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Neuroimaging in glioma therapy.

The introduction of computed tomographic and magnetic resonance imaging into clinical practice is among the most important of all advances in the care of patients with brain tumors. Diffuse astrocytomas of the adult cerebral hemispheres are unique among human tumors for the degree to which their imaging features correlate with pathologic characteristics and clinical behavior. However, there is still little understanding of the value of various imaging features in measuring response and progression in brain tumors. This review focuses on some of the unsolved problems in the use of neuroimaging in measuring the response of brain tumors to therapy.

Antineoplastic Agents↗

Functional neuroimaging of primary headache disorders.

Until recently, primary headache disorders, such as migraine and cluster headache were considered to be vascular in origin. However, advances in neuroimaging techniques, such as positron emission tomography, single photon emission computed tomography and functional magnetic resonance imaging have augmented the growing clinical evidence that these headaches are primarily driven from the brain. This review covers functional imaging studies in migraine, cluster headache, rarer headache syndromes and experimental head pain. Together with newer techniques, such as voxel-based morphometry and magnetic resonance spectrometry, functional imaging continues to play a role in elucidating and targeting the neural substrates in each of the primary headache syndromes.

Blood Flow Velocity↗

Hemiparetic cerebral palsy: etiological risk factors and neuroimaging.

The purpose of this paper, which was conducted on 175 children with hemiparetic cerebral palsy (H-CP), was to verify the etiological risk period for this disease. Etiological risk factors (ERF) were detected through anamnesis: 23% in the prenatal period, 18% in the perinatal period and 59% of the patients the period was undefined (ERF in the prenatal and perinatal period was 41% and no ERF was 18% of the cases. The computerized tomographic scan (CT) and MRI were performed on all the patients, who were then classified according to their etiopathogenic data: CT1= normal (18%); CT 2= unilateral ventricular enlargement (25%); CT 3= cortical/ subcortical cavities (28%); CT4= hemispheric atrophy and other findings (14%); CT 5= malformations (15%). CT 5 was associated with physical malformations beyond the central nervous system and with prenatal ERF's, while CT 2 was associated with the perinatal ERF's, mainly in premature births. Magnetic resonance imaging was performed on 57 patients and demonstrated a good degree of concordance with the CT. Etiology remained undefined in only 37% of the cases after neuroimaging was related to ERF. A high perinatal RF frequency (59%) was observed and emphasized the need for special care during this period.

Cerebral Palsy↗

Neuropsychological, neuroimage and psychiatric aspects of primary Sjögren's syndrome.

We report a case of a 49-year-old woman diagnosed with primary Sjögrens Syndrome (pSS) who was submitted to extensive neuropsychobiological assessment. Examination revealed a Wechsler Adult Intelligence Scale-Revised (WAIS-R) Full Scale IQ of 97 with no Verbal/Performance IQ discrepancy and performance below estimated premorbid levels on arithmetic skills, visual tracking, naming and delayed paired associate learning/memory. CT scans of the brain were normal. However, there were subcortical hyperintensities on MRI and left parieto-temporal hypoperfusion on SPECT. Neuropsychological impairment is consistent with the pattern of neuroimage findings. We hypothesize that the pathophysiological mechanisms of pSS involve direct immune attack on neurons in addition to indirect effects through small-vessel angiopathy and thereby induce natural fracture lines in behavior according to location in the central nervous system.

Female↗

[Neuroimaging abnormalities in parkinsonism: study of five cases].

We report the brain magnetic resonance (MR) imaging abnormalities observed at the basal ganglia system of 5 patients (2 female and 3 male), who fulfilled the criteria of parkinsonism. The onset of parkinsonian syndrome ranged from 5 to 52 years old. All patients underwent MR exams with a 1.5T MR equipment. High field T2-weighted sequences disclosed hypersignal bilateral and symmetrically located exclusively at substantia nigra (3 cases), exclusively at globus pallidus (1case) and simultaneously at substantia nigra, globus pallidus and nigro-strital interconnections (1case). For three patients, the diagnose of secondary parkinsonism was supported by clinical data: the first had the onset of the symptoms after the exposure to an herbicide (glyphosate); the second after vaccination against measles; the third after coma due to encephalitis. For the other two patients, the onset of PS was progressive, resembling a typical idiopathic Parkinson's disease (PD) but the findings at the MR dimissed this initial diagnose. In this study, the contribution of neuroimaging was crucial to recognize secondary parkinsonism though the ethiological agents could not be determined in these patients.

Adolescent↗

[Semantic dementia: clinical and neuroimaging evaluation. Case report].

Semantic dementia is a clinical syndrome in the spectrum of frontotemporal lobar degeneration group. We report on a 63 years old man who presented with memory disorder of semantic nature for visual and mainly verbal material when he was 57 years old. Mild behavior impairment was present and related to exaggerated responses to algic stimuli and repetitive behavior. Structural and functional neuroimaging methods disclosed asymmetric bitemporal damage, mainly on the left. Differential diagnosis should be considered with Alzheimer's disease, another subtypes of the frontotemporal lobar degeneration group and any other syndrome that presents with a fluent aphasic progressive disorder.

Dementia↗

[Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil].

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinsons disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean+/-SD) (0.38+/-0.12) compared to controls (BP=0.84+/-0.16; p<0.01). A 100% sensitivity and 100% specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho=-0.7, p<0.001) and motor scales (rho=-0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.

Adult↗

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy.

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

Atrophy↗

Using advances in neuroimaging to detect, understand, and monitor disease progression in Huntington's disease.

Transgenic mouse models and other screens are being used to identify potential therapeutic agents for use in clinical trials in Huntington's disease (HD). The development of surrogate markers that can be used in clinical therapeutics is an active area of research. Because HD is relatively uncommon and only a portion of available subjects meet inclusion and exclusion criteria, therapeutic trials are limited by the availability of potential subjects as well as the relative insensitivity of the clinical measures used. Neuroimaging methods offer the potential to provide noninvasive, reproducible, and objective methods not only to better understand the disease process but also to follow in clinical studies to determine if a drug is effective in slowing down disease progression or perhaps even in delaying onset. Following is a review of the literature, which highlights the studies that have been published to date.

Biomarkers↗

Neuroimaging of ischemia and infarction.

Since the introduction of thrombolytic therapy as the foundation of acute stroke treatment, neuroimaging has rapidly advanced to empower therapeutic decision making. Diffusion-weighted imaging is the most sensitive and accurate method for stroke detection, and, allied with perfusion-weighted imaging, provides information on the functional status of the ischemic brain. It can also help to identify a response to thrombolytic and neuroprotective therapies. Additionally, multimodal magnetic resonance imaging, including magnetic resonance angiography, offers information on stroke mechanism and pathophysiology that can guide long-term medical management. Multimodal computed tomography is a comprehensive, cost-effective, and safe stroke imaging modality that can be easily implemented in the emergency ward and that offers fast and reliable information with respect to the arterial and functional status of the ischemic brain. Accessibility, contraindications, cost, speed, and individual patient-determined features influence which is the best imaging modality to guide acute stroke management.

Animals↗

Neuroimaging of infections.

Neuroimaging plays a crucial role in the diagnosis and therapeutic decision making in infectious diseases of the nervous system. The review summarizes imaging findings and recent advances in the diagnosis of pyogenic brain abscess, ventriculitis, viral disease including exotic and emergent viruses, and opportunistic disease. For each condition, the ensuing therapeutic steps are presented. In cases of uncomplicated meningitis, cranial computed tomography (CT) appears to be sufficient for clinical management to exclude acute brain edema, hydrocephalus, and pathology of the base of skull. Magnetic resonance imaging (MRI) is superior in depicting complications like sub-/epidural empyema and vasculitic complications notably on FLAIR (fluid-attenuated inversion recovery)-weighted images. The newer technique of diffusion-weighted imaging (DWI) shows early parenchymal complications of meningitis earlier and with more clarity and is of help in differentiation of pyogenic abscess (PA) from ring enhancing lesions of other etiology. Proton magnetic resonance spectroscopy (PMRS) seems to produce specific peak patterns in cases of abscess. The presence of lactate cytosolic amino acids and absence of choline seems to indicate PA. Also in cases of suspected opportunistic infection due to toxoplasma DWI may be of help in the differentiation from lymphoma, showing no restriction of water diffusion. In patients with herpes simplex and more exotic viruses like West Nile and Murray Valley virus DWI allows earlier lesion detection and therapeutic intervention with virustatic drugs.

Animals↗

Neuroimaging and therapeutics in movement disorders.

In this review, we discuss the role of neuroimaging in assessing treatment options for movement disorders, particularly Parkinson's disease (PD). Imaging methods to assess dopaminergic function have recently been applied in trials of potential neuroprotective agents. Other imaging methods using regional metabolism and/or cerebral perfusion have been recently introduced to quantify the modulation of network activity as an objective marker of the treatment response. Both imaging strategies have provided novel insights into the mechanisms underlying a variety of pharmacological and stereotaxic surgical treatment strategies for PD and other movement disorders.

Animals↗

Neuroimaging of epilepsy: therapeutic implications.

Neuroimaging has important applications in the diagnosis and treatment of patients with seizures and epilepsy. Having replaced computed tomography (CT) in many situations, MRI is the preferred imaging technique for patients with epilepsy. Advances in radionuclide-based techniques such as single-photon emission CT/positron emission tomography and electromagnetic source imaging with magnetoencephalography are providing new insights into the pathophysiology of epilepsy. In addition, techniques such as magnetic resonance spectroscopy are beginning to impact treatment. In this review, I discuss how these techniques are used in clinical practice but more importantly, how imaging findings play an increasing role in neurotherapeutics.

Epilepsy↗

Impairment of GABAergic transmission in depression: new insights from neuroimaging studies.

Several lines of evidence suggest that abnormalities in GABAergic neurotransmission are associated with the neurobiology of depression. Animal studies demonstrate that GABA agonists and antagonists can modulate commonly used behavioral models of depression and that chronic administration of antidepressant drugs induce marked changes in GABAergic function. In humans, depressed patients have lower plasma and CSF GABA concentrations than nondepressed comparison subjects. The recent discovery that several anticonvulsant and GABA-mimetic agents possess mood stabilizing and antidepressant properties has further increased interest in these findings. Novel imaging techniques now allow investigation of the GABAergic contribution to affective disorder pathophysiology. Through the techniques of PET, SPECT, and MRS, GABAergic function can be evaluated in vivo. Preliminary studies employing these techniques are finding new evidence suggesting that GABAergic abnormalities are associated with stress, anxiety, and depression. This article reviews the existing literature investigating the possible involvement of GABA in the neurobiology of depression and briefly highlights how these novel neuroimaging techniques can be used to further assess this hypothesis.

Animals↗

On aims and methods in the neuroimaging of derived relations.

Ingenious and seemingly powerful technologies have been developed recently that enable the visualization in some detail of events in the brain concomitant upon the ongoing behavioral performance of a human participant. Measurement of such brain events offers at the very least a new set of dependent variables in relation to which the independent variables familiarly manipulated in the operant laboratory may be explored. Two related paradigms in which a start has been made in such research concern the derivation of novel or emergent relations from a baseline set of trained relations, and include the phenomenon of transitive inference (TI), observed in studies of stimulus equivalence (SE) and serial learning (SL) or seriation. This paper reviews some published and forthcoming neuroimaging studies of these and related phenomena, and considers how this line of research both demands and represents a welcome synthesis between types of question and levels of explanation in behavioral science that often have been seen as antithetical.

Animals↗

Neuroimaging in human dystonia.

Functional neuroimaging, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provides a valuable technique for detecting regional changes in brain metabolic activity associated with human disease. These techniques have been applied in different dystonic disorders including primary generalized dystonia and dopa-responsive dystonia (DRD), as well as focal dystonic syndromes such as torticollis, writer's cramp, and blepharospasm. A common finding is abnormality of the basal ganglia and associated outflow pathways to sensorimotor cortex and other regions involved with motor performance. Other recent imaging research has utilized diffusion-based MRI techniques to localize distinct microstructural abnormalities in dystonia patients and gene carriers. This presentation will focus on an integrated approach to understanding the pathophysiology of this genetic and biochemically diverse disorder.

Anisotropy↗

Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies.

Despite vast clinical experience with antipsychotics, there is no broad consensus on the doses of these substances that should be administered. Currently, most antipsychotics are administered empirically according to clinical dose-finding studies, in which arbitrarily selected doses were tested to find the "most efficient" dose range in a patient population, with no regard for the molecular effects of the tested drug. Brain imaging studies using nuclear medical techniques, such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), can now provide a rationale for doses, directly derived from the central effects of the drugs on neurotransmitter receptors measured in vivo. PET results indicate that occupancy of at least 65% of dopamine D(2) receptors is needed for clinical response to antipsychotics, and that occupancy rates exceeding 72 and 78% are associated with a high risk for elevation of prolactin levels and motor adverse effects, respectively. For example, clinical studies with haloperidol do not point to an advantage of dosages exceeding 5 mg/day. The relevance of D(2) receptor occupancy for drug administration is also borne out by studies relating the effects of antipsychotics to their D(2) receptor occupancy in relevant animal models. Taken together, neuroimaging and clinical studies, as well as animal models, provide a rationale for the use of relatively low doses of typical antipsychotics and equivalent doses of novel antipsychotics. The lower risk of adverse effects with appropriate doses of antipsychotics may further enhance compliance and outcome. This seems to be particularly important in individuals experiencing a first episode of schizophrenia, as they appear to be especially responsive to pharmacotherapy and quite sensitive to adverse effects.

Animals↗

Neuroimaging and neuropathologic findings in AIDS patient with cytomegalovirus infection.

This 21-year-old male with hemophilia A developed cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS). He had a history of numerous blood transfusions. Serum antibody titers became positive for human immunodeficiency virus (HIV), when the patient was 18 years of age. Three years later, he developed CMV retinitis due to his immunosuppression. Ganciclovir (DENOSINE, TANABE SEIYAKU CO., LTD., Osaka, Japan) therapy given for 4 weeks produced a marked improvement in the ocular fundal findings, but the neurologic signs and symptoms, including headache, hypoesthesia, disorientation, and dementia became worse. T2-weighted magnetic resonance imaging (MRI) demonstrated a diffuse high intensity area in the periventricular white matter and small focal or patchy lesions in the hippocampus, basal ganglia, midbrain, medulla oblongata and the nucleus dentatus. The patient died of HIV encephalopathy and CMV infection. Characteristic CMV intranuclear inclusion bodies were observed histologically in most sites of the brain including the hippocampus, white matter, basal ganglia, midbrain, medulla oblongata, nucleus dentatus and the retina. Infiltration by monocyte-macrophage and multinucleated giant cells, which are characteristic of HIV encephalopathy, were observed in the periventricular white matter and the hippocampus. In this patient, the neuroimaging findings were compatible with the neuropathologic observations. MR imaging proved useful in detecting the central nervous system (CNS) lesions of AIDS and CMV infection.

AIDS Dementia Complex↗