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Brain and Nerve = Shinkei Kenkyu No... May 2024Neurological immune-related adverse events (irAEs) associated with cancer treatment with immune checkpoint inhibitors (ICI) present diverse clinical characteristics.... (Review)
Review
Neurological immune-related adverse events (irAEs) associated with cancer treatment with immune checkpoint inhibitors (ICI) present diverse clinical characteristics. Neurological irAEs affect the peripheral nervous system and muscles more than they affect the central nervous system. Among the various subsets of peripheral neuropathies, polyradiculoneuropathy, which includes Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy, stands out as the most severe form, leading to significant muscle weakness. ICIs can induce dysautonomia, including autoimmune autonomic ganglionopathy. Autonomic neuropathy represents a neurological irAE. Neurological irAEs of neuromuscular junctions include myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). Diagnosing MG or myositis independently can be challenging when they occur as irAEs. Myocarditis is sometimes observed as an irAE in patients with MG and can cause both severe heart failure and lethal arrhythmias, resulting in fatal outcomes. Anti-Kv1.4 antibodies are biomarkers of the severe form of MG and myocarditis. The administration of ICI in patients with small cell lung cancer increases the risk of LEMS. The distinction between LEMS is an irAE or a manifestation of paraneoplastic neurological syndrome is unclear as both conditions share common immunological mechanisms.
Topics: Humans; Peripheral Nervous System Diseases; Muscular Diseases; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 38741503
DOI: 10.11477/mf.1416202650 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Autoimmune autonomic ganglionopathy (AAG) and acute autonomic sensory neuropathy (AASN) are immune-mediated neuropathies that affect the autonomic and/or dorsal root... (Review)
Review
Autoimmune autonomic ganglionopathy (AAG) and acute autonomic sensory neuropathy (AASN) are immune-mediated neuropathies that affect the autonomic and/or dorsal root ganglia. Autoantibodies against the nicotinic ganglionic acetylcholine receptor (gAChR) detected in the sera of patients with AAG play a key role in the pathogenesis of this condition. Notably, gAChR antibodies are not detected in the sera of patients with AASN. Currently, AAG and AASN are not considered to be on the same spectrum with regard to disease concept based on clinical symptoms and laboratory findings. However, extra-autonomic brain symptoms (including psychiatric symptoms and personality changes) and endocrine disorders occur in both diseases, which suggests shared pathophysiology between the two conditions.
Topics: Humans; Ganglia, Autonomic; Autoantibodies; Autonomic Nervous System Diseases; Autoimmune Diseases of the Nervous System; Receptors, Nicotinic; Acute Disease; Autoimmune Diseases
PubMed: 38741497
DOI: 10.11477/mf.1416202644 -
Diabetic Medicine : a Journal of the... May 2024Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through...
AIMS
Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM.
METHODS
Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared.
RESULTS
Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001).
CONCLUSIONS
IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.
PubMed: 38741266
DOI: 10.1111/dme.15340 -
Clinical Autonomic Research : Official... Apr 2024
Topics: Humans; Immunoglobulins, Intravenous; Autonomic Nervous System Diseases; Male; Female; Middle Aged; Immunologic Factors
PubMed: 38733551
DOI: 10.1007/s10286-024-01034-3 -
Cureus Apr 2024Introduction This study aimed to evaluate hemodynamic changes using heart rate variability (HRV) measurements in diabetic and nondiabetic patients who will undergo...
Introduction This study aimed to evaluate hemodynamic changes using heart rate variability (HRV) measurements in diabetic and nondiabetic patients who will undergo laparoscopic cholecystectomy and to provide our preoperative measurements to guide us for better perioperative anesthesia management. Materials and methods The study included 143 patients aged 40 years and older who would undergo elective laparoscopic surgery, did not have any comorbidities other than diabetes mellitus (DM) type II, and were in the American Society of Anesthesiologists (ASA) class I-III risk group. Patients were divided into two groups: the control group (n = 77) and the DM group (n = 66). The preoperative glycated hemoglobin (HbA1C) level was measured. Peripheral oxygen saturation (SpO2) and hemodynamic parameters such as systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and HRV parameters were measured preoperatively, perioperatively, and postoperatively. Intra-abdominal pressure (IAP) was administered at 10-12 mmHg. Results Even though SAP, DAP, MAP, and HR decreased with induction, they increased with insufflation, and an overall decrease was seen at the postoperative 24th hour for all parameters. When the groups were evaluated, no difference was observed except that the DAP was significantly lower in the DM group (p = 0.029) at insufflation and the HR was higher in the DM group at induction, and the difference was significant (p = 0.001). Preoperative HRV parameters were significantly lower in the DM group. According to the HRV parameters, although a decrease was observed after induction and insufflation, conversely, an increase was observed postoperatively. When the postoperative and preoperative values were compared, the standard deviation of the NN (R-R) intervals (SDNN), SDNN index, high frequency (HF), low frequency (LF), and LF/HF parameters were found to be significantly lower in the DM group than in the control group. Conclusion Diabetic patients are more sensitive to increased intra-abdominal pressure (IAP) in laparoscopic surgery, and the effects on cardiac autonomic functions can be determined by HRV measurements without clinically reflecting on hemodynamic data. Additionally, in diabetic patients with preoperative LF and/or HF values less than 100, we believe that careful follow-up in terms of autonomic neuropathy complications and anesthesia management should be done more meticulously in these patients.
PubMed: 38725775
DOI: 10.7759/cureus.57890 -
BMC Cardiovascular Disorders May 2024Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation....
BACKGROUND
Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.
MATERIALS AND METHODS
A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0.
RESULTS
Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively).
CONCLUSION
The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.
Topics: Humans; Male; Polymorphism, Single Nucleotide; Middle Aged; Female; Case-Control Studies; Kazakhstan; Genetic Predisposition to Disease; Risk Factors; PPAR gamma; Aged; Phenotype; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Risk Assessment; Genetic Association Studies; X-ray Repair Cross Complementing Protein 1; Heart Diseases; Autonomic Nervous System Diseases; Adult; Diabetic Neuropathies; Autonomic Nervous System; Genetic Markers; alpha-Synuclein
PubMed: 38724937
DOI: 10.1186/s12872-024-03912-0 -
BMC Gastroenterology May 2024A growing body of research indicates that poor functional status before chemotherapy may be correlated with the severity of chemotherapy-induced peripheral neuropathy...
BACKGROUND
A growing body of research indicates that poor functional status before chemotherapy may be correlated with the severity of chemotherapy-induced peripheral neuropathy (CIPN) after the neurotoxic treatment. However, little is known about the associations between pre-chemotherapy physical function and CIPN in patients with pancreatic cancer.
PURPOSE
To identify the predictors of CIPN in relation to pre-chemotherapy physical function in patients with pancreatic cancer.
METHODS
This secondary analysis included data from patients with pancreatic cancer who participated in a longitudinal research study at National Cheng Kung University Hospital, Tainan, Taiwan. Four physical function tests (i.e., grip strength, Timed Up and Go (TUG), 2-minute step test (2MST), and Romberg test) and two questionnaires (The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and Chemotherapy-Induced Peripheral Neuropathy Module [CIPN20]) were assessed at baseline (i.e., before first chemotherapy session) and 2-, 3-, 4-, and 6-month follow-up. Multiple linear regression with adjustment for confounding factors was used to assess the associations between the four functional tests at baseline and the CIPN20 total score and individual subscale scores (sensory, motor, and autonomic) at 6-month follow-up.
RESULTS
Data from a total of 209 pancreatic cancer patients (mean age: 64.4 years, 54.5% male) were analyzed. The findings showed that the severity of CIPN at 6-month follow-up was significantly associated with the baseline TUG completion time (β = 0.684, p = 0.003). The TUG completion time was also positively correlated with the 6-month CIPN sensory and autonomic subscales. In addition, a baseline positive Romberg test (β = 0.525, p = 0.009) was a significant predictor of the severity of motor neuropathy at 6-month follow-up.
CONCLUSION
The TUG completion time and positive Romberg test before chemotherapy may be predictive factors of the CIPN severity 6 months after the commencement of chemotherapy. Accordingly, the incorporation of TUG and Romberg tests into the clinical assessment protocol emerges as imperative for individuals diagnosed with pancreatic carcinoma undergoing chemotherapy regimens.
Topics: Humans; Peripheral Nervous System Diseases; Pancreatic Neoplasms; Male; Female; Middle Aged; Aged; Longitudinal Studies; Antineoplastic Agents; Surveys and Questionnaires; Quality of Life; Hand Strength; Taiwan; Severity of Illness Index
PubMed: 38711006
DOI: 10.1186/s12876-024-03227-6 -
Journal of the Peripheral Nervous... Jun 2024ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded...
BACKGROUND
ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR.
OBJECTIVES
To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients.
METHODS
Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0-II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment.
RESULTS
At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) -9.3 versus -4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS-6) questionnaire, (2) -2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus -0.6 (p = .01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis-treated patients, whereas it rose across all the biopsies in the control group. At the 4-year follow-up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of -3.0 vs. -9.3 fibers/mm) and the distal leg (mean difference [MD] -4.9 vs. -8.6 fibers/mm). ADI in tafamidis-treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm) and the distal leg (23 vs. 40 amyloid/mm) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years.
CONCLUSIONS
Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes.
Topics: Humans; Male; Female; Middle Aged; Amyloid Neuropathies, Familial; Benzoxazoles; Aged; Skin; Biomarkers; Prealbumin; Adult; Treatment Outcome; Nerve Fibers
PubMed: 38706223
DOI: 10.1111/jns.12624 -
Journal of Pediatric Urology Apr 2024It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with...
BACKGROUND
It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes.
OBJECTIVE
To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests.
STUDY DESIGN
Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed.
RESULTS
The main results are shown in the Summary figure.
DISCUSSION
In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo et al. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system.
CONCLUSION
In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction.
PubMed: 38705761
DOI: 10.1016/j.jpurol.2024.04.007 -
Medicine May 2024Guillain-Barré syndrome (GBS) epitomizes an acute peripheral neuropathy hallmarked by an autoimmune retort directed at the myelin sheath enwrapping peripheral nerves.... (Review)
Review
RATIONALE
Guillain-Barré syndrome (GBS) epitomizes an acute peripheral neuropathy hallmarked by an autoimmune retort directed at the myelin sheath enwrapping peripheral nerves. While it is widely acknowledged that a majority of GBS patients boast a history of antecedent infections, the documentation of postoperative GBS occurrences is progressively mounting. Drawing upon an exhaustive compendium of recent case reports, the disease's inception spans a gamut from within 1 hour to 1.2 years.
PATIENT CONCERNS
At this juncture, we proffer a singular case: an instance involving a 51-year-old gentleman who underwent lumbar spine surgery, only to encounter immediate debilitation of limb and respiratory musculature.
DIAGNOSES
Post elimination of variables linked to anesthetic agents, encephalon, and spinal cord pathologies, a potent suspicion of superacute GBS onset emerged.
INTERVENTIONS
Subsequent to immunoglobulin therapy, plasmapheresis, and adjunctive support, the patient's ultimate demise became manifest.
OUTCOMES
No progress was found to date.
LESSONS
Given GBS's potential to instigate paralysis, respiratory collapse, and autonomic nervous system aberrations, alongside other pernicious sequelae, coupled with the exceptional rarity of the temporal onset in this particular instance, it undeniably proffers an imposing conundrum for anesthetists in the realm of differential diagnosis and therapeutic conduct. During the postoperative convalescence phase under anesthesia, should the patient evince deviant limb musculature vigor and compromised respiratory sinews, the prospect of GBS must not be consigned to oblivion. Precision in diagnosis conjoined with apt therapeutic measures could well be the harbinger of a divergent denouement for the afflicted patient.
Topics: Humans; Guillain-Barre Syndrome; Middle Aged; Male; Postoperative Complications; Elective Surgical Procedures; Lumbar Vertebrae
PubMed: 38701319
DOI: 10.1097/MD.0000000000037925