BREMSO: a simple score to predict early the natural course of multiple sclerosis.

BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

Fluctuations of MS births and UV-light exposure.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

Clinical and radiological characteristics of tumefactive demyelinating lesions: follow-up study.

BACKGROUND: Demyelinating lesions over 20 mm in size, referred to as tumefactive demyelinating lesions, can be misdiagnosed as being either a tumor or an abscess. Although some radiological characteristics can help make a differential diagnosis easier, a cerebral biopsy may still be necessary. OBJECTIVE: Our objective was to assess the clinical characteristics of tumefactive lesions, with or without a diagnosis of multiple sclerosis (MS), and present follow-up data for 54 patients with tumefactive lesions. METHODS: Demographic, clinical, radiological and laboratory data were gathered and treatment responses were evaluated in a total of 54 patients from five medical centers. RESULT: Twenty-nine patients were diagnosed with tumefactive lesions at the onset, whereas 25 patients were diagnosed with tumefactive lesions after a diagnosis of MS. Median follow-up was 38.12 months. At final examination, 19 of the patients with a tumefactive lesion diagnosis at the onset eventually developed relapsing-remitting MS, while 10 remained with the condition as a clinically isolated syndrome. The tumefactive lesions studied were mostly focal, with closed-ring enhancement. We found that oligoclonal band positivity was less frequent in the patients with tumefactive onset. CONCLUSION: Although our demographic data were similar to formerly collected Turkish MS data, we found that the distribution of the patients' clinical course differed if there was an absence of primary progressive MS and that there was a lower frequency of secondary progressive MS cases in our group of patients. We believe that less frequent oligoclonal band positivity and the difference we witnessed in the clinical course of disease in our study groups suggest that there is a need for further studies to compare all the biological and immunological differences between MS and tumefactive lesion cases, in order to reveal whether there are different pathogenetic mechanisms involved.

The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.

BACKGROUND: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. METHODS: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. RESULTS: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). CONCLUSIONS: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.

Susac Syndrome: Clinical characteristics, diagnostic findings and treatment in 19 cases.

Susac's Syndrome (SS), which was first described in 1979, is a rare and presumably autoimmune disorder characterized by encephalopathy, hearing loss, and visual disturbance resulting from branch retinal artery occlusion (BRAO). This study reports 19 SS patients' clinical characteristics, MRI features, CSF analysis, treatment strategies and outcomes. At initial presentation, only three of 19 patients demonstrated the complete clinical triad. Clinic presentation varied from isolated hemiparesis to the full triad (encephalopathy, hearing loss and visual disturbances). Corpus callosum (CC) involvement was noted in the MRI of 18 patients (97%) and BRAO was detected in 17 (95%) patients. All patients were treated with intravenous methylprednisolone after the initial assessment. This case series is presented to emphasize the differences in clinical presentation of SS and the importance of MRI and FFA in diagnosis.

Status epilepticus after stroke.

BACKGROUND AND PURPOSE: objective of our study was to determine the risk and predictive factors of status epilepticus (SE) after stroke. METHODS: From 1988 to 2000, 1174 patients were admitted to the Department of Neurology at the Karadeniz Technical University Farabi Hospital with first-time strokes. Of these, 180 patients had poststroke first-time seizures (PFSs). We followed these 180 PFS patients for an average of 3.7 years or until death to determine the occurrence rate of SE. By comparing these data with those of PFS patients without SE, we investigated whether there were significant differences. RESULTS: A total of 17 of the 180 PFS patients (9%) had SE. There was no relationship between the occurrence of SE and stroke risk factors, stroke type (ischemic or hemorrhagic stroke), stroke topography and cause, cortical involvement, size of lesion, seizure type, or electroencephalographic findings. SE occurred more frequently among patients with a higher disability rating (Rankin scale >3; odds ratio, 4.36). Recurrent SE was identified in 5 of 17 patients with SE. In all 5 of these patients, the first episode of SE occurred within the first 7 days after stroke (early-onset SE). Statistical analysis demonstrated that early-onset SE was associated with a higher risk for SE recurrence (P=0.003) and a higher mortality rate (P=0.04). CONCLUSIONS: SE was not associated with a higher mortality rate but with higher functional disability. We also found that early-onset SE (within the first 7 days after stroke) was associated with a higher risk for SE recurrence and a higher mortality rate than late-onset SE (after 7 days after stroke).

Cerebral infarction following intravenous immunoglobulin therapy for Guillain-Barre syndrome.

Intravenous immunoglobulin (IVIg) therapy is used increasingly for different immune-mediated diseases, such as the Guillain-Barre syndrome. We report the case of a 55-year-old man who developed a cerebral infarction 2 days after completion of treatment with intravenous immunoglobulin for Guillain-Barre syndrome.

Local cold effect on the excitability recovery curve of the sympathetic skin response.

The sympathetic skin response (SSR) is an established technique used to assess the activity of the sympathetic sudomotor pathway, but it is limited in application by the habituation process. The nature of habituation is not clear. In this study we aimed to further understand the role of the peripheral mechanism in the habituation of the SSR. We recorded SSRs to paired stimuli with interstimulus intervals of 1, 2, 3, 4 and 5 seconds on both hands of 15 volunteers simultaneously, while the right hand was cooled to 23-24 degrees C and the left hand was between 32 and 33 degrees C. The amplitude and latency generated by the first stimulus (SSR1) and the second stimulus (SSR2) were measured. While SSR2 first occurred at ISI 2 in 7 subjects and ISI 3 in 8 subjects on the normal side, SSR2 first occurred at ISI 4 in 7 subjects and ISI 3 in 8 subjects on the cooled side. The SSR amplitude recovery percentage, which was obtained by dividing the amplitude of SSR2 by the amplitude of SSR1, was significantly different on the cooled side. No significant differences were found between SSR1 and SSR2 latencies, which were measured at ISI 3, 4 and 5 on the normal side and at ISI 5 on the cooled side. Our findings further support that a peripheral component might be involved in the modification and habituation of the SSR in terms of amplitude, but not of latency.

Transient tic disorder following carbon monoxide poisoning.

We report a 12-year-old male patient who developed transient motor and vocal tics twelve days after carbon monoxide (CO) poisoning. Cranial magnetic resonance image (MRI) of the patient showed bilateral symmetric hyperintensity in the caudate nucleus and putamen. Tic disorder was successfully treated with haloperidol. Thirty-three months after CO poisoning, the patient was asymptomatic and MRI revealed atrophy in caudate nucleus and putamen. The mechanism of tic disorder in CO intoxication is discussed.

Cerebral venous thrombosis after high dose steroid in multiple sclerosis: a case report.

Cerebral venous thrombosis (CVT) is a clinical condition which is caused by the partial or complete occlusion of the dural sinuses and cerebral veins. Cases of associated CVT and multiple sclerosis (MS) have been reported and CVT development has been attributed to the previous lumbar puncture (LP) in majority of these cases. We report a case of 32-year-old woman with no previous history of recent LP, who developed CVT after high dose intravenous methylprednisolone and discuss the possible role of high dose steroids in development of CVT in MS patients.

Cervical vestibular evoked myogenic potentials to air-conducted sound in early amyotrophic lateral sclerosis.

OBJECTIVES: Cervical vestibular evoked myogenic potentials (cVEMPs) provide assessment of lower-brainstem lesions affecting their neuronal pathways. We aimed to determine whether cVEMPs to air-conducted sound (ACS) are also abnormal in patients with early stages of amyotrophic lateral sclerosis (ALS), with or without bulbar involvement. METHODS: cVEMPs were recorded in 22 ALS patients and 23 age- and sex-matched healthy volunteers. Their latencies and amplitudes were compared between the ALS patients and the control group. RESULTS: cVEMPs were obtained in all ALS patients and controls. P(13) and N(23) latencies and P(13)-N(23) amplitudes did not significantly differ between controls and ALS patients, either with or without bulbar involvement. CONCLUSIONS: We postulate that the ACS-cVEMP neural pathway is not affected in patients with early stages of ALS, even with clinical findings of bulbar involvement. Therefore, ACS-cVEMP is not a sensitive diagnostic tool for early detection of brainstem involvement in patients with ALS.

Reduced effectiveness of long-term interferon-beta treatment on relapses in neutralizing antibody-positive multiple sclerosis patients: a Canadian multiple sclerosis clinic-based study.

Multiple sclerosis (MS) patients treated with interferon-beta (IFN-beta) often form anti-IFN-beta antibodies accompanied by a reduction in IFN-beta bioavailability. The clinical effect of these antibodies remains controversial. MS patients in British Columbia, Canada, must be diagnosed and evaluated annually by neurologists in an MS clinic in order to be reimbursed for their IFN-beta prescriptions. We have identified at the UBC MS clinic a cohort of 262 patients, each having been treated with a single IFN-beta preparation more than three years, some for nearly a decade. Of 119 patients treated with Betaseron (IFN-beta1b), 18 (15.1%) were neutralizing antibody positive (NAb+) at the time of the study, whereas of 131 treated with subcutaneous Rebif (IFN-beta1a SC), 16 (12.2%) were NAb+, but none of 12 treated with intramuscular Avonex (IFN-beta1a) had detectable neutralizing antibodies. During the first two years of treatment, the relapse rate was significantly reduced from pre-treatment rates (P<0.001) and appeared to be unaffected by the subsequent NAb status. However, the relapse rates in the NAb+ patients were significantly greater than in the NAb- patients during years 3 (P<0.010) and 4 (P<0.027). Betaseron-treated NAb+ patients tended to have more relapses than NAb- patients during year 3 and this almost reached significance (P=0.056) but their relapse rate did not differ in year 4 and later. In contrast, Rebif-treated NAb+ patients tended to have more relapses in year 3 than Rebif-treated NAb- patients (P=0.074), but in year 4 they clearly (P=0.009) had more relapses than Rebif-treated NAb- patients. There was no convincing effect on progression of disability in any group.

The impact of migraine on epilepsy: a prospective prognosis study.

The effect of migraine on the prognosis of epilepsy has not been reported. The aim of this prospective 5-10-year follow-up study was to examine some outcome measures and the cumulative probability of being seizure-free in epilepsy patients with migraine, and to compare their results with those of epilepsy patients without migraine. Fifty-nine patients (40 women; mean age 25 years) were diagnosed with both epilepsy and migraine (EM group). The control group consisted of 56 patients with epilepsy but without migraine (E group). Both groups were recruited and followed up over similar periods. We compared the outcome variables in the EM group with those in the E group. Kaplan-Meier methods were used to assess the seizure-free curves. The EM group had a significantly lower cumulative probability of being seizure-free over 10 years compared with the E group. The other epilepsy outcome measures at follow-up differed significantly between the groups, with the EM group having a longer duration of epilepsy, a lower early treatment response, and a higher incidence of intractable epilepsy and achieving remission with polytherapy, and more seizure control and medication problems for at least the last 2 years of follow-up. Comorbid migraine had a negative effect on the prognosis of epilepsy.

Acute disseminated encephalomyelitis after bee sting.

Acute disseminated encephalomyelitis (ADEM) usually follows a viral infection or an immunization and is thought to be an immunomediated disease. We describe a patient with ADEM after multiple yellow jacket bee stings. The patient recovered after treatment with a high dose of methylprednisolone. Although the pathologic mechanism exact remains unclear, potential cross-reactivity between bee toxins and the central nervous system myelin could induce demyelination. ADEM should be considered a rare complication of bee stings.

Increased plasma endothelin-1 levels in patients with intracerebral hemorrhage.

Endothelins (ETs) are discovered peptides that are widely distributed in neurons and nonneuronal cells of the human nervous system. Previous studies showed that ischemic stroke may be associated with increased plasma ET-1 levels. There are no studies to show plasma ET-1 levels in intracerebral hemorrhage. Plasma ET-1 levels in 30 patients with cerebral hemorrhage within 72 hours after the onset of focal neurological deficit were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The clinical neurological status in the patients was evaluated according to the modified Matthew Scale. The mean plasma ET-1 level in hemorrhagic stroke patients was significantly higher than in control subjects (2.39±2.08 v 0.65±0.32 fmol/mL, (P < .05). There was a significant difference in ET levels between patients who died in the hospital and patients who survived (P < .05). The mean ET-1 concentration in patients with severe neurologic deficit was significantly higher than in patients with mild neurologic deficit (P < .05). There was a correlation between hematoma volumes and plasma ET-1 levels in the patients (r = 0.66, Pt < .001). The mean plasma ET-1 concentration was found to be significantly higher in patients with intraventricular hemorrhage than in patients without intraventricular hemorrhage (P < 0.05). There were no significant differences in ET-1 levels between supratentorial and infratentorial subgroups or among supratentorial subgroups (P > .05). It was concluded that plasma ET-1 levels were increased in the acute period of hemorrhagic stroke. Plasma ET-1 levels may be associated with hematoma volume, which is related to a poor prognosis of the cerebral hematoma. We suggest that increased plasma ET-1 levels may be a consequence of local cerebral hemorrhage or the acute stress condition of the disease.