Vasomotor Disturbances Research Articles

10. Complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments. The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized. Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen. CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.

Dietary Supplementation of Myo-Inositol, Cocoa Polyphenols, and Soy Isoflavones Improves Vasomotor Symptoms and Metabolic Profile in Menopausal Women with Metabolic Syndrome: A Retrospective Clinical Study.

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2-3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4-9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.

Exploring the Spectrum of RHOBTB2 Variants Associated with Developmental Encephalopathy 64: A Case Series and Literature Review.

Rho-related BTB domain-containing protein 2 (RHOBTB2) is a protein that interacts with cullin-3, a crucial E3 ubiquitin ligase for mitotic cell division. RHOBTB2 has been linked to early infantile epileptic encephalopathy, autosomal dominant type 64 (OMIM618004), in 34 reported patients. We present a case series of seven patients with RHOBTB2-related disorders (RHOBTB2-RD), including a description of a novel heterozygous variant. We also reviewed previously published cases of RHOBTB2-RD. The seven patients had ages ranging from 2 years and 8 months to 26 years, and all had experienced seizures before the age of one (onset, 4-12 months, median, 4 months), including various types of seizures. All patients in this cohort also had a movement disorder (onset, 0.3-14 years, median, 1.5 years). Six of seven had a baseline movement disorder, and one of seven only had paroxysmal dystonia. Stereotypies were noted in four of six, choreodystonia in three of six, and ataxia in one case with multiple movement phenotypes at baseline. Paroxysmal movement disorders were observed in six of seven patients for whom carbamazepine or oxcarbazepine treatment was effective in controlling acute or paroxysmal movement disorders. Four patients had acute encephalopathic episodes at ages 4 (one patient) and 6 (three patients), which improved following treatment with methylprednisolone. Magnetic resonance imaging scans revealed transient fluid-attenuated inversion recovery abnormalities during these episodes, as well as myelination delay, thin corpus callosum, and brain atrophy. One patient had a novel RHOBTB2 variant (c.359G>A/p.Gly120Glu). RHOBTB2-RD is characterized by developmental delay or intellectual disability, early-onset seizures, baseline movement disorders, acute or paroxysmal motor phenomena, acquired microcephaly, and episodes of acute encephalopathy. Early onsets of focal dystonia, acute encephalopathic episodes, episodes of tongue protrusion, or peripheral vasomotor disturbances are important diagnostic clues. Treatment with carbamazepine or oxcarbazepine was found to be effective in controlling acute or paroxysmal movement disorders. Our study highlights the clinical features and treatment response of RHOBTB2-RD.

Women's health nurses' experiences of menopause: Considerations for nurse leaders.

Women's health nurses' experiences of menopause: Considerations for nurse leaders.

Selenium Levels based on Various Menopause Complaints Assessed by Menopause-specific Quality of Life Questionnaire before and after Selenium Intervention

BACKGROUND: Menopausal symptoms can greatly affect a woman’s personal, social, and work life. Selenium functions as a cofactor for glutathione peroxidase and helps minimize oxidative damage through cellular metabolism in postmenopausal women when estradiol production decreases, antioxidant protection is lost and therefore oxidative stress is increased. AIM: The aim of the study was to evaluated effect of selenium supplementation on selenium levels based on menopausal complaints assessed by menopause-specific quality of life questionnaire (MENQOL). MATERIALS AND METHODS: This research is an analytical study with quasi-experimental pre-test and post-test one group only design. The research was conducted on all postmenopausal women in Medan who were aged &gt;51-years-old and met inclusion and exclusion criteria. The research subjects underwent blood tests to assess serum selenium levels. If data were normally distributed, dependent T test will be used, while if data were not normally distributed, Wilcoxon test will be used. The analysis results were stated to be significant with p &lt; 0.05. RESULTS: Mean selenium serum levels before selenium administration were 93.20 ± 17.253 μg/L which increased to 132.12 ± 19.866 μg/L after selenium administration. Comparison test results of selenium levels before and after administration found p = 0.000 (p &lt; 0.05), which means there was a significant difference of selenium serum levels before and after selenium administration. Besides that, there were no significant scores difference in aspects of vasomotor disorders (p = 1.000 [p &gt; 0.05]), psychosocial disorders (p = 0.090 [p &gt; 0.05]), physical disorders (p = 0.323 [p &gt; 0.05]), and sexual disorders (p = 0.959 [p &gt; 0.05]) between before and after selenium administration. CONCLUSION: Total MENQOL scores and complaints based on aspects of vasomotor, psychosocial, physical, and sexual disturbances did not show statistically significant changes after administration selenium tablets 100 mcg/day for 7 days.

From a Symptom-Based to a Mechanism-Based Pharmacotherapeutic Treatment in Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a debilitating painful condition of a distal extremity that can develop after tissue damage. CRPS is thought to be a multimechanism syndrome and ideally the most prominent mechanism(s) should be targeted by drugs in an individually tailored manner. This review gives an overview of the action and evidence of current and future pharmacotherapeutic options for CRPS. The available options are grouped in four categories by their therapeutic actions on the CRPS mechanisms, i.e. inflammation, central sensitisation, vasomotor disturbances and motor disturbances. More knowledge about the underlying mechanisms of CRPS helps to specifically target important CRPS mechanisms. In the future, objective biomarkers could potentially aid in selecting appropriate mechanism-based drugs in order to increase the effectiveness of CRPS treatment. Using this approach, current and future pharmacotherapeutic options for CRPS should be studied in multicentre trials to prove their efficacy. The ultimate goal is to shift the symptom-based selection of therapy into a mechanism-based selection of therapy in CRPS.

Mucoadhesive Buccal Film of Estradiol for Hormonal Replacement Therapy: Development and In-Vivo Performance Prediction.

The age-related loss of circulating estrogen that occurs during the menopausal transition manifests itself through a variety of symptoms including vasomotor (hot flushes and night sweats), genito-urinary syndrome (vaginal dryness and urinary symptoms), sexual dysfunction, mood, and sleep disturbance that often last longer than a decade. Furthermore, reductions in estrogen level increase the risks of chronic complications such as osteoporosis, cardiovascular disease, and cognitive decline among others, thereby affecting the quality of life of women. Although oral estrogens are the most widely used therapy for menopausal symptoms, they suffer from poor bioavailability, and there are concerns over their safety, creating a significant concern to consumers. Mucoadhesive buccal films are an innovative dosage form that offers several advantages including avoidance of the first-pass metabolism, fast onset of action, and importantly, improved patient acceptance. In the current work, we developed mucoadhesive estradiol film for hormonal replacement therapy using film-forming polymers. Two approaches, namely, co-solvency and nano-emulsion were evaluated to increase solubility and hence incorporate estradiol, a poorly water-soluble drug, into a formulation made from the hydrophilic polymer/s. The films were characterised for their mechanical and physicochemical properties. In-vitro release study showed that about 80% of the drug was released within 6 min from films prepared by the nano-emulsion approach, whereas it took about 10.5 min to get similar drug release from films prepared by the co-solvency approach. The ex-vivo permeation result indicates that about 15% of the drug permeated across the porcine buccal mucosa in the first 10 h from films prepared by the nano-emulsion approach, while permeation across porcine buccal mucosa was only observed at around 24 h from films prepared by the co-solvency method. The nano-emulsion films were evaluated for in vivo performance using a convolution technique using R software. The predicted Cmax and Tmax were found to be 740.74 ng mL−1 and 7 min, respectively, which were higher than previously reported in vivo concentration from oral tablets. The results demonstrated that mucoadhesive film of estradiol based on the nano-emulsion approach could be a promising platform for the delivery of estradiol through the buccal mucosa for the treatment of menopausal symptoms.

Long-Term Sequelae of Frostbite-A Scoping Review.

Frostbite is tissue damage caused by freezing temperatures and constitutes an important cause of morbidity in cold climate zones and high altitude. The direct effects of sub-zero temperatures lead to tissue freezing, electrolyte shifts and pH alterations, microvascular damage, and eventually to cell death. Upon rewarming, inflammatory reperfusion injury and thrombosis may lead to further tissue damage. Several studies and various case reports show that many patients suffer from long-term sequelae such as vasomotor disturbances (associated with susceptibility to refreezing), and neuropathic and nociceptive pain, as well as damage to skeletal structures. There are still many uncertainties regarding the pathophysiology of these sequelae. It has been shown that the transient receptor potential channel (TRP) family plays a role in cold allodynia. Botulinum Toxin type A (BTX-A) injections have been reported to be beneficial in vasomotor and neuropathic disturbances secondary to frostbite. Epidural sympathetic block has been used for short-term treatment of frostbite induced chronic pain. Furthermore, amitriptyline, gabapentinoids, and duloxetine may have some benefits. Frostbite arthritis clinically resembles regular osteoarthritis. In children there is a risk of epiphyseal cartilage damage leading to bone deformities. Despite some promising therapeutic concepts, the scarcity of data on frostbite long-term sequelae in the literature indicates the need of more in-depth studies of this pathology in all its aspects.

Physician attitudes and knowledge on prophylactic salpingectomy in perimenopausal patients

PurposeEighty percent of the approximately 500,000 hysterectomies performed annually in the US are for benign indications. There is lack of consensus regarding concurrent removal of fallopian tubes and/or ovaries. Ovarian cancer risk reduction is the principal benefit but the adverse consequences of ovarian removal can include vasomotor disturbance, vaginal dryness, cardiovascular disease, osteoporosis, and cognitive decline. Emerging evidence on the role of fallopian tubes in ovarian carcinogenesis and the consequences of oophorectomy have led the American College of Obstetricians-Gynecologists (ACOG) to recommend bilateral salpingectomy with ovarian conservation during benign hysterectomy for women at population risk for ovarian cancer. MethodsFive hundred members of the ACOG Collaborative Ambulatory Research Network (CARN) were randomly selected to participate in this survey study. Results165 completed the survey (35.3% response rate). Most respondents reported that a family history of breast, ovarian or colon cancer and patient age influence their decision to offer salpingectomy more than 75% of the time. Factors that a majority of respondents reported discussing during counseling included possible ovarian cancer risk reduction, surgical menopause, severity of symptoms, and the effects on bone and cardiovascular health. The respondents mean score for the knowledge-based questions was only 1.7 (±0.92) out of 4 points. ConclusionSeveral factors may affect decision making for prophylactic salpingectomy at the time of hysterectomy however paramount among these is cancer risk reduction. Most physicians found it difficult to discuss and implement a change in care for patients with preconceived notions of ovarian preservation or removal.

Modified impression technique for extreme mouth-opening limitation caused by systemic scleroderma.

Systemic scleroderma is a relatively rare, autoimmune, chronic, and debilitating disease, and its etiology is unknown. The disease is characterized by vasomotor disturbances causing skin and mucosa hardening, hand stiffness, excess production of collagen fibers, and impairment of the internal organs associated with the immune system. Extreme mouth-opening limitation is one of the symptoms in the oral cavity, and compromises dental intervention. One of the fundamental steps when performing a dental procedure is dental arch impression. In the presented clinical case, limited mouth opening hindered the impression accuracy. The objective was to present an alternative impression technique for a patient affected by scleroderma, with limited mouth opening and the need for oral rehabilitation with a removable partial prosthesis in the maxillary arch. An individualized tray was developed with design characteristics that allowed access to the oral cavity and removal, after which it was possible to perform the oral impression, reproducing the areas of interest without causing injury to the oral tissues. The orientation plan was elaborated after obtaining the cast. The teeth were assembled, tested in the mouth, and sent to the laboratory for acrylization. The prosthesis was placed once ready. The alternative impression technique enabled oral rehabilitation of the patient despite the mouth-opening limitation, and provided an accurate impression and a good prosthetic result.

517 Racial differences in modified finnegan neonatal abstinence scoring for neonatal opioid withdrawal syndrome

Neonates exposed in-utero to opioids are commonly evaluated for neonatal opioid withdrawal syndrome (NOWS) using modified Finnegan Neonatal Abstinence Scoring System (FNASS). FNASS includes 21 different components of central nervous system, metabolic, vasomotor, respiratory, and GI disturbances. Consecutive cumulative scores ≥8 are suggestive for starting pharmacologic treatment. Our objective was to identify significant differences in FNASS scoring in neonates stratified by race. Retrospective cohort study of patients with opioid use disorder (OUD) who received co-located prenatal and addiction care from 2013 to 2020 at a large academic institution. Non-Hispanic Black (NHB) patients were matched to non-Hispanic White (NHW) patients by year and gestational age at delivery. Race and ethnicity were self-reported by the mother. The primary outcome was differences in individual scoring components. 42 NHB mother-newborn dyads were compared to 42 matched NWH dyads. There were no significant differences in baseline demographics between the groups. NHB newborns were significantly less likely than NHW to be scored for observed red, blotchy skin changes consistent with skin mottling (79% vs 100%, P<0.01). All NHB and NHW newborns were scored for mild tremors when disturbed and increased muscle tone; there were no significant scoring differences in the remaining FNASS components. NHB newborns were less likely to receive a FNASS ≥8 (69% vs. 81%, RR 0.85, CI 0.66-1.09) compared to NHW infants, and to receive pharmacological treatment for NOWS (76% vs. 98%, RR 0.78, CI 0.66-0.93) compared with NHW newborns. However, within this cohort of NHB newborns, receiving a score for mottling would have resulted in earlier and/or increased rates of pharmacologic treatment for NOWS in 36% (n=15) of patients. Infants born to NHB patients were less likely to receive score for skin mottling on modified FNASS. Lack of recognition of mottling maybe due to skin pigmentation differences and could potentially result in underscoring and delay of pharmacological treatment for NOWS.

The pericyte: A critical cell in the pathogenesis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease presenting with migraine, mood and cognitive disorders, focal neurological deficits, recurrent ischemic attacks, lacunar infarcts and brain white matter changes. As they age, CADASIL patients invariably develop cognitive impairment and subcortical dementia. CADASIL is caused by missense mutations in the NOTCH3 gene resulting in a profound cerebral vasculopathy affecting primarily arterial vascular smooth muscle cells, which target the microcirculation and perfusion. Based on a thorough review of morphological lesions in arteries, veins, and capillaries in CADASIL, we surmise that arteriolar and capillary pericyte damage or deficiency appears a key feature in the pathogenesis of the disease. This may affect critical pericyte-endothelial interactions causing stroke injury and vasomotor disturbances. Changes in microvascular permeability due to perhaps localized blood-brain barrier alterations and pericyte secretory dysfunction likely contribute to delayed neuronal as well as glial cell death. Moreover, pericyte-mediated cerebral venous insufficiency may explain white matter lesions and the dilatation of Virchow-Robin perivascular spaces typical of CADASIL. The postulated central role of the pericyte offers some novel approaches to the study and treatment of CADASIL and enable elucidation of other forms of cerebral small vessel diseases and subcortical vascular dementia.

Cortisol profiles and clinical severity in MECP2 duplication syndrome

BackgroundMECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder primarily affecting males which is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Core clinical features of MDS include choreiform movements, progressive spasticity, recurrent respiratory infections, developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism. Prior studies suggest that HPA axis activity may be altered in MDS and measures of HPA axis activity may offer insight into disease severity.MethodsTo ascertain whether cortisol profiles are a potential biomarker of clinical severity, diurnal profiles of cortisol and the cortisol awakening response were examined from saliva samples in 31 participants with MDS (ages 2–24 years), and 27 of these samples were usable. Documentation of a positive diagnostic test for MECP2 duplication was required for entry into the study. Samples were collected on each of two consecutive weekdays at four time points during the day: immediately after waking, 30 min after waking, between 3 and 4 PM, and in the evening before bedtime. Correlations with duplication size, clinical severity, sleep problems, and behavior were also examined.ResultsResults revealed that a majority of participants with MDS exhibit a declining cortisol awakening response (n = 17). A declining CAR was significantly associated with increased clinical severity scores (r = − .508; p = .03), larger duplication size, waking later, and an increased number of hospitalizations for infections.ConclusionsFuture mechanistic studies will have to determine whether the declining CAR in MDS is attributable to problems with “flip-flop switching” of regional brain activation (involving the suprachiasmatic nucleus and the hippocampus, and the HPA axis) that is responsible for the switch from reduced to increased adrenal sensitivity. Taken together, results suggest the possibility that cortisol profiles could potentially be a biomarker of clinical severity and utilized for the purposes of patient stratification for future clinical trials in MDS.

Comparison of oxidative stress between premenopausal and postmenopausal women

Background: Menopause is a natural biological phenomenon during which irreversible changes in the hormonal and reproductive functions of the ovaries lead to physical, social, and psychological changes in women. The progressive loss of estrogen and its protective effects predisposes to the development of oxidative stress and related diseases in postmenopausal women which, in turn, can impair their quality of life. Aims and Objectives: This study aims to study and compare the levels of serum malondialdehyde (MDA) and superoxide dismutase (SOD) in premenopausal and postmenopausal females. Materials and Methods: A cross-sectional comparative study was conducted in 100 healthy women, of which 50 were postmenopausal in the age group of 50–60 years and 50 were premenopausal in the age group of 30–40 years. The data were analyzed using Statistical Package for the Social Sciences version 18. Results: Oxidative stress was increased in postmenopausal women as evidenced by significantly elevated MDA and reduced SOD. Conclusion: Menopause is associated with oxidative stress which predisposes to the development of cardiovascular diseases, vasomotor disturbances, osteoporosis, depression, diabetes, and hypertension. Dietary management, antioxidant supplementation, and moderate physical activity would help them to prevent diseases related to menopause.

Highlighting the Role of Biomarkers of Inflammation in the Diagnosis and Management of Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS) is characterized by continuous pain that is often accompanied by sensory, motor, vasomotor, sudomotor, and trophic disturbances. If left untreated, it can have a significant impact on the quality of life of patients. The diagnosis of CRPS is currently based on a set of relatively subjective clinical criteria: the New International Association for the Study of Pain clinical diagnostic criteria for CRPS. There are still no objective laboratory tests to diagnose CRPS and there is a great need for simple, objective, and easily measurable biomarkers in the diagnosis and management of this disease. In this review, we discuss the role of inflammation in the multi-mechanism pathophysiology of CRPS and highlight the application of potential biomarkers of inflammation in the diagnosis and management of this disease.

Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic cause of cerebral ischemia, but reliable biomarkers to monitor the disease are lacking. To evaluate cerebral autoregulation (CA), vasoreactivity (VR), and neurovascular coupling (NVC) in CADASIL patients through a battery of dynamic transcranial Doppler tests. We screened our database for all pre-dementia CADASIL cases. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler, blood pressure, and expiratory carbon dioxide (CO2) non-invasively. CA was assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV, VR with inhalation of CO2 at 5%, and hyperventilation and NVC by the CBFV response to visual stimulation. We included 27 CADASIL patients and 20 healthy controls with similar age and sexes. CA and VR were similar between groups. However, NVC was significantly affected in CADASIL patients, with lower magnitudes of CBFV upsurge (overshoot 19 ± 5 vs 26 ± 6%, p = 0.013; gain 12 ± 7 vs 17 ± 5%, p = 0.003) and altered time behavior during visual stimulation (natural frequency 0.18 ± 0.06 vs 0.24 ± 0.06Hz, p = 0.005; rate time 0.7 ± 1.7 vs 2.7 ± 3.5s, p = 0.025). Our results express a primary and selective involvement of the neurovascular unit in CADASIL rather than a generalized cerebral vasomotor disturbance. Functional cerebrovascular testing could be useful in patient evaluation and monitoring.

Characterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.

Individuals with methyl CpG binding protein 2 (MECP2) duplication syndrome (MDS) have varying degrees of severity in their mobility, hand use, developmental skills, and susceptibility to infections. In the present study, we examine the relationship between duplication size, gene content, and overall phenotype in MDS using a clinical severity scale. Other genes typically duplicated within Xq28 (eg, GDI1, RAB39B, FLNA) are associated with distinct clinical features independent of MECP2. We additionally compare the phenotype of this cohort (n = 48) to other reported cohorts with MDS. Utilizing existing indices of clinical severity in Rett syndrome, we found that larger duplication size correlates with higher severity in total clinical severity scores (r = 0.36; P = 0.02), and in total motor behavioral assessment inventory scores (r = 0.31; P = 0.05). Greater severity was associated with having the RAB39B gene duplicated, although most of these participants also had large duplications. Results suggest that developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism are common in MDS. This is the first study to show that duplication size is related to clinical severity. Future studies should examine whether large duplications which do not encompass RAB39B also contribute to clinical severity. Results also suggest the need for creating an MDS specific severity scale.

Assessment of autonomic innervation of the foot in familial amyloid polyneuropathy.

Distal involvement of autonomic nerve fibers is critical in familial amyloid polyneuropathy (FAP) due to transthyretin (TTR) mutation. This study compares different methods for assessing autonomic foot innervation in TTR-FAP patients. Three groups of seven TTR-FAP patients were included, according to disease severity: clinically asymptomatic, moderate or advanced neuropathy. The autonomic investigation included the eutectic mixture of local anesthetics test and laser Doppler flowmetry for vasomotor aspects and the Sudoscan® (measuring electrochemical skin conductance) and Neuropad® test for sudomotor aspects. Somatic innervation was assessed by performing nerve conduction studies, quantitative sensory testing [including vibration, cold and warm detection threshold (WDT) measurements] and laser evoked potentials. The results of all neurophysiological tests varied according to TTR-FAP severity (P≤0.01, Kruskal-Wallis test), except for the eutectic mixture of local anesthetics test and laser Doppler flowmetry variables. In addition, the sudomotor tests (Sudoscan or Neuropad) or WDT measurement provided early markers of neuropathy in two of the seven asymptomatic carriers. Finally, all neurophysiological results correlated with the Neuropathy Impairment Score (r values between -0.88 and -0.66, P<0.005, Spearman test), except the cold detection threshold. The Neuropad test could be used to detect TTR-FAP onset, but confirmation requires electrochemical skin conductance and WDT measurement. The Sudoscan technique, but not the Neuropad test (at least assessed at a fixed time point), could be valuable to follow the progression of the neuropathy. Follow-up investigation should also include large-fiber investigation (e.g. nerve conduction studies and vibration detection threshold). Conversely, reliable tests for assessing vasomotor disturbances in limb extremities of TTR-FAP patients are still awaited.

Perfusion index as a reliable parameter of vasomotor disturbance in complex regional pain syndrome

BackgroundDiscrepancy between a patient's subjective thermal symptoms and objective measured temperature value is common in complex regional pain syndrome (CRPS) in clinical settings. For that reason, the diagnostic validity of a single temperature measurement method has been criticised. Several studies showed that the perfusion index (PI), which is derived from pulse oximetry, is a more sensitive and earlier indicator of sympathetic blockade than temperature measurement. MethodsForty-six participants (CRPS group, n=23; healthy control group, n=23) were enrolled. CRPS patients with subjective sensation of coldness on the affected side were chosen for this study. Temperature and PI were measured at the affected and contralateral hands in the CRPS group, and right and left hands in the healthy control group. To evaluate each method's efficacy for detecting thermal symptoms, differences in the parameters (temperature: ΔT, PI: ΔPI) were compared with receiver operating characteristic curves. ResultsΔPI was significantly larger in the CRPS compared with the healthy control group (P=0.002), but ΔT was not (P=0.171). The accuracy of PI measurement for reflecting thermal symptoms was good (area under the curve for ΔPI: 0.873, P<0.0001). The optimal cut off value of ΔPI was calculated as 0.50% with a sensitivity of 78.26%, whereas the sensitivity of ΔT using the conventional criterion of ≥1°C was only 34.78%. ConclusionsThe accuracy of detection of subjective abnormal thermal sensations was superior for PI compared with the temperature measurement method. PI was a more sensitive measure for detecting vasomotor symptoms in CRPS compared with temperature.

Autonomic function testing in Friedreich\u2019s ataxia

BackgroundFriedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking.MethodsGenetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed.Results20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50).ConclusionsFRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.