Spinal pain.

The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic pain, much more difficult to treat. The clinical assessment of pain source can be a challenge because of the complex anatomy and function of the spine; the advanced imaging methods are often not sufficient for a definitive diagnosis because similar findings could be present in either asymptomatic and symptomatic subjects: a clinical correlation is always mandatory and the therapy cannot rely uniquely upon any imaging abnormalities. Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. Special attention will be done to the discogenic pain, actually considered as the most frequent cause of chronic low back pain.

Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis.

BACKGROUND: Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. OBJECTIVE: The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. METHODS: Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected). RESULTS: Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index. CONCLUSIONS: Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS.

Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

BACKGROUND: Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. OBJECTIVES: The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. METHODS: Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. RESULTS: CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. CONCLUSIONS: This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Imaging in congenital deformities of the spinal cord.

Vertebromedullary malformations are a heterogeneous group of anomalies of mesenchymal and neuroectodermal tissue differentiation or closure in the midline of the back. On the basis of an embryological analysis, the authors describe the more common malformations, placing them at different times of onset and describing the pathological features and radiological findings based on the use of the most appropriate imaging techniques. The most common malformations have been divided into dysraphic and nondysraphic types and malformations affecting the vertebral bodies. The most complex malformations are detected during the antenatal period by ultrasound or foetal magnetic resonance imaging (MRI). Conversely, during the postnatal period, when the patient's clinical conditions do not warrant emergency surgical treatment, the disorder can be better defined with a detailed MRI scan of the brain and spinal cord. In less complex dysraphisms, although MRI is the imaging modality of choice, it may be useful to integrate the study with plain radiography (X-ray) and multidetector computed tomography (MDCT) for a better assessment of the skeletal components. In these disorders, the use of imaging is aimed at both identifying malformative defects and postoperative follow-up of more complex forms.

Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

BACKGROUND: Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. METHOD: Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. RESULTS: We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. CONCLUSIONS: Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia.

Does the default-mode functional connectivity of the brain correlate with working-memory performances?

The "default-mode" network is an ensemble of cortical regions that are typically deactivated during demanding cognitive tasks in functional magnetic resonance imaging (fMRI) studies. Using functional connectivity analysis, this network can be studied as a "stand-alone" brain system whose functional role is supposed to consist in the dynamic control of intrinsic processing activities like attention focusing and task-unrelated thought generation and suppression. Independent component analysis (ICA) is the method of choice for generating a statistical image of the "default-mode" network (DMN) using a task- and seed-independent distributed model of fMRI functional connectivity without prior specification of node region extent and timing of neural activation. We used a standard graded working-memory task (n-back) to induce fMRI changes in the default-mode regions and ICA to evaluate to DMN functional connectivity in nineteen healthy volunteers. Based on the known spatial variability of the ICA-DMN maps with the task difficulty levels, we hypothesized the ICA-DMN may also correlate with the subject performances. We confirmed that the relative extent of the anterior and posterior midline spots within the DMN were oppositely (resp. positively in the anterior and negatively in the posterior cingulate cortex) correlated with the level of task difficulty and found out that the spatial distribution of DMN also correlates with the individual task performances. We conclude that the working-memory function is related to a spatial re-configuration of the DMN functional connectivity, and that the relative involvement of the cingulate regions within the DMN might function as a novel predictor of the working-memory efficiency.

Phenylketonuria: white-matter changes assessed by 3.0-T magnetic resonance (MR) imaging, MR spectroscopy and MR diffusion.

PURPOSE: This study evaluated the sensitivity of a 3.0-Tesla (T) magnetic resonance imaging (MRI) in measuring cerebral phenylalanine using proton magnetic resonance spectroscopy and in assessing MR-documented white-matter changes by means of diffusion studies (diffusion-weighted imaging, apparent diffusion coefficient map; diffusion tensor imaging) in patients with phenylketonuria. MATERIALS AND METHODS: Thirty-two patients with the classical clinical and biochemical deficits of phenylketonuria underwent biochemical (blood phenylalanine), genotypic (phenylalanine hydroxylase gene) and radiological investigation by means of MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging with a 3.0-T scanner. RESULTS: Periventricular and subcortical white-matter changes were detected on all MR scans. In 29/32 patients, proton magnetic resonance spectroscopy easily documented abnormal signal elevation at 7.36 ppm, corresponding to phenylalanine, despite its low concentration. Phenylalanine signal amplitude relative to the creatine/phosphocreatine signal increased linearly with blood phenylalanine values (r 0.7067; p<0.001). Diffusion MRI demonstrated hyperintensity in the areas exhibiting MRI changes as well as decreased apparent diffusion coefficient values, but fractional anisotropy indices were normal. CONCLUSIONS: The high signal, together with better spectral, spatial, contrast and temporal resolution, makes the 3.0-T MR the most suitable technique in the study of the phenylketonuria. In particular, the multimodal approach with MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging can provide more information than previous studies performed with low-field systems.

Role of advanced MR imaging modalities in diagnosing cerebral gliomas.

The objective of this study was to evaluate the potential role of newly developed, advanced magnetic resonance (MR) imaging techniques (spectroscopy, diffusion and perfusion imaging) in diagnosing brain gliomas, with special reference to histological typing and grading, treatment planning and posttreatment follow-up. Conventional MR imaging enables the detection and localisation of neoplastic lesions, as well as providing, in typical cases, some indication about their nature. However, it has limited sensitivity and specificity in evaluating histological type and grade, delineating margins and differentiating oedema, tumour and treatment side-effects. These limitations can be overcome by supplementing the morphological data obtained with conventional MR imaging with the metabolic, structural and perfusional information provided by new MR techniques that are increasingly becoming an integral part of routine MR studies. Incorporation of such new MR techniques can lead to more comprehensive and precise diagnoses that can better assist surgeons in determining prognosis and planning treatment strategies. In addition, the recent development of new, more effective, treatments for cerebral glioma strongly relies on morphofunctional MR imaging with its ability to provide a biological interpretation of these characteristically heterogeneous tumours.

Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of cerebral gliomas.

PURPOSE: This study was performed to clarify the role of perfusion-weighted imaging (PWI) at 3 Tesla in the characterisation of haemodynamic heterogeneity within gliomas and surrounding tissues and in the differentiation of high-grade from low-grade gliomas. MATERIALS AND METHODS: We examined 36 patients with histologically verified gliomas (25 with high-grade and 11 with low-grade gliomas). PWI was performed by first-pass gadopentetate dimeglumine T2*-weighted echo-planar images, and cerebral blood volume (CBV) maps were computed with a nondiffusible tracer model. Relative CBV (rCBV) was calculated by dividing CBV in pathological areas by that in contralateral white matter. RESULTS: In high-grade gliomas, rCBV were markedly increased in mass [mean+/-standard deviation (SD), 4.3+/-1.2] and margins (4.0+/-1.1) and reduced in necrotic areas (0.3+/-0.3). Oedematous-appearing areas were divided in two groups according to signal intensity on T2-weighted images: tumour with lower (nearly isointense to grey matter) and oedema with higher (scarcely isointense to cerebrospinal fluid) signal intensity. Tumour showed significantly higher rCBV than did oedema (1.8+/-0.5 vs. 0.5+/-0.2; p<0.001) areas. In low-grade gliomas, mass (2.0+/-1.5) and margin (2.2+/-1.2) rCBV were significantly lower than in high-grade gliomas (p<0.001). CONCLUSIONS: Three-Tesla PWI helps to distinguish necrosis from tumour mass, infiltrating tumour from oedema and high-grade from low-grade gliomas. It enhances the magnetic resonance (MR) assessment of cerebral gliomas and provides useful information for planning surgical and radiation treatment.

3.0-T functional brain imaging: a 5-year experience.

The aim of this paper is to illustrate the technical, methodological and diagnostic features of functional imaging (comprising spectroscopy, diffusion, perfusion and cortical activation techniques) and its principal neuroradiological applications on the basis of the experience gained by the authors in the 5 years since the installation of a high-field magnetic resonance (MR) magnet. These MR techniques are particularly effective at 3.0 Tesla (T) owing to their high signal, resolution and sensitivity, reduced scanning times and overall improved diagnostic ability. In particular, the high-field strength enhances spectroscopic analysis due to a greater signal-to-noise ratio (SNR) and improved spectral, space and time resolution, resulting in the ability to obtain high-resolution spectroscopic studies not only of the more common metabolites, but also--and especially--of those which, due to their smaller concentrations, are difficult to detect using 1.5-T systems. All of these advantages can be obtained with reduced acquisition times. In diffusion studies, the high-field strength results in greater SNR, because 3.0-T magnets enable increased spatial resolution, which enhances accuracy. They also allow exploration in greater detail of more complex phenomena (such as diffusion tensor and tractography), which are not clearly depicted on 1.5-T systems. The most common perfusion study (with intravenous injection of a contrast agent) benefits from the greater SNR and higher magnetic susceptibility by achieving dramatically improved signal changes, and thus greater reliability, using smaller doses of contrast agent. Functional MR imaging (fMRI) is without doubt the modality in which high-field strength has had the greatest impact. Images acquired with the blood-oxygen-level-dependent (BOLD) technique benefit from the greater SNR afforded by 3.0-T magnets and from their stronger magnetic susceptibility effects, providing higher signal and spatial resolution. This enhances reliability of the localisation of brain functions, making it possible to map additional areas, even in the millimetre and submillimetre scale. The data presented and results obtained to date show that 3.0-T morphofunctional imaging can become the standard for high-resolution investigation of brain disease.

3.0-T morphological and angiographic brain imaging: a 5-years experience.

Ever since the introduction of magnetic resonance (MR), imaging with 1.5 Tesla (T) has been considered the gold standard for the study of all areas of the body. Until not long ago, higher-field MR equipment was exclusively employed for research, not for clinical use. More recently, the introduction of 3.0-T MR machines for new and more sophisticated clinical applications has resulted in important benefits, especially in neuroradiology. Indeed, their high gradient power and field intensity (3.0 T) allow adjunctive and more advanced diagnostic methodologies to be performed with excellent resolution in a fraction of the acquisition time required with earlier machines. The purpose of this paper is to illustrate the distinctive semeiological characteristics of 3.0-T morphological and angiographic brain imaging compared with lower-field systems and highlight the respective advantages and drawbacks based on the experience gained in the first 5 years from the installation of a 3.0-T magnet.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Spectroscopic, diffusion and perfusion magnetic resonance imaging at 3.0 Tesla in the delineation of glioblastomas: preliminary results.

Recent advances in magnetic resonance imaging (MRI) have allowed the evaluation of metabolic, diffusion and hemodynamic features of malignant gliomas. The aim of this study was to evaluate whether such information provided useful, complementary information to conventional MRI for improving the evaluation of glioblastoma extent. Ten patients with glioblastoma multiforme underwent conventional MRI, proton MR spectroscopic imaging (1H-MRSI), perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Metabolite signals, including normalized choline, N-acetylaspartate, creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. In edematous-appearing areas, 3 multiparametric patterns were identified: infiltrating tumor, with abnormal metabolite ratios, lower ADC and higher rCBV; pure edema, with normal metabolite ratios, higher ADC and lower rCBV; and tumor-infiltrated edema, with abnormal metabolite ratios and intermediate ADC and rCBV. In normal-appearing areas, 2 multiparametric patterns were identified: tumor-infiltrated tissue, with abnormal metabolite ratios and higher rCBV; and normal tissue, with normal MR parameters. The combination of 1H-MRSI, DWI and PWI features contributed to delineation of glioblastomas, offering information not available with conventional MRI. This approach may enhance the assessment of brain gliomas, providing useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Supratentorial low-grade gliomas. Neuroradiology.

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumors is magnetic resonance imaging. A brain tumors can be reliably ruled out, if the standard magnetic resonance examination is performed properly and experts interpret the results as negative for tumor. In this paper we will illustrate morphological aspects of low-grade supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low-grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell astrocytoma). Then the main practical applications of functional imaging in neurosurgery will be also debated.

Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder characterised by early pendular nystagmus, often rotatory and muscular hypotonia with subsequent ataxia, spasticity and mental retardation. Various point mutations or duplications in the PLP gene on the X chromosome are responsible for PMD in the majority of patients. Autosomal recessive inheritance, particularly in the connatal form, cannot be excluded. Three different forms of the disease have been identified based on their onset, progression and severity of myelin pathology indicated by MRI features. Objective. To determine if MR spectroscopy is useful in the diagnosis of the connatal form of PMD. MATERIALS AND METHODS: Proton MR spectroscopy was performed on two children with connatal PMD. RESULTS: Our patients showed a markedly decreased peak of Cho. This alteration is well represented by quantitative analysis of the NAA-to-Cho ratio, which is the most important ratio affected. A significant decrease of the Cho-to-Cr ratio is also present. In the connatal form of PMD, global lack of myelination may be relevant, as demonstrated by a significant Cho peak reduction. CONCLUSIONS: Proton MR spectroscopy may be of diagnostic value in metabolic and destructive disorders of the brain. A greater number of patients with connatal PMD is needed in order to elucidate the significance of reduction of the Cho peak.

Proton magnetic resonance spectroscopy of the brain in pediatric patients.

H1-MRS is a non-invasive technique which provides different levels of information on brain tissue: the N-acetyl aspartate (NAA) is an indicator of neuronal development, the choline containing compound peak (Cho) provides information on myelination and on cell membrane turnover and gliosis, inositol (Ins) is considered a marker of neuronal degeneration. Lactate may be detected in presence of defective energy metabolism. In the perineonatal period, the brain is apt to be insulted by a variety of events including asphyxia, hypoxemia, hemorrhage, which may subsequently cause delay in development. It is clinically important to assess the degree of brain damage and to obtain the prognostic information in the neonatal and early infantile period. MRS has become available for clinical examinations of the brain during development and these techniques can be used to document improvement or the progression towards irreversible damage.