Multiple antibody detection in 'seronegative' myasthenia gravis patients.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease caused by antibody mediated impairment in the neuromuscular junction. Seronegative MG (SNMG) without antibodies against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) by routine assays accounts for about 20% of all MG patients. METHODS: Plasma from 81 Chinese MG patients previously found to be seronegative was tested by routine assays for AChR and MuSK antibodies. These samples were screened by (i) a novel, highly sensitive radioimmunoassay for AChR antibodies; (ii) cell-based assays for clustered AChR, MuSK and lipoprotein receptor-related protein 4 (LRP4) antibodies; (iii) a radioimmunoassay for titin antibodies. RESULTS: Antibodies to AChR, MuSK, LRP4 and titin were found in 25% (20/81), 4% (3/81), 7% (6/81) and 6% (5/78) of SNMG patients, respectively. In total, 37% of SNMG patients were found to be positive for at least one of the tested antibodies. AChR antibody positive patients had more severe disease (P = 0.008) and a trend towards fewer remissions/minimal manifestations than AChR antibody negative patients. The four patients with coexistence of antibodies had more severe disease, whilst the seronegative patients had milder MG (P = 0.015). CONCLUSIONS: Detection of multiple muscle antibodies by more sensitive assays provides additional information in diagnosing and subgrouping of MG and may guide MG treatment.

Myasthenia gravis and risks for comorbidity.

Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle-specific tyrosine kinase or lipoprotein receptor-related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG-related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side-effects. Thymectomy is regarded as a safe procedure both short and long term. Non-MG-related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow-up is necessary to identify and treat all types of coexisting disease in MG.

Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.

BACKGROUND AND PURPOSE: Comorbidity in myasthenia gravis (MG) is important for diagnosis, treatment and prognosis. Disease complexity was assessed by examining total drug treatment, immune therapy and comorbidity in a complete national MG cohort. METHODS: All recipients of the MG-specific drug pyridostigmine 2004-2010 registered in the compulsory Norwegian Prescription Database who met the inclusion criteria were included. The pyridostigmine group was compared with the general Norwegian population. RESULTS: Myasthenia gravis patients received co-medication more often than the controls for nearly all groups of medication, including insulins (95% confidence interval 2.0-3.7), thyroid therapy (1.7-2.5), antidepressants (1.3-1.7), anti-infectives (1.2-1.4), lipid-modifying agents (1.1-1.4) and immunomodulating agents (6.8-8.8). CONCLUSIONS: Myasthenia gravis patients are more often treated with non-MG prescription drugs than controls, reflecting frequent co-medication and comorbidity.

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort.

BACKGROUND: Pyridostigmine is the first drug of choice for patients with myasthenia gravis (MG). The drug is not prescribed regularly to any other patient groups. We aimed to determine the prevalence, incidence and gender-specific characteristics of patients with MG needing drug treatment in a well-defined population cohort. METHODS: Data were retrieved from the Norwegian Prescription Database (NorPD) 2004-2007, containing information on all dispensed drugs in Norway. The study population comprised 677 recipients of pyridostigmine who met the following inclusion criteria (one or more): (i) More than one prescription 1 January 2004-31 December 2007, (ii) prescription from a specialist in neurology, (iii) prescription for MG being specified in NorPD. RESULTS: A total of 435 (64%) women and 242 men were included; female:male ratio 1.8:1. Point prevalence (1 January 2008) of symptomatic MG was 131 per million; 92 for men, 170 for women. Seventy-four new users of pyridostigmine were registered in 2007 (42 women, 32 men), i.e. the incidence rate for 2007 being 16 per million; 14 for men, 18 for women. Mean age of incident cases was 59 years; 64 and 55 years, respectively. Prevalence and incidence were significantly higher in the age group ≥ 50 years than < 50 years (P < 0.001), and highest at 70-79 years. Prevalence and incidence did not differ in the five geographical health regions in Norway. CONCLUSIONS: Reported prevalence and incidence are amongst the highest found in similar studies. This may be explained by optimal case identification, higher incidence of drug requiring MG amongst the elderly, and recurrences of previous MG.

Does myasthenia gravis provide protection against cancer?

OBJECTIVES: Reports have been made of an altered rate of extrathymic malignancies in patients with myasthenia gravis (MG). This study compared the rate of such malignancies in a group of MG patients with an optimal control group. MATERIALS AND METHODS: From the Norwegian Cause of Death Registry, we identified 249 dead MG patients (1951-2001) and a control group of 1,245 individuals (five per patient) dead in the same period, matched for sex and year of birth. RESULTS: Patients with MG had a lower occurrence of malignant disease as underlying or contributing cause of death than the controls (8.8% vs 27.2%, P < 0.001). The main difference was found for colorectal cancer, breast cancer and cancer in the upper digestive tract (esophagus and stomach). CONCLUSIONS: We report a significantly lower rate of extrathymic malignancies in patients with MG than in controls, and we hypothesize that MG treatment or the immunological mechanisms involved in MG may protect patients with MG from developing an extrathymic malignancy.

Causes of death among patients with myasthenia gravis in Norway between 1951 and 2001.

OBJECTIVE: This study investigated the causes of death among patients with myasthenia gravis (MG), with emphasis on respiratory tract and cardiac disease. METHODS: The Norwegian Cause of Death Register contains information on all deaths among Norwegian citizens. In total, 249 deceased patients with MG were identified (1951-2001). These were compared with 1245 controls deceased in the same period and matched for sex and year of birth. RESULTS: The death certificates of patients with MG had a significantly higher occurrence of respiratory tract disease as cause of death than controls (28.1% v 20.9%, p = 0.012). The difference was most pronounced for male patients, for patients dying between 30 and 69 years of age, and for deaths occurring before 1996. For cardiac disease there was a significantly lower occurrence among patients with MG than among controls at 50-69 years of age, for both men (19.4% v 52.0%, p = 0.001) and women (14.6% v 29.6%, p = 0.036). Age and year of death were important determinants for the causes of death, but could not account for the differences between the patients with MG and controls. CONCLUSIONS: This study shows that patients with MG dying between 1951 and 1995 had a higher occurrence of respiratory tract disease listed as cause of death than had a matched control group. The lack of difference after 1995 probably reflects improved treatment of MG and its complications. The reduced occurrence of cardiac disease among patients with MG is probably explained by competing factors (respiratory tract disease) causing death.

The yield of expanding the therapeutic time window for tPA.

OBJECTIVES: Intravenous thrombolysis with recombinant tissue plasminogen activator (tPA) for acute ischemic stroke has been proved to be effective when given within 3 h of onset of stroke symptoms. Partly due to this time limit, less than 10% of stroke patients are treated with tPA. This study assessed the potential for increased tPA utilization with a theoretical time limit of 6 h. MATERIALS AND METHODS: A total of 117 patients admitted with a diagnosis of acute cerebrovascular disease were prospectively registered over a 3-month period, with emphasis on timing and criteria for tPA treatment. RESULTS: Eighty-eight of 117 patients (75%) had an acute ischemic stroke. Of these, 23% arrived within 3 h, 8% within 3-6 h, and 69% later than 6 h after symptom onset. Of the seven patients in the 3-6 h group, only one had time delay as the only contraindication to tPA. CONCLUSIONS: This study suggests that reducing patient delay, rather than increasing the time limit for thrombolytic treatment, may increase the frequency of tPA utilization. Changing time limits for thrombolysis may reduce time delay from stroke onset to arrival in hospital due to more rapid handling of patients by the emergency medical services.