminating between individual patients at risk and control subjects is difficult. OBJECTIVE: We investigated whether the precursor of homocysteine, S-adenosylhomocysteine, is a more sensitive indicator of risk. DESIGN: We measured plasma total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, creatinine, folate, and vitamin B-12 in 30 patients with proven cardiovascular disease and 29 age- and sex-matched control subjects. RESULTS: The homocysteine values (+/-SD) were 12.8 +/- 4.9 (95% CI: 11.0, 14.7) micromol/L for patients and 11.0 +/- 3.2 (9.8, 12.2) micromol/L for control subjects. The S-adenosylhomocysteine values were 40.0 +/- 20.6 (32.3, 47.7) nmol/L for patients and 27.0 +/- 6.7 (24.5, 30.0) nmol/L for control subjects (P = 0.0021). The S-adenosylmethionine values were 121.8 +/- 42.9 (105.8, 137.8) nmol/L for patients and 103.9 +/- 21.8 (95.6, 112.2) nmol/L for control subjects (P = 0.0493). The creatinine values were 110 +/- 27 (97, 120) micromol/L for patients and 97 +/- 9 (80, 100) micromol/L for control subjects (P = 0.0025). Values for folate and vitamin B-12 did not differ significantly between groups. CONCLUSIONS: Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine. Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients.

Reduction of the substantia nigra width and motor decline in aging and Parkinson's disease.

We studied the functional significance of the involutional and degenerative changes in the substantia nigra as seen on magnetic resonance imaging. The width of the pars compacta correlated with motor performance in both healthy elderly subjects and idiopathic Parkinson's disease groups. Patients exhibited significant reduction of the width of the pars compacta and the level of this reduction correlated strongly with the clinical status evaluated by the Unified Parkinson's Disease Rating Scale. These results suggest that pars compacta shrinkage may account for a substantial part of the structural substratum of motor decline in the elderly. Moreover, an analysis of the relationship of the midbrain damage with specific symptoms in Parkinson's disease could contribute to a better understanding of the pathogenesis of this degenerative process.

Leuko-araiosis on magnetic resonance imaging and speed of mental processing.

The clinical significance of white matter abnormalities seen in brain imaging studies, termed leuko-araiosis (LA), still remains uncertain. Leuko-araiosis has been associated with a global decline in cognitive performance, although little is known about the cognitive functions that LA may account for. We present the correlates between LA severity on magnetic resonance imaging and mental deterioration in a selected sample of 41 elderly patients with vascular risk factors. We found that LA was related to performance on tasks measuring the speed of information processing and, in particular, on those that involve complex processes. This impairment can be important in producing reduction in daily living activities as it is in the support to the relationship found with some commonly used behavioral rating scales. Leuko-araiosis is also related to the presence of some primitive reflexes, suggesting that their disinhibition may be due to diffuse corticofugal fibers damage.

Cerebral lateralization of language in normal left-handed people studied by functional MRI.

OBJECTIVE: To use functional MRI (fMRI) to further define the occurrence of left-hemisphere, bilateral, and right-hemisphere language in a normal left-handed population. METHODS: A total of 100 healthy volunteers, consisting of 50 left-handed subjects and a reference group of 50 right-handed subjects, were studied by fMRI of the frontal cortex during silent word generation. RESULTS: Ninety-six percent of right-handed subjects showed fMRI changes lateralized to the left hemisphere, whereas 4% showed a bilateral activation pattern. In contrast, left-hemisphere lateralization occurred in 76% of left-handers, bilateral activation in 14%, and right-hemisphere lateralization in the remaining 10%. The predominance of right-hemisphere activation, however, was weak in these cases; only a single left-handed subject (2%) showed complete right-hemisphere lateralization. CONCLUSIONS: Silent word generation lateralizes to the left cerebral hemisphere in both handedness groups, but right-hemisphere participation is frequent in normal left-handed subjects. Exclusive right-hemisphere activation rarely occurred in the frontal lobe region studied.

MRI pallidal hyperintensity and brain atrophy in cirrhotic patients: two different MRI patterns of clinical deterioration?

In cirrhotic patients, even in a stable nonencephalopathic state, MRI may show cerebral atrophy and increased signal in globus pallidus on T1-weighted sequences. We investigated the relationship between cerebral atrophy and increased pallidal signal and the clinical status of 30 cirrhotic patients. We found a weak association between the two MRI findings. There were different patterns of clinical variables related to the imaging findings. Performance on motor tasks involving speed correlated with the pallidal signal and plasma ammonia levels but not with atrophy. Test results for memory and frontal-premotor function were associated with brain atrophy but not with the pallidal signal or with ammonia.

Lesions in the left arcuate fasciculus region and depressive symptoms in multiple sclerosis.

Depression is a common mood disturbance in multiple sclerosis (MS) patients. Epidemiologic data suggest a causative relationship between depressive symptoms and cerebral demyelination, although a specific lesion site responsible for depressed mood has not been identified. Given that depression in neurologic disease is closely related to frontal and temporal lobe damage, we focused our study on investigating the extent to which lesions in the white matter connecting both cerebral lobes may account for depressive symptoms in MS. Forty-five patients were assessed using the Beck Depression Inventory and an MRI protocol conceived to quantify lesions separately in the basal, medial, and lateral frontotemporal white matter. The presence of lesions in the left suprainsular white matter, the region that mainly includes the arcuate fasciculus, was specifically associated with depressive symptoms, accounting for a significant 17% of the depression score variance. Although a multifactorial origin is suspected for depression in MS, this finding gives support to the existence of a direct negative effect of demyelination on mood.

Persistence of MRI hyperintensity of the globus pallidus in cirrhotic patients: a 2-year follow-up study.

We investigated the long-term persistence and short-term stability of globus pallidus (GP) hyperintensity on T1-weighted MRI in 19 cirrhotic patients. After a mean interval of 25.8 months, the hyperintensity of the GP persisted in 17 patients. Hyperintensity disappeared in two patients with hepatocarcinoma, indicating that hyperintensity can revert to normal in circumstances other than liver transplants. Ten patients participated in a 6-month study with repeated evaluations of GP signal intensity, plasma ammonia levels, and selected neuropsychological tests. The GP signal was fairly stable during the follow-up, and the variables considered maintained significant relationships. GP hyperintensity appears as a stable indicator of the functional status of cirrhotic patients.

Neurospectroscopic alterations and globus pallidus hyperintensity as related magnetic resonance markers of reversible hepatic encephalopathy.

In patients with chronic hepatic encephalopathy, proton magnetic resonance spectroscopy can be used to detect specific metabolic abnormalities in the brain; MRI shows a hyperintense globus pallidus on T1-weighted sequences. We investigated the relationship between these two MR findings in a series of 25 patients with the use of quantitative data and a multiple regression analysis model. The cerebral increase in glutamine compounds and the decrease in myoinositol and choline correlated separately with globus pallidus hyperintensity, and each was complementary in accounting for this imaging finding. Such as association suggests that spectroscopic and imaging alterations are two different expressions of the reversible events that occur in the brain of patients with hepatic encephalopathy in that both disappear after liver transplantation. Globus pallidus hyperintensity seems to be a global indicator of the cerebral metabolic disorder, and the spectroscopic pattern denotes the specific metabolic alterations.

Motion of the cerebellar tonsils in Chiari type I malformation studied by cine phase-contrast MRI.

We studied the effects on CSF dynamics at the foramen magnum and the clinical significance of the abnormal tonsillar motion in 14 patients with Chiari type I malformation and 14 control subjects using cine phase-contrast MRI. Dynamic MRI consisted of axial and sagittal cine phase-contrast sequences. CSF and tonsillar motion were qualitatively and quantitatively evaluated, and the subarachnoid space at the foramen magnum measured. In Chiari patients, cine phase-contrast MRI detected the abnormal pulsatile motion of the cerebellar tonsils, which produced a selective obstruction of CSF flow from the cranial cavity to the spine. The amplitude of the tonsillar pulsation and the severity of the arachnoid space reduction were associated with the symptom of cough-strain headache, but not with the presence of syringomyelia. The finding of abnormal valve dynamics of the cerebellar hernia revealed by cine phase-contrast MRI conforms to the pathophysiologic mechanisms suggested in pressure register studies and opens a new possibility in the presurgical assessment of Chiari patients with exertional symptoms.

Left-ear extinction in patients with MRI periventricular lesions.

A dichotic listening test was administered to 22 elderly vascular patients with periventricular white matter changes on magnetic resonance imaging. We found four patients with a moderate-to-severe extent of these changes who showed a pattern of left-ear extinction. These findings suggest that periventricular lesions in patients with vascular risk factors may be associated with a functional disconnection of the interhemispheric auditory pathways.