Bedside tested ocular motor disorders in multiple sclerosis patients.

Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated. Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (n = 150, 92%) or clinically isolated syndrome (n = 13, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed. Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability (P = 0.0005) and showed more frequently infratentorial MRI lesions (P = 0.004). Localization of previous relapses was not associated with presence of OMDs. Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue.

PURPOSE: This study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue. MATERIALS AND METHODS: We enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05). RESULTS: Compared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex. CONCLUSIONS: Patients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.

Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis.

OBJECTIVE: The aim of the study was to determine whether the presence of anti-Epstein-Barr virus (EBV) antibodies is associated with MRI measures of brain injury and neurodegeneration in patients with multiple sclerosis (MS). METHODS: 135 patients with MS (86 women, 49 men) underwent brain MRI and testing for antibodies against EBV. MRI measurements included gadolinium enhancing lesion volume, T1 and T2 lesion volumes and fractions of whole brain parenchyma (BPF), white matter and grey matter (GMF). The anti-EBV panel included anti-EBV early antigen IgG, anti-EBV nuclear antigen IgG and anti-EBV viral capsid antigen (VCA) IgG levels. The relationships between antibody levels and MRI measurements were assessed in regression analysis. Repeat measurements of anti-EBV VCA IgG and MRI measures were available for a subset of 50 patients after a mean follow-up of 3.1 years. RESULTS: GMF (R(2) = 0.24 for overall model, p = 0.002) and BPF (R(2) = 0.39 for overall model, p<0.001) showed negative associations with anti-EBV-VCA IgG levels. A greater decline in BPF over 3 years was significantly associated with increased 3 years prior time point anti-EBV VCA IgG levels (p<0.001). CONCLUSIONS: The results suggest that the presence of anti-EBV antibodies is associated with MRI markers of GM atrophy in MS and with increased loss of brain volume over 3 years.

Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy.

BACKGROUND: Brain atrophy, as assessed by magnetic resonance imaging (MRI), has been correlated with disability in patients with multiple sclerosis (MS). Recent evidence indicates that both white matter (WM) and gray matter (GM) are subject to atrophy in patients with MS. Although neurological deficiencies in MS are primarily due to loss of WM, the clinical significance of GM atrophy has not been fully explored in MS. METHODS: We have undertaken a three-year, open-label study, comparing 26 patients who elected to receive intramuscular interferon beta-1a (IFN beta-1a) therapy, with 28 patients who elected not to receive therapy. Both groups had quantitative cranial MRI scans at study entry and after three years, and standardized clinical assessments every six months. Brain parenchymal fraction (BPF), GM fraction (GMF), and WM fraction (WMF) percent changes were calculated, and T2- and T1-lesion volumes (LVs) assessed. RESULTS: After three years, mean percent (%) change in BPF favored the IFN beta-1a treatment group (IFN beta-1a -1.3% versus the control group -2.5%, P=0.009), as did the mean percent change in GMF (+0.2 versus -1.4%, P=0.014), and the mean percent change in T1-LV (-9.3 versus +91.6%, P=0.011). At the end of the study, there was a significant within-patient decrease in BPF for both groups (P=0.02 for the IFN beta-1a treatment group, and P<0.001 for the control group), a significant within-patient decrease in WMF for the IFN beta-1a treatment group (P=0.01), and a significant decrease in GMF for the control group (P=0.013) when compared with baseline. CONCLUSION: Over a three-year period, treatment with IFN beta-1a significantly slowed the progression of whole-brain and GM atrophy, and of T1-hypointense LV accumulation, when compared with the control group.

Outcome of medication overuse headache after abrupt in-patient withdrawal.

One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans (P=0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake (P=0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.

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.

Persistent aura without infarction: decription of the first case studied with both brain SPECT and perfusion MRI.

To the best of our knowledge, persistent visual symptoms, lasting months or years without evidence of infarction, a rare complication of migraine with aura, has been reported in only 20 patients. We report the case of a 43-year-old woman with a 31-year history of migraine with typical visual aura. At presentation, she experienced a visual aura in her right hemifield followed by a pulsating headache. The visual symptoms persisted. There were no abnormal findings on neurological and ophthalmological examinations, EEG, visual evoked potentials (VEPs), brain computed tomography and magnetic resonance imaging (MRI). Both brain single photon emission computed tomography (SPECT) and brain perfusion MRI revealed decreased left fronto-parieto-occipital and right occipital blood perfusion. A perfusion MRI, performed 7 months after symptom onset and almost complete extinction of symptoms, was normal. As previously reported, we demonstrated a cortical hypoperfusion by SPECT in a case of persistent visual aura. For the first time this finding was confirmed by perfusion MRI.

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.

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.

Gaucher's disease with Parkinson's disease: clinical and pathological aspects.

The association between type 1 Gaucher disease and PD has been reported in the literature. The clinical picture is characterized by the predominance of bilateral akinetic-rigid signs and poor response to levodopa therapy. The authors describe four patients (two siblings) with type 1 Gaucher disease presenting with the following signs of typical PD: asymmetric onset of rigidity, resting tremor, bradykinesia, and a favorable response to Parkinson therapies.

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.

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.

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.

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.

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

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.

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease.

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsonian state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total L-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.

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.