Registration of Amyotrophic Lateral Sclerosis: Validity in the Danish National Patient Registry.

Purpose: Health care databases are a valuable source for epidemiological research on amyotrophic lateral sclerosis (ALS) if diagnosis codes are valid. We evaluated the validity of the diagnostic codes for ALS in the Danish National Patient Registry (DNPR). Patients and Methods: We obtained data from the DNPR for all adult (>17 years) patients registered with ALS in Denmark between 1987 and 2022 (median population of 4.2 million during the study period). We randomly selected adult patients living in the North Denmark Region and Central Denmark Region (median population 1.4 million), with a primary discharge diagnosis code of ALS, diagnosed at three departments of neurology. We retrieved and reviewed medical records and estimated the positive predictive value (PPV) of the ALS diagnosis. Results: Over 36 years, we identified 5679 patients. From the validation cohort of 300 patients, we were able to retrieve 240 (80%) medical records, and 215 ALS diagnoses were confirmed. The overall positive predictive value was 89.6% (95% confidence interval (CI): 85.1-92.8). The highest PPV was achieved for diagnoses registered for patients aged ≥70 years (93.8; 95% CI: 86.2-97.3) compared to patients <60 years (83.4; 95% CI: 73.3-90.7). Conclusion: We found a high PPV of primary diagnostic codes for ALS from Danish departments of neurology, demonstrating high validity. Thus, the DNPR is a well-suited data source for large-scale epidemiological research on ALS.

Hospital-diagnosed morbidities and recent surgery as risk factors for developing Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: This study was undertaken to determine the association of hospital-diagnosed morbidity and recent surgery with risk of subsequent Guillain-Barré syndrome (GBS) development. METHODS: We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 2004 and 2016 and 10 age-, sex-, and index date-matched population controls per case. Hospital-diagnosed morbidities included in the Charlson Comorbidity Index were assessed as GBS risk factors up to 10 years prior to the GBS index date. Incident major surgery was assessed within 5 months prior. RESULTS: In the 13-year study period, there were 1086 incident GBS cases, whom we compared with 10,747 matched controls. Any pre-existing hospital-diagnosed morbidity was observed in 27.5% of GBS cases and 20.0% of matched controls, yielding an overall matched odds ratio (OR) of 1.6 (95% confidence interval [CI] = 1.4-1.9). The strongest associations were found for leukemia, lymphoma, diabetes, liver disease, myocardial infarction, congestive heart failure, and cerebrovascular disease, with 1.6- to 4.6-fold increased risks of subsequent GBS. GBS risk was strongest for morbidities newly diagnosed during the past 5 months (OR = 4.1, 95% CI = 3.0-5.6). Surgical procedures within 5 months prior were observed in 10.6% of cases and 5.1% of controls, resulting in a GBS OR of 2.2 (95% CI = 1.8-2.7). Risk of developing GBS was highest during the first month following surgery (OR = 3.7, 95% CI = 2.6-5.2). CONCLUSIONS: In this large nationwide study, individuals with hospital-diagnosed morbidity and recent surgery had a considerably increased risk of GBS.

Increased risk of depression after Guillain-Barré syndrome.

INTRODUCTION/AIMS: Guillain-Barré syndrome (GBS) is a potentially life-threatening disorder, and some patients may develop subsequent depression related to traumatic stress or permanent loss of motor function. We determined the short-term (0 to 2 years) and long-term (>2 years) risk of depression after GBS. METHODS: Individual-level data from nationwide registries were linked in this population-based cohort study of all first-time hospital-diagnosed GBS patients in Denmark between 2005 and 2016 and individuals from the general population. After exclusion of individuals with previous depression, we computed cumulative rates of depression, defined as either antidepressant drug prescription or depression hospital diagnosis. We used Cox regression analyses to calculate adjusted depression hazard ratios (HRs) after GBS. RESULTS: We identified 853 incident GBS patients and recruited 8639 individuals from the general population. Depression within 2 years was observed in 21.3% (95% confidence interval [CI], 18.2% to 25.0%) of GBS patients and in 3.3% (95% CI, 2.9% to 3.7%) of those in the general population, resulting in a HR of 7.6 (95% CI, 6.2 to 9.3). The highest depression HR was observed within the first 3 months after GBS (HR, 20.5; 95% CI, 13.6 to 30.9). After the first 2 years, GBS patients and the general population members had similar long-term depression risks with an HR of 0.8 (95% CI, 0.6 to 1.2). DISCUSSION: During the first 2 years after GBS hospital admission, patients with GBS had a 7.6-fold increased hazard of depression compared with individuals in the general population. Two years after GBS, the risk of depression was similar to that of the background population.

Guillain-Barré syndrome following influenza vaccination: A 15-year nationwide population-based case-control study.

BACKGROUND AND PURPOSE: Influenza vaccination may increase the risk of developing Guillain-Barré syndrome (GBS) due to an elicited immune response, but the exact magnitude and duration of risk is unclear and hence the aim of this study. METHODS: We conducted a retrospective nationwide population-based case-control study of prospectively collected data on all patients with first-time hospital-diagnosed GBS in Denmark between 2002 and 2016 and 10 age-, sex- and index date-matched population controls per case. The primary exposure was incident influenza vaccination 1 month prior to admission with GBS. We used medical registries to ascertain a complete hospital contact history of pre-existing morbidities. To examine duration of GBS risk, we repeated the analysis for five consecutive 1-month risk periods following vaccination. RESULTS: Of the 1295 GBS cases and 12,814 controls, 20 cases (1.5%) and 119 controls (0.9%) had received an influenza vaccination within the last month, yielding a comorbidity-adjusted odds ratio of 1.9 (95% confidence interval 1.1-3.2) for GBS. Stratified analyses by calendar time, gender and age showed similar results. The increased risk of GBS was largely confined to 1 month following influenza vaccination. The population-attributable fraction of GBS from influenza vaccination in Denmark was 0.4%. CONCLUSIONS: Influenza vaccination was associated with a slightly elevated risk of GBS occurrence within 1 month after vaccination. However, only 1.5% of GBS cases in Denmark are associated with recent influenza vaccination. Thus, the benefit of influenza vaccines in preventing influenza infections and associated morbidity and mortality needs to be weighed against the small absolute risk of GBS.

Association Between Incident Cancer and Guillain-Barré Syndrome Development: A Nationwide Case-Control Study.

BACKGROUND AND OBJECTIVES: Cancer may increase the risk of developing Guillain-Barré syndrome (GBS) due to molecular mimicry or immunosuppression, but the exact relationship is unclear. We aimed to determine the association between incident cancer and the following risk of GBS development. METHODS: We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 age-, sex-, and index date-matched population controls per case. We identified incident cancer diagnoses between 6 months before and 2 months after the GBS index date. We used conditional logistic regression to compute odds ratios (ORs) as a measure of relative risk and performed stratified analyses to assess the impact of cancer on GBS risk in strata of calendar periods, sex, and age. In sensitivity analyses, to assess any potential risk of survival bias induced by including cancer diagnoses potentially made after GBS diagnosis, we examined incident cancers in both a broader exposure window (1 year before to 3 months after GBS index date) and a narrower window (6 months to 1 month before the GBS index date). RESULTS: Of the 2,414 patients with GBS and 23,909 controls included, 49 cases (2.0%) and 138 controls (0.6%) had a recent cancer diagnosis, yielding a matched OR of 3.6 (95% CI 2.6-5.1) for GBS associated with cancer. Stratification by calendar time, sex, and age showed robust results for the association between cancer and GBS, with no major variations. Broadening and narrowing the exposure window produced slightly weakened associations of OR of 2.4 (95% CI 1.8-3.3) and 2.5 (95% CI 1.5-4.1), respectively. The GBS ORs were highest for cancers of the lymphatic and hematopoietic tissue (OR 7.2, 95% CI 2.9-18.0), respiratory tract (OR 5.6, 95% CI 2.7-11.9), prostate and other male genital organ (OR 5.0, 95% CI 2.1-11.6), and breast (OR 5.0, 95% CI 1.7-14.5) cancer. DISCUSSION: In this large nationwide epidemiologic study, incident cancer was associated with a markedly increased risk of subsequent GBS development. The results suggest that as-yet unidentified factors present in several types of cancer drive this association.

Increased mortality following Guillain-Barré syndrome: A population-based cohort study.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) may be fatal in the acute phase but also affect long-term prognosis due to irreversible sequelae and secondary medical complications. We determined the short-term, intermediate, and long-term mortality of GBS compared to the general population. METHODS: Individual-level data from nationwide registries were linked in this matched cohort study of all first-time hospital-diagnosed GBS patients in Denmark between 1987 and 2016 and 10 individuals from the general population, matched on age, sex, and index date. We used Cox regression analysis to calculate matched mortality hazard ratios (HRs) following GBS, assessing short-term (0-6 months), intermediate (>6 months-4 years), and long-term (>4 years) mortality. RESULTS: We identified 2414 patients with GBS and 23,909 matched individuals from the general population. Short-term mortality was 4.8% (95% confidence interval [CI] = 4.0-5.8) and 0.8% (95% CI = 0.7-0.9) for GBS patients and general population members, respectively, resulting in an HR of 6.6 (95% CI = 4.0-5.8). Intermediate mortality was 7.6% (95% CI = 6.5-8.9), compared with 5.8% (95% CI = 5.5-6.1) for general population members, corresponding to an HR of 1.5 (95% CI = 1.3-1.8). After the first 4 years, long-term mortality showed similar results for GBS patients and general population members (HR = 1.1, 95% CI = 0.9-1.2). CONCLUSIONS: During the first 6 months after GBS hospital admission, GBS was associated with a 6.6-fold increased mortality as compared with the background population of the same age. Mortality remained increased for approximately 4 years following GBS, and then leveled off to a similar long-term mortality rate.

Association of Hospital-Diagnosed Infections and Antibiotic Use With Risk of Developing Guillain-Barré Syndrome.

OBJECTIVE: To determine whether hospital-diagnosed and community-treated infections are important Guillain-Barré syndrome (GBS) risk factors, we investigated the magnitude and duration of associated GBS risk. METHODS: We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 matched population controls per case. Hospital-diagnosed infections were determined in the 1987-2016 period and community antibiotic prescriptions in the 2004-2016 period. We used conditional logistic regression to examine the relative risk of GBS associated with having a recent infection. RESULTS: Hospital-diagnosed infections within 60 days were observed in 4.3% of 2,414 GBS cases vs 0.3% of 23,909 controls, with a matched odds ratio (OR) of 13.7 (95% confidence interval [CI], 10.2-18.5). The strongest association with subsequent GBS was observed for lower respiratory tract infection, gastrointestinal tract infection, and septicemia. Community antibiotic prescriptions within 60 days were observed in 22.4% of 1,086 GBS cases and 7.8% of 10,747 controls, with a matched OR of 3.5 (95% CI, 3.0-4.1). The risk of GBS declined considerably with time since infection, with high ORs of 21.3 (95% CI, 14.5-31.2) and 4.7 (95% CI, 3.9-5.7) observed within the first month after a hospital-diagnosed infection and a community antibiotic prescription, respectively. However, GBS risk remained increased 2.4-fold (95% CI, 1.1-5.5) and 1.5-fold (95% CI, 1.2-2.0) even in the fifth month after infection. CONCLUSION: There is a strong, temporal association between community antibiotic use and especially infections necessitating hospitalization and risk of subsequent GBS.

Quantitative electromyography: Normative data in paraspinal muscles.

BACKGROUND: Quantitative electromyography of paraspinal muscle is a valuable diagnostic tool, but normative data are lacking. METHODS: Needle electromyography (EMG) was obtained in 65 healthy subjects (49% men, 51% women) aged 21 to 82 years at C7, Th10, and L5 segments bilaterally. The incidence of spontaneous activity; motor unit potential (MUP) amplitudes, durations, and the incidence of polyphasic potentials; and the recruitment pattern at maximal voluntary contraction (MVC) were evaluated. RESULTS: The incidence of fibrillation potentials was similar to limb muscles. The mean MUP duration and amplitude, and the amplitude at MVC increased caudally, while the incidence of polyphasic potentials was similar at all levels. EMG parameters did not correlate with sex or age. CONCLUSIONS: In contrast to limb muscles, EMG parameters did not change with age, while polyphasic potentials were more frequent in paraspinal muscle than in limb muscles. The EMG gradient suggests larger motor units at more caudal segments.

Pediatric Guillain-Barré Syndrome in a 30-Year Nationwide Cohort.

BACKGROUND: Guillain-Barré syndrome is the most common cause of acute flaccid paresis in childhood. Few validated large-scale population-based data are available concerning pediatric Guillain-Barré syndrome, including incidence, risk factors, and initial clinical characteristics. METHODS: In the Danish National Patient Registry, we identified all children aged below 16 years (N = 212) diagnosed with Guillain-Barré syndrome and admitted to any Danish department of pediatrics between 1987 and 2016. A total of 145 (68%) medical files could be retrieved and reviewed, enabling classification of patients with true Guillain-Barré syndrome. The nationwide Guillain-Barré syndrome incidence rate was calculated and stratified by age, gender, time periods, and season. Risk factors and initial Guillain-Barré syndrome characteristics were assessed by medical record review. RESULTS: The positive predictive value of Guillain-Barré syndrome diagnosis codes was 86%. The crude Guillain-Barré syndrome incidence rate was 0.69 per 100,000 person years and peaked at two years of age. The incidence rate was higher among men (0.80) than women (0.58) and was relatively stable over the 30-year period. No seasonal difference of the incidence rate was found. Of the 125 Guillain-Barré syndrome cases, 63% were preceded by infection, whereas none were preceded by surgery or malignant disease. Medically treated pain was documented in 70%, mainly confined to the lower extremities. CONCLUSIONS: Pediatric Guillain-Barré syndrome diagnoses in the Danish National Patient Registry have high validity, the incidence peaks at age two years, and is preceded by infection in two-thirds of children. Lower extremity pain is a common clinical presentation in the acute setting.

Guillain-Barré syndrome in Denmark: validation of diagnostic codes and a population-based nationwide study of the incidence in a 30-year period.

Purpose: To validate the diagnostic codes for Guillain-Barré syndrome (GBS) in the Danish National Patient Registry (DNPR). Secondly, to examine 30-year trends in the incidence of GBS in Denmark. Patients and methods: We used the DNPR to identify all patients aged 16 and above diagnosed with a primary GBS diagnosis at any Danish department of neurology between 1987 and 2016. Medical files were reviewed according to the clinical criteria of the National Institute of Neurological Disorders and Stroke Committee and classified according to the Brighton criteria. The incidence rate (IR) was calculated based on data from 1987 to 2016 and stratified by season, gender, and age. Results: Over 30 years, we identified 2,319 patients aged 16 and above in the DNPR. From a validation cohort of 573 patients, we were able to retrieve 425 (74.2%) medical files; 356 GBS diagnoses were confirmed. The overall positive predictive value was 83.8% (95% confidence interval (CI): 80.0-87.0). In 99% of the confirmed patients, the Brighton criteria level 1-3 for GBS were met. The IR was fairly stable over 30 years at 1.77 per 100,000 person years (95% CI: 1.70-1.84). The incidence was higher in the winter season (IR ratio compared with summer: 1.18 (95% CI: 1.09-1.29)), and was strongly associated with male gender (IR ratio vs females: 1.44 (95% CI: 1.33-1.57)). IRs rose with age at diagnosis, particularly after the age of 50 in both men and women and a minor peak was observed for total IR in young adults. Conclusion: Primary diagnostic codes for GBS at Danish departments of neurology have high validity. The DNPR is a well-suited data source for epidemiological research on GBS. The Danish nationwide 30-year GBS IR is stable over time and similar to GBS IRs reported in other European and North American populations.