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PubMed2000

West syndrome in tuberous sclerosis complex.

West syndrome occurs commonly in children with tuberous sclerosis complex and is associated with a grave prognosis for cognitive and seizure outcomes. We sought to determine the epilepsy outcome of children with tuberous sclerosis complex and West syndrome and whether EEG, MRI, or steroid therapy duration were different in those whose epilepsy improved compared with those with intractable seizures. Seventeen patients with tuberous sclerosis complex and West syndrome were identified. For each patient, two sets of clinical evaluations, EEG and MRI data, and treatment information separated by at least 12 months were obtained. The patients were divided into two seizure outcome groups. EEG, MRI, and treatment data were compared between the groups. The intellectual deficiency was either severe (76%) or moderate (24%). Seizure control improved in 10 and worsened in seven, without mortality (follow-up range = 12-216 months). No significant differences in EEG background, MRI findings, or steroid treatment duration were evident between the groups. The difference in EEG-sleep approached statistical significance (P = 0.06). Our findings did not confirm reports of high mortality and poor epilepsy outcome in intellectually deficient children with West syndrome and tuberous sclerosis complex. EEG sleep was the best indicator of seizure control and approached statistical significance. The duration of steroid therapy had no influence on seizure control.

Adolescent↗

PubMed1997

[Bourneville's tuberous sclerosis and autism].

Tuberous sclerosis is often associated with developmental and behavioural disorders including typical or partial autistic syndrome. However, it may be difficult to recognize tuberous sclerosis behind an infantile autism during the early stages of the disease. Therefore, tuberous sclerosis must be regularly looked for on the basis of its major and minor criteria in any cases of infantile autism. The child psychiatrist is preferentially involved in the management of the various aspects of this association, ie, behavioural or character disorders, difficulties in social relationships and communication, mental retardation, feeding disorders, and psychological consequences for the families. The support provided may be complemented by that offered by the Association for Bourneville's tuberous sclerosis.

Autistic Disorder↗

PubMed2003

Birth cohort effects in multiple sclerosis.

PURPOSE: To identify potential birth cohort effects in multiple sclerosis in Sweden and particularly in Stockholm county. METHODS: Data on multiple causes of death from multiple sclerosis during 1962 to 1995 in Sweden and 1968 to 1995 in Stockholm county were analyzed using age-period-cohort models and curvature. RESULTS: Mortality from multiple sclerosis was higher in Sweden than in Stockholm county, with stable time trends, slight period effects and marked age effects. Cohorts born before or after a central period, from 1910 through 1930, registered lower mortality. A periodic wave-form mortality pattern was identified, following a 5-to-6-year cycle for cohorts born before 1925 both in and outside Stockholm county, and changing to longer or irregular cycles for cohorts born after 1930. CONCLUSIONS: Although methodological constraints inducing the saw-tooth pattern cannot be excluded, these results are consistent with etiologic hypotheses claiming a role for environmental factors in multiple sclerosis.

Adult↗

PubMed2003

From swelling to sclerosis: acute change in mesial hippocampus after prolonged febrile seizure.

Mesial temporal sclerosis (MTS) has been linked to prolonged febrile seizures. The sequence of changes in the temporal lobe/hippocampus following prolonged febrile seizures and status epilepticus is beginning to be elucidated. We obtained repeated magnetic resonance imaging (MRI) volumetric analysis of the hippocampi in a 23-month-old boy after a prolonged focal febrile seizure. Three days after a prolonged left focal febrile seizure, brain MRI showed increased T2 weighted signal and increased volume (swelling) of the right hippocampus. Repeat MRI 2 months later demonstrated sclerosis of the right hippocampus. Review of the literature shows four other children with prolonged focal seizures associated with the MRI sequence of temporal lobe swelling followed by sclerosis. All had left focal seizures followed by right MTS. Our patient demonstrates a shorter interval for the radiologic development of hippocampal sclerosis compared to other reports.

Brain Edema↗

PubMed2000

Circadian and hypothermia-induced effects on visual and auditory evoked potentials in multiple sclerosis.

OBJECTIVES: Body cooling has been proposed as a symptomatic treatment for multiple sclerosis. This study aimed to assess the effects of body cooling and of circadian variations on clinical parameters and on visual and auditory evoked potential measures in multiple sclerosis patients. METHODS: Clinical status was assessed and VEPs, BAEPs and MLAEPs (all with two stimulus frequencies) were recorded a total of 4 times on two separate days (two times per day at 08:30 and 15:00 h each day) in 10 multiple sclerosis patients and 10 controls. On one of these days, the subjects were submitted to body cooling before the afternoon session. RESULTS: Tympanic temperature was significantly higher in the afternoon. Cooling lowered the temperature by 1.4 degrees C. No clinical effects were observed. Circadian effects were detected on VEP amplitude, which increased both in controls and in patients at low stimulus frequency (P<0.01), and increased in controls and decreased in patients at high stimulus frequency (interaction: P<0.01). Cooling determined an increase in BAEP I-V peak-to-peak time in controls, and a reduction in patients at high stimulus frequency (interaction: P<0.01). In patients, cooling also determined a great increase in MLAEP amplitude (interaction: P<0.001). We did not find cooling effects on VEP measures. CONCLUSIONS: Visual and auditory evoked potentials showed differences in circadian and cooling effects between controls and multiple sclerosis patients. These differences are consistent with the hypothesis of temperature-dependent conduction blocks in demyelinated fibers. Cooling may have a clinical effect in selected patients only.

Acoustic Stimulation↗

PubMed2006

Optical coherence tomography in multiple sclerosis.

We do not have currently satisfactory clinical and anatomical correlates to gauge disability in multiple sclerosis. Structural biomarkers (such as MRI) are hindered because they cannot precisely segregate demyelination from axonal elements of tissue injury within the CNS. Axonal degeneration in multiple sclerosis is related to irreversible disability, which suggests that the confirmation of neuroprotective strategies needs highly quantifiable measures of axon loss that can be correlated with reliable measures of physiological function. The coupling of quantifiable measures of visual function with ocular imaging techniques, such as optical coherence tomography, enables us to begin to understand how structural changes in the visual system influence function in patients with multiple sclerosis. In this review, we consider the usefulness of optical imaging of the retina as a biomarker for neurodegeneration in multiple-sclerosis.

Biomarkers↗

PubMed2006

Vestibular evoked myogenic potential: new perspectives in multiple sclerosis.

AIM: To evaluate vestibular evoked myogenic potentials in patients with multiple sclerosis as method of diagnostic support. STUDY DESIGN: Case-control. MATERIAL AND METHOD: We studied a group of normal individuals (n=15) and a Studied group (n=15) that comprised patients with diagnosis of multiple sclerosis. Both groups were submitted to vestibular evoked myogenic potential exam. In each ear it was applied 200 stimuli by clicks and repeated for 2 consecutive cycles with the purpose of evaluating reproducibility. The active electrode of surface was put on the superior S++ of sternocleidomastoid muscle and the reference electrode on the anterior border of the clavicle. The individuals were instructed to rotate theirs head to the opposite side to the stimulated ear. RESULTS: Vestibular evoked myogenic potential responses were prompt, reproducible and biphasic. The latency of wave P1 and N2 and P1-N2 amplitude showed a higher value in the studied group when compared with the normal group. There was no significant difference when the ears were compared in P1 and N2 amplitude. We noticed that individuals with multiple sclerosis showed no response in 30% of the cases. In evaluating the individuals of the Studied group with otoneurology symptoms and compared with individuals without symptoms, it was observed that P1 and N2 latencies and P1-N2 amplitude were higher in symptomatic cases. CONCLUSION: Vestibular evoked myogenic potential was considered a good method of diagnostic support of vestibulospinal tract in cases of multiple sclerosis.

Acoustic Stimulation↗

PubMed1990

A cluster-focus of multiple sclerosis at Henribourg, Saskatchewan.

This study presents the clinical characteristics of 8 victims of multiple sclerosis from the hamlet of Henribourg, Saskatchewan with a population of less than 75 people. A diligent victim of the disease had observed that six female classmates from the early 1940's had later developed multiple sclerosis. Two male military personnel who had also resided briefly in close proximity, during the same common exposure time, also later developed multiple sclerosis. The mean onset time of developing the disease after leaving the area was 20 years. This cluster-focus suggests a common exposure to an environmental factor or a common infective agent in the etiology of multiple sclerosis.

Adult↗

PubMed1996

The occurrence of multiple sclerosis in the Hutterites of North America.

OBJECTIVE: To report the occurrence, clinical characteristics and genealogical analysis of multiple sclerosis in the Hutterites of North-Western United States and Western Canada. BACKGROUND: The incidence of multiple sclerosis is reported to be lower or rare in certain ethnic groups and genetic isolates and was previously observed to be absent in the Hutterite population. METHODS: After long-term surveillance, six patients were identified and clinical examinations and laboratory investigations including VER and MRI were completed. RESULTS: The six cases included two brothers, two first cousins, male and female, another male and female, all representing two of the three endogamous groups of Hutterites, are linked to two common ancestors through lines of descent dating to 1723. The individual pedigrees were analyzed from extensive genealogical records covering eight generations. CONCLUSION: The incidence of multiple sclerosis in Hutterites is low in a high risk area of North America. A specific mode of inheritance pattern has not been established and a common founder effect may play a role in the development of multiple sclerosis. The genetic contribution of the Hutterites seems greater than previously recognized.

Adult↗

PubMed1994

A prevalence study of multiple sclerosis in the Crowsnest Pass region of southern Alberta.

Reports of a high prevalence rate for multiple sclerosis in Southern Alberta led to an epidemiologic study of this disease in the Crowsnest Pass and Cardston regions. In Cardston, the prevalence rate for multiple sclerosis was 88 per 100,000. In the Crowsnest Pass, the prevalence rate was 217 per 100,000. Previous epidemiologic studies of the prevalence rate of multiple sclerosis in Western Canada have shown rates between 93 and 111 per 100,000. Two prevalence studies of multiple sclerosis in Barrhead County, Alberta and Westlock County, Alberta show prevalence rates of 196 and 201 per 100,000. The prevalence rate in the Crowsnest Pass is comparable to the prevalence in Barrhead County and Westlock County, Alberta. However, there is no statistically significant difference between prevalence rates in the Cardston and Crowsnest Pass regions and our overall feeling is that the results of studies of small populations should be interpreted with caution.

Adult↗

PubMed2004

Treatment optimization in multiple sclerosis.

The treatment of multiple sclerosis has finally become possible with the advent of the current disease-modifying therapies (DMTs) that have had a significant impact on those living with this disease. Though demonstrating clear efficacy on a number of short-term outcome measures, unfortunately, these agents are not "cures" and many patients with multiple sclerosis continue to experience disease activity in spite of treatment. Clinicians are becoming more comfortable initiating therapy with DMTs, but it is now important to focus attention on monitoring the results of the chosen therapy and deciding whether or not a patient is responding well to treatment. At present, however, clinicians lack criteria for defining optimal versus suboptimal responses to DMTs as well as evidence-based guidelines on how to improve treatment outcomes. Using a recently published model as a framework, The Canadian Multiple Sclerosis Working Group developed practical recommendations on how neurologists can assess the status of patients on DMTs and decide when it may be necessary to modify treatment in order to optimize outcomes. The Canadian Multiple Sclerosis Working Group's recommendations are based on monitoring relapses, neurological progression and MRI activity. Other possible causes of suboptimal treatment responses or treatment failure are also considered.

Decision Support Techniques↗

PubMed2002

Increased expression of "peripheral-type" benzodiazepine receptors in human temporal lobe epilepsy: implications for PET imaging of hippocampal sclerosis.

Increased binding sites for "peripheral-type" benzodiazepine receptor (PTBR) ligands have been described in a wide range of neurological disorders including both human and experimental epilepsy. This study was undertaken to assess PTBR expression in relation to the presence of hippocampal sclerosis in human temporal lobe epilepsy (TLE). For this purpose, hippocampal CA1 subfields were dissected from surgical samples from patients with therapy-refractive TLE with (n = 5) or without (n = 2) hippocampal sclerosis and from age-matched nonepileptic postmortem controls (n = 5). PTBR expression was assessed by immunohistochemistry and reverse-transcription polymerase chain reaction. Receptor sites were evaluated using an in vitro binding assay and the selective PTBR ligand [3H]PK11195. Epileptic patients with hippocampal sclerosis showed increases in PTBR binding sites, immunoreactivity, and mRNA expression compared to both nonsclerotic TLE patients and postmortem nonepileptic controls. Induction of PTBR expression and binding sites were directly correlated with the presence of hippocampal sclerosis and the accompanying reactive gliosis.

Epilepsy, Temporal Lobe↗

PubMed2001

Correlations between in vitro effects of preparations of interferon and its inducers on blood cells in patients with multiple sclerosis.

We studied in vitro production of interferon-alpha and interferon-gamma by peripheral blood leukocytes from 15 patients with multiple sclerosis. The priming effects of interferon preparations weakly correlated with interferon-alpha production by leukocytes from patients with multiple sclerosis, but negatively correlated with interferon-gamma production. The effects of interferon inducers in most cases positively correlated with its spontaneous production. We found a weak positive correlation between the priming effect of natural interferon-alpha and the effect of recombinant interferons. There were positive or strong positive correlations between the effects of recombinant interferons on leukocytes from patients with multiple sclerosis. The relationship between the effects of medicinal interferon inducers and interferon preparation varied from negative to strong positive correlations. These data suggest that correlation analysis can be used for dynamic control and elaboration of methods for combined immunotherapy of multiple sclerosis with various interferon preparations or interferon and its inducers.

Acridines↗

PubMed2000

Decreased stability of alpha2-macroglobulin purified from patients with multiple sclerosis.

OBJECTIVES: To investigate conformational properties of alpha2-macroglobulin from multiple sclerosis patients. MATERIALS AND METHODS: alpha2-macroglobulin was purified to homogeneity from plasma of 4 multiple sclerosis patients and 5 healthy controls. The plasma and the purified alpha2-macroglobulin from each individual were investigated using polyacrylamide gel electrophoresis. RESULTS: Impaired stability of purified alpha2-macroglobulins from multiple sclerosis patients was demonstrated with spontaneous conversion to an electrophoretic "fast" form upon purification and following storage not ascribable to bait region cleavage. CONCLUSION: alpha2-macroglobulin from multiple sclerosis patients displays altered stability. Possible functional impairments of proteinase inhibition mechanisms are discussed.

Adult↗

PubMed2000

Determination of medullasin levels for the diagnosis of multiple sclerosis.

OBJECTIVES: To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. PATIENTS AND METHODS: Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. RESULTS: A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals + 2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. CONCLUSION: This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis.

Adolescent↗

PubMed2000

Multiple sclerosis and poliomyelitis. A Danish historical cohort study.

OBJECTIVE: To evaluate whether persons with a history of poliomyelitis are at an increased risk of developing multiple sclerosis (MS). MATERIAL AND METHODS: All patients diagnosed with acute poliomyelitis in the greater capital area of Copenhagen, Denmark, between 1919 and 1954 were identified and followed with respect to MS. Information on vital status and diagnosis of sclerosis was obtained through linkage with the Danish Civil Registration System and The Danish Multiple Sclerosis Registry, respectively. Follow-up started on the date of the establishment of the Danish Civil Registration System (April 1, 1968) until death, emigration or December 31, 1996, whichever came first. The observed incidence of MS among polio patients was compared with the expected incidence calculated according to national gender, age and period specific rates of MS. RESULTS: During 149,364 years of follow-up, 19 cases of multiple sclerosis were observed among 5652 polio patients compared with 11.0 expected (SIR = 1.73 (1.04-2.74)). The increased risk of MS was most pronounced in polio patients hospitalized during adolescence. Neither gender nor the acute severity of poliomyelitis modified the risk of MS. CONCLUSION: Our results are based on small numbers of events, however the findings suggest that the polio patients might be at an increased risk of MS.

Adult↗

PubMed2000

Cannabinoids control spasticity and tremor in a multiple sclerosis model.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, delta9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis, and provides a means of evaluating more selective cannabinoids in the future.

Animals↗

PubMed2005

A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis.

Genetic susceptibility to multiple sclerosis is associated with genes of the major histocompatibility complex (MHC), particularly HLA-DRB1 and HLA-DQB1 (ref. 1). Both locus and allelic heterogeneity have been reported in this genomic region. To clarify whether HLA-DRB1 itself, nearby genes in the region encoding the MHC or combinations of these loci underlie susceptibility to multiple sclerosis, we genotyped 1,185 Canadian and Finnish families with multiple sclerosis (n = 4,203 individuals) with a high-density SNP panel spanning the genes encoding the MHC and flanking genomic regions. Strong associations in Canadian and Finnish samples were observed with blocks in the HLA class II genomic region (P < 4.9 x 10(-13) and P < 2.0 x 10(-16), respectively), but the strongest association was with HLA-DRB1 (P < 4.4 x 10(-17)). Conditioning on either HLA-DRB1 or the most significant HLA class II haplotype block found no additional block or SNP association independent of the HLA class II genomic region. This study therefore indicates that MHC-associated susceptibility to multiple sclerosis is determined by HLA class II alleles, their interactions and closely neighboring variants.

Canada↗