Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis.
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R Zivadinov
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Semi-automatic brain region extraction (SABRE) reveals superior cortical and deep gray matter atrophy in MS.
In multiple sclerosis (MS), atrophy occurs in various cortical and subcortical regions. However, it is unclear whether this is mostly due to gray (GM) or white matter (WM) loss. Recently, a new semi-automatic brain region extraction (SABRE) technique was developed to quantify parenchyma volume in 13 hemispheric regions. This study utilized SABRE and tissue segmentation to examine whether regional brain atrophy in MS is mostly due to GM or WM loss, correlated with disease duration, and moderated by disease course. We studied 68 MS patients and 39 normal controls with 1.5 T brain MRI. As expected, MS diagnosis was associated with significantly lower (P < 0.001) regional brain parenchymal fractions (RBPFs). While significant findings emerged in 11 GM comparisons, only four WM comparisons were significant. The largest mean RBPF percent differences between groups (MS < NC) were in the posterior basal ganglia/thalamus region (-19.3%), superior frontal (-15.7%), and superior parietal (-14.3%) regions. Logistic regression analyses showed GM regions were more predictive of MS diagnosis than WM regions. Eight GM RBPFs were significantly correlated (P < 0.001) with disease duration compared to only one WM region. Significant trends emerged for differences in GM, but not WM between secondary progressive (SP) and relapsing-remitting MS patients. Percent differences in GM between the two groups were largest in superior frontal (-9.9%), medial superior frontal (-6.5%), and superior parietal (-6.1%) regions, with SP patients having lower volumes. Overall, atrophy in MS is diffuse and mostly related to GM loss particularly in deep GM and superior frontal-parietal regions.
Adult↗
Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis.
To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.
Adult↗
beta2-microglobulin serum level is not a marker of disease activity in multiple sclerosis.
Beta2-microglobulin (beta2-MG) is a pharmacodynamic marker of interferon-beta activity in multiple sclerosis (MS). Its role in the natural course of the disease is not fully known. We analyzed the spontaneous fluctuation of beta2-MG in free-treatment MS patients during a short-time course to quantify beta2-MG as a marker of disease activity/progression. Thirty MS patients were clinically assessed and imaged monthly over a 3-month period. Sera were collected concomitantly for the evaluation of beta2-MG, by means of an enzyme-linked immunosorbent assay. Sera from 20 healthy individuals (HI) were drawn and used as controls. The Mann-Whitney test was used when appropriate and time effect on radiological and biological measures was assessed by means of the random effect models. Eight (26.7%) patients experienced a clinical relapse but three (10%) required steroid treatment. A reduction in the contrast-enhancing lesion load (P = 0.02) and a trend (P = 0.07) toward a decrease in brain parenchyma fraction were observed. Baseline levels of beta2-MG were similar in patients and HI. Patients' beta2-MG values increased over the 3-month time period (P = 0.05) but did not exceed those detected in HI at any time point. These results failed to demonstrate the validity of beta2-MG as a surrogate marker of disease in MS.
Adult↗
Risk factors of multiple sclerosis: a case-control study.
We assessed the risk of multiple sclerosis (MS) associated with a series of putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1 years; SD= 10.2 years; disease duration, 10.9 years, SD= 7.5 years) and 131 sex-and age-matched controls. Using a structured questionnaire, we collected information related to demographic data, socio-economic status, education, ethnicity, changes of domiciles, migration, occupation, environmental, nutritional and hormonal factors, exposure to various bacterial and viral agents, vaccinations, and family history of diseases. In multiple logistic regression analysis, we found independent risk factors of MS to be: familiarity for MS (OR= 12.1; 95% CI, 1.3-110.7), autoimmune diseases (OR= 3.8; 95% CI, 2.0-7.1) and migraine (OR= 8.7; 95% CI, 1.0-75.4); comorbidity with autoimmune disease (OR= 6.8; 95% CI, 1.4-32.0) and migraine (OR= 13.5; 95% CI, 1.5-116.6); and vaccination against measles (OR= 92.2; 95%, 12.1-700.2). Familial susceptibility to MS, autoimmune diseases and migraine, and vaccination to measles are associated with an increased risk of MS. The data collected in this study are confirmatory and support the hypothesis that etiology of MS constitutes the effect of interplay between genetic and environmental risk factors. However, the relatively small number of cases and controls prevents firm conclusions.
Adolescent↗
Migraine and tension-type headache in Croatia: a population-based survey of precipitating factors.
The careful monitoring of the trigger factors of headache could be an important step in treatment, because their avoidance may lessen the frequency and severity of attacks. Furthermore, they may provide a clue to the aetiology of headache. The aim of the present study was to estimate the prevalence of tension-type headache (TTH) and to establish the frequency of precipitating factors in subjects with migraine and TTH in the adult population of Bakar, County of the Coast and Gorski Kotar, Croatia. Another important purpose of the study was to examine the relationship of the precipitating factors with migraine and TTH, and with migraine subtypes: migraine with aura (MA) and migraine without aura (MO). We performed a population-based survey using a 'face-to-face door-to-door' interview method. The surveyed population consisted of 5173 residents aged between 15 and 65 years. The 3794 participants (73.3%) were screened for headache history according to the International Headache Society (IHS) criteria. Headache screen-positive responders, 2475 (65.2%), were interviewed by trained medical students with a structured detailed interview focused on the precipitating factors. The following precipitating factors in lifetime migraineurs and tension-type headachers have been assessed: stress, sleep disturbances, eating habits, menstrual cycle, oral contraceptives, food items, afferent stimulation, changes in weather conditions and temperature, frequent travelling and physical activity. A total of 720 lifetime migraineurs and 1319 tension-type headachers have been identified. The most common precipitants for both migraine and TTH were stress and frequent travelling. Stress (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.17, 1.69) was associated with migraine, whereas physical activity (OR 0.72, 95% CI 0.59, 0.87) was related to TTH. Considering MA and MO, frequent travelling (OR 2.2, 95% CI 1.59, 2.99), food items (OR 2.2, 95% CI 1.35, 3.51) and changes in weather conditions and temperature (OR 1.75, 95% CI 1.27, 2.41) exhibited a significant positive association with MA. The present study demonstrated that precipitant-dependent attacks are frequent among both migraineurs and tension-type headachers. Lifetime migraineurs experienced headache attacks preceded by triggering factors more frequently than tension-type headachers. MA was more frequently associated with precipitating factors than MO. We suggest that some triggering factors may contribute to the higher occurrence of precipitant-dependent headache attacks in susceptible individuals.
Adolescent↗
Correlation of sexual dysfunction and brain magnetic resonance imaging in multiple sclerosis.
Sixty-two patients (40 women and 22 men) with multiple sclerosis (MS) were examined with 1.5 tesla magnetic resonance imaging (MRI) of the brain. Information on sexual and sphincteric disturbances has been collected, and data on disability, independence, cognitive performances and psychological functioning have been assessed. Calculations of T1- and T2-lesion load (LL) of total brain, frontal lobes and pons have been performed using a reproducible semiautomated technique. Whole brain, frontal and pontine atrophies were estimated using a normalized measure, the brain parenchymal fraction (BPF), obtained with a computerized interactive program. When comparing patients with and without sexual dysfunction (SD), there were no differences in total brain, frontal and pontine T1- and T2-LL, as well as in measures of whole brain and frontal atrophy. The only significant difference was in the pontine BPF (P = 0.026). In linear multiple regression analysis, SD was associated with depression (R = 0.56, P < 0.001) and, after adjusting for depression and anxiety, with bladder dysfunction (R = 0.43, P = 0.003) and pontine BPF (R = 0.56, P < 0.001). No association between SD and any of the measures of T1- and T2-LL was found. The findings showed a relationship between SD and pontine atrophy, confirmed the correlation of SD with bladder dysfunction and highlighted the role of psychological factors in determining SD.
Adult↗
Familial and environmental risk factors in Parkinson's disease: a case-control study in north-east Italy.
BACKGROUND AND OBJECTIVE: The aetiology of Parkinson's disease remains unknown, although both genetic susceptibility and environmental factors are considered putative contributors to its origin. We performed a case-control study to investigate the association of familial and environmental risk factors with Parkinson's disease (PD). METHODS: We studied 136 patients with neurologist confirmed PD and 272 age- and sex-matched controls, affected by neurological diseases not related to PD. The risk of developing idiopathic PD associated with the following familial and environmental factors: positive family history of PD, positive family history of essential tremor (ET), age of mother at subject's birth, rural birth, rural living, well water use, farming as an occupation, exposure to pesticides, head tremor, exposure to general anaesthesia and to ionizing radiations, food restriction, concentration camp imprisonment and smoking has been assessed by using univariate and multivariate statistical techniques. RESULTS: In the conditional multiple logistic regression analysis, positive family history of PD (OR 41.7, 95% CI 12.2-142.5, P < 0.0001), positive family history of ET (OR 10.8, 95% CI 2.6-43.7, P < 0.0001), age of mother at subject's birth (OR 2.6, 95% CI 1.4-3.7, P=0.0013), exposure to general anaesthesia (OR 2.2, 95% CI 1.3-3.8, P=0.0024), farming as an occupation (OR 7.7, 95% CI 1.4-44.1, P=0.0212) and well water use (OR 2.0, 95% CI 1.1-3.6, P=0.0308) exhibited a significant positive association with PD, whereas smoking showed a trend toward an inverse relationship with PD (OR 0.7, 95% CI 0.4-1.1, P < 0.06). CONCLUSIONS: We conclude that both familial and environmental factors may contribute to PD aetiology.
Aged↗
Depressive symptoms and MRI changes in multiple sclerosis.
To determine whether changes in specific regions of the brain can contribute to the development of depression in patients with multiple sclerosis (MS). We prospectively studied 90 patients with clinically definite MS. Disability, independence, cognitive performances, and depressive and anxiety symptoms have been assessed at baseline and 2 years later. At these two time-points, patients underwent a 1.5-T magnetic resonance examination of the brain including T1- and T2-weighted images. Calculation of regional and total lesion loads (LL) have been performed by a semiautomatic technique; total and regional brain volumes have been calculated by a fully automatic highly reproducible computerized interactive program. Measurements of LL did not show any significant difference between depressed and non-depressed patients. Brain atrophy was significantly more conspicuous in the left frontal lobe (P=0.039), in both frontal lobes (P=0.046) and showed a trend towards a difference in the right frontal lobe (P=0.056), in the right temporal lobe (P=0.057) and in both temporal lobes (P=0.072) of depressed patients. Disability, independence and cognitive performances were similar in depressed and non-depressed patients (P=NS). Spearman correlation analysis and multiple-regression analysis demonstrated that the severity of the depressive symptoms score was associated both with the disability score and the right temporal brain volume. Destructive lesions in the right temporal lobe can contribute to the severity of depression in patients with MS but the influence of the severity of neurological impairment should be taken into account.
Adult↗
Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS.
BACKGROUND: IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy. OBJECTIVE: To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS. METHODS: The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months. RESULTS: Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years. CONCLUSIONS: In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.
Adolescent↗
Sexual dysfunction in multiple sclerosis: a 2-year follow-up study.
BACKGROUND AND OBJECTIVE: Sexual dysfunction severely affects the quality of life of patients, but longitudinal studies of sexual function in multiple sclerosis are lacking. We performed a study on a group of patients with multiple sclerosis to evaluate the change in sexual function and to examine the relationship between sexual dysfunction and other clinical variables over time. METHODS: A 2-year follow-up study on 99 patients with definite multiple sclerosis. Information on sexual and sphincteric disturbances have been collected through face-to-face structured interviews. Disability, independence, cognitive performances and psychological functioning have also been assessed. Spearman rank correlation analysis corrected for multiple comparisons, and linear regression analysis have been performed to test variables relationship and remove the effect of potential confounding covariates. RESULTS: The proportion of patients with sexual dysfunction remained over 70% and did not change during the 2-year follow-up, but the extent and number of symptoms increased significantly The number of symptoms of sexual dysfunction did not change significantly after an exacerbation. Significantly, more patients than before the study resorted to counseling and discussed with doctors of sexual matters. In the univariate analysis, changes in sexual function over time correlated with changes in bladder function (r=0.47, p<0.0001) and EDSS score (r=0.41, p<0.0001), but the multivariate analysis demonstrated that only bladder dysfunction was independently related to sexual dysfunction (R=0.36, p=0.003) when the effect of psychological factors were removed. CONCLUSIONS: Symptoms of sexual dysfunction increase in significance and number over time in patients with multiple sclerosis. Relapses did not influence the number of symptoms of sexual dysfunction, but a worsening of pre-existing symptoms cannot be excluded. The change of sexual function appears to be independently associated to bladder dysfunction.
Adult↗
MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis.
Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores < or = 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8%) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease.
Adult↗
Depression and anxiety in multiple sclerosis. A clinical and MRI study in 95 subjects.
The aim of the present study was to investigate the relationship between involvement of specific areas of the brain and the occurrence of depression and anxiety in patients with multiple sclerosis. We studied 95 patients (62 women and 33 men, mean age 39.5 years, SD 11.2) with definite MS, 97 patients (65 women and 32 men, mean age 40.7, SD 11.9) suffering from chronic rheumatoid diseases and 110 healthy subjects (71 women and 39 men, mean age 40.1, SD 12.7). The disability, the independence, the cognitive performances, the depressive and anxiety symptoms were assessed. The diagnosis of major depression was made according to the DSM-IV. The patients with multiple sclerosis underwent a 1.5 Tesla magnetic resonance examination including T1 and T2 weighted images. Calculation of regional and total lesion loads and brain volumes were performed. The number (%) of subjects with a diagnosis of major depression was 18 (18.9) among MS cases, 16 (16.5) among controls with chronic disease (p=NS), and 4 (3.6) among healthy volunteers (p < 0.0001). The Hamilton Depression and Anxiety rating scales median scores were 5 and 18, respectively in the MS patients, 5 (p= NS) and 14 (p= NS) in the chronic rheumatoid diseases controls, and 3 (p= < 0.0001) and 6 (p= < 0.0001) in the healthy controls. Both severity of depressive symptoms and diagnosis of major depression correlated, albeit weakly, with right frontal lesion load (r=0.22, p=0.035, and r=0.23, p=0.026, respectively) and right temporal brain volume (r=0.22, p=0.005 and r=0.22, p=0.036, respectively). The severity of depression was related significantly also with total temporal brain volume (r=0.26, p=0.012), right hemisphere brain volume (r=0.25, p=0.015), disability (r=0.30, p=0.003) and independence of MS cases (r=-0.26, p=0.01). The anxiety did not correlate significantly with any of the measures of regional and total lesion loads and brain volume or with any of the considered clinical variables. The similar frequency of depression and severity of depressive symptoms in MS patients and in chronic disease patients, the significant difference in this respect with the normal controls, and the significant correlation between depression and the disability measures would suggest a psychological reaction to the impact of the disease but the relationship between depression and the alterations in the frontal and temporal lobes of the right hemisphere supports, on the contrary, the causative role of organic brain damage. The lack of any significant association between symptoms of anxiety and either MRI abnormalities or clinical variables led us to the opinion that anxiety is a reactive response to the psychosocial pressure put on the patients.
Adult↗
Prevalence of migraine in Croatia: a population-based survey.
OBJECTIVES: The aim of the present study was to estimate the prevalence of migraine among Croatian adults. This is the first epidemiological study of migraine in Croatia in which the operational diagnostic criteria of the International Headache Society have been applied. METHODS: The study population consisted of all residents (aged 15 to 65 years) of Bakar, County of The Coast and Gorski Kotar, Croatia. A population-based survey was undertaken using a "face-to-face, door-to-door" interview METHOD: The participation rate was 73.3%. All participants were screened for headache history according to the International Headache Society criteria. Headache screen positive responders (65.7%) were interviewed by trained medical students with a structured detailed interview focused on migraine. RESULTS: A total of 720 lifetime migraineurs were identified. The lifetime prevalence of migraine was 22.9% (95% confidence interval, 20.9 to 25.1) in women, 14.8% (95% confidence interval, 13.1 to 16.8) in men, and 19% (95% confidence interval, 17.6 to 20.5) in both sexes. The highest lifetime prevalence of migraine was in women in the age group 40 to 49 years (38.1%). Among 636 active migraineurs, 399 (62.7%) were women and 237 (37.3%) were men; 55.8% had migraine without aura, 35.2% migraine with aura, and 6.9% migraine both with and without aura. The 1-year prevalence of migraine, migraine without aura, migraine with aura, and migraine both with and without aura in women was 18%, 11.3%, 8.6%, and 2.2%, respectively. In men, the 1-year prevalence of migraine, migraine without aura, migraine with aura, and migraine both with and without aura was 12.3%, 7.3%, 3%, and 0.7%, respectively. CONCLUSIONS: The prevalence of migraine in this Croatian population showed rates quite similar to those reported in neighboring countries, such as Italy and France. Further studies are needed to estimate the prevalence rates of migraine in the total Croatian population.
Adolescent↗
A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis.
OBJECTIVE: (a) To establish whether the cognitive decline of the early phase of relapsing-remitting multiple sclerosis depends on the progression of the burden of disease, or on the loss of brain parenchyma, or is influenced by both; (b) to monitor the loss of brain parenchyma in the early phase of the disease; and (c) to examine its possible relation with the progression of physical disability. METHODS: For 2 years 53 patients with clinically definite relapsing-remitting multiple sclerosis with disease duration 1-5 years and expanded disability status scale < or =5.0 at baseline were monitored. The neuropsychological performances, the psychological functioning, the neurological impairment, and the disability have been assessed at baseline and after 2 years. Patients also underwent PD/T2 and T1 weighted brain MRI. T2 and T1 lesion volumes were measured by a semiautomatic technique. Quantification of brain parenchymal volumes was obtained using a highly reproducible computerised interactive program. The relation between cognitive impairment and MRI findings has been investigated by partial correlation and stepwise multiple regression analyses excluding the effects of age, education, anxiety, depression, and total days of steroid use. RESULTS: In the 2 years of the study the mean change for T2 and T1 lesion volumes and brain parenchymal volumes were +1.7 ml (95% confidence interval (95% CI) 1.3-2.2, p=0.005, (29.8%); +0.2 ml, 95% CI 0.15-0.26, p=0.004, (25%); and -32.3 ml, 95% CI 24.2-42.3, p<0.0001, (2.7%), respectively. Overall, 14 patients (26.4%) were judged to be cognitively impaired at baseline and 28 (52.8%) at the end of the follow up. Of the 18 neuropsychological tests and subtests employed in the study, patients with multiple sclerosis failed 5.8 (SD 2.3) tests at the baseline and 8.4 (SD 2.9) (p<0.0001) tests at the end of the study. When the cognitive changes were examined in individual patients, five (9.4%) of them were considered cognitively improved, 33 (62.3%) remained stable, and 15 (28.3%) worsened over 2 years. T2 and T1 volume changes in improved, stable, and worsened patients did not show any significant difference, whereas brain parenchymal volume decrease in cognitively worsened patients was significantly greater (-66 ml (5.4%), 95% CI 37-108.9, p=0.0031). The cognitive impairment was independently predicted over 2 years only by the change of brain parenchymal volumes (R=0.51, p=0.0003). Ten patients (18.9%), who worsened by one or more points in the EDSS during the follow up period had significant decreases in brain parenchymal volumes (-99 ml (8%), 95% CI 47.6-182.3, p=0.005). At the end of the study the loss of brain parenchyma correlated significantly with change in EDSS (r= 0.59, p<0.0001). CONCLUSIONS: In the early phase of relapsing-remitting multiple sclerosis the cognitive deterioration relies more on the development of brain parenchymal volume atrophy than on the extent of burden of disease in the brain. The loss of brain parenchymal volume underlies the progressive accumulation of physical disability from the initial phase of the disease, which becomes more demonstrable only if studied with longer observation periods. Probably, the main pathological substrate of brain atrophy in the early stage of the disease is early axonal loss, which causes the progression of neurological deficits and the development of cognitive impairment. These data support the debated opinion that disease modifying therapy should be initiated as early as possible.
Adult↗
Bilingual aphasia and subcortical-cortical lesions.
The use of the mother tongue relies on implicit memory procedures that are mainly controlled by subcortical structures. A second language depends on the integrity of the explicit memory system, largely subserved by cortical areas. Therefore, bilinguals can be considered as neurolinguistic models which contribute to the understanding of how the cortical and subcortical language systems communicate while maintaining independent functions. We describe a patient who developed an impairment of the mother tongue after an infarct of the caudate. During follow-up, a dramatic improvement of the mother tongue accompanied by worsening of the second language became evident after the extension of the ischemic lesion to the cortex.
Amygdala↗
Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study.
BACKGROUND: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. METHODS: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. RESULTS: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=-0. 739, P<0.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=-0.90, P<0.0001). CONCLUSIONS: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.
Adult↗
Olfactory loss in multiple sclerosis.
The objectives of the present study were to test odor identification ability in patients with multiple sclerosis (MS) and to examine possible correlations between smell identification test scores and various clinical variables. We performed a case-control study comparing the Cross Cultural Smell Identification Test scores of 40 patients with definite multiple sclerosis with those obtained in 40 age-, sex- and smoking-habit-matched healthy controls. The neurological impairment, the disability, the cognitive performances and the psychological functioning were also assessed. Patients with multiple sclerosis scored significantly poorer than controls on the Cross-Cultural Smell Identification Test (P<0.001). Olfactory function was borderline normal in four (10%) and abnormal in five (12.5%) MS patients, whereas it was normal in all controls (P<0.02). Significant correlations between the smell identification score and symptoms of anxiety (r=-0.43, P=0.006), depression (r=-0.42, P=0. 008) and severity of neurological impairment (r=-0.32, P=0.05) were found. Only two (5%) patients with multiple sclerosis reported having episodes of smell loss, suggesting a low level of awareness of this problem. Although smell changes are rarely reported, olfactory function is impaired in a considerable number of patients with MS. The observed association between decreased odor identification ability and symptoms of anxiety and depression in our patients suggests that mood and anxiety disorders have to be considered in assessing olfaction in MS patients. Clearly, smell disturbances deserve greater attention from health professionals and caregivers dealing with such patients.
Adult↗