In Search of Safe Spaces: An Exploratory Study of the Anticipated Help-Seeking Needs and Preferences of Protestant Christian Women in Singapore with Respect to a Hypothetical Abortion Scenario.

Research suggests that religious beliefs may contribute to abortion stigma, resulting in increased secrecy, reduced social support and help-seeking as well as poor coping and negative emotional consequences such as shame and guilt. This study sought to explore the anticipated help-seeking preferences and difficulties of Protestant Christian women in Singapore with regard to a hypothetical abortion scenario. Semi-structured interviews were conducted with 11 self-identified Christian women recruited through purposive and snowball sampling. The sample was largely Singaporean and all participants were ethnically Chinese females of a similar age range (late twenties to mid-thirties). All willing participants were recruited regardless of denomination. All participants anticipated experiences of felt, enacted and internalized stigma. These were affected by their perceptions of God (e.g., how they see abortion), their personal definitions of "life" and their perceptions of their religio-social environment (e.g., perceived social safety and fears). These concerns contributed to participants choosing both faith-based and secular formal support sources with caveats, despite a primary preference for faith-based informal support and secondary preference for faith-based formal support. All participants anticipated negative post-abortion emotional outcomes, coping difficulties and short-term decision dissatisfaction. However, participants who reported more accepting views of abortion also anticipated an increase in decision satisfaction and well-being in the longer term.

Reminder through mobile messaging application improves outpatient attendance and medication adherence among patients with depression: An open-label randomised controlled trial.

INTRODUCTION: Non-attendance and medication adherence are longstanding concerns in psychiatric outpatient settings. This study aimed to determine effectiveness of reminders using mobile messaging applications (messaging apps) in improving outpatient attendance and medication adherence among patients with depression. METHODS: This was a parallel, open-label randomised controlled trial with participants recruited from psychiatric outpatient services of a teaching hospital in Kuala Lumpur and a secondary hospital in Melaka. Adults (≥18 years) diagnosed with major depressive disorder; capable of reading and understanding English or Bahasa Malaysia; prescribed with at least one antidepressant and owns a smart phone were subsequently randomly assigned (1:1) to receive treatment reminders (intervention) or standard treatment without reminders (control), using a computergenerated randomisation programme. The intervention group received two reminder categories: Outpatient appointment reminders (a day before appointment); and medication reminders (weekly basis). Participants were followed-up over two months. We utilised Montgomery- Asberg Depression Rating Scale (MADRS) to measure the severity of depression; and Brief Adherence Rating Scale (BARS) to assess medication adherence. Primary outcomes were outpatient attendance rates and medication adherence assessed at two months. Secondary outcomes included changes in depression severity within each group at two months; comparison of changes in depression severity between both groups; preferences of participants towards treatment reminders, and reasons for non-attendance among participants. This trial was registered with the National Medical Research Registry, NMRR-19-3466-52001. RESULTS: Between February and April 2020, 183 participants were randomised to each group, of whom 179 reached study endpoint (91 [98.9%] of 92 in intervention group and 88 [96.7%] of 91 in control group). All recruited participants (n=183) were analysed using intention-to-treat approach. At two months, intervention group has significantly higher outpatient attendance rates (76.8%) than control group (56.4%) (p=0.002), and reported higher medical adherence percentage (mean difference 23.1, [95%CI 0.4, 35.8]; p<0.001). There was also significant difference in the MADRS score change between both groups (mean difference 3.4, [95%CI 0.4, 6.3]; p=0.025). Treatment reminders preferences among participants varied; forgetfulness was the most commonly reported reason (53%) for missing outpatient appointments. CONCLUSION: Reminders through mobile messaging applications significantly improved outpatient attendance and medication adherence among patients with depression. Our findings support the use of messaging apps for treatment reminders in psychiatric outpatient settings. However, concerns regarding confidentiality require careful measures to be taken.

Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.

BACKGROUND: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis. AIMS: To compare effects of hemin and placebo infusions on HO1 activity and protein, GE, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. METHODS: In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, GE with 13 C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. KEY RESULTS: Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (p = 0.0002) and 7 (p = 0.008) and HO1 activity on day 3 (p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. CONCLUSIONS & INFERENCES: Hemin failed to sustain increased HO1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve GE.

Direct in vivo evidence of activated macrophages in human osteoarthritis.

OBJECTIVE: Through binding to folate receptor-ß (FR-ß), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in vivo. The goal of this study was to investigate macrophage-related inflammation in osteoarthritis (OA). METHODS: Twenty-five individuals (50 knees) with symptomatic OA of at least one knee underwent SPECT-CT imaging of both knees and planar imaging of the whole body after injection of Etarfolatide. Scans and knee radiographs were scored blinded to clinical information including knee and other joint site pain severity. Measures of association controlled for age, gender, body mass index (BMI) and employed repeated measures to adjust for correlation between knees. DESIGN: Activated macrophages were present in the majority (76%) of knees. The quantity of knee-related macrophages was significantly associated with knee pain severity (R = 0.60, P < 0.0001) and radiographic knee OA severity including joint space narrowing (R = 0.68, P = 0.007), and osteophyte (R = 0.66, P = 0.001). Macrophages were also localized to joints commonly affected by OA including hand finger joints (12%), thumb bases (28%), shoulders (26%), great toes (18%) and ankles (12%). The presence of joint pain at fingers, wrists, ankles and great toes was significantly positively associated with presence of activated macrophages at these sites (P < 0.0001-0.04). CONCLUSIONS: This study provides the first direct in vivo evidence for macrophage involvement in OA in a substantial proportion of human knees. The association of quantity of activated macrophages with radiographic knee OA severity and joint symptoms suggests that drugs targeting macrophages and macrophage-associated inflammatory pathways may have the potential to be both symptom and structure modifying.

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders.

BACKGROUND: Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. METHODS: In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. KEY RESULTS: The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity (p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. CONCLUSIONS & INFERENCES: Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer-acting ACIs for treating antroduodenal dysmotility warrant further study.

Putative neuropathological interactions in MSA: focus in the rostral ventrolateral medulla.

We used double immunocytochemistry for α-synuclein and markers of sympathoexcitatory neurons, oligodendrocytes, iron metabolism, and autophagy to study putative neuropathological interactions in multiple system atrophy. We focused in the rostral ventrolateral medulla as a prototype vulnerable region. We found that loss of C1 neurons and oligodendrocytes related to glial cytoplasmic inclusion accumulation, downregulation of iron transport, and upregulation of autophagy and ferritin expression in these area.

Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis.

The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27(+) but not HLA-B27(-) AS patients or controls. Forty-nine AS cases and 22 healthy controls were grouped according to HLA-B27 status and AS-associated ERAP1 rs30187 genotypes: HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective), HLA-B27(-)ERAP1(risk) and HLA-B27(-)ERAP1(protective). Expression levels of ER-stress markers GRP78 (8 kDa glucose-regulated protein), CHOP (C/EBP-homologous protein) and inflammatory cytokines were determined in peripheral blood mononuclear cell and ileal biopsies. We found no differences in ER-stress gene expression between HLA-B27(+) and HLA-B27(-) cases or healthy controls, or between cases or controls stratified by carriage of ERAP1 risk or protective alleles in the presence or absence of HLA-B27. No differences were observed between expression of IL17A or TNF (tumour necrosis factor) in HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective) and HLA-B27(-)ERAP1(protective) cases. These data demonstrate that aberrant ERAP1 activity and HLA-B27 carriage does not alter ER-stress levels in AS, suggesting that ERAP1 and HLA-B27 may influence disease susceptibility through other mechanisms.

Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome.

BACKGROUND: Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome (POTS). However, few studies have evaluated gastrointestinal transit in POTS. Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS. METHODS: We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated. KEY RESULTS: Among 163 patients (140 women, mean [± SEM] age 30 [± 1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty-eight patients (36%) had clinical features of physical deconditioning, which was associated (p = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common (p < 0.003), and anxiety or depression, which was less common (p = 0.02). The tilt-associated increase in heart rate and reduction in systolic BP at 1 min was associated (p < 0.05), being greater in patients with delayed gastric emptying. CONCLUSIONS & INFERENCES: Two-thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.

Parabrachial nucleus involvement in multiple system atrophy.

UNLABELLED: Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance. OBJECTIVES: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA. METHODS: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. RESULTS: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p<0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p<0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p<0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p<0.0001). CONCLUSIONS: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.

Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. METHODS: Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. RESULTS: Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. CONCLUSION: Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.

Empowering clients through e-Health in healthcare services: case Brunei.

The adoption of Web 2.0 in many business sectors is increasing because it offers the ability for customers to have a greater control in generating contents to their personalized web. Customers are empowered in the sense of controlling the process of interaction(s) between a firm with its customers, and among customers themselves. However, providing empowerment in any state of interaction levels to customers (patients) in a healthcare organization is challenging. Many healthcare organizations have adopted empowerment in their e-health scenario; therefore, it needs a mechanism to measure at which level they have implemented empowerment within their organizations. This article proposes three layers of customers' empowerment in e-health systems based on a reference model called Personal Health Cycle (PHC). The layers of empowerment are personal, social, and medical layers respectively. The modular approach is used to simplify healthcare organizations identifying which modules to be adopted in implementing a strategy for customers' empowerment. The model is derived based on recent studies of empowerment in healthcare organizations. A survey also has been conducted in Brunei Darussalam (Brunei) to verify and improve our initial model and to understand the responses of people regarding empowerment in the e-health services. Questions for the survey are derived from the features of the PHC. The respondents reacted positively to the features of empowerment proposed. We use PHC to define and distinguish electronic health record (EHR) from electronic medical record (EMR).

Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes.

There are substantial advances in understanding disordered gastrointestinal autonomic dysfunction in diabetes. It occurs frequently. The underlying pathogenesis is complex involving defects in multiple interacting cell types of the myenteric plexus as well. These defects may be irreversible or reversible. Gastrointestinal symptoms represent a major and generally underestimated source of morbidity for escalating health care costs in diabetes. Acute changes in glycaemia are both determinants and consequences of altered gastrointestinal motility. 35-90% of diabetic men have moderate-to-severe erectile dysfunction (ED). ED shares common risk factors with CVD. Diagnosis is based on medical/sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to patient's complaints and risk factors. Treatment is based on PDE5-inhibitors (PDE5-I). Other explorations may be useful in patients who do not respond to PDE5-I. Patients at high cardiovascular risk should be stabilized by their cardiologists before sexual activity is considered or ED treatment is recommended. Estimates on bladder dysfunction prevalence are 43-87% of type 1 and 25% of type 2 diabetic patients, respectively. Common symptoms include dysuria, frequency, urgency, nocturia and incomplete bladder emptying. Diagnosis should use validated questionnaire for lower urinary tract symptoms. The type of bladder dysfunction is readily characterized with complete urodynamic testing. Sudomotor dysfunction is a cause of dry skin and is associated with foot ulcerations. Sudomotor function can be assessed by thermoregulatory sweat testing, quantitative sudomotor axon reflex test, sympathetic skin response, quantitative direct/indirect axon reflex testing and the indicator plaster.

Alternating hemiplegia of childhood: successful treatment with topiramate and flunarizine, a case report.

Alternating hemiplegia of childhood (AHC) is a rare neurological disorder which usually presents before 18 months of age and is characterised by recurrent alternating episodes of hemiparesis. A single effective treatment for this condition is yet to be established; flunarizine is currently the most widely used but with varying degrees of success. An 18-month-old child presented with AHC and treatment with a combination of topiramate and flunarizine made a significant difference in controlling the frequency and severity of the attacks. This possibly allowed a better developmental outcome than in most children with this condition. Topiramate combined with flunarizine for treating AHC has much potential for further research.

Substrate effects on surface morphologies and magnetic properties of nanostructured FePt thin films.

The substrate effects on surface morphologies, crystal structures, and magnetic properties of the sputter-deposited FePt thin films on Corning 1737, normal glass, and Si wafer substrates, respectively, were investigated. High in-plane coercivities of 10 kOe were obtained for the air-annealed films on Corning 1737 and Si wafer, where both films similarly have granular-like morphologies. Besides, increasing grain size and surface roughness of all the FePt films with the post-anneal temperature were observed. Moreover, partially separated grains were seen in the film on Si wafer, where the formation of Fe silicides during post-anneal is suspected, in which has enhanced the magnetic ordering.

TDP-43 pathology occurs infrequently in multiple system atrophy.

AIMS AND METHODS: The α-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. RESULTS: TDP-43 pathology was generally rare, and there were no FUS lesions. The TDP-43 lesions were located predominantly in medio-temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. CONCLUSIONS: The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP-43 or FUS pathology, but rather from widespread white matter α-synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary α-synuclein-mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP-43.

Headache diagnosis, disability and co-morbidities in a multi-ethnic, heterogeneous paediatric Asian population.

This was a questionnaire survey on headache and migraine prevalence in 2873 Singaporean schoolchildren aged 6 to 16 years. ICHD-II headache classification, disability assessment with PedMIDAS and screening of psychosocial co-morbidities with the Paediatric Symptom Checklist were conducted. Lifetime headache prevalence was high at 80.6%, migraine prevalence was 8.6% and tension headache prevalence was 10.0%. Headache and migraine prevalence was high compared with that found in other Asian studies. Factors significantly associated with headache included adolescent age (OR = 1.5 [95% CI 1.3-1.9], p < .001), female gender at primary (OR = 1.4 [95% CI 1.1-1.8], p = .003) and secondary (OR = 1.8 [95% CI 1.3-2.5], p < .001) levels and Malay ethnicity at the primary level (OR = 2.8 [95% CI 1.6-4.9], p < .001). The average PedMIDAS score for headache disability was 3.2 +/- 8.4, and migraine disability (PedMIDAS 8.1 +/- 11.2-15.2 +/- 29.6) was lower than in some studies. Self-medication (20.5%) and use of alternative therapy (59.0%) were high among chronic daily headache sufferers. Routine sleep and stress screening is recommended for children with headaches. Recognition of the influence of genetics, lifestyle and cultural factors on headache management should be emphasized.

Erythrocyte adducin: a structural regulator of the red blood cell membrane.

Adducin is an alpha, beta heterotetramer that performs multiple important functions in the human erythrocyte membrane. First, adducin forms a bridge that connects the spectrin-actin junctional complex to band 3, the major membrane-spanning protein in the bilayer. Rupture of this bridge leads to membrane instability and spontaneous fragmentation. Second, adducin caps the fast growing (barbed) end of actin filaments, preventing the tetradecameric protofilaments from elongating into macroscopic F-actin microfilaments. Third, adducin stabilizes the association between actin and spectrin, assuring that the junctional complex remains intact during the mechanical distortions experienced by the circulating cell. And finally, adducin responds to stimuli that may be important in regulating the global properties of the cell, possibly including cation transport, cell morphology and membrane deformability. The text below summarizes the structural properties of adducin, its multiple functions in erythrocytes, and the consequences of engineered deletions of each of adducin subunits in transgenic mice.

Sudomotor dysfunction in autoimmune autonomic ganglionopathy.

BACKGROUND: Autoimmune autonomic ganglionopathy is characterized by impairment of multiple autonomic domains of which sudomotor function is among the most common. Many patients with this disorder have difficulties with thermoregulation and anhidrosis. Our objective was to characterize the distribution and severity of sudomotor dysfunction in this disorder. METHODS: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic alpha3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test. RESULTS: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic alpha3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron. CONCLUSIONS: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy.