Marit Grønning

Disability and prognosis in multiple sclerosis: demographic and clinical variables important for the ability to walk and awarding of disability pension

Objective: To evaluate disability and prognosis in an untreated population-based incidence cohort of multiple sclerosis (MS) patients. Methods: The Expanded Disability Status Scale (EDSS) score was recorded in 220 MS patients. Disease progression was assessed by life table analysis with different endpoints and multivariate Cox regression analysis was performed for evaluation of prognostic factors. Results: The probability of being alive after 15 years was 94.8+1.8% (s.e.), of managing without a wheelchair (EDSS57.0) 75.8+3.2%, of walking without walking assistance (EDSS56.0) 60.3+3.6%, and of not being awarded a disability pension 46.0+3.7%. The probability of still having a relapsing-remitting (RR) course after 15 years was 62.0+4.1%. A RR course and long interval between the initial (onset) and second episode (43 years) predicted favorable outcome. There was also a trend towards favorable outcome in patients with optic neuritis, sensory symptoms and low age at onset, but these factors were associated with the RR course. Motor symptoms and high age at onset indicated unfavorable outcome, but these factors were associated with the primary progressive course. Conclusions: A RR course and long inter-episode intervals in the early phase of the disease were associated with a better outcome. Other onset characteristics indicating a favorable outcome were associated with the RR course while characteristics indicating an unfavorable outcome were associated with the PP course.

Altered antibody pattern to Epstein-Barr virus but not to other herpesviruses in multiple sclerosis: a population based case-control study from western Norway

OBJECTIVE The prevalence of anti-EBV antibodies was studied in a group of 144 patients with multiple sclerosis and 170 age, sex, and area matched controls from the county of Hordaland, western Norway. The prevalence of three other herpesviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV), were also included. METHODS Antibodies to various virus antigens were determined by enzyme linked immunosorbent assay (ELISA) and indirect immunfluorescence (IIF) in serum samples from 144 patients with multiple sclerosis and 170 controls. RESULTS All of the 144 patients with multiple sclerosis had IgG antibodies to EBV compared with 162 of 170 controls (p=0.008). The frequency of IgG antibodies to EBV capsid antigen (VCA), nuclear antigen (EBNA), and early antigen (EA) was significantly higher in patients with multiple sclerosis compared with the controls (p<0.000001, p=0.01, and p<0.0001 respectively). The presence of antibodies was independent of the initial course of the disease and the disease activity at the time of blood sampling. The prevalence of IgG antibodies to HSV, CMV, and VZV did not differ between cases and controls. CONCLUSION The results suggest a role for EBV in the aetiology of multiple sclerosis.

A 50-year follow-up of the incidence of traumatic spinal cord injuries in Western Norway

Study design:Retrospective population-based epidemiological study.Objective:To assess the prevalence and temporal trends in the incidence of traumatic spinal cord injuries (TSCI), and demographic and clinical characteristics of an unselected, geographically defined cohort in the period 1952–2001.Methods:The patients were identified from hospital records. Crude rates and age-adjusted rates were calculated for each year. The multivariate relationship between cause of injury, age at injury, decade of injury and gender was examined using a Poisson regression model.Results:Of 336 patients, 199 patients were alive on 1 January 2002, giving a total prevalence of 36.5 per 100 000 inhabitants. The average annual incidence increased from 5.9 per million in the first decade to 21.2 per million in the last. Mean age at injury was 42.9 years and the male to female ratio 4.7:1. Fall was the most common cause of injury (45.5%), followed by motor vehicle accidents (MVA) (34.2%). The incidence of MVA-related injuries increased during the observation period, especially among men <30 years. The lesion level was cervical in 52.4%, thoracic in 29.5% and lumbar/sacral in 18.2%. The lesion was clinically incomplete in 58.6% and complete in 41.4%. The incidence of fall-related injuries and the proportion of incomplete cervical lesions increased during the observation period, especially among men >60 years.Conclusions:The incidence of TSCI has increased during the past 50 years. Falls and MVA are potentially preventable causes. The increasing proportion of older patients with cervical lesions poses a challenge to the health system.

Mortality after traumatic spinal cord injury: 50 years of follow-up

Objective To study mortality and causes of death in an unselected geographically defined cohort of patients with traumatic spinal cord injury (TSCI), 1952–2001. Methods Patients were identified from hospital records. The date of death was obtained from the National Population Register, and causes of death recorded by linkage to the Norwegian Cause of Death Registry. Patient mortality was compared with mortality in the Norwegian population using standardised mortality ratios (SMR) adjusted for age and gender. Results 401 patients (70 women and 331 men) were identified. By 31 August 2008, 173 were dead. Median survival time in deceased patients was 7.4 years; 6.9 years for patients with cervical injuries and 8.2 years for patients with thoracolumbosacral injuries (TLS). TSCI patients had an increased mortality (SMR 1.85) compared with the Norwegian population. SMR did not change during the observation period. SMR was significantly higher for women than for men (2.88 vs 1.72), and higher in patients with complete TSCI compared with patients with incomplete TSCI (4.23 vs 1.25). SMR was 6.70 for patients with complete cervical injuries and 3.07 for patients with complete TLS injuries. Cause specific SMR were 1.96 for respiratory disease, and for suicide including accidental poisoning 3.70 for men and 37.59 for women. Conclusions Patients with a TSCI, and especially women, have an increased mortality despite modern treatment and care. Special attention should be paid to respiratory dysfunction and pulmonary infections, and to prevent suicide and accidental poisoning.

Management of Medication Overuse Headache: 1-Year Randomized Multicentre Open-Label Trial

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month x headache intensity x headache hours) at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had ≥ 50% reduction in monthly headache days compared with 25% in the withdrawal group (P = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).

Prognostic factors for life expectancy in multiple sclerosis analysed by

To determine if such factors as first symptom, sex, age at onset and initial clinical course have any influence on life expectancy of multiple sclerosis patients, a survival analysis from date of diagnosis for 598 MS-patients in Norway was performed. To study the effect of all the variables simultaneously we used the Cox proportional hazards regression model with incomplete data. Median survival time was 27 years after diagnosis. The variable which most strongly predicted the duration of the disease was age at onset. High age at onset and a progressive course of the disease were correlated with a more unfavourable prognosis. The onset symptom, vertigo, was also correlated with a shorter life expectancy. No significant effect of sex was found. We found in this material an indication of improved survival over the study period.

Diagnostic coding accuracy for traumatic spinal cord injuries

Study design:Retrospective register study enhanced and verified by medical records.Objectives:To study whether electronic searches of discharge diagnosis are valid for epidemiological research of traumatic spinal cord injury (SCI), using the International Classification of Diseases (ICD).Settings:Haukeland University Hospital, Bergen, NorwayMethods:We identified all hospital admissions with discharge codes suggesting a traumatic SCI from ICD-8 to ICD-10 in the electronic database at Haukeland University Hospital, and ascertained the cases by reviewing all hospital records.Results:1080 patients had an ICD diagnostic code suggesting a traumatic SCI. Only 260 were verified when reviewing the hospital records. The ICD-10 codes had superior positive predictive values (PPV) and likelihood ratios (LR+) compared with the codes from ICD-8 and ICD-9. Combining seven codes from ICD-10 (S14.0, S14.1, S24.0, S24.1, S34.1, S34.3, T91.3) gave the highest sensitivity (0.83), specificity (0.97), PPV (0.88) and LR+ (30.23).Conclusion:Obtaining hospital discharge diagnoses solely from electronic databases overestimates the incidence of traumatic SCI. Identification of patients using ICD-10 codes is more complicated because acute traumatic SCI and traumatic SCI sequelae are listed with several codes. The latest ICD version proved to be most reliable when identifying patients with traumatic SCI. However, ICD data cannot be trusted without extensive validity checks for either research or for health planning and administration.

The clinical significance of spinal cord injuries in patients older than 60 years of age.

Objectives –  To study the causes and the rehabilitation outcome of traumatic spinal cord injury (SCI) in patients older than 60 years at the time of injury.

Spasticity following spinal cord injury.

BACKGROUND Up to 70% of patients with spinal cord injuries develop spasticity. The main aim of the paper is to provide an overview of spasticity management, primarily in patients with spinal cord injuries. METHOD The article is based on literature searches in PubMed using the keyphrases «spasticity» and «spasticity AND spinal cord injury», and own clinical experience and research. RESULTS Spasticity may be general, regional or localised. Factors such as an over-filled bladder, obstipation, acute infections, syringomyelia or bone fractures may substantially influence the degree of spasticity and must be determined. An assessment of the clinical and functional consequences for the patient is decisive before management. Active exercise, physiotherapy and peroral drugs are the simplest and cheapest options. Baclofen is the only centrally acting spasmolytic registered in Norway and is the first choice for peroral treatment. Benzodiazepines can also be used. The effect of the tablets is generally limited and there are often pronounced side effects. Local spasticity can be treated with botulinum toxin injections. The effect is time-limited and the treatment must be repeated. International guidelines recommend a combination of botulinum toxin injections and physiotherapy. In cases of regional spasticity, particularly in the lower limbs, intrathecal baclofen administered via a programmable pump may provide a continuous spasm-reducing effect. Orthopaedic surgery or neurosurgery may be an option for selected patients with intractable spasticity. INTERPRETATION Spasticity following a spinal cord injury must be assessed regularly. The treatment strategy depends on the degree of functional failure caused by the spasticity and its location.

Treatment of spasticity related to multiple sclerosis with intrathecal baclofen: a long-term follow-up.

BACKGROUND Spasticity is a frequent disabling symptom in patients with multiple sclerosis, which contributes to functional deterioration. OBJECTIVE To evaluate the long-term effect of intrathecal baclofen therapy in multiple sclerosis-related spasticity and to evaluate the side-effects of long-term therapy, and the doses of baclofen required. METHODS Fourteen patients with multiple sclerosis were followed up clinically for a mean of 62 months (range 19-137 months). Clinical evaluation was made using individual goals, modified Ashworth scale, and Kurtzke Expanded Disability Status Scale. RESULTS Spasticity, measured with the modified Ashworth score, decreased in all patients by a mean of 1 point. The score on the Expanded Disability Status Scale improved in 2 cases. Prior to implantation, 10 patients (72%) reported severe pain. After implantation 3 improved and 7 became pain-free. The daily doses needed for treatment were highly individual. The effect of intrathecal baclofen on spasticity lasted observation time. One patient experienced progressive cognitive impairment as a side-effect of baclofen. CONCLUSION Intrathecal baclofen is well-tolerated and the effect lasts for up to 12 years. A thorough continuous clinical assessment is required because the differentiation between symptoms of multiple sclerosis progression and side-effects of baclofen may be difficult. Intrathecal baclofen should be considered as an option for long-term treatment of patients with advanced spasticity. Pain control can also be achieved by optimized intrathecal baclofen treatment.