Treatment Of Autonomic Dysfunction Research Articles

From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction.

Since its regulatory approval over a half-century ago, botulinum toxin has evolved from one of the most potent neurotoxins known to becoming routinely adopted in clinical practice. Botulinum toxin, a highly potent neurotoxin produced by Clostridium botulinum, can cause botulism illness, characterized by widespread muscle weakness due to inhibition of acetylcholine transmission at neuromuscular junctions. The observation of botulinum toxin's anticholinergic properties led to the investigation of its potential benefits for conditions with an underlying etiology of cholinergic transmission, including autonomic nervous system dysfunction. These conditions range from disorders of the integument to gastrointestinal and urinary systems. Several formulations of botulinum toxin have been developed and tested over time, significantly increasing the availability of this treatment for appropriate clinical use. Despite the accelerated and expanded use of botulinum toxin, there lacks an updated comprehensive review on its therapeutic use, particularly to treat autonomic dysfunction. This narrative review provides an overview of the effect of botulinum toxin in the treatment of autonomic dysfunction and summarizes the different formulations and dosages most widely studied, while highlighting reported outcomes and the occurrence of any adverse events.

Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of autonomic dysfunction in patients with post-acute sequelae of SARS-CoV-2 infection (PASC).

Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of autonomic dysfunction in patients with post-acute sequelae of SARS-CoV-2 infection (PASC).

Management of tetanus complication

The mortality rate of tetanus is still high; it is because of various complications due to muscle spasms, autonomic dysfunction, as well as due to prolonged critical care. Management of tetanus with its complications is in intensive care facilities. Management goals include stopping toxin production, neutralization of unbound toxin, management of the airway, muscle spasm control, treatment of autonomic dysfunction and general supportive management. Currently, diazepam is still an effective medication to control of muscle spasm and rigidity. Therapy for autonomic dysfunction that supported by evidence is MgSO4. Also, general supportive management for long-term care remains necessary to prevent other complications such as thromboembolism, infection, malnutrition, and others.

The treatment of autonomic dysfunction in tetanus

We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

The treatment of autonomic dysfunction in tetanus

The treatment of autonomic dysfunction in tetanus

Autonomic Dysfunction: How to Identify and When to Treat?

Cardiovascular autonomic dysfunction (AD) is a particular condition that can be detected by means of ambulatory blood pressure monitoring (ABPM). ABPM is helpful to identify some specific characteristics of haemodynamic AD, including non-dipping/reverse-dipping pattern, orthostatic and post-prandial hypotension and elevated blood pressure variability. These characteristics may be misdiagnosed with traditional, clinic blood pressure measurements. AD is relativelycommon in thereal world. By analysing about 1000 recordings in a Cardiology unit, AD was found in 6.8% of the exams. Several diseases may be the underlying causes of AD. In our sample half of the subjects were diabetic (54.4%), 17.7% were patients with alpha-synucleinopathy (Parkinson disease or multiple system atrophy), and 27.9% had other underlying causes of AD including chronic kidney disease, α-lytic drug assumption and AD from unknown causes. According to the different aetiology, different clinical characteristics can be found, in particular in diabetics these peculiar aspects are less pronounced compared to the other subgroups. These characteristics have been found to bepredictors of cardiovascular events, organ damage, andmortality. For these reasons, early identification of these behaviours is important, in order to better define patient's cardiovascular risk profile. As regard treatment of AD, several drugs have been tested, however none of this showed efficacy in all kinds of patients. Another open aspect is "safe" reference values for supine hypertension.

Autonome Nervenkrankheiten - Früherkennung und leitliniengerechte Behandlung

Among the few well-established techniques to diagnose autonomic dysfunction are head-up-tilt table testing, heart rate variability measurement and axon-reflex based sudomotor testing. Recent research focused on the development of novel techniques to assess autonomic function based on axon-reflex testing in both vasomotor and pilomotor nerve fibers. However, these techniques are clinically not widely used due to technical limitations and the lack of data on their utility to detect autonomic dysfunction in patients with neuropathy. The treatment of autonomic neuropathies should focus on the management of the underlying disease. In addition, symptomatic treatment of autonomic dysfunction should be provided in an individual patient-centered multimodal regimen that may incorporate both pharmacological and non-pharmacological strategies. The use of medication in autonomic dysfunction requires a careful risk-benefit assessment and should be individually adjusted based on both therapeutic success and occurrence of adverse effects.

Autonomic dysfunction in patients with advanced cancer; prevalence, clinical correlates and challenges in assessment

BackgroundThe results of a small number of studies of autonomic function in patients with advanced cancer suggest that autonomic dysfunction (AD) is common. In other disease-specific groups this is associated with decreased survival, falls and symptoms such as postural hypotension, nausea, early satiety and fatigue. The contribution of AD to symptoms in advanced cancer is unknown.MethodsWe conducted a prospective cohort study designed to identify the risk factors for falls in patients with advanced cancer. Ambulant adult patients admitted consecutively to palliative care services were invited to participate. Participants underwent an assessment at baseline which included standard clinical tests of autonomic function, assessment of symptom severity, muscle strength, anthropometric measurements, walking speed, medication use, comorbidities and demographics. Information regarding survival was recorded ten months following cessation of recruitment. The clinical correlates of AD, defined as definite or severe dysfunction using Ewing's classification, were examined by univariate and multivariate logistic regression analysis. Survival analysis was conducted using Kaplan-Meier plots and the log rank test.ResultsOf 185 patients recruited, 45% were unable to complete all of the clinical tests of autonomic function. Non-completion was associated with scoring high on clinical indicators of frailty. It was possible to accurately classify 138/185 (74.6%) of participants as having either definite or severe versus normal, early or atypical AD: 110 (80%) had definite/severe AD. In logistic regression analysis, age (OR = 1.07 [95% CI; 1.03-1.1] P = 0.001) and increased severity of fatigue (OR = 1.26 [95% CI; 1.05-1.5] p = 0.016) were associated with having definite/severe AD. In analysis adjusted for age, median survival of participants with definite/severe AD was shorter than in those with normal/early/atypical classification (χ2 = 4.3, p = 0.038).ConclusionsAutonomic dysfunction is highly prevalent in patients with advanced cancer and is associated with increased severity of fatigue and reduced survival. Due to frailty, up to 45% of participants were unable to complete standard clinical tests of autonomic function. In order to further investigate the impact of AD and the therapeutic potential of treatment of AD in patients with advanced cancer, the validity of alternative novel methods of assessing autonomic function must be appraised.

Potential prevention and treatment of oxaliplatin associated peripheral neuropathy

8093 Background: The major toxicities of oxaliplatin are two different types of peripheral neuropathies, a reversible one related to the drug's infusion and an irreversible one based on the cumulative dose received.The incidence of onset and the severity of the neuropathy increase as the number of cycles increase as does the prevalence of the toxicity. Gabapentin (Neurontin) and carbamazepine (Tegretol) are two drugs used in the treatment of autonomic dysfunction and peripheral neuropathic pain. Given the similar syndromes, a trial was first conducted to see if the use of these agents could prevent the progression of this oxaliplatin-associated toxicity. A second trial was then begun to see if these agents could totally prevent oxaliplatin-associated neurotoxicity. Methods: 34 consecutive patients receiving oxaliplatin-5-FU-leukovorin rescue chemotherapy for stage IV colon cancer were available for study. Treatment was determined by random drawing of treatment options. Results: In the intial study of 24 patients, grade 1 toxicity had to be reported before treatment was intiated with either drug, usually after the 2nd cycle. Treatment was begun a week before the 3rd cycle. Gabapentin was begun at 900 mg/day and escalated to 2700 mg/day, as needed. Carbamazepine was begun at 400 mg/day and escalated to 800 mg/day, as needed. A success rate for preventing any grade 3 or higher sensory symptomatology occurred in 75% (9/12) in both groups. No life-threatening nor persistent neuropathy occurred. To judge whether these agents could totally prevent the sensory neuropathy, the next 10 patients have been randomized at the start of their treatment to either gabapentin, carbamazepine or nothing. After 3 cycles the 6 treated patients have grade 1 sensory neuropathy while 2 of the 4 non-prophylaxed patients had grade 2 sensory neuropathy and were started on therapy before cycle 3. No drug toxicity associated with either carbamazepine or gabapentin was observed. Conclusions: While a prospective, double-blinded randomized trial needs to confirm these findings, gabapentin or carbamazepine can be considered as adjuvant therapy to minimize the sensory neuropathic toxicity of oxaliplatin. No significant financial relationships to disclose.

Potential prevention and treatment of oxaliplatin associated peripheral neuropathy

8093 Background: The major toxicities of oxaliplatin are two different types of peripheral neuropathies, a reversible one related to the drug's infusion and an irreversible one based on the cumulative dose received.The incidence of onset and the severity of the neuropathy increase as the number of cycles increase as does the prevalence of the toxicity. Gabapentin (Neurontin) and carbamazepine (Tegretol) are two drugs used in the treatment of autonomic dysfunction and peripheral neuropathic pain. Given the similar syndromes, a trial was first conducted to see if the use of these agents could prevent the progression of this oxaliplatin-associated toxicity. A second trial was then begun to see if these agents could totally prevent oxaliplatin-associated neurotoxicity. Methods: 34 consecutive patients receiving oxaliplatin-5-FU-leukovorin rescue chemotherapy for stage IV colon cancer were available for study. Treatment was determined by random drawing of treatment options. Results: In the intial study of 24 p...

Antiidiotypic antibodies neutralize autoantibodies that inhibit cholinergic neurotransmission.

Functional autoantibodies that inhibit M(3) muscarinic receptor (M3R)-mediated neurotransmission have been reported in patients with Sjögren's syndrome (SS) and in patients with scleroderma. Because of limited reports that intravenous immunoglobulin (IVIG) improves dysautonomia in primary SS, we investigated whether IVIG neutralizes the effect of anti-M3R antibodies on colon smooth muscle contractions, in an in vitro functional assay. IgG obtained from patients with primary SS, patients with rheumatoid arthritis and secondary SS, and patients with scleroderma was tested, before and after coincubation with equimolar amounts of IVIG or its F(ab')(2) and Fc fractions, for the ability to inhibit carbachol-evoked colon smooth muscle contractions. In addition, patient IgG was passed through an IVIG F(ab')(2) column, and unretained IgG was tested for functional activity on colon smooth muscle strips. Purified IgG obtained from healthy adults was also examined for a neutralizing effect on anti-M3R antibody activity. Inhibition of colon contractions was mediated by the Fab fraction of patient IgG. Coincubation of IgG from the 3 patient groups with IVIG or its F(ab')(2) fragment neutralized anti-M3R antibody-mediated inhibition of cholinergic smooth muscle contractions. Preabsorption of patient IgG with Sepharose-bound IVIG F(ab')(2) removed the anti-M3R inhibitory activity. In addition, purified IgG from each of 4 healthy adults neutralized the functional autoantibodies. Anti-M3R antibody activity does not require receptor crosslinking. Antiidiotypic antibodies present in pooled IgG neutralize patient IgG-mediated inhibition of M3R cholinergic neurotransmission, providing a rationale for IVIG as a treatment of autonomic dysfunction in patients with SS and patients with scleroderma. Furthermore, antiidiotypic antibodies in healthy individuals may prevent the emergence of pathogenic anti-M3R autoantibodies.

Management of tetanus: a review of 18 cases.

Eighteen patients with generalized tetanus seen during an 8-year period in three regional hospitals in Hong Kong are reviewed. Eighty-nine per cent of the patients were intravenous heroin addicts who developed a severe type of generalized tetanus with autonomic dysfunction. Pain or stiffness of the neck or back was the commonest presenting symptom, followed by trismus and dysphagia. Most of the patients developed muscle spasms within 24 h of the onset of presenting symptoms. Early ventilatory support and tracheostomy, together with intensive nursing care, were the mainstay of the treatment. Pulmonary and gastrointestinal complications were common during the course of illness and treatment of autonomic dysfunction was often unsatisfactory. The case fatality rate was 25% among the heroin addicts, but full recovery was the usual outcome for those who survived. The simultaneous administration of intrathecal tetanus immunoglobulin tends to reduce mortality.

Clinical Autonomic Disorders: Evaluation and Management

Clinical Autonomic Disorders was compiled as a comprehensive summary of current knowledge about the diagnosis and treatment of autonomic dysfunction, with an emphasis on disorders of peripheral nerves. On the whole, Dr Low has fulfilled that ambition. Although the book clearly reflects the author's own special interests, both as a clinician dealing with autonomic neuropathies and as founder of an autonomic laboratory at the Mayo Clinic, its 800 pages and 56 chapters present a broad view of autonomic function and failure. It is reasonably up-to-date, references in most chapters extending to 1991. The massive text is organized into three major sections: basic science, clinical evaluation, and clinical disorders. This plan inevitably leads to repetition and overlap, but, if the book is used as a source of individual short monographs, this may not be a problem. Careful attention by the editor has ensured good consistency among the authors, so that there

The treatment of autonomic dysfunction.

Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs.

Disorders of the autonomic nervous system: Part 2. Investigation and treatment.

Autonomic function may be adequately tested with noninvasive tests of sympathetic and parasympathetic pathways, including: the response of blood pressure to change in posture and isometric contraction, heart rate response to standing, variation in heart rate with respiration, Valsalva ratio, sweat tests, and plasma noradrenaline measurements. Abnormal results in two or more of these tests indicate autonomic dysfunction. Intraarterial catheterization and tests of vasomotor function are usually required only in doubtful cases or for research purposes. Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension. Orthostatic hypotension is best treated with physical measures, pharmacologically with 9-alpha-fluorohydrocortisone and dihydroergotamine mesylate. A number of other agents may be tried but results have been less effective.