The first year after diagnosis: psychological impact on people with multiple sclerosis.

The impact of multiple sclerosis (MS) diagnosis on newly diagnosed individuals remains so far little explored. Our aim is to outline affective, personality and quality of life (QoL) correlates of MS patients shortly after MS diagnosis. Thirty-eight (22 F and 16 M) newly-diagnosed MS patients (mean interval from diagnosis communication 4.7 ± 3.8 months, range 1-12 months) underwent the Montgomery-Åsberg Depression Rating Scale and a comprehensive psychological evaluation: Beck Depression Inventory-II, State-Trait Anxiety Inventory, Psychophysiological Questionnaire-Revised, Fear Survey Schedule, Maudsley Obsessional-Compulsive Questionnaire, Impact of Event Scale-Revised, Personal Meaning Questionnaire, Problem Solving Inventory and Multiple Sclerosis Quality of Life-54. The Expanded Disability Status Scale was assessed during the neurological examination. Depressive symptomatology, only partially related to disability, was observed in approximately 40% of patients. The prevalent approach to MS diagnosis was one of avoidance in 65.8% of cases. QoL reductions in self-perception and psychological well-being emerged, together with a peculiar perception of change in health that was not related to neurological disability. With regard to personality assessment, depressive personal meaning organization correlates inversely with important QoL measures. Newly-diagnosed patients go through a complex network of psychological changes still in the initial phases immediately after diagnosis. A thorough understanding of these adjusting aspects by the neurologist could be crucial in improving patients' QoL, participation in relevant disease decisions and adherence to pharmacological therapy.

From primary progressive aphasia to corticobasal syndrome: two clinical and rCBF functional reports.

We describe two cases, both presenting with a 2-year history of isolated language disorders, one compatible with logopenic variant and the other with non-fluent variant of primary progressive aphasia (PPA). Afterwards, each developed a corticobasal syndrome (CBS) with alien limb phenomenon and a multi-domain cognitive impairment. Regional cerebral perfusion (rCBF) study using 99mTc-ECD single photon emission computed tomography (SPECT) revealed hypoperfusion patterns consistent with these aphasia types and with the presence of limb apraxia. We report two cases of PPA variants associated with CBS and we suggest that SPECT rCBF correlates can be useful in making a differential diagnosis within the PPA spectrum.

Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis.

BACKGROUND: There is limited information on fatigue and its clinical and psychosocial correlates in children and adolescents with multiple sclerosis (MS). OBJECTIVE: To assess the relationships between fatigue, cognitive functioning and depression in paediatric MS. METHODS: The study cohort consisted of patients with MS recruited for an Italian collaborative study on cognitive and psychosocial functioning in paediatric MS. The present assessment included evaluation of fatigue on the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale, cognitive functioning on an extensive neuropsychological battery and depression on the Children's Depression Inventory (CDI). A psychiatric interview through the Kiddie-SADS-Present and Lifetime Version was also administered. RESULTS: In total, 57 patients with relapsing-remitting MS were compared with 70 healthy controls. Percentages of fatigued patients ranged from 9% to 14% according to self-reports, and from 23% to 39% according to parent reports. Fatigue was significantly related with higher scores on the CDI (p < 0.03). Higher levels of self-reported cognitive fatigue were associated with impaired performance on a problem-solving test, whereas higher levels of parent-reported cognitive fatigue were associated with impairment on tests of verbal learning, processing speed, complex attention and verbal comprehension. CONCLUSIONS: Our data show that fatigue can affect a sizeable proportion of paediatric MS patients, and confirm the association between fatigue and depressive symptoms in MS. They also highlight the difficulties of fatigue assessment in the paediatric population and provide a few clues to further research in the field.

Neurodegeneration in the course of Langerhans cell histiocytosis.

Cerebral involvement in the course of Langerhans cell histiocytosis has been described especially in children. It is mainly characterized by hypothalamic-pituitary functional deficit, due to granuloma growth. Here we describe a rare case of adult-onset histiocytosis developing a neurodegenerative disease resembling multiple system atrophy. The patient we describe here started suffering from subtle personality changes which progressed to a severe neurological syndrome 2 years after the diagnosis of histiocytosis. Twenty years before she developed a diabetes insipidus, without any apparent cause. Brain MRI scans at the time of neurodegeneration revealed slight signal alterations at the cerebellum, especially involving the dentate nuclei and the white matter. Despite being rare, histiocytosis should be considered in adult patients with cerebellar abnormalities and/or with unexplained diabetes insipidus to rapidly discern and treat histiocytosis before the onset of its neurodegenerative, untreatable phase.

Treatment of Wernicke's encephalopathy with high dose of thiamine in a patient with pyloric sub-stenosis: description of a case.

Wernicke's encephalopathy (WE) is an acute or subacute syndrome that results from a deficiency in vitamin B1 (thiamine). The syndrome is characterised by a classical triad of symptoms: nystagmus and ophthalmoplegia,mental-status changes, and unsteadiness of stance and gait. When patients with WE are inappropriately treated with low doses of thiamine, mortality rates average out at 20% and Korsakoff's Psychosis develops in about 85% of survivors(Sechi and Serra in Lancet Neurol 6(5):442­455,2007). We report the case of a patient with a pyloric substenosis that developed a WE, and was treated with high doses of thiamine showing after few days of treatment a great improvement of neurological and neuroradiological assessment, even though cognitive impairment was still severe at discharge and at 6 months follow-up.

Psychosocial issue in children and adolescents with multiple sclerosis.

In adult-onset multiple sclerosis (MS) cases, major depression, fatigue and psychological distress are common, whereas there is little information on these issues in children with the disease. The aim of this study was to assess psychosocial disorders in an Italian cohort of children and adolescent with MS. We evaluated 56 patients through self-assessment scales of depression (Children Depression Inventory) and fatigue (Fatigue Severity Scale), a psychiatric interview [Kiddie-SADS-Present and Lifetime Version (K-SADS-PL)] and an interview on school and everyday activities. Significant fatigue was found in 11 patients (20%). Twelve of the 39 patients who underwent the K-SADS-PL received a formal diagnosis of an affective disorder. Moreover, MS affected school activities in 28% of cases, daily living activities in 41% and social relationships in 28%. Our study confirms the critical role of psychosocial difficulties in children and adolescents with MS and provides a few cues to clinical management.

Temporal variations in the diet of pearly razorfish Xyrichtys novacula (Osteichthyes: Labridae).

The diet of pearly razorfish Xyrichtys novacula, caught monthly along the shores of the Island of Lampedusa, appeared to be mainly composed of crustaceans, followed by colonial ascidians, molluscs and polychaetes. Among prey, sand dwellers and phanerogam-associated species were recorded. In winter months, the diet was characterized by a small number of prey items, dominated by colonial ascidians, while in spring and summer a wider prey array was recorded. Dietary indices show that X. novacula do not strictly exploit benthic prey but also pelagic organisms, such as copepods. This feeding behaviour reached its peak in March and October, when the abundance of primary consumers was at its highest after phytoplankton blooms. Furthermore, X. novacula caught prey organisms according to their availability and seasonal patterns during their life cycles, irrespective of fish size.

Frequency and clinical features of Lewy body dementia in Italian memory clinics.

BACKGROUND: The latest developments in Lewy Body Dementia (DLB) raise some controversies on clinical features, neuroimaging and therapy. The aim of our study is to determine clinical, neuropsychological, neuroimaging and EEG profile of DLB through retrospective and prospective data of 102 patients. METHODS: data were collected with an analytical form that was developed by an expertise of neurologists. RESULTS: DLB represented 4.8% of the dementia population, with no sex difference. Family history of dementia was common (24.5%), while familiarity for parkinsonism was rare (4.9%). Cognitive disturbances were the predominant clinical presentation at onset (49%), followed by behavioral symptoms (29.4%) and parkinsonism (21.6%). Clinical features at consultation were: memory disturbances (almost all cases), symmetrical (68.6%) or asymmetrical (18.6%) parkinsonism, cognitive fluctuations (49%), visuospatial deficits (53.9%), and visual hallucinations (44.1%). Autonomic signs were present in a third of the cases, while sleep disorders were present in 44.1%. Some clinical response to antiparkinsonian drugs was evident in half of the cases. MRI, SPET, EEG and Neuropsychiatric Inventory data were available in a subgroup of patients. CONCLUSIONS: Most of our data were in accordance with the previous literature. However, some data underline the relationship between DLB, Alzheimer's and Parkinson's disease.

Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation.

Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder resulting from the inherited deficiency of the arylsulfatase A (ARSA) enzyme. Currently, no valid therapeutic options are available for affected patients. A thorough knowledge of disease progression in its diverse clinical variants, together with the identification of reliable prognostic factors, could be instrumental in accurate patient selection for new upcoming therapeutic opportunities, such as enzyme replacement and gene therapy. The described correlation between genotype and clinical presentation proved helpful in predicting patient's prognosis, only in the minority of MLD patients harboring common mutations. Molecular characterization of a cohort of 26 MLD patients allowed us to identify 18 mutations, excluding the common 0 and R alleles, 10 of which are rare and 8 are novel. By categorizing the rare mutations, we were able to confirm a correlation between ARSA gene mutations, age at onset and patterns of disease progression, not only in those patients bearing common mutations, but also in those carrying rare mutant alleles. Moreover, in the case of absent or delayed molecular diagnosis, or of newly identified mutations, the involvement of peripheral nervous system from disease onset proved to be a sensitive prognostic marker predicting a severe progression.

A longitudinal study of cognition in primary progressive multiple sclerosis.

There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.

Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis.

OBJECTIVE: This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS: There were 30 clinically definite MS patients, with different disease courses. EXCLUSION CRITERIA: psychoactive/steroid treatments, mood disorders, acute relapse phase. MAIN OUTCOME MEASURES: Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans. RESULTS: Patients with frontal lobe deficits (n=15) or memory impairment (n-17) had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment (p=0.04). MRI lesion loads correlated significantly with some neuropsychological test scores. CONCLUSIONS: Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.

A multiparametric MRI study of frontal lobe dementia in multiple sclerosis.

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Functional MR imaging correlates of neuropsychological impairment in primary-progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive deficits affect

Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up.

OBJECTIVE: To assess the evolution of cognitive and psychosocial functioning in a cohort of childhood and juvenile multiple sclerosis (MS) cases after a mean period of 2 years had elapsed since baseline evaluation. METHODS: In this cohort study, we used the same extensive neuropsychological battery with alternative versions of the tests assessing memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. The cognitive performance of the patients was compared with that of demographically matched healthy controls (HC). RESULTS: Fifty-six patients and 50 HC were assessed. At follow-up, criteria for cognitive impairment (failure on at least 3 tests) were fulfilled in 39 patients (70%) and 75% of the cases were classified as having a deteriorating cognitive performance. Changes were prominent in tests of verbal memory, complex attention, verbal fluency, and receptive language. In the regression analysis, the only significant predictor of cognitive deterioration was older age of the subject (odds ratio 1.9, 95% confidence interval 1.2-2.9, p = 0.003). Psychiatric disorders, most frequently depression, were diagnosed in 12 patients (30.5%). Fatigue was reported by 21% of the patients. MS negatively affected school and everyday activities in 30% to 40% of the subjects. CONCLUSIONS: Our findings confirm the importance of systematic assessment of cognitive and psychosocial issues in children and teens with MS. The progressive nature of the cognitive difficulties emphasizes the need for developing effective treatment strategies.

Cognitive impairment and structural brain damage in benign multiple sclerosis.

OBJECTIVE: Although in benign multiple sclerosis (BMS) locomotor disability is absent or only minimal, subclinical cognitive impairment seems to occur in many cases. Diffusion tensor (DT) MRI enables us to quantify the extent of "actual" tissue damage, which goes undetected when using conventional MRI. Against this background, we investigated the extent of structural brain damage underlying cognitive dysfunction in BMS, with the ultimate aim to move a first step toward a more reliable definition of this disease phenotype. METHODS: Conventional and DT MRI scans of the brain were acquired from 62 BMS patients. Thirty-six secondary progressive multiple sclerosis (SPMS) patients and 19 healthy subjects served as controls. In BMS patients, neuropsychological tests exploring memory, attention, and frontal lobe functions were administered. Normalized brain volume (NBV), mean diffusivity (MD), and fractional anisotropy (FA) of the normal-appearing white matter (NAWM) and MD of the gray matter (GM) were computed. RESULTS: Twelve BMS patients (19%) fulfilled predefined criteria for cognitive impairment. BMS patients had abnormal MD and FA values from both NAWM and GM. Whereas BMS patients without cognitive impairment had lower T2 LV (p = 0.03), higher NBV (p = 0.006), and lower average GM MD (p = 0.03) than SPMS patients, BMS patients with cognitive impairment did not significantly differ from SPMS patients for any MRI-derived metric. CONCLUSIONS: In benign multiple sclerosis (BMS), cognitive dysfunction is associated with severe structural brain damage, which resembles that of patients with a much more disabling disease course. A reliable definition of BMS should, therefore, include the preservation of cognitive functioning as an additional requisite.

Cognitive and psychosocial features of childhood and juvenile MS.

OBJECTIVE: To assess the impact of multiple sclerosis (MS) on cognitive and psychosocial functioning in childhood and juvenile cases. METHODS: We used an extensive neuropsychological battery assessing IQ, memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. Performance of cases was compared with that of demographically matched healthy controls. RESULTS: Sixty-three patients and 57 healthy controls were assessed. Five patients (8%) exhibited a particularly low IQ (<70). Criteria for cognitive impairment (failure on at least three tests) were fulfilled in 19 patients (31%), whereas 32 patients (53%) failed at least two tests. Beyond deficits in memory, complex attention, and executive functions, the profile of deficits was characterized by involvement of linguistic abilities. In the regression analysis, the only significant predictor of cognitive impairment was an IQ score lower than 90 (odds ratio [OR] 18.2, 95% CI 4.6-71.7, p < 0.001). Considering the IQ score as a dependent variable, the only significant predictor was represented by younger age at onset (OR 0.7, 95% CI 0.5-0.9, p = 0.009). Depressive symptoms were reported by 6% of the cases, and fatigue was reported by 73% of the cases. MS negatively affected school and everyday activities in 56% of the subjects. CONCLUSIONS: In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.

The contribution of voxel-based morphometry in staging patients with mild cognitive impairment.

OBJECTIVE: To assess whether different patterns of regional gray matter loss in patients with mild cognitive impairment (MCI) are associated with different risks of conversion to Alzheimer disease (AD), using MRI and voxel-based morphometry (VBM). METHODS: The authors recruited 22 patients with MCI, 22 patients with probable AD, and 20 healthy subjects (HS). T1 volumes from each subject were postprocessed according to an optimized VBM protocol. All patients were clinically followed up (mean [SD] time = 28.7 [5.7] months), and patients with MCI were reclassified into two groups (converters and nonconverters to AD). RESULTS: When comparing patients with AD to HS, widespread areas of reduced gray matter density were found predominantly in temporal, frontal, and parietal lobes and in the insula. Comparing MCI converters and nonconverters with HS, the converters showed more widespread areas of reduced gray matter density than nonconverters, with a pattern of abnormalities similar to that seen in patients with AD. Conversely, when comparing the same groups with patients with AD, MCI nonconverters showed a pattern of gray matter density similar to that of HS. Areas of decreased gray matter density were also found in MCI converters compared with nonconverters. CONCLUSIONS: Different patterns of gray matter density distribution in patients with mild cognitive impairment may be associated to different rates of conversion to Alzheimer disease.

Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings.

OBJECTIVE: To explore functional corticocortical connections in multiple sclerosis by means of coherence of the EEG, and to evaluate their correlations with the degree of cognitive impairment and with brain lesion load assessed by MRI. METHODS: EEG coherence was studied from 28 patients with clinically definite multiple sclerosis. Ten minutes of resting EEG were recorded with 20 scalp electrodes, with binaural reference. FFT power and coherence were calculated in artifact free epochs of 1 second and compared with values from 22 control subjects of comparable age and sex distribution. Patients also underwent MRI (n=27) and neuropsychological examination (n=21). RESULTS: Compared with controls, patients with multiple sclerosis showed increased theta power in the frontotemporal-central regions (p<0.005). theta Band coherence was decreased between homologous areas (p<0.02). alpha Band coherence was decreased both in the local and long distance connections (p<0.0005). These findings were most striking both in patients with high MRI subcortical lesion load and in patients with cognitive involvement. A significant correlation was found between interhemispheric theta (p=0.02) and alpha (p=0. 017) and anteroposterior alpha (p=0.013) coherence and subcortical MRI lesion load, but not with exclusively periventricular lesion load. CONCLUSIONS: These findings support the hypothesis that cognitive impairment in multiple sclerosis is mostly dependent on involvement of corticocortical connections related to demyelination and/or axonal loss within the white matter immediately underlying the cortex.

Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR.

In this study we evaluated the correlation between neuropsychological impairment (measured with the Brief Repeatable Battery Neuropsychological Tests) and (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a conventional and fast spin echo sequence and fast FLAIR sequence, and neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of (juxta)cortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques. While the number of non-cortical lesions correlated with the expanded disability status scale (r=0.32, P=0.045), the number of (juxta)cortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study underlines the high number of (juxta)cortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI. It also stresses the importance of (juxta)cortical lesions on determining neuropsychological impairment. Multiple Sclerosis (2000) 6 280 - 285