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To describe the diagnostic and prognostic performance, and longitudinal trajectories, of potential biomarkers of neuroaxonal degeneration and neuroinflammation in amyotrophic lateral sclerosis (ALS). This case-control study included 192 incident ALS patients, 42 ALS mimics, 114 neurological controls, and 117 healthy controls from Stockholm, Sweden. Forty-four ALS patients provided repeated measurements. We assessed biomarkers of (1)neuroaxonal degeneration: neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF) and NfL in serum, and (2)neuroinflammation: chitotriosidase-1 (CHIT1) and monocyte chemoattractant protein 1 (MCP-1) in CSF. To evaluate diagnostic performance, we calculated the area under the curve (AUC). To estimate prognostic performance, we applied quantile regression and Cox regression. We used linear regression models with robust standard errors to assess temporal changes over time. Neurofilaments performed better at differentiating ALS patients from mimics (AUC: pNfH 0.92, CSF NfL 0.86, serum NfL 0.91) than neuroinflammatory biomarkers (AUC: CHIT1 0.71, MCP-1 0.56). Combining biomarkers did not improve diagnostic performance. Similarly, neurofilaments performed better than neuroinflammatory biomarkers at predicting functional decline and survival. The stratified analysis revealed differences according to the site of onset: in bulbar patients, neurofilaments and CHIT1 performed worse at predicting survival and correlations were lower between biomarkers. Finally, in bulbar patients, neurofilaments and CHIT1 increased longitudinally but were stable in spinal patients. Biomarkers of neuroaxonal degeneration displayed better diagnostic and prognostic value compared with neuroinflammatory biomarkers. However, in contrast to spinal patients, in bulbar patients neurofilaments and CHIT1 performed worse at predicting survival and seemed to increase over time. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aims to provide a comprehensive account of death in Swedish patients with ALS, including clinical status preceding death, the death setting, as well as symptoms. The study presents detailed information on a cohort of patients with ALS from Stockholm, Sweden, deceased in 2018–2020. In addition, selected information is presented on a larger complementary cohort of ALS patients from all regions of Sweden deceased in 2011–2020. Data were obtained from patient medical records, the Swedish Motor Neuron Disease Quality Registry, and the Swedish Quality Registry of Palliative Care. Ninety-three patients were included in the main cohort and 2224 patients in the complementary cohort. In the main cohort, there was a slow decline in weight and motor function during the 12 months preceding death. Most (93.4%) anticipated/prolonged deaths occurred in a palliative care unit, at home, or in an assisted living facility while 44.8% of precipitous deaths occurred in a hospital ward. Next of kin or health care staff were present at death for most patients (78.7%). In the final week of life, 41.1% experienced at least one symptom (either pain, anxiety, confusion, or dyspnea) that was only partially relieved or not at all. The majority of patients died in their own homes or at a palliative unit in the presence of next of kin and most symptoms were adequately managed. This paper might be used in educating patients, next of kin as well as health professionals, decreasing uncertainty surrounding the end of life. [ABSTRACT FROM AUTHOR]

Objective: To provide a detailed and differentiated description of the path to receiving the correct amyotrophic lateral sclerosis (ALS) diagnosis, including delay times, referrals, alternate diagnoses, and clinical progression. Methods: Medical records until the date of ALS diagnosis were reviewed and linked to the Swedish Motor Neuron Disease Quality Registry. Results: The study included 353 Stockholm ALS patients diagnosed in 2016–2021. Patients were divided into four groups: 117 (33.1%) with lower extremity (LE), 85 (24.1%) with upper extremity (UE), 136 (38.5%) with bulbar, and 15 (4.2%) with respiratory onset. The time from onset to diagnosis was 16.0 (9.4–27.5) months in LE, 12.9 (8.8–17.8) months in UE, 11.7 (7.4–16.0) months in bulbar, and 8.3 (4.7–15.6) months in respiratory onset. Patients with UE or LE onset were often referred to orthopedics or a spinal/hand surgery clinic (29.3% for LE and 41.8% for UE), while bulbar patients were more frequently referred to ENT (66.3%). For those with LE or UE onset, the most common alternate diagnosis was spinal/foraminal stenosis whereas myasthenia gravis and stroke were more common for bulbar onset patients. For the respiratory group, cardiopulmonary diagnoses predominated. The proportion of all patients in King's stage 3 or 4 increased from 11.3% to 46.1% from the initial health care visit to diagnosis. Conclusions: There was great variation in the path to ALS diagnosis according to the onset clinical phenotype. In all groups, the diagnostic delay and clinical progression was substantial. We identified subgroups where the delay was the longest and might be reduced. [ABSTRACT FROM AUTHOR]

Objective: To test two hypotheses: (1) partners of ALS patients have higher mortality due to outcomes related to psychological distress, and (2) parents and siblings of ALS patients have higher mortality due to diseases that co-occur with ALS. Methods: We performed a nationwide, register-based cohort study in Sweden. We included ALS-free partners, biological parents and full siblings (N = 11,704) of ALS patients, as well as ALS-free partners, biological parents and full siblings (N = 14,460,150) of ALS-free individuals, and followed them during 1961–2013. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall and cause-specific mortality were derived from Cox regression. Results: Partners of ALS patients, compared to partners of ALS-free individuals, displayed higher mortality due to external causes (HR 2.14; 95% CI 1.35–3.41), including suicide (HR 2.44; 95% CI 1.09–5.44) and accidents (HR 2.09; 95% CI 1.12–3.90), after diagnosis of the ALS patients. Parents of ALS patients had a slightly higher overall mortality (HR 1.03; 95% CI 1.00–1.07), compared with parents of ALS-free individuals. This was driven by mortality due to dementias and cardiovascular, respiratory, and skin diseases. Parents of ALS patients had, however, lower mortality than parents of ALS-free individuals due to neoplasms. Siblings of ALS patients had higher mortality due to dementias, and digestive and skin diseases. Conclusions: Increased mortality due to suicide and accidents among partners of ALS patients is likely attributable to severe psychological distress following the ALS diagnosis. Increased mortality due to dementias among parents and full siblings of ALS patients suggests shared mechanisms between neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objective: To test whether high-sensitivity cardiac troponin T (hs-cTnT) could act as a diagnostic or prognostic biomarker in ALS, comparing hs-cTnT to neurofilament light (NfL). Methods: We performed a case-control study, including 150 ALS patients, 28 ALS mimics, and 108 healthy controls, and a follow-up study of the ALS patients, during 2014–2020 in Stockholm, Sweden. We compared concentrations of hs-cTnT in plasma and NfL in the cerebrospinal fluid between cases and controls. To evaluate the diagnostic performance, we calculated the area under the curve (AUC). Hazard ratios (HRs) were estimated from Cox models to assess associations between hs-cTnT and NfL at ALS diagnosis and risk of death. The longitudinal analysis measured changes of hs-cTnT and NfL since ALS diagnosis. Results: We noted higher levels of hs-cTnT in ALS patients (median: 16.5 ng/L) than in ALS mimics (11 ng/L) and healthy controls (6 ng/L). Both hs-cTnT and NfL could distinguish ALS patients from ALS mimics, with higher AUC noted for NfL (AUC 0.88; 95%CI 0.79–0.97). Disease progression correlated weakly with hs-cTnT (Pearson's r = 0.18, p = 0.04) and moderately with NfL (Pearson's r = 0.41, p < 0.001). Shorter survival was associated with higher levels of NfL at diagnosis (HR 1.08, 95%CI 1.04–1.11), but not hs-cTnT. hs-cTnT increased (12.61 ng/L per year, 95%CI 7.14–18.06) whereas NfL decreased longitudinally since ALS diagnosis. Conclusions: NfL is a stronger diagnostic and prognostic biomarker than hs-cTnT for ALS. However, hs-cTnT might constitute a disease progression biomarker as it increases longitudinally. The underlying causes for this increase need to be investigated. [ABSTRACT FROM AUTHOR]