Altered Autonomic Functions and Gut Microbiome in Individuals with Autism Spectrum Disorder (ASD): Implications for Assisting ASD Screening and Diagnosis.

Autism spectrum disorder (ASD) is a complex neurological and developmental disorder, and a growing body of literature suggests the presence of autonomic nervous system (ANS) dysfunction in individuals with ASD. ANS is part of the "gut brain axis", which consists of an intricate interplay between the gut microbiome, mucosal immune system, enteric nervous system, ANS, and central processes receiving input from the vagus nerve. Measurements of the gut microbiome and the autonomic indices can serve as non-invasive markers of the status of the gut-brain axis in ASD. To our knowledge, no previous studies have explored the relationship between ANS and gut microbiome in individuals with ASD. Furthermore, while previous studies investigated the use of autonomic indices and gut microbiome independently as markers of ASD-related comorbidities, such as anxiety, cardiovascular issues, and gastrointestinal dysfunction, the use of combined autonomic indices and gut microbiome factors to classify ASD and control subjects has not been explored. In this study, we characterized autonomic function of a group of individuals with ASD in comparison to their paired, first-degree relative controls. Second, we explored the ASD gut-brain-axis through the relationship between gut microbiome markers and autonomic indices, as well as the correlation between the gut-brain-axis and clinical presentation of ASD. Lastly, this study explores the predictive capability of gut-brain-axis biomarkers (including autonomic and microbiome indices) in subtyping ASD cases, serving as a starting point to investigate the possibility of assisting in ASD screening and diagnosis that still heavily relies on psychological testing, which may be based on highly subjective standards.

Investigations on a polyherbal formulation for treatment of cognitive impairment in a cholinergic dysfunctional rodent model.

Alzheimer's disease is a multifactorial neurodegenerative condition manifested through acute cognitive decline, amyloid plaque deposits and neurofibrillary tangles. Complete cure for this disease remains elusive as the conventional drugs address only a single molecular target while Alzheimer's disease involves a complex interplay of different sets of molecular targets and signaling networks. In this context, the possibility of employing multi-drug combinations to rescue neurons from the dysregulated metabolic changes is being actively investigated. The present work investigates a poly-herbal formulation, Brahmi Nei that has been traditionally used for anxiolytic disorders and immunomodulatory effects, for its efficiency in ameliorating cognitive decline through a combination of behavioral, biochemical, histopathological, gene and protein expression analyses. Our results reveal that the formulation shows excellent neuroregenerative properties, rescues neurons from inflammatory damage, reduces neuritic plaque deposits and improves working memory in rodent models with scopolamine-induced dementia. The microarray analysis shows that the formulation induces the expression of pro-survival pathways and positively modulates genes involved in memory consolidation, axonal growth and proliferation in a concentration-dependent manner with therapeutic concentrations restoring the normal conditions in the brain of the diseased animals. The neuritic spine morphology confirms the long-term memory potentiation through improved mushroom spine density, increased dendritic length and connectivity. Taken together, our study provides mechanistic evidence to prove that the traditional formulation can be a superior therapeutic strategy to treat cognitive decline when compared to the conventional mono-drug treatment.

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes.

AIMS: To investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. METHODS: Participants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). RESULTS: Ninety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. CONCLUSION: CAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies.

Impaired awareness of hypoglycemia (IAH) is a reduction in the ability to recognize low blood glucose levels that would otherwise prompt an appropriate corrective therapy. Identified in approximately 25% of patients with type 1 diabetes, IAH has complex pathophysiology, and might lead to serious and potentially lethal consequences in patients with diabetes, particularly in those with more advanced disease and comorbidities. Continuous glucose monitoring systems can provide real-time glucose information and generate timely alerts on rapidly falling or low blood glucose levels. Given their improvements in accuracy, affordability and integration with insulin pump technology, continuous glucose monitoring systems are emerging as critical tools to help prevent serious hypoglycemia and mitigate its consequences in patients with diabetes. This review discusses the current knowledge on IAH and effective diagnostic methods, the relationship between hypoglycemia and cardiovascular autonomic neuropathy, a practical approach to evaluating cardiovascular autonomic neuropathy for clinicians, and recent evidence from clinical trials assessing the effects of the use of CGM technologies in patients with type 1 diabetes with IAH.

Autonomic and diastolic dysfunction association with quality of life impairment in cirrhotic patients.

BACKGROUND AND STUDY AIMS: Cirrhosis is a multisystem disorder characterized by hyperdynamic circulation which can progress to multiple organ dysfunctions. Recent studies have demonstrated autonomic dysfunction and cirrhotic cardiomyopathy including diastolic dysfunction, systolic dysfunction with electrophysiologic abnormalities in patients with cirrhosis. Due to the long and complicated course of the disease, health related quality of life is affected. We aimed to evaluate the frequency of diastolic dysfunction and autonomic dysfunction in cirrhosis, and the effects on health-related quality of life. PATIENTS AND METHODS: Hundred cirrhotic patients were enrolled in the study. According to the Child-Pugh classification 35 patients were of Child A, 36 of Child B and 29 of Child C. The proportion of autonomic dysfunction was 52%, and diastolic dysfunction 51%. Autonomic dysfunction was diagnosed using bedside maneuvers and tests; diastolic dysfunction was diagnosed using the E/A ratio in echocardiographic findings. Health-related quality of life measurements was obtained from an SF-36 questionnaire. RESULTS: Patients with advanced Child-Pugh classifications were found to have significantly lower health-related quality of life values (p < 0.05). Likewise, health-related quality of life values were observed to be significantly lower in patients with autonomic dysfunction (p < 0.05). No significant difference was found in health related quality of life measurements between patients with and without diastolic dysfunction. CONCLUSION: Our study showed that autonomic dysfunction and diastolic dysfunction are found in patients with cirrhosis. Further studies are needed to assess the effects of autonomic dysfunction and diastolic dysfunction on health-related quality of life.

Clinical autonomic dysfunction in narcolepsy type 1.

STUDY OBJECTIVES: (1) To compare the presence of autonomic symptoms using the validated SCOPA-AUT questionnaire in untreated patients with narcolepsy type 1 (NT1) to healthy controls, (2) to study the determinants of a high total SCOPA-AUT score in NT1, and (3) to evaluate the effect of drug intake on SCOPA-AUT results in NT1. METHODS: The SCOPA-AUT questionnaire that evaluates gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction was completed by 92 consecutive drug-free adult NT1 patients (59 men, 39.1 ± 15.6 years old) and 109 healthy controls (63 men, 42.6 ± 18.2 years old). A subgroup of 59 NT1 patients completed the questionnaire a second time, under medication (delay between two evaluations: 1.28 ± 1.14 years). RESULTS: Compared to controls, NT1 patients were more frequently obese, had more dyslipidemia, with no difference for age and gender. The SCOPA-AUT score of NT1 was higher than in controls in crude and adjusted models. Patients experienced more problems than controls in all subdomains. A higher score in NT1 was associated with older age, longer disease duration, altered quality of life and more depressive symptoms, but not with orexin levels and disease severity. Among patients evaluated twice, the SCOPA-AUT score total did not differ according to treatment status, neither did each subdomain. CONCLUSION: We captured a frequent and large spectrum of clinical autonomic dysfunction in NT1, with impairment in all SCOPA-AUT domains, without key impact of medication intake. This assessment may allow physicians to screen and treat various symptoms, often not spontaneously reported but associated with poor quality of life.

Cardiovascular autonomic neuropathy and falls in Parkinson disease: a prospective cohort study.

BACKGROUND: Falls represent one of the main complications of Parkinson's disease (PD), significantly lowering quality of life. Cardiovascular autonomic neuropathy (cAN) is one of the key contributing factors to PD-associated falls. However, a direct quantification of its impact on the risk of falling in PD is still lacking. In this 12-month prospective study, we sought to evaluate the association between cAN and falls. METHODS: Fifty consecutive patients were evaluated with a standardized battery of autonomic testing, Unified Parkinson's Disease Rating Scale, push and release (P&R) test, timed up and go test, freezing of gait (FOG) questionnaire, Montreal cognitive assessment (MoCA). Dyskinesia severity and presence of REM sleep behavioral disorder (RBD) were additionally considered. Patients were followed-up for 12 months. RESULTS: We observed a 38% prevalence of cAN. At baseline, 36% of patients reported at least one fall in the previous 6 months. This figure increased to 56% over the follow-up. After adjusting for age, disease duration, axial symptoms, MoCA and dopaminergic treatment, cAN was significantly associated with a 15-fold (OR 15.194) higher probability of falls; orthostatic hypotension (OH), the most common expression of cAN, with a 10-fold probability (OR 10.702). In addition P&R test (OR 14.021), RBD (OR 5.470) and FOG (OR 1.450) were independently associated with greater probability of falls. CONCLUSIONS: cAN, including but not limited to OH, is a strong independent predictor of falls in PD. Future research endeavors clarifying to what extent pharmacological and non-pharmacological treatments targeting autonomic dysfunctions might reduce the risk of falls are warranted.

Body perception in a sample of nonclinical youngsters with joint hypermobility / Percepción corporal en una muestra de jóvenes no clínicos con hipermovilidad articular

BACKGROUND: Participants with Joint Hypermobility Syndrome (JHS) often suffer from anxiety, stress related illnesses and also from dysautonomia. The autonomic nervous system (ANS) is hypothesized to play a key role in the relationship between these variables. However, to date, no studies have assessed body awareness and the reactivity of autonomically-regulated organs in JHS using the Body Perception Questionnaire. METHOD: A cross sectional study including 117 nonclinical youngsters (mean age 16.96 ± 0.87 years old) assessed JHS in relation to body perception. JHS screening was done using the self-reported Screening Questionnaire for Collagen condition and Hypermobility assessment (SQCH) and body perception was assessed using the Spanish version of the Body Perception Questionnaire (BPQ). RESULTS: The JHS was found in 33.3% of the sample and it was significantly higher in females (χ2 = 12.15; p = <.001). Participants with JHS had higher scores in body awareness (p = .012), stress response (p = .007), ANS reactivity (p = .01), and in the health history inventory (p = <.001). In this last subscale, higher frequency of anxiety (p = <.001), unhappiness (p = <.001), depression (p = <.001), bulimia (p = .012), anorexia (p = .023), eczema (p = .003), and severe menstrual cramps (in females only) (p = .016) were found among the JHS participants. Moreover, JHS participants made significantly more visits to mental health professionals (p = .019) than their non JHS counterparts. CONCLUSIONS: Participants with JHS have a body perception profile characterized by higher body awareness and stress response and greater ANS reactivity. These participants also have higher frequency of anxiety, depression, bulimia, anorexia, unhappiness, severe menstrual cramps (in females only) and eczema. These findings support the hypothesis that the ANS and body perception may play a key role in the development of anxiety and somatic illnesses among participants with JHS, but this needs to be further evaluated in subsequent studies

ANTECEDENTES: Las personas con síndrome de hipermovilidad articular (SHA) padecen a menudo ansiedad, estrés relacionado con la enfermedad y también disautonomía. Se ha conjeturado que el sistema nervioso autónomo juega un papel clave en la relación entre estas variables, pero hasta la fecha ningún estudio ha evaluado la conciencia corporal y la reactividad de los órganos regulados autonómicamente en el SHA utilizando el cuestionario de imagen corporal. MÉTODO: Estudio transversal que incluyó a 117 jóvenes no clínicos (edad media 16,96 ± 0,87años) en quienes se valoró el SHA en relación con la imagen corporal. Se realizó un cribado de SHA utilizando el cuestionario autoinformado de cribado para la valoración del estado de colágeno e hipermovilidad (SQCH), evaluándose la percepción corporal mediante la versión española del cuestionario de imagen corporal (BPQ). RESULTADOS: Se encontró SHA en el 33,3% de la muestra, siendo significativamente superior en las mujeres (χ2=12,15; p ≤ 0,001). Las personas con SHA reflejaron mayores puntuaciones en cuanto a conciencia del cuerpo (p = 0,012), respuesta al estrés (p = 0,007), reactividad del sistema nervioso autónomo (p = 0,01) e inventario de antecedentes de salud (p ≤ 0,001). En esta última subescala se encontró una mayor frecuencia de ansiedad (p ≤ 0,001), infelicidad (p≤0,001), depresión (p ≤ 0,001), bulimia (p = 0,012), anorexia (p = 0,023), eccema (p = 0,003) y dolores menstruales severos (solo en mujeres) (p = 0,016) entre las personas con SHA. Además, las personas con SHA realizaron un número de visitas considerablemente superior a los profesionales sanitarios (p = 0,019) que los participantes sin SHA. CONCLUSIONES: Las personas con SHA tienen un perfil de percepción corporal caracterizado por una mayor conciencia sobre el cuerpo y una reactividad superior del sistema nervioso autónomo. Estos participantes también poseen una mayor frecuencia de ansiedad, depresión, bulimia, anorexia, infelicidad, dolores menstruales severos y eccema. Estos hallazgos respaldan la hipótesis de que el sistema nervioso autónomo y la imagen corporal pueden jugar un papel principal en el desarrollo de la ansiedad y las enfermedades somáticas entre las personas con SHA, aunque esto debe evaluarse en mayor profundidad en estudios futuros

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

PURPOSE: To report the use of intranasal dexmedetomidine, an α2-adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. METHODS: Case series. RESULTS: Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. CONCLUSIONS: Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

Respiratory Sinus Arrhythmia Predicts Restricted Repetitive Behavior Severity.

In addition to social communication deficits, restricted repetitive behaviors (RRBs) are a key diagnostic feature of autism spectrum disorder (ASD). Dysfunction of the autonomic nervous system (ANS) in ASD has been posited as a mechanism of RRBs; however, most studies investigating ANS activity in ASD have focused on its relation to social functioning. This study used respiratory sinus arrhythmia (RSA) patterns to measure ANS functioning and analyze its relation to RRBs in children with and without an ASD diagnosis. Baseline RSA and RSA reactivity predicted RRB severity and exploratory analyses revealed these measures may be associated with RRB subgroups. These results are discussed in regards to the behavioral literature on RRBs and the benefits of finding biomarkers for these behaviors.

Impact of autonomic dysfunctions on the quality of life in Parkinson's disease patients.

Autonomic dysfunctions are part of a spectrum of non-motor symptoms in Parkinson's disease (PD) patients. The aim of the study was to assess the prevalence of autonomic dysfunctions and their influence on the quality of life (QoL) in PD patients, adjusted for age, sex, disease duration and motor symptoms. Patients were evaluated for motor function (Unified Parkinson's Disease Rating Scale, UPDRS part III), disease stage (Hoehn and Yahr scale, H&Y scale), autonomic dysfunction (Scales for Outcomes in Parkinson's disease, Autonomic, SCOPA-AUT) and QoL (Parkinson's Disease Questionnaire-39, PDQ-39). Urinary, gastrointestinal and sexual autonomic dysfunctions were most frequently reported, while the most severe symptoms were reported for sexual and urinary systems. Age and motor symptoms did not correlate with autonomic dysfunction, while disease duration correlated with cardiovascular dysfunction. There were sex differences on the thermoregulation subscale. All types of autonomic dysfunction influenced QoL, mostly gastrointestinal and thermoregulatory dysfunctions, except for sexual one. Many aspects of QoL (activity of daily living, emotion, cognitive functions, communication and social support) except for stigma and mobility were affected by autonomic dysfunctions. Age, disease duration, sex and motor symptoms were not found to affect global QoL scores, but had detrimental effects on different PDQ-39 dimensions. Autonomic dysfunctions influence QoL in more aspects than motor symptoms, age, disease duration and sex. Patients tend to be more stigmatized with motor than non-motor symptoms.

Impaired heart rate variability in cervical dystonia is associated to depression.

Causes of cardiovascular autonomic dysfunction in cervical dystonia (CD) are poorly understood. Studies examining effects of botulinum neurotoxin (BoNT) therapy on heart rate variability (HRV) yielded contradictory results. There is compelling evidence that depression shifts autonomic balance towards sympathetic predominance. As depression is the most frequent non-motor symptom in CD, we sought to determine if it is associated to dysfunction of cardiovascular autonomic regulation. Standardized interviews, clinical examinations, self-rating forms, autonomic symptom questionnaire, and automated autonomic testing in outpatients with idiopathic CD were used. Cardiovascular autonomic screening encompassed five different analyses of HRV, and testing of orthostasis. 85 CD patients participated in the study. 21% of them had HRV impairment, 14% orthostatic hypotension. 30% of CD patients had symptoms of depression. In those, decreased HRV was more frequent than in CD patients without mood disturbance (40 vs. 13%; p = 0.008). CD patients with and without depression had no other significant differences, including demographics, dystonia severity, comorbidity, medication, or BoNT therapy. Cardiovascular autonomic imbalance with sympathetic predominance is a non-motor manifestation of CD, associated to depression. Impaired HRV is a cardiovascular risk factor, moreover, emphasizing the need to identify and treat depression in dystonia.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation.

Alternative Quantitative Tools in the Assessment of Diabetic Peripheral and Autonomic Neuropathy.

Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss.

A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings.

BACKGROUND AND PURPOSE: Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare progressive neurological disorder caused by Lamin B1 duplication (LMNB1). Our aim was to investigate longitudinally the pattern of the autonomic dysfunction and the degree of neuropsychological involvement. METHODS: Three related ADLD patients and one asymptomatic carrier of LMNB1 duplication underwent a standardized evaluation of autonomic nervous system, including cardiovascular reflexes, pharmacological testing, microneurography, skin biopsy, Metaiodobenzylguanidine scintigraphy and a complete neuropsychological battery. RESULTS: An early neurogenic orthostatic hypotension was detected in all patients and confirmed by a low rise in noradrenaline levels on Tilt Test. However infusion of noradrenaline resulted in normal blood pressure rise as well as the infusion of clonidine. At the insulin tolerance test the increase in adrenaline resulted pathological in two out three patients. Microneurography failed to detect muscle sympathetic nerve activity bursts. Skin biopsy revealed a poor adrenergic innervation, while cardiac sympathetic nerves were normal. None of ADLD patients showed a global cognitive deficit but a selective impairment in the executive functions. CONCLUSION: Autonomic disorder in ADLD involves selectively the postganglionic sympathetic system including the sympatho-adrenal response. Cognitive involvement consisting in an early impairment of executive tasks that might precede brain MR abnormalities.

Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes Is Not Associated With Autonomic Dysfunction or Peripheral Neuropathy.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in people with insulin-treated diabetes; autonomic neuropathy has been suggested to underlie its development. The aim was to evaluate a putative association between IAH and autonomic dysfunction using novel and sensitive measures of autonomic neural function. RESEARCH DESIGN AND METHODS: Sixty-six adults with type 1 diabetes were studied, 33 with IAH and 33 with normal awareness of hypoglycemia (NAH), confirmed by formal testing. Participants were matched for age, sex, and diabetes duration. Clinical and laboratory evaluations included extensive autonomic function testing, peripheral nerve conduction studies, and quantitative sensory testing. Composite abnormality Z scores were used for group comparisons. RESULTS: The IAH and NAH group had similar median (interquartile range) age of 48 (14.5) vs. 47 (14.5) years, diabetes duration of 30 (13.5) vs. 31 (13.5) years, and mean ± SD HbA1c 7.8 ± 2.2% vs. 8.1 ± 1.9%, respectively. The autonomic composite Z score did not differ between the two groups (mean difference -0.15, 95% CI -0.46, 0.16; P = 0.33), nor did the thermal detection (mean difference 0.15, 95% CI -0.31, 0.61; P = 0.51) or nerve conduction scores (mean difference 0.03, 95% CI -0.43, 0.49; P = 0.89). CONCLUSIONS: In adults with type 1 diabetes, IAH was not associated with autonomic dysfunction or peripheral neuropathy.

Effect of orthostatic hypotension on sustained attention in patients with autonomic failure.

INTRODUCTION: Orthostatic hypotension has been associated with impaired cognitive function, but cognitive function during orthostatic hypotension has hardly been studied. We studied the effect of orthostatic hypotension, induced by head-up tilt (HUT), on sustained attention in patients with autonomic failure. METHODS: We studied the sustained attention to response task (SART) in the supine position and during HUT in 10 patients with autonomic failure and 10 age-matched and sex-matched controls. To avoid syncope, the tilting angle was tailored to patients to reach a stable systolic blood pressure below 100 mm Hg. Controls were all tilted at an angle of 60°. Cerebral blood flow velocity, blood pressure and heart rate were measured continuously. RESULTS: In patients, systolic blood pressure was 61.4 mm Hg lower during HUT than in the supine position (p<0.001). Patients did not make more SART errors during HUT than in the supine position (-1.3 errors, p=0.3). Controls made 2.3 fewer errors during SART in the HUT position compared to the supine position (p=0.020). SART performance led to an increase in systolic blood pressure (+11.8 mm Hg, p=0.018) and diastolic blood pressure (+5.8 mm Hg, p=0.017) during SART in the HUT position, as well as to a trend towards increased cerebral blood flow velocity (+3.8 m/s, p=0.101). DISCUSSION: Orthostatic hypotension in patients with autonomic failure was not associated with impaired sustained attention. This might partly be explained by the observation that SART performance led to a blood pressure increase. Moreover, the upright position was associated with better performance in controls and, to a lesser extent, also in patients.

[The multicenter non-interventional, prospective observational program on the study of practical use of teraligen in patients diagnosed with autonomic disorder (START2): a local Russian experience with the use of the Russian version of The Four-Dimensional Symptom Questionnaire (4DSQ). An intermediate analysis].

AIM: To develop a new instrument able to identify pathological states and assess their changes during medication treatment. We aimed to study the typical practice of using alimemazine (teraligen) in patients with the diagnosis of autonomic nervous system disorder and to test the Russian version of @The Four-Dimensional Symptom Questionnaire@ (4DSQ) for measuring distress, depression, anxiety and somatization. MATERIAL AND METHODS: We examined 3053 patients (mean age 42.09 ± 11.71 years) who received teraligen in doses gradually increasing from 5 to 15 mg per day. The observational program was carried out in over 600 outpatient clinics of the Russian Federation. The 4DSQ was administered before treatment and 4 weeks after treatment. The Clinical Global Impression (CGI) scale was used before, during (after 2 weeks) and after (4 weeks) treatment with teraligen. RESULTS AND CONCLUSION: There was a significant improvement of patient's state assessed both by physicians (CGI scale) and by patients (96 and 98%, respectively). The 4DSQ was sensitive to the parameters of response to treatment with teraligen: parameters obtained at baseline and 4 weeks after the beginning of treatment differed significantly demonstrating a significant decrease in distress, anxiety and somatization.

Altered autonomic nervous system activity in women with unexplained recurrent pregnancy loss.

AIM: Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL). METHODS: Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale. RESULTS: The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups. CONCLUSIONS: The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL.

Central cholinergic dysfunction in the adult form of Niemann Pick disease type C: a further link with Alzheimer's disease?

Adult patients with Niemann-Pick disease type C (NPC) usually develop cognitive impairment progressing to dementia, whose pathophysiology remains still unclear. Noteworthy parallels exist in cognitive impairment and cellular pathology of NPC and Alzheimer's disease (AD). In particular, alterations of cholinergic system, which represent one of the pathological hallmarks and contribute to cognitive deterioration in AD, have recently been demonstrated in a human brain autopsy and in an experimental model of NPC. This finding raised the issue that central cholinergic circuits dysfunction may contribute to pathophysiology of cognitive impairment in NPC as well, and prompted us to evaluate the cholinergic functional involvement in NPC patients by applying a neurophysiologic technique, named short-latency afferent inhibition (SAI). We describe clinical, biochemical, molecular and neuropsychological features, and SAI findings in three patients affected by NPC. Diagnosis of NPC was assessed by molecular analysis of the NPC1 gene in all patients. In two of them, biochemical analysis of intracellular accumulation of unesterified cholesterol was also performed. The main clinical features were cerebellar ataxia, vertical supranuclear gaze palsy and a variable degree of cognitive impairment ranging from only memory impairment to severe dementia. Electrophysiological evaluation revealed a reduced SAI in all three patients. Our SAI findings provide evidence of cholinergic dysfunction in patients with the adult form of NPC, supporting that cholinergic alterations may play a role in cognitive impairment in NPC, and strengthening the similarities between NPC and AD.