Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival.

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally,both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features(no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging(DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when a MRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV<1.46 and minimum rADC>1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of a MRI to differentiate between LGG and HGG and to predict survival improved as the number of a MRI techniques considered increased. In a selected population of suspected LGG,classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series.

BACKGROUND AND PURPOSE: The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. The disease, first described in Canadian families from Québec, is characterized by cerebellar ataxia, pyramidal tract involvement and peripheral neuropathy. METHODS: Analysis of SACS gene allowed the identification of 14 patients with ARSACS from 13 unrelated Italian families. Clinical phenotype, gene mutations and magnetic resonance imaging (MRI) findings were analysed. RESULTS: We found 16 novel SACS gene mutations, including a large in-frame deletion. The age at onset was in infancy, but one patient presented the first symptoms at age 32. Progression of the disease was variable, and increased muscle tone was mostly recognized in later stages. Structural MRI showed atrophy of the superior cerebellar vermis, a bulky pons exhibiting T2-hypointense stripes, identified as the corticospinal tract (CST), thinning of the corpus callosum and a rim of T2-hyperintensity around the thalami in 100% of cases. The presence of iron or other paramagnetic substances was excluded. Diffusion tensor imaging (DTI) revealed grossly over-represented transverse pontine fibres (TPF), which prevented reconstruction of the CST at this level (100% of cases). In all patients, significant microstructural alterations were found in the supratentorial white matter of forceps, cingulum and superior longitudinal fasciculus. CONCLUSIONS: Our findings further enlarge the genetic spectrum of SACS mutations and widen the study of clinical phenotype. MRI characteristics indicate that pontine changes and supratentorial abnormalities are diagnostic. The over-representation of TPF on DTI suggests a developmental component in the pathogenesis of the disease.

Decreased diffusivity in the caudate nucleus of presymptomatic huntington disease gene carriers: which explanation?

BACKGROUND AND PURPOSE: The neostriatum is known to be affected in HD. In this work, our aim was to determine whether microstructural and volumetric alterations occur in the neostriatum of presymptomatic HD gene carriers and in patients with early-stage HD. MATERIALS AND METHODS: We studied a group of 15 presymptomatic gene carriers who were far from the estimated symptom onset (16% probability of developing the disease within 5 years), a group of 9 patients with early symptomatic HD, and 2 groups of age-matched controls. Volumetric MR imaging and DWIs were acquired, and statistical analyses were performed on the volumes of the caudate nucleus and putamen and on the corresponding MD measurements. RESULTS: Neostriatal volumes were significantly smaller in both presymptomatic HD gene carriers and symptomatic patients with respect to controls. However, whereas the diffusivity in the caudate nucleus was increased in the symptomatic patients, it was decreased in the presymptomatic gene carriers. CONCLUSIONS: Altered diffusivity and reduced volume of the caudate nucleus in presymptomatic HD gene carriers indicate that the neostriatum is affected well before the onset of symptoms. The observed initial decrease and subsequent increase of MD might be related to the combined effect of increased oligodendroglial population, putatively a developmental abnormality, and incipient neurodegeneration.

Diffusion tensor imaging shows different topographic involvement of the thalamus in progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADC(ave)) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADC(ave) values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADC(ave) was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

White matter involvement in idiopathic Parkinson disease: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) offers a unique window on the connectivity changes, extending beyond the basal ganglia, which accompany the cognitive symptoms of Parkinson disease (PD). The primary purpose of this study was to assess the microstructural damage to cerebral white matter occurring in idiopathic PD. MATERIALS AND METHODS: Our sample included patients with PD without dementia (n = 10; Hoehn and Yahr stages I and II; Unified Parkinson Disease Rating Scale, 20.5 +/- 8.3; and Mini-Mental State Examination, 28.3 +/- 1.5) and age-matched healthy control subjects (n = 10). DTI was performed on a 1.5T scanner, and mean diffusivity (MD) and fractional anisotropy (FA) maps were obtained. Regions of interest (ROIs) were drawn on the major fiber bundles as well as on gray matter nuclei. RESULTS: In patients, the MD was increased at borderline significance in the substantia nigra but was unaltered in the thalamus, globus pallidus, putamen, and in the head of the caudate nucleus. The FA and MD were unaltered in the corticospinal tract in the midbrain and at the level of the internal capsule, and in the splenium of the corpus callosum. By contrast, the MD was increased and the FA was decreased in the genu of the corpus callosum and in the superior longitudinal fasciculus; in the cingulum, only the MD was altered. The observed changes were not significantly lateralized. CONCLUSIONS: Widespread microstructural damage to frontal and parietal white matter occurs already in the early stages of PD.

A novel phenotype of sporadic Creutzfeldt-Jakob disease.

An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.

Diffusion tensor imaging of spinocerebellar ataxias types 1 and 2.

BACKGROUND AND PURPOSE: Structural MR imaging does not enable reliable differentiation of spinocerebellar ataxia (SCA) types 1 and 2 (SCA1 and SCA2), and imaging may be normal during the first years after the onset of symptoms. We aimed at determining whether measurements of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) may enable their differentiation. MATERIALS AND METHODS: We enrolled 14 patients with SCA1, 11 with SCA2, and 9 age-matched controls. Diffusion tensor imaging (DTI) was performed on a 1.5T scanner, with b = 1000s/mm2 and 12 directions. ADC and FA were measured by means of regions of interest, positioned in the corticospinal tract at the level of the cerebral peduncle and at the level of the pons, in the transverse pontine fibers, in the superior and middle cerebellar peduncle, and in the hemispheric cerebellar white matter. RESULTS: With respect to controls, the ADC was significantly elevated in the middle cerebellar peduncle and in hemispheric white matter in SCA1, and in all regions under consideration in SCA2. It was significantly higher in SCA2 than in SCA1 in all regions under consideration. With respect to controls, the FA was significantly reduced in all regions under consideration in SCA1 and in SCA2. It was significantly lower in SCA2 than in SCA1 in the transverse pontine fibers and in the corticospinal tract at the level of the cerebral peduncle. Correlations with clinical scores were found. CONCLUSIONS: DTI did not enable differentiation between SCA1 and SCA2. However, strongly significant differences between the 2 subtypes and with respect to controls and correlations with clinical scores were found.

MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review.

In vivo magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and diffusion-tensor imaging (DTI) have recently opened new possibilities for noninvasively assessing the metabolic, functional, and connectivity correlates of aging in research and clinical settings. The purpose of this article is to provide a conceptual review intended for a multidisciplinary audience, covering physical principles and main findings related to normal aging and senile cognitive impairment. This article is divided into 3 sections, dedicated to MRS, to fMRI, and to DTI. The spectroscopy section surveys physiological function of the observable metabolites, concentration changes in normal aging and their interpretation, and correlation with cognitive performance. The functional MRI section surveys the hemispheric asymmetry reduction model from compensation and de-differentiation viewpoints, memory encoding, retrieval and consolidation, inhibitory control, perception and action, resting-state networks, and functional deactivations. The DTI section surveys age-related changes, correlation with behavioral scores, and transition to cognitive impairment.

Imaging degeneration of the substantia nigra in Parkinson disease with inversion-recovery MR imaging.

BACKGROUND AND PURPOSE: Visualizing with MR imaging and obtaining quantitative indexes of degeneration of the substantia nigra in Parkinson disease have been long-sought goals. We investigated the potential role of area and T1 contrast measurements in differentiating patients from controls and their age-related changes. METHODS: Eight patients with Parkinson disease, 8 age-matched controls, and 8 young controls were imaged. We obtained the pixel-wise difference between 2 sets of inversion-recovery images, acquired parallel to the bicommissural plane, with different inversion times. Pixel-intensity ratios between lateral and medial nigral regions, and nigral area and substantia-nigra/midbrain area ratios were computed. RESULTS: Compared with that of controls, loss of substantia nigra was evident in patients, its borders taking a smoother and more irregular appearance. Patients were characterized by a lateral-to-medial gradient, due to reduced hypointensity of the lateral portion of the substantia nigra and relative sparing of its medial portion. The visible nigral area was significantly smaller in patients compared with matched controls (P = .04). The substantia nigra/midbrain area ratio enabled considerably better separation (P = .0001). The lateral/medial pixel-intensity ratio was significantly higher in patients compared with matched controls (P = .01) and in young controls compared with age-matched controls (P = .01). CONCLUSION: Inversion-recovery sequences may provide a convenient way to visualize nigral degeneration. Relative area and pixel-intensity measurements may integrate other techniques (such as diffusion-tensor imaging on nigrostriatal pathways) in the neuroradiologic diagnosis and follow-up of Parkinson disease by quantitatively assessing the degeneration of the substantia nigra.

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice.

In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.

Iron chelation therapy in aceruloplasminaemia: study of a patient with a novel missense mutation.

We describe a novel missense mutation of ceruloplasmin in a patient with aceruloplasminaemia causing the replacement of a neutral amino acid (phenylalanine) with a polar one (serine) at position 198, probably leading to abnormal folding and secretion of the protein. The patient showed mild microcytic anaemia, mild hepatic iron overload, and marked brain iron overload. Six months of therapy with deferiprone was ineffective in removing iron from the tissues. Deferoxamine was more efficient in removing excess iron from the liver but aggravated the disease related anaemia. After more than one year of chelation treatment, the brain magnetic resonance imaging signal did not change. Overall, these findings indicate that treatment of iron overload in aceruloplasminaemia is a difficult challenge and that new iron chelators, more efficient in crossing the blood-brain barrier, are needed.

Neuroradiological features of vertigo.

The diagnostic pathway in a patient with vertigo starts with the accurate evaluation of medical history followed by a general physical and neurological examination. This step can often lead to the identification of the correct cause of the disease or, at least, to a distinction between peripheral and central vertigo. Neuroradiological investigations have to be considered as elective diagnostic procedures and include: computed tomography (CT), magnetic resonance (MR), MR angiography (MRA), angiography. For the diagnosis of peripheral vertigo, benign paroxysmal positional vertigo, labyrinthitis, Meniere disease, perilymphatic fistula, local trauma, toxic labyrinthitis, acute otitis media and chronic middle ear effusion,the role of imaging techniques is controversial. CT and MR are performed to rule out other pathologies and to confirm the diagnosis. Increased resolution and application of special MR sequences enhancing the intralabyrinthine fluids have enabled more detailed analysis of labyrinthine structures and pathology. Both T2 and T1 contrast sequences are necessary. A high resolution CT study is required when otitis media is suspected and in the follow-up of post-traumatic vertigo. The causes of central vertigo are numerous and include: vertebro-basilar circulation vascular events, multiple sclerosis (MS), migraine-associated vertigo, cerebellar and brainstem tumors, CNS infections. Among them cerebrovascular ischemia and multiple sclerosis are the most frequent. In these situations imaging studies become mandatory. CT can diagnose most cerebellar hemorrhages and some cerebellar and brainstem acute ischemia, enhanced MR has proved to be the most sensitive tool to detect posterior fossa lesion. Diffusion-weighted MR can reveal acute ischemic changes before routine MR. There has been evidence that MR angiography, providing angiogram-like images of the intracranial vessels may sometimes avoid invasive angiography. MRA resolution is not as good as traditional angiography and may also be compromised by movements and other artifacts. Selective angiography of the posterior circulation is often indicated for therapeutic decisions.

Pathogenic effect of an intermediate-size SCA-6 allele (CAG)(19) in a homozygous patient.

SCA6 is caused by CAG expansion in the alpha 1A voltage-dependent calcium channel subunit gene. The authors studied an Italian family in which one patient carried a fully expanded SCA6 allele with 26-CAG repeats, whereas the other affected family member was homozygous for an intermediate-size allele of 19-CAG repeats. Three family members, heterozygous for the intermediate allele, were clinically unaffected. The findings demonstrate a dose-dependent pathogenic effect of an intermediate CAG expansion in the SCA6 gene.

Imaging dementias.

Dementia is the progressive loss of intellectual functions due to involvement of cortical or subcortical areas. Specific involvement of certain brain areas in the different diseases leads to impairment of different functions, e. g., memory, language, visuospatial abilities, and behavior. Magnetic resonance imaging and other neuroradiological studies may indicate which structures are mainly or selectively involved in a demented patient, thus allowing clinical-radiological correlations. Clinical presentation and evolution of the disease, supported by imaging studies, may lead to a highly probable diagnosis. The most common disorders, or the most relevant from the neuroradiological point of view, such as Alzheimer's disease, frontotemporal dementia, vascular dementias, dementia associated with parkinsonism, Huntington's disease, Creutzfeldt-Jakob disease, and normal-pressure hydrocephalus, are briefly discussed.

Clinical and neuroradiological aspects of Sneddon's syndrome and primary antiphospholipid antibody syndrome. A follow-up study.

We performed a study to investigate differences and similarities between patients with Sneddon's syndrome and those with primary antiphospholipid syndrome (PAS), by clinical follow-up, magnetic resonance imaging (MRI) and angiography. Nine patients with Sneddon's syndrome and 11 patients with PAS were assessed at diagnosis and followed for a mean of 6 years. The clinical and MRI findings indicated that Sneddon's syndrome and PAS are distinct entities. Patients with Sneddon's syndrome had a progressive clinical course with increasing disability and cognitive deterioration; patients with PAS had a more benign course. Infarcts in territories of the main cerebral arteries were frequent in PAS, while leukoaraiosis and small lacunar infarcts were more common in Sneddon's syndrome. In 3 of 7 women initially diagnosed with PAS, the diagnosis was changed to systemic lupus erythematosus during follow-up. Differential diagnosis of Sneddon's syndrome and PAS is important, as early therapy is effective for the latter, more benign, condition.