Fatigue in multiple sclerosis patients with different clinical phenotypes: a clinical and magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The prevalence of fatigue and its relation with clinical, neuropsychological and brain magnetic resonance imaging (MRI) variables in a large cohort of multiple sclerosis (MS) patients was investigated. METHOD: The Modified Fatigue Impact Scale and its subdomains were collected from 725 healthy controls and 366 MS patients [238 relapsing-remitting (RRMS) and 128 progressive (PMS)]. For the Modified Fatigue Impact Scale global and subdomains, MS patients were classified as fatigued (F-MS) or non-fatigued (NF-MS) according to cut-off values provided by logistic regression models with a specificity of 90% (i.e. a 10% false-positive rate in classifying healthy controls). MS patients underwent neurological, neuropsychological and MRI evaluations. Clinical and MRI measures were compared between F-MS and NF-MS patients using age-, sex- and phenotype-adjusted linear models. Heterogeneities between phenotypes were tested with specific interaction terms. RESULTS: Global fatigue affected 174 (47.5%) MS patients, being more prevalent in PMS (PMS 64.1% vs. RRMS 38.7%, P < 0.001). For all dichotomizations, F-MS were older (P from <0.001 to 0.012) and more depressed (P < 0.001) than NF-MS patients. Compared to NF-MS, cognitive F-MS patients had lower education (P = 0.035). Compared to NF-MS, patients with global and physical fatigue had higher Expanded Disability Status Scale only for RRMS (P < 0.001). Only RRMS patients with physical fatigue had lower brain (P = 0.05), white matter (P = 0.039) and thalamic volumes (P = 0.022) compared to NF-MS patients. CONCLUSIONS: In MS, fatigue is associated with older age, lower education and higher depression. Only in RRMS, fatigue is associated with Expanded Disability Status Scale and brain atrophy. A plateauing effect of disability and structural damage can explain the lack of associations in PMS.

Structural and functional brain connectomes in patients with systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an immune-mediated disease that may affect the nervous system. We explored the topographical organization of structural and functional brain connectivity in patients with SLE and its correlation with neuropsychiatric (NP) involvement and autoantibody profiles. METHODS: Graph theoretical analysis was applied to diffusion tensor magnetic resonance imaging (MRI) and resting-state functional MRI data from 32 patients with SLE and 32 age- and sex-matched healthy controls. Structural and functional connectivity matrices between 116 cortical/subcortical brain regions were estimated using a bivariate correlation analysis, and global and nodal network metrics were calculated. RESULTS: Structural, but not functional, global network properties (strength, transitivity, global efficiency and path length) were abnormal in patients with SLE versus controls (P < 0.0001), especially in patients with anti-double-stranded DNA (ADNA) autoantibodies (P = 0.03). No difference was found according to NP involvement or anti-phospholipid autoantibody status. Patients with SLE and controls shared identical structural hubs and the majority of functional hubs. In patients with SLE, all structural hubs showed reduced strength and clustering coefficient compared with controls (P from 0.001 to <0.0001), especially in patients with ADNA autoantibodies. Only a few differences in functional hub properties were found between patients with SLE and controls. Structural and functional hub measures did not differ according to NP involvement or anti-phospholipid autoantibody status. Significant correlations were found between clinical, MRI and network measures (r from -0.56 to 0.60, P from 0.0003 to 0.05). CONCLUSIONS: Abnormalities of global and nodal structural connectivity occur in patients with SLE, especially with ADNA autoantibodies, with a diffuse disruption of structural integrity. Functional network integrity may contribute to preserve clinical functions.

Influence of the topography of brain damage on depression and fatigue in patients with multiple sclerosis.

OBJECTIVES: Involvement of selected central nervous system (CNS) regions has been associated with depression and fatigue in MS. We assessed whether specific regional patterns of lesion distribution and atrophy of the gray (GM) and white matter (WM) are associated with these symptoms in MS. METHODS: Brain dual-echo and 3D T1-weighted images were acquired from 123 MS patients (69 depressed (D), 54 non-depressed (nD), 64 fatigued, 59 non-fatigued) and 90 controls. Lesion distribution, GM and WM atrophy were estimated using VBM and SPM8. RESULTS: Gender, age, disease duration and conventional MRI characteristics did not differ between D-MS and nD-MS patients. Fatigued patients experienced higher EDSS and depression than non-fatigued ones. Lesion distribution and WM atrophy were not related to depression and fatigue. Atrophy of regions in the frontal, parietal and occipital lobes had a combined effect on depression and fatigue. Atrophy of the left middle frontal gyrus and right inferior frontal gyrus were selectively related to depression. No specific pattern of GM atrophy was found to be related to fatigue. CONCLUSIONS: Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Microstructural magnetic resonance imaging of cortical lesions in multiple sclerosis.

BACKGROUND: Pathologic and magnetic resonance imaging (MRI) studies have shown that cortical lesions (CLs) are a frequent finding in multiple sclerosis (MS). OBJECTIVE: To quantify microstructural damage in CLs and normal appearing (NA) cortex in relapse-onset MS patients at different stages of the disease. METHODS: Brain double inversion recovery (DIR), diffusion tensor (DT) MRI and 3D T 1-weighted scans were acquired from 35 relapsing-remitting (RR) patients, 23 secondary progressive (SP) patients, 12 benign (B) MS patients and 41 healthy controls (HC). Diffusivity values in CLs, cortex, white matter (WM) lesions and normal-appearing white matter (NAWM) were assessed. RESULTS: Compared to HC, MS patients had a significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the cortex and NAWM. CLs had higher FA vs HC cortex and vs patients' cortex. Compared to RRMS patients, SPMS patients had higher WM lesion volume, higher MD in the cortex, and more severe damage to the NAWM and WM lesions. Compared to SPMS patients, BMS patients had lower MD and FA of CLs. Damage in other compartments was similar between SPMS and BMS patients. Damage in CLs had a high power to discriminate BMS from SPMS (area under the curve: 79-91%), with high specificity (85%), sensitivity (100%) and accuracy (90%). CONCLUSIONS: Microstructural imaging features of CLs differ from those of WM lesions and are likely to reflect neuronal damage and microglial activation. The nature and extent of CL damage can be used to help distinguish the different MS clinical phenotypes.

Neuromyelitis optica spectrum disorder and multiple sclerosis in a Sardinian family.

The coexistence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in the same family is a rare event. We report a familial case originating from Sardinia of two siblings: one with NMOSD and one with MS. Human leukocyte antigen (HLA) typing showed that the two affected siblings were HLA-identical, sharing risk-increasing alleles, while a younger unaffected sister was haploidentical to her siblings but she also carried protective alleles. Our findings confirm the role of HLA in raising the risk to develop CNS inflammatory diseases and provide further knowledge on the relationship between NMOSD and MS.

A Semiautomatic Method for Multiple Sclerosis Lesion Segmentation on Dual-Echo MR Imaging: Application in a Multicenter Context.

BACKGROUND AND PURPOSE: The automatic segmentation of MS lesions could reduce time required for image processing together with inter- and intraoperator variability for research and clinical trials. A multicenter validation of a proposed semiautomatic method for hyperintense MS lesion segmentation on dual-echo MR imaging is presented. MATERIALS AND METHODS: The classification technique used is based on a region-growing approach starting from manual lesion identification by an expert observer with a final segmentation-refinement step. The method was validated in a cohort of 52 patients with relapsing-remitting MS, with dual-echo images acquired in 6 different European centers. RESULTS: We found a mathematic expression that made the optimization of the method independent of the need for a training dataset. The automatic segmentation was in good agreement with the manual segmentation (dice similarity coefficient = 0.62 and root mean square error = 2 mL). Assessment of the segmentation errors showed no significant differences in algorithm performance between the different MR scanner manufacturers (P > .05). CONCLUSIONS: The method proved to be robust, and no center-specific training of the algorithm was required, offering the possibility for application in a clinical setting. Adoption of the method should lead to improved reliability and less operator time required for image analysis in research and clinical trials in MS.

The relational history of the family with a schizophrenic member.

Coherently with the systemic view, the authors consider the family interaction patterns in schizophrenia. Some typical redundant behaviours in the family system appear to be typical of the schizophrenic family. The authors investigate the family system and story through the international literature. Special emphasis in this work is placed upon the modalities of weaning from the parental figures, the conjugal bind of the parents and the interactive patterns with grandparents. In order to study these binds and according with many authors a fictitious family history is reported.

Interactive typology in depression according to cognitive theory and systemic theory.

Both systemic and cognitive theories agree upon the importance of early learning in the development of depressive personality. The two theories disagree upon the meaning they give to the early experiences. According to cognitive theory the emotions bound to a significant and not reparable loss turn themselves into a pursuit of autonomy in order to prevent further grieves. In the grown-up person if autonomy is not reached or is lost, a depressive episode will rouse. According to the systemic theory, children learn emotions and behaviours of a depressed parent. The child also learns by himself or through the healthy parent the feeling of importance/inability to help. The grown-up person will make use of the depressed behaviour when he will feel unable to face by himself critical life events or to elice to care or attention by the partner.

Relationship patterns in "folie à deux".

"Folie à deux" is characterized by the communication of delusional ideas from one subject to other ones who have been living closely with him for a long time, usually his relatives. Before illness shows, there is a leader-follower relationship between partners, who are lacking of external sources of pleasure and are socially or culturally isolated. The dominating partner usually is a paranoic subject who strongly needs his ideas to be accepted by other people, while the dominated partner is a dependent subject who shares the other one's ideas in order to get pleasure from him and who is not able to criticize these ideas because of the lack for external influences. The two partners project hostility into the external world because, if the dominated partner does not share the other one's ideas, hostility will be projected into him and he will become very anxious. Interpersonal mechanisms in "folie à deux" are similar to those which take place in brainwashing, hypnosis and psychotherapy.

Interactive patterns in the schizophrenic family during hospitalization.

Our research is based on the cases of 40 patients diagnosed as schizophrenics and the patterns of their family interaction at the moment of the hospitalization, in order to formulate an initial analysis of the reason of admission as the first phase in a therapeutic process. With this intent the authors have conducted a catamnestic research on the charts of patients who have been divided in three groups according to the presence or absence of the parents. The following variables have been therefore taken into consideration: the referrals, her/his behavior at the moment of hospitalization, expectations and difficulties in widening the field of observation within the family.

Interactive typology of the hypochondriacal patient.

Many authors agree on the idea that the affective and behavioural characteristic of a certain type of family encourages the use of the body as a primary means of communication with others. This way of communicating has usually been acquired during childhood and later, in the adult life, it appears again in the different social contests. Some authors like Alby, Levy, Baker, Parker, Lipscombe, Marcelli, Bianchi and others focus on this type of family interaction and the single characteristic of the personalities of each family member. These authors describe some relationship patterns used by hypochondriac patient such as: avoiding unpleasant situations, blaming others, adopt a sick-role as a way of controlling the relationship between existential events and somatic symptoms; relationship with physicians and the need to confirm her/himself.

Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis.

OBJECTIVE: To assess the correlation between cognitive impairment and overall vs regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI tractography in multiple sclerosis (MS). METHODS: Brain dual-echo, T1-weighted, and DT MRI data were acquired from 82 patients with MS. DT tractography was used to produce maps of white matter (WM) tracts involved in cognition. The sensory thalamocortical projections and optic radiations were studied as "control" WM tracts. The contribution of global brain damage (T2 lesion volume, normalized brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal-appearing WM and GM damage) and damage to selected WM tracts to overall cognitive impairment and to impairment at individual neuropsychological tests was assessed using a random forest (RF) analysis. RESULTS: Thirty-three patients had cognitive impairment. The majority of MRI measures differed significantly between cognitively impaired and cognitively preserved (CP) patients. Significant correlations were found between performance in the majority of neuropsychological tests and global or regional brain damage (r ranging from -0.60 to 0.57). The RF analysis showed a high performance in classifying cognitively impaired vs CP patients, with a classification (C)-index = 76.8, as well as in classifying patients' impairment in individual neuropsychological tests (C-index between 75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather than measures of normal-appearing WM damage in the same tracts or global brain/WM/GM damage, resulted in the highest classification accuracy. CONCLUSIONS: Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.