Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability.

BACKGROUND: Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. OBJECTIVE: To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. METHODS: We studied 222 relapsing remitting MS patients with low disability (scores or=5; n=197) and low-fatigue groups (FSS

The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients-- twenty-four months follow-up.

The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN beta therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti-inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN beta therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN beta and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to 2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).

A possible spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa, Sicily.

We carried out an epidemiological survey to determine prevalence and incidence of multiple sclerosis in the little town of Linguaglossa in the Province of Catania. We calculated prevalence rate as point prevalence at 1 January 2001 and incidence during 1991-2000. We studied the frequency of multiple sclerosis in the community of Linguaglossa in a population of 5,422 inhabitants in the 2001 census. The primary sources for the case ascertainment were the general practitioners of Linguaglossa, the local Italian Multiple Sclerosis Association and the neurological departments, Multiple Sclerosis Centers and private neurologists of the province of Catania. We considered as prevalent and incident cases all patients who satisfied the Poser's diagnostic criteria. We detected 11 patients with multiple sclerosis who had had the onset of disease on prevalent day (P.D.). The onset-adjusted prevalence rate was 203/100,000 (95% CI 107-352). Prevalence was higher in women (247/100,000) than in men (154/100,000). From 1991 to 2000, 10 subjects with MS had clinical onset of disease. The mean annual incidence risk was 18.2/100,000 (C. I. 95 % 5.9-42.5). Conversely in the same population prevalence on 1 January 1991 was 37/100,000 while the onset adjusted annual incidence risk during the previous decade (1981-1991) was 3.6/100,000. Prevalence and incidence rates of MS during the last decade in the little town of Linguaglossa are higher than those found in the same area during the previous ten years and also than those reported in other Sicilian and Italian surveys suggesting a possible cluster of MS.

Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta.

Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards whose anti-inflammatory and immunosuppressive effects have been utilised to treat selected cases of multiple sclerosis with a progressive and worsening course. To halt the progression of disease in patients refractory to disease modifying drugs CTX has been given, and several open-label studies have recently shown clinical benefits. In a previous study we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and interferon beta (IFN-beta) in 10 patients with "rapidly transitional" form of multiple sclerosis characterised by severe and frequent attacks and rapid progression of disability. The present study reports the clinical and MRI follow-up 36 months after the discontinuation of CTX showing the maintenance of the results obtained in relapse rate (p<0.001), EDSS (p<0.001), T2 MRI total lesion load (p<0.001) and T2 lesions number (p<0.001) compared to the pre-treatment period. These encouraging findings and the absence of significant recorded side effects affirm that the association of CTX plus interferon-beta is amenable, safe and can be recommended in rapidly worsening MS patients.

The impact of outpatient rehabilitation on quality of life in multiple sclerosis.

It is well accepted that rehabilitative treatment can be effective in reducing disability and optimizing quality of life (QoL) of people with multiple sclerosis (MS). The aim of this study was to evaluate the effects of a comprehensive outpatient rehabilitative treatment on QoL in patients suffering from MS. We selected 111 patients from a sample of 407 patients who had consecutively entered the MS Center of Catania (which is located in southern Italy) in 1998. Fifty-eight were randomly assigned to the study treatment and 53 to a waiting list (control treatment). Kurtzke's EDSS and quality of Life (QoL)were the primary endpoints. QoL was measured with the generic multi-item SF-36 scales. We also used: the Beck Depression Inventory (BDI) for depression, the Tempelaar Social Experience Check-list (SET) for social activities and the Fatigue Impact Scale (FIS). The study treatment group was treated for 6 consecutive weeks, 6 days a week with a comprehensive rehabilitative outpatient model. The control treatment group was in a waiting list and was trained to self-exercises at home. EDSS remained unchanged in both groups. All health related QoL domains significantly improved in the study treatment (p < 0.001 in physical functioning, role physical, bodily pain, general health, and social functioning; p < 0.05 in vitality, role emotional and mental health). FIS, SET and BDI also improved significantly after the rehabilitative treatment in the study group (p < 0.001). The results of this study confirm the effectiveness of a short comprehensive outpatient model of rehabilitative treatment in people with MS and in particular in their QoL.

The costs of multiple sclerosis: a cross-sectional, multicenter cost-of-illness study in Italy.

OBJECTIVES: To estimate the socio-economic impact of multiple sclerosis (MS) in Italy. METHODS: Outpatients with MS were enrolled at 44 centres across Italy. Socio-demographic, clinical and resource utilization data were collected using a validated questionnaire. Each patient completed a weekly diary of expenses due to MS over a three-month period. Direct health care costs and indirect costs (lack of productivity for the patient and for caregivers) were assessed for the whole population and were compared among five groups, categorised by disease severity (EDSS score). An analysis of variance was carried out on socio-demographic variables. RESULTS: For the total population of 566 patients, the mean direct cost over three months was ITL 2,134,000, the mean indirect cost was ITL 7,775,000. Costs were significantly higher for male patients (p < 0.05) and showed a significant increase with increasing age (p < 0.0005), disease duration (p < 0.0005) and disease severity (p < 0.0005). Costs for patients in a progressive phase were significantly higher (p < 0.0005). There were no significant geographical differences among the regions of Italy. CONCLUSIONS: This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. Unpaid caregivers remain the culturally accepted mode of care for MS patients in Italy and this study illustrates the impact of their loss of earnings. As costs increase with disease progression, these findings suggest that treatment efforts should focus on patients in the early stages of MS, in order to slow down disease progression.

Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients--a randomised controlled trial.

It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-epsilon4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. OBJECTIVE: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. METHODS: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms. RESULTS: Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the epsilon4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable. CONCLUSION: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.

Apolipoprotein E genotype does not influence the progression of multiple sclerosis.

OBJECTIVE: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS. METHODS: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the -491 A/T polymorphism of the APOE promoter were determined. RESULTS: No association was observed between the APOE epsilon4 allele and clinical characteristics of our study population. We also investigated the -491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the -491 A/T polymorphism and the selected clinical variables. CONCLUSIONS: In our population the APOE epsilon4 allele and the -491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS.

Health-related quality of life and depression in an Italian sample of multiple sclerosis patients.

Only few publications have been reported on Health-related Quality of Life (HRQoL) in patients with multiple sclerosis (MS). EDSS is the most common outcome measure for either impairment or disability of MS, but it is not able to catch other aspects of MS impact on HRQoL. The authors performed a cross-sectional study on the group of all patients with MS who were diagnosed at least 4 years before 1998 in Catania (South Italy). One hundred and eighty patients out of 308 were enrolled in the study. SF-36 was used to catch the HRQoL of MS patients. EDSS, Beck Depression Inventory (BDI) and time since diagnosis were investigated as variables affecting the HRQoL of MS patients. The patients showed significant lower mean scores for all SF-36 health dimensions compared with sex- and age-adjusted scores in a general healthy Italian population (p<0.001). EDSS scores correlated only with physical functioning (r=-0.76 p<0.001). As expected, the more severe was the disease, the longer its duration and the lower the patients' skillness on HRQoL. BDI showed high partial correlations with all SF-36 health domains with r=-0.38 to -0.65 (p<0.001). This study showed that SF-36 is able to assess the HRQoL of MS patients. Depression strongly influenced the HRQoL of MS patients. EDSS and time since diagnosis also affected the HRQoL of MS patients. Our results are comparable with other European studies.

A screening instrument for a Sicilian neuroepidemiological survey in the elderly.

We evaluated the sensitivity and specificity of a screening instrument developed for use in a two-phase neuroepidemiological survey in Sicily. The Sicilian Epidemiological Dementia Study (SEDES) project will evaluate the prevalence and incidence of dementia, parkinsonisms and essential tremor in four Sicilian municipalities. It is a two-phase door-to-door survey. To identify subjects with possible neurological disorders, in this study, we developed a screening instrument including a symptoms questionnaire and simple physical tasks for parkinsonisms and essential tremor. The Mini-Mental State Examination (MMSE) was chosen for screening dementia. The symptoms questionnaire and simple tasks developed to identify possible patients with parkinsonism and essential tremor, was tested in a hospital setting. To evaluate sensitivity, we selected 20 patients with essential tremor and 40 with Parkinson's disease (20 with Stages I-II and 20 with Stages III-V) [Neurology 17 (1967) 427]. To evaluate specificity we also selected 20 healthy subjects. The screening instrument was administered in a hospital setting by trained interviewers. Sensitivity of the screening instrument (questionnaire plus simple tasks) was 100% for essential tremor and parkinsonisms regardless of the stage. Specificity of the instrument was 90% (95% CI 66.9-98.2); the predictive positive value was 90.9%, while the negative predictive value was 100%. Even if validity was assessed in a hospital setting, the high sensitivity and specificity obtained suggest that the instrument could be an appropriate screening tool for parkinsonisms and essential tremor in a two-phase neuroepidemiological survey.

Relationship between clinical variables and cognitive performances in migraineurs with and without aura.

Conflicting data on cognitive defects in migraine could be explained by differences in the clinical variables of the populations studied. We investigated 21 patients with migraine with aura and 24 with migraine without aura, diagnosed according to the International Headache Society criteria. The patients were submitted to a comprehensive battery of neuropsychological tests and grouped according to attack frequency and side of pain. Attack frequency was not associated with significant differences in any of the tasks, while location of pain was found to be significantly related to poorer performance on both the immediate and delayed recall of Rey Complex Figure in migraineurs both with and without aura, and a significant relationship between side of pain and number of clusters in the second trial of California Verbal Learning Test was found only in migraine with aura patients. The finding of worse performances in patients with right-sided pain seems to support a right hemisphere dysfunction hypothesis.

Epilepsy and neurocysticercosis in rural Bolivia: a population-based survey.

PURPOSE: To evaluate the frequency of neurocysticercosis (NCC) in a well-defined prevalent cohort of epilepsy patients in the rural area of the Cordillera province. METHODS: We carried out a two-phase door-to-door neuroepidemiologic survey in a sample of 10,124 subjects in a rural area of the Cordillera Province, Bolivia, to detect the prevalence of the most common neurologic disorders including epilepsy. A team of health workers administered a standard screening instrument for neurologic diseases; subjects found positive at the screening phase underwent a complete neurologic examination. Epilepsy patients were diagnosed according to the definition proposed by the International League Against Epilepsy (ILAE, 1993). Epilepsy patients identified this way underwent electroencephalographic recording, computed tomography (CT) scan, and serologic evaluation to detect antibodies against Taenia solium by enzyme-linked immunoelectrotransfer blot. RESULTS: At the end of the survey, we detected 124 defined prevalent epilepsy patients. On the basis of the classification proposed by the ILAE in 1981, partial seizures were the most common type diagnosed (66 patients, 53.3%). Of the 124 patients, 105 underwent CT scan, and a serum sample was taken to detect antibodies against T. solium in 112 patients; for 97 patients, both neuroradiologic and serologic data were available. Considering radiologic, serologic, and clinical features, of these 124 patients, 34 (27.4%) fulfilled the diagnostic criteria for definitive or probable NCC proposed in 2001. Of these 34 patients 24 (70.6%) had partial seizures. CONCLUSIONS: Our data confirm a high frequency of NCC among a well-defined prevalent cohort of epilepsy patients.

Nontraumatic spinal cord injury: an Italian survey.

OBJECTIVE: To describe the demographic and clinical characteristics and the clinical course of patients with nontraumatic spinal cord injury (SCI). DESIGN: A multicenter prospective study. SETTING: Thirty-two rehabilitation centers in several Italian regions. PARTICIPANTS: Patients with nontraumatic SCI (N=330) on first admission (February 1, 1997-January 31, 1999) to rehabilitation centers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Indicators of rehabilitation process quality were efficient bladder and bowel management. The indica-tor of neurologic recovery was improvement in American Spinal Injury Association Impairment Scale (AIS) level at discharge. The indicator of rehabilitation outcome was return home. Length of stay (LOS) was also measured as an indicator of the care process. RESULTS: Of the 330 patients, 30% exhibited an improvement in AIS classification at discharge, and 73% returned home. In multivariate analysis, a longer LOS was associated with vascular etiology, complete lesions, residence outside the district of the rehabilitation center, and presence of clinical complications. Neurologic improvement was related to incompleteness of the lesion and longer LOS. Factors predicting a return home were married status, incompleteness of lesion, clinical improvement, efficient bowel and bladder management, absence of pressure ulcers, and longer LOS. CONCLUSIONS: Patients showed long waiting times between diagnosis and initiation of rehabilitation, a good chance of improvement on the AIS, and low rates of home returns.

Epilepsy and multiple sclerosis in Sicily: a population-based study.

PURPOSE: To evaluate the association between epilepsy and multiple sclerosis (MS), we analyzed the incidence of epilepsy in a population-based incidence cohort of MS in Catania, Sicily. METHODS: According to Poser's diagnostic criteria, 170 incident cases of MS have been identified from 1975 to 1994 in the city of Catania. All these subjects underwent a complete neurological examination to confirm the diagnosis of MS and to identify those patients with a history of seizures. Diagnosis of epilepsy was based on the criteria proposed by the International League Against Epilepsy (ILAE) in 1993, and seizures were classified according to the classification of the ILAE, 1981. RESULTS: From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence of MS was 2.3/100,000 (95% CI, 2.0-2.6). Of the 170 defined MS patients, four developed epilepsy after the onset and also diagnosis of MS, giving an incidence rate of epilepsy of 285/100,000 person years at risk (95% CI, 119-684) and 147.8/100,000 when age adjusted to the world standard population. The cumulative risk of developing epilepsy after the onset of MS, evaluated by using the life-table methods, was zero at 1 year and 1.76% at 5 years. Of these four patients, three were classified as having partial seizures with secondary generalization and one with tonic-clonic seizures. CONCLUSIONS: Our data are consistent with those reported in literature suggesting that the risk of developing epilepsy is threefold higher among MS patients than in the general population.

Impact of sociodemographic characteristics on cognitive performance in an elderly Sicilian population.

OBJECTIVE: To assess cognitive levels in an elderly Sicilian population and to evaluate the role of education and other sociodemographic characteristics in cognitive performance. BACKGROUND: The pattern of cognitive performance in the elderly has not been investigated extensively in well-defined Italian populations. This study was conducted as part of a door-to-door survey of common neurologic disorders (the Sicilian Neuro-Epidemiologic Study project). METHODS: Thirteen physicians administered an Italian version of the Short Portable Mental Status Questionnaire (SPMSQ) to all subjects aged 50 years or older who, on November 1, 1987, resided in either of two Sicilian municipalities (Terrasini, Palermo province, and Riposto, Catania province; n = 3,999). Performance was scored as the number of errors on the SMPSQ. To define cognitive impairment we corrected the score for education as suggested by Pfeiffer [J Am Geriatr Soc 1975;23:433-441]. RESULTS: The median SPMSQ score was equal to 2, and cognitive impairment was present in 4.6% of the subjects. In a bivariate analysis, age, sex, education, employment status at interview and principal lifetime occupation were all significantly associated with cognitive impairment. In a multivariate analysis, the same pattern was seen, except that principal lifetime occupation lost its significance. CONCLUSION: Our findings suggest that age, sex, education and employment status are the sociodemographic characteristics associated with cognitive impairment in the elderly as measured by the SPMSQ.