Biomedical subjects

Vittorio Martinelli

Publications and source records attributed to Vittorio Martinelli.

16 recordsLinked to original sources

PubMed2005

The level of spinal cord involvement influences the pattern of movement-associated cortical recruitment in patients with isolated myelitis.

Using fMRI, an increased recruitment of the ipsilateral primary sensorimotor cortex (SMC), supplementary motor area, and middle frontal gyrus has been detected in patients with cervical cord myelitis of possible demyelinating origin. The aim of this study was to evaluate, using fMRI, whether the level of cord involvement influences cortical reorganization by comparing patients with isolated myelitis of the cervical and the dorsal portions of the cord, and to investigate whether the extent of cortical reorganization is associated with the extent of cervical cord pathology measured using magnetization transfer (MT) MRI. We studied 24 right-handed patients (14 with a previous involvement of the cervical cord and 10 with an involvement of the dorsal cord) in a chronic and clinically stable phase following an isolated myelitis of possible demyelinating origin and 15 sex- and age-matched healthy controls. During a single session, we obtained fMRI during repetitive flexion-extension of the last four fingers of the right and left hands and cervical cord MT MRI. Average cord MTR was lower in patients with cervical (P < 0.0001) and dorsal (P = 0.0001) myelitis than in controls. Compared to controls and for both tasks, patients with myelitis had an increased recruitment of the ipsilateral primary SMC, which was independent of the level of cord involvement. On the contrary, patients with cervical myelitis had a more widespread recruitment of frontal and parietal regions, whereas those with dorsal myelitis had a more widespread recruitment of temporal and cerebellar regions. Strong correlations (r values ranging from -0.72 to -0.88) were found between relative activations of cortical areas and the severity of cervical cord damage. Patients with isolated myelitis have different patterns of movement-associated cortical activations according to the level of cord involvement. This "level-dependent" functional reorganization of the cortex is likely to have an adaptive role in limiting the clinical outcome of cord damage and should be considered when designing rehabilitation strategies for these patients.

Adult↗

PubMed2005

Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis.

BACKGROUND: Diffusion-tensor (DT) magnetic resonance imaging (MRI) has the potential to elucidate some characteristics of tissue microstructure inaccessible to other MRI techniques. OBJECTIVE: To investigate whether normal-appearing brain tissue abnormalities occur in patients with multiple sclerosis at the earliest clinical stage and whether their severity is predictive of a short-term disease evolution by using DT MRI. DESIGN: Forty-five patients and 22 healthy control subjects were studied. All patients had had a clinically isolated syndrome within the 3 months preceding study enrollment and paraclinical evidence of disease dissemination in space. During a single session, dual-echo, pulsed-gradient spin-echo echo-planar, and postgadolinium T1-weighted images of the brain were obtained from each subject. In patients, dual-echo and enhanced images were obtained after 3 and 12 months, to detect MRI signs of disease dissemination in time. An on-study neurological examination was also conducted to ascertain the occurrence of clinical relapses. Mean diffusivity and fractional anisotropy maps were derived from DT images. Normal-appearing white matter (NAWM) and normal-appearing gray matter mean diffusivity and fractional anisotropy histograms were produced and analyzed. RESULTS: During the study period, 29 patients showed MRI evidence of disease dissemination in time. When compared with healthy controls, patients showed higher average NAWM mean diffusivity (P = .01), lower average NAWM mean diffusivity peak height (P < .001), and fractional anisotropy (P < .001). The DT MRI characteristics of patients did not differ between those with and those without disease dissemination in time at follow-up. CONCLUSIONS: In patients with multiple sclerosis at the earliest clinical stage, the severity of NAWM damage does not predict new lesion formation in the short term, suggesting that the "diffuse" component of tissue damage is, at least partially, independent of the "discrete," predominantly inflammatory aspects of the disease since its clinical onset.

Adult↗

PubMed2005

Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes.

BACKGROUND: Movement-associated cortical reorganisation is known to occur in multiple sclerosis (MS). We aimed to define the development of such cortical reorganisation by comparing data from patients with different disease phenotypes. METHODS: We studied patients with different phenotypes of MS: 16 patients with a clinically isolated syndrome (CIS), 14 patients with relapsing-remitting MS (RRMS) and no disability, 15 patients with RRMS and mild clinical disability, and 12 patients with secondary progressive MS (SPMS). Patients did a simple motor task with their unimpaired dominant hand during MRI, which was compared across the phenotype groups. FINDINGS: Patients with a CIS activated more of the contralateral primary sensorimotor cortex than those with RRMS and no disability, whereas patients with RRMS and no disability activated more of the supplementary motor area than those with a CIS. Patients with RRMS and no disability activated more of the primary sensorimotor cortex, bilaterally, and more of the ipsilateral supplementary motor area than patients with RRMS and mild clinical disability. Conversely, patients with RRMS and mild clinical disability activated more of the contralateral secondary somatosensory cortex and inferior frontal gyrus, and the ipsilateral precuneus. Patients with RRMS and mild clinical disability activated more of the contralateral thalamus and of the ipsilateral secondary somatosensory cortex than those with SPMS. However, patients with SPMS activated more of the inferior frontal gyrus, bilaterally, the middle frontal gyrus, bilaterally, the contralateral precuneus, and the ipsilateral cingulate motor area and inferior parietal lobule. INTERPRETATION: Movement-associated cortical reorganisation in patients with MS seems to vary across individuals at different stages of disease. Our study suggests that early in the disease course more areas typically devoted to motor tasks are recruited. Then bilateral activation of these regions is seen, and late in the disease course, areas that healthy people recruit to do novel or complex tasks are activated.

Adaptation, Physiological↗

PubMed2005

Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype.

BACKGROUND AND PURPOSE: Progressive brain atrophy is a well-known feature of multiple sclerosis (MS). We characterized the spatial evolution of atrophy in different MS phenotypes. METHODS: Dual-echo and T1-weighted MR images were obtained in 70 patients with MS and 10 healthy control subjects at entry and after 15 months. Within-group changes in regional atrophy were assessed by applying Structural Image Evaluation Using Normalization of Atrophy software and statistical parametric mapping analysis. Reported differences are for P <.001. RESULTS: During follow-up, patients with relapsing-remitting MS (RRMS) differences significant atrophy around the ventricular system; pericerebellar spaces; cerebellar tentorium; putamen; corpus callosum; cingulate sulcus; hippocampus; parieto-occipital fissure; lateral fissure; and frontal, parietal, temporal, and occipital cortex. Patients with secondary progressive MS developed significant atrophy of the cingulate sulcus; pulvinar; caudate nucleus; anterior orbital gyrus; mammillary body; fourth ventricle; and regions of frontal, parietal, temporal, and occipital cortex. Patients with primary progressive MS developed significant atrophy of the bilateral central sulcus; caudate nucleus; prepontine and quadrigeminal cisterns; lateral ventricle; and regions of frontal, parietal, temporal, and occipital cortex. In all phenotypes, the development of atrophy in some regions was significantly correlated with the accumulation of T2- and T1-visible lesions and clinical disability (r = -0.57 to -0.86). CONCLUSION: In MS, brain atrophy develops involving different structures in the different phenotypes. While ventricular enlargement is predominant in RRMS, cortical atrophy seems to be more important in the progressive forms. Measures of regional brain atrophy were significantly correlated with disability, suggesting that this approach is promising for bridging the gap between clinical and MR imaging findings in MS.

Adult↗

PubMed2005

A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis.

BACKGROUND AND PURPOSE: Movement-associated cortical changes have been detected at the earlier clinical stage multiple sclerosis. Our purpose was to assess whether different patterns of cortical recruitment are associated with the short-term evolution of definite multiple sclerosis (MS). METHODS: We followed for 1 year a group of patients with clinically isolated syndromes (CISs) suggestive of MS and compared the baseline movement-associated patterns of cortical activations between those patients with and those without evolution to definite MS. RESULTS: Those patients in whom MS did not evolve had more significant activations of several areas part of the "classic" motor network; those who went on to develop MS had more significant activations of several regions in the frontal, parietal, temporal, and occipital lobes. CONCLUSION: In CIS patients, the extent of early cortical reorganization following tissue injury might be a factor associated with a different disease evolution.

Adult↗

PubMed2004

Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.

The mechanisms underlying the progressive course of multiple sclerosis (MS) are not fully understood yet. Since diffusion tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult brain damage related to MS, the present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of white and gray matter (GM) pathology in patients with primary progressive (PP) and secondary progressive (SP) MS. Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months. Dual-echo, T1-weighted, and DT MRI scans of the brain were acquired on both occasions. Total lesion volumes (TLV) and percentage brain volume changes (PBVC) were computed. Mean diffusivity (MD) and fractional anisotropy (FA) maps of the normal-appearing white (NAWM) and gray matter (NAGM) were produced, and histogram analysis was performed. In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up. No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure. No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC. No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period. Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with progressive MS. The accumulation of DT MRI-detectable gray matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of brain volume. These observations suggest that progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in progressive MS.

Adult↗

PubMed2004

High tumor necrosis factor-alpha [corrected] levels in cerebrospinal fluid of cobalamin-deficient patients.

We studied 14 patients with neurological manifestations of subacute combined degeneration (SCD) and 40 control patients not cobalamin (Cbl)-deficient. The cerebrospinal fluid (CSF) markers of Cbl deficiency (Cbl and total homocysteine [tHCYS] levels) and the CSF levels of tumor necrosis factor (TNF)-alpha and epidermal growth factor (EGF) were measured. Significantly higher levels of tHCYS and TNF-alpha, and significantly lower levels of Cbl and EGF were found in the SCD patients. In human CSF, as in human serum and the rat central nervous system, decreased Cbl concentrations are concomitant with an increase in TNF-alpha and a decrease in EGF-levels. Ann Neurol 2004;56:886-890.

Adult↗

PubMed2004

Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.

Adult↗

PubMed2004

Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica.

OBJECTIVES: To evaluate the clinical characteristics, course and prognosis of Devic's neuromyelitis optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria. METHODS: Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS centres. Inclusion criteria were: 1) two or more acute episodes of neurological dysfunction indicating involvement of the optic nerve and spinal cord, in a simultaneous or subsequent temporal relationship; 2) no evidence of lesions beyond the optic nerve or the spinal cord; 3) brain MRI at onset negative or non-specific for multiple sclerosis (MS) (white matter lesions < or = 2). Disability was scored by means of Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: 46 patients with relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 +/- 16.3 years (range 12-77 years). The follow up duration was 8.8 +/- 3.5 years, the mean annualised relapse rate was 1.3 +/- 1.2. After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases, EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases. The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2(nd) attack, and relapse rate. The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate. During the follow up, brain white matter lesions appeared in 8 subjects. Spinal cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects. One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being pleocytosis (38.6 %), oligoclonal bands (34.1 %), high protein level (25 %), and high albumin ratio (20.5 %). CONCLUSIONS: DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe. Brain and spinal cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins.

Adolescent↗

PubMed2003

Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.

The correlation between conventional MRI lesion load accumulation and multiple sclerosis clinical evolution is only modest. The assessment of brain parenchymal volume and of its changes over time may provide adjunctive MRI markers reflecting the more disabling aspects of multiple sclerosis pathology. Magnetization transfer (MT) MRI is sensitive to 'occult' multiple sclerosis-related brain damage and might also contribute to overcome the clinical/MRI paradox. In this study, we assessed the value of conventional and MT MRI-derived metrics in predicting the medium-term clinical evolution of patients with different multiple sclerosis phenotypes. We studied 73 patients, with relapsing-remitting multiple sclerosis (n = 34), secondary progressive multiple sclerosis (n = 19) and clinically isolated syndromes suggestive of multiple sclerosis (n = 20), and 16 healthy subjects. Brain dual-echo, T1-weighted (only in patients) and MT MRI scans were obtained at baseline and after 12 months. T2-hyperintense and T1-hypointense lesion volumes, normalized brain volume and average lesion MT ratio (MTR) were measured. MTR histograms from the whole brain tissue were also obtained. Clinical multiple sclerosis evolution and neurological disability were re-assessed in all patients after a median follow-up of 4.5 years. A multivariate analysis was performed to establish which clinical and MRI-derived variables were significant predictors of neurological deterioration at the end of the study period. At the end of follow-up, 34 patients showed significant neurological deterioration. The final multivariable model included average brain MTR percentage change after one year [P = 0.02, odds ratio (OR) = 0.86] and baseline T2-hyperintense lesion volume (P = 0.04, OR=1.04) as independent predictors of medium-term disability accumulation (r2 = 0.23). In this cohort of patients, abnormal values of average brain MTR changes showed a relatively high specificity (76.9%) and positive predictive value (59.1%) for Expanded Disability Status Scale score deterioration in individual cases. In patients with multiple sclerosis, a comprehensive estimation of the short-term changes of both conventional and MT MRI-detectable lesion burden might provide useful prognostic information for the medium-term clinical disease evolution.

Adult↗

PubMed2003

Demyelination and cortical reorganization: functional MRI data from a case of subacute combined degeneration.

Although it is accepted that functional changes of the cortex can occur in patients with white matter diseases of the brain and might have an adaptive role in limiting the clinical consequences of subcortical injury, the pathological substrates able to elicit such cortical changes are still unknown. This multiparametric magnetic resonance study of a patient with an early diagnosis of subacute combined degeneration suggests that demyelination alone does not necessarily induce adaptive functional changes of the cerebral cortex.

Cerebral Cortex↗

PubMed2003

Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Previous work has suggested that functional reorganization of cortical areas might have a role in limiting the clinical impact of axonal pathology in patients with established multiple sclerosis (MS). Since there is evidence for irreversible tissue damage even in patients with early MS, we assessed, using functional MRI (fMRI) and a general search method, the brain pattern of movement-associated cortical activations in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS. To elucidate the role of cortical reorganization in these patients, we also investigated the extent to which the fMRI changes correlated with the extent of overall axonal injury of the brain. From 16 right-handed patients at presentation with CIS and 15 right-handed, age- and sex-matched healthy volunteers, we obtained: (1). fMRI (repetitive flexion-extension of the last four fingers of the right hand), (2). conventional MRI scans, and (3). a new, unlocalized proton MR spectroscopy ((1)HMRS) sequence to measure the concentration of N-acetylaspartate of the whole brain (WBNAA). Compared to controls, patients with CIS had more significant activations of the contralateral primary somatomotor cortex (SMC), secondary somatosensory cortex, and inferior frontal gyrus. They also had significant decreased WBNAA concentration. Relative activation of the contralateral primary SMC was strongly correlated with WBNAA levels (r = -0.78, P < 0.001). This study shows that axonal pathology and functional cortical changes over a rather distributed sensorimotor network occur in patients at presentation with CIS suggestive of MS and that these two aspects of the disease are strictly correlated. This suggests that the increased functional recruitment of the cortex in these patients might have an adaptive role in limiting the clinical impact of irreversible tissue damage.

Adaptation, Physiological↗

PubMed2003

Somatosensory evoked potentials and sensory involvement in multiple sclerosis: comparison with clinical findings and quantitative sensory tests.

Sensory disturbances are one of the most common findings in patients with multiple sclerosis (MS). However, they are usually assessed at the standard neurological examination only. Quantitative Sensory Tests (QSTs) for temperature and vibratory sense allow a more objective evaluation. In a group of 19 clinically definite MS patients, we compared vibratory and temperature thresholds with sensory symptoms or signs at clinical neurological examination and somatosensory evoked potentials (SEPs) at the four limbs. The frequency of abnormalities of clinical symptoms/signs, vibration threshold and median SEPs were 69%, 33% and 55%, respectively. Correlation between degree of abnormality of SEPs and clinically assessed vibration sense (V) was statistically significant (P<0.007; Spearmann rank coefficient), as well as between SEPs and vibration perception threshold (P<0.02). Clinical evaluation of thermal sense did not show false positive results compared to quantitative thermal threshold, but false negative findings (35%). This study suggests that the combined use of vibration threshold and SEPs allows a better objectivation of sensory function, allowing the detection of subclinical abnormalities and possibly reducing the number of false positive results introduced by clinical assessment. Moreover QSTs are to be preferred to clinical evaluation in the assessment of thermal sense, due to their superior sensitivity.

Adult↗

PubMed2002

Cognitive dysfunction in patients with mildly disabling relapsing-remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging.

Previous studies assessing the magnetic resonance imaging (MRI) correlates of cognitive dysfunction in multiple sclerosis (MS) achieved conflicting results. Diffusion tensor (DT)-MRI provides metrics that are sensitive to the macro- and microscopic MS lesion load with increased specificity to the more destructive aspects of MS pathology than conventional imaging. We performed an exploratory study to assess the magnitude of the correlation between quantities derived from DT-MRI and measures of cognitive impairment in patients with relapsing-remitting (RR) MS.T2, T1, DT-MRI scans of the brain and an extensive battery of neuropsychological tests (exploring language, complex reasoning, attention and memory) were obtained from 34 RRMS patients. We measured T2 and T1 lesion volumes (LV) and brain volume. Average lesion mean diffusivity (D) and fractional anisotropy (FA) were calculated. D and FA histograms from the brain tissue (BT), the normal-appearing brain tissue (NABT), the normal-appearing white matter (NAWM) and the normal-appearing gray matter (NAGM) were also obtained. Nine patients (26.5%) were found to be cognitively impaired. Moderate correlations were found between symbol digit modalities test, verbal fluency test and 10/36 spatial recall test scores and T2 LV, T1 LV and average lesion, WBT, NABT, NAWM and NAGM values (r values ranging from -0.30 to -0.53). No correlations were found between any of the neuropsychological test scores and brain volume, average lesion FA and WBT FA.DT-MRI provides quantitative metrics that seem to reflect the severity of language, attention and memory deficits in patients with RRMS. This study also suggests that the extent and the intrinsic nature of the macroscopic lesions as well as the damage of the NAWM and NAGM all contribute to the neuropsychological deficits of RRMS patients.

Adult↗

PubMed2002

Irreversible disability and tissue loss in multiple sclerosis: a conventional and magnetization transfer magnetic resonance imaging study of the optic nerves.

OBJECTIVES: To assess, by magnetic resonance imaging, the volumes and magnetization transfer ratio (MTR) values of optic nerves (ONs) from patients with multiple sclerosis (MS) who had incomplete or no visual recovery after optic neuritis; and to compare these quantities with those derived from ONs from patients with MS who showed a marked clinical recovery after optic neuritis, ONs from healthy volunteers, and ONs from patients with Leber hereditary optic neuropathy (LHON). METHODS: Conventional and magnetization transfer magnetic resonance images of the ONs were obtained from 30 patients with MS, 18 healthy volunteers, and 10 patients with LHON. The ON from patients with MS were classified as clinically unaffected (n = 18); clinically affected with recovery (n = 20; visual acuity > or =20/25 at least 6 months after optic neuritis); and clinically affected with incomplete or no recovery (n = 22; visual acuity <20/25 at least 6 months after optic neuritis). The ON volumes and MTR values were measured. RESULTS: Volumes (P =.002) and MTR values (P<.001) of the ONs from patients with MS and incomplete or no recovery were both lower than those of the ONs from patients with MS and recovery, but not different from those of the ONs from patients with LHON. Volumes and MTR values of the affected ONs from patients with MS and recovery did not differ from those of clinically unaffected ONs, which were similar to those of healthy volunteers. CONCLUSION: These findings suggest that, in patients with MS, neurodegeneration is associated with persistent functional deficits secondary to incomplete recovery from relapses.

Adolescent↗

PubMed2002

Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis: a diffusion-tensor magnetic resonance imaging study.

BACKGROUND: Diffusion-tensor magnetic resonance imaging is sensitive to the more destructive aspects of multiple sclerosis (MS) evolution occurring outside and within T2-visible lesions and, as a consequence, holds promise for providing a more complete picture of primary progressive (PP) MS-related tissue damage than conventional magnetic resonance imaging. OBJECTIVE: To improve our understanding of PPMS by assessing the extent of occult pathological features in the normal-appearing white and gray matter of the brain using diffusion-tensor magnetic resonance imaging. METHODS: Ninety-six patients with PPMS, 47 patients with secondary progressive (SP) MS, and 44 healthy control subjects were studied. T2-hyperintense and T1-hypointense lesion volumes were calculated, and the volume of the whole brain tissue was measured. Diffusion-tensor magnetic resonance imaging scans were postprocessed and analyzed to obtain the mean diffusivity and fractional anisotropy histograms from the brain and from the normal-appearing white and gray matter in isolation. RESULTS: The mean T2-hyperintense and T1-hypointense lesion volumes were lower in patients with PPMS than in patients with SPMS, while the mean absolute brain volumes were similar in the 2 groups. The average lesion diffusivity was significantly higher in patients with SPMS than in patients with PPMS (P<.001). Histogram-derived metrics of the brain tissue and normal-appearing white and gray matter were significantly different between patients with PPMS and healthy subjects (range, P =.004 to <.001). Average diffusivity values were significantly higher in patients with SPMS than in patients with PPMS for all the tissues studied (range, P =.001 to <.001). Fractional anisotropy histogram-derived quantities did not significantly differ between the 2 patient groups (range, P =.94 to.03). CONCLUSION: This study confirms that, in patients with PPMS, normal-appearing white and gray matter are not spared by disease-related pathological processes, although they are affected to a lesser degree than in patients with SPMS.

Adult↗