Håkon Hofstad

Heart disease in myasthenia gravis

Abstract– Patients with myasthenia gravis (MG) may develop heart disease. Our data on 108 MG patients were examined to assess the type and frequency of this. 17 of 108 patients (16%) showed signs of heart disease which could be regarded as MG‐related. 11 of these, of whom 5 died suddenly, had clinical symptoms, mainly arrhythmias. Signs of heart disease were most frequent in thymoma patients (5 of 10), and all 3 microscopically examined hearts from these patients showed a focal myocarditis. 44 spinal muscular atrophy patients serving as controls showed a 16% frequency of signs of heart disease of unknown etiology. However, only 1 of 44 spinal muscular atrophy patients (2%) had clinical symptoms as compared to 11 of 108 MG patients (10%). Together with the characteristic focal nature of the myocarditis and the microscopic similarities between lesions of heart and skeletal muscle, this indicates that the heart disease is specifically related to MG.

Virtual reality training for upper extremity in subacute stroke (VIRTUES): study protocol for a randomized controlled multicenter trial

BackgroundNovel virtual reality rehabilitation systems provide the potential to increase intensity and offer challenging and motivating tasks. The efficacy of virtual reality systems to improve arm motor function early after stroke has not been demonstrated yet in sufficiently powered studies. The objective of the study is to investigate whether VR training as an adjunct to conventional therapy is more effective in improving arm motor function in the subacute phase after stroke than dose-matched conventional training, to assess patient and therapist satisfaction when working with novel virtual reality training and to calculate cost-effectiveness in terms of resources required to regain some degree of dexterity.Methods/DesignRandomized controlled observer-blind trial.One hundred and twenty patients up to 12 weeks after stroke will be randomized to either a group receiving VR training or dose-matched and therapist attention-matched conventional arm training in addition to standard rehabilitation. During a period of four weeks the patients will be offered additional 4–5 training sessions a week of 45–60 minutes duration by a physiotherapist or an occupational therapist.Study outcomes: Arm motor function, dexterity and independence in daily life activities will be evaluated at baseline, post treatment and three months follow-up assessments with the Action Research Arm Test, Box and Blocks Test and the Functional Independence Measure, respectively. Patient and therapist satisfaction with the implementation of a VR rehabilitation system will also be assessed with questionnaires and interviews.DiscussionVirtual reality systems are promising tools for rehabilitation of arm motor function after stroke. Their introduction in combination with traditional physical and occupational therapy may enhance recovery after stroke, and at the same time demand little personnel resources to increase training intensity. The VIRTUES trial will provide further evidence of VR-based treatment strategies to clinicians, patients and health economists.Trial registrationClinicalTrials.gov NCT02079103

CA‐antibody: an immunological marker of thymic neoplasia in myasthenia gravis?

Abstract We have examined sera from 141 patients with myasthenia gravis and 11 non‐myasthenia gravis patients with thymoma for antibodies to a citric acid extract of skeletal muscle (CA‐antibodies). Sera were obtained from 5 different centers. The thymus histology was defined in each case. Sera from 56/66 patients (85%) with thymoma contained CA‐antibodies, while such antibodies were only detected in 6/75 (8%) of the non‐thymoma patients. None of the patients with thymus hyperplasia had CA‐antibodies. One MG patient who developed MG after a bone‐marrow transplantation, also developed CA‐antibodies. The remaining 5 CA positive non‐thymoma MG patients were all >65 years and had thymic atrophy. Two of them had myasthenia gravis and polymyalgia rheumatica. In 2 thymoma patients with non‐detectable levels of CA‐antibodies before thymectomy, such antibodies were demonstrated in high titres after the operation. In 2 other sera from thymoma patients, the titres of CA‐antibodies fell to <32 after thymectomy. There were 3 sera with CA‐antibodies among 11 sera from non‐MG patients with thymic tumours.

The Trunk Impairment Scale – modified to ordinal scales in the Norwegian version

Purpose: To translate the Trunk Impairment Scale (TIS), a measure of trunk control in patients after stroke, into Norwegian (TIS-NV), and to explore its construct validity, internal consistency, intertester and test–retest reliability. Method: TIS was translated according to international guidelines. The validity study was performed on data from 201 patients with acute stroke. Fifty patients with stroke and acquired brain injury were recruited to examine intertester and test–retest reliability. Construct validity was analyzed with exploratory and confirmatory factor analysis and item response theory, internal consistency with Cronbach’s alpha test, and intertester and test–retest reliability with kappa and intraclass correlation coefficient tests.Results: The back-translated version of TIS-NV was validated by the original developer. The subscale Static sitting balance was removed. By combining items from the subscales Dynamic sitting balance and Coordination, six ordinal superitems (testlets) were constructed. The TIS-NV was renamed the modified TIS-NV (TIS-modNV). After modifications the TIS-modNV fitted well to a locally dependent unidimensional item response theory model. It demonstrated good construct validity, excellent internal consistency, and high intertester and test–retest reliability for the total score.Conclusions: This study supports that the TIS-modNV is a valid and reliable scale for use in clinical practice and research. Implications for Rehabilitation Trunk control is an essential part of balance and postural control, thereby an important prerequisite for daily activities and function Impairments of trunk control is a common problem in stroke The TIS-modNV is a valid and reliable measure to evaluate impairments in trunk control The TIS-modNV containing ordinal superitems is recommended for use in clinical practice and research

Heart Muscle Antibodies in Myasthenia Gravis

Myasthenia gravis (MG) may in some patients, especially in those with a thymoma, involve the heart. Using an ELISA, we measured heart muscle antibodies in sera from 75 MG patients and in 173 control sera. Heart muscle antibodies were detected in 29/30 thymoma MG patients, in none of 30 young onset MG patients with thymic hyperplasia and in 7/15 late onset MG patients with thymic atrophy. Among the controls, four sera had a very low concentration of heart muscle antibodies. Absorption studies showed that the heart muscle antibodies cross-react with skeletal muscle, but are unrelated to acetylcholine receptor antibodies.

Bannwarth's syndrome: serum and CSF IgG antibodies against Borrelia burgdorferi examined by ELISA

ABSTRACT— A newly identified spirochete, Borrelia burgdorferi, has recently been established as the causal agent of chronic meningoradiculitis (Bannwarths syndrome, BS). An etiological diagnosis can be obtained by specific antibody determination. To detect intrathecally produced Borrelia antibodies, we examined paired serum and CSF samples from 10 BS patients and 41 controls. CSF/serum IgG specific antibody indices were calculated by relating the CSF/serum ratio of specific antibody activity to the CSF/serum ratio of total IgG and of albumin; 8/10 BS patients compared to 4/39 controls had elevated index values. In only one of the 4 positive controls could spirochetal infection be excluded. We conclude that determination of specific antibody indices is a reliable and sensitive diagnostic test for nervous system B. burgdorferi infection.

Balance and walking after three different models of stroke rehabilitation: early supported discharge in a day unit or at home, and traditional treatment (control)

Objective To compare the effects on balance and walking of three models of stroke rehabilitation: early supported discharge with rehabilitation in a day unit or at home, and traditional uncoordinated treatment (control). Design Group comparison study within a randomised controlled trial. Setting Hospital stroke unit and primary healthcare. Participants Inclusion criteria: a score of 2–26 on National Institutes of Health Stroke Scale, assessed with Postural Assessment Scale for Stroke (PASS), and discharge directly home from the hospital stroke unit. Interventions Two intervention groups were given early supported discharge with treatment in either a day unit or the patients own home. The controls were offered traditional, uncoordinated treatment. Outcome measures Primary: PASS. Secondary: Trunk Impairment Scale—modified Norwegian version; timed Up-and-Go; 5 m timed walk; self-reports on problems with walking, balance, ADL, physical activity, pain and tiredness. The patients were tested before randomisation and 3 months after inclusion. Results From a total of 306 randomised patients, 167 were tested with PASS at baseline and discharged directly home. 105 were retested at 3 months: mean age 69 years, 63 men, 27 patients in day unit rehabilitation, 43 in home rehabilitation and 35 in a control group. There were no group differences, either at baseline for demographic and test data or for length of stroke unit stay. At 3 months, there was no group difference in change on PASS (p>0.05). Some secondary measures tended to show better outcome for the intervention groups, that is, trunk control, median (95% CI): day unit, 2 (0.28 to 2.31); home rehabilitation, 4 (1.80 to 3.78); control, 1 (0.56 to 2.53), p=0.044; and for self-report on walking, p=0.021 and ADL, p=0.016. Conclusions There was no difference in change between the groups for postural balance, but the secondary outcomes indicated that improvement of trunk control and walking was better in the intervention groups than in the control group. Trial registration This study is part of the Early Supported Discharge after Stroke in Bergen, ClinicalTrials.gov (NCT00771771).

Thymic lymphoepitheliomas and skeletal muscle expressing common antigen(s)

Rabbit antiserum to a citric acid extract of human skeletal muscle (CA) stained epithelial thymoma cells as well as skeletal muscle. Thymomas from two myasthenia gravis (MG) pàtients showing no circulating anti‐CA antibodies prior to thymectomy were also stained by the antiserum. Thus, in these patients as well, the thymoma and skeletal muscle possess common antigens. The rabbit and the human antibodies most probably reacted with different antigens, apparently located close to each other in the cell membrane. The reason why anti‐CA antibodies cannot be detected in serum from a few MG patients with a thymoma may be that the thymoma‐associated antigen is not present in vivo in these cases, or that an inhibiting factor blocks the antibody synthesis. Both patients developed anti‐CA antibodies post‐operatively, which favours the latter explanation.

The Ultrastructural Localization of Antigens for Skeletal Muscle Antibodies in Myasthenia Gravis

Approximately 80% of patients with myasthenia gravis (MG) and thymoma have circulating antibodies against skeletal muscle antigens other than the acetylcholine receptor. Only 20% of MG patients without thymoma have nonreceptor antibodies.’ When nonreceptor-antibody-containing MG sera are used for immunofluorescence microscopy with normal skeletal muscle, considerable heterogeneity of the crossstriational staining patterns becomes apparent? The aim of our study has been to determine the ultrastructural correlate of such staining patterns. We used sera from 17 MG patients, all containing nonreceptor skeletal muscle antibodies. Twelve of these sera reacted against components of the citric acid (CA) extract of skeletal muscle (CA-positive sera). Five sera were CA-negative but revealed cross-striational patterns by immunofluorescence microscopy. Pooled normal human sera and serum from MG patients lacking nonreceptor antibodies were used as controls. Skeletal muscle tissue from cattle, rats, and mice, fixed in aldehyde according to the pH-shift technique of Berod et al.,’ were sliced on a vibratome and incubated with the sera. The antibody binding was visualized by indirect immunoperoxidase staining with biotin-avidin‘ and osmium-thiosemicarbazide-osmium enhancement5 before plastic embedding, semithin sectioning, and light microscopy. Positively stained areas were selected for reembedding and ultrathin sectioning before transmission electron microscopy. When viewed in the light microscope, none of the control sera gave positive staining of skeletal muscle. The CA-positive sera all gave similar, positively stained double and triple lines corresponding to the I bands. The pattern with CA-negative sera, on the other hand, was a single line corresponding to the I-band (see FIG. 1). Only the immunostaining of CA-positive sera has so far been examined in the electron microscope. An intense positive reaction was confined to the terminal cisterns of the sarcoplasmic reticulum (SR) on both sides of the T tubules and to the longitudinal SR tubules at I-band level (FIG. 2). The longitudinal SR tubules at A-band level were negative. Previous failures to demonstrate this SR localization for the antigens to nonreceptor antibodies in MG may depend on the use of less sensitive

Muscle antibodies in the cerebrospinal fluid from patients with myasthenia gravis

IgG antibodies to nicotinic acetylcholine receptor (AChR) and to a muscle antigen extracted by citric acid, were quantified in serum and cerebrospinal fluid (CSF) from 28 patients with myasthenia gravis, and the serum:CSF ratios compared with those of total IgG. Agarose‐electrophoresis and calculations of the IgG index and Tourtellottes formula were performed. No evidence of intrathecal antibody synthesis was demonstrated. Compared to the total IgG concentrations in serum and CSF, the CSF concentrations of IgG AChR antibodies were lower than expected.