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Ian J Baguley - One of the best experts on this subject based on the ideXlab platform.
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Dysautonomia after pediatric brain injury
Developmental medicine and child neurology, 2012Co-Authors: Ian J BaguleyAbstract:Dysautonomia is an under-recognized and often misdiagnosed condition following acquired brain injury. The condition is largely a diagnosis of exclusion, given that the cardinal signs of the disorder (hyperthermia, hypertension, tachycardia, tachypnoea, diaphoresis associated with muscle overactivity) are relatively non-specific and have multiple differential diagnoses. This has resulted in many clinicians not recognizing the condition, instead diagnosing it as opiate withdrawal or infection (organism not identified). This is not to say that patients with Dysautonomia do not get infections, only that not all temperatures are bacterial in origin. Part of the difficulty with the diagnosis of Dysautonomia has been a lack of adequate diagnostic criteria. While the use of diagnostic criteria has become more common in recent research, Kirk et al. go one step further than these observational systems by applying a statistical model to determining ‘caseness’. Their predictive model, incorporating hypertension, sweating, and dystonia, provides another means of thinking about the diagnosis of Dysautonomia. It is unlikely that this triad will be as useful in an adult rehabilitation population, where data shows that hypertension rarely persists more than 4 weeks post injury. Alternatively, recent research has suggested that over-reactivity to normally non-noxious stimuli is pathognomonic of the condition. Determining diagnostic criteria remains an area of ongoing research. Although under-diagnosed, Dysautonomia is a surprisingly common condition. Estimates of the incidence consistently fall around 10% of the sample across adult and paediatric samples, irrespective of whether the research is undertaken in the intensive care unit or in the rehabilitation setting. This high incidence is accompanied by a poorer prognosis across multiple studies, as measured by longer length of stay, poorer rehabilitation outcomes, greater likelihood of requiring longterm institutional care, and higher health care costs. While clinicians often assume that Dysautonomia and worse outcome are epiphenomena related to the severity of the patient’s injury (and hence unavoidable), this has yet to be shown in empirical research. Perhaps, controversially, there are multiple reasons to believe that Dysautonomia might produce secondary brain damage. As such, it is surprising that the condition has been completely ignored in prospective multicentre ⁄ international traumatic brain injury outcome studies. Furthermore, there is a sufficiently large body of research to suggest that it is inappropriate to ignore treatment of this condition on the basis that Dysautonomia ‘burns out’ over time. In a well-designed study of consecutive admissions to a rehabilitation centre, Kirk et al. provide further confirmatory evidence of the importance of the condition. The paper extends the limited paediatric literature on the condition, and in doing so highlights the overlap between the condition in children and that reported in the more extensive adult data set. Furthermore, their data confirms previous suggestions that the incidence of the condition is higher following severe hypoxic brain injury. Thus, while an estimated 80% of Dysautonomia cases in world literature result from traumatic brain injury, their work confirms that Dysautonomia is three times more common following cardiac arrest; it is only that severe hypoxic brain injury is a less common clinical scenario. While the majority of published research has used the term Dysautonomia, this appears to have been for accidental and historical reasons. By definition, the term Dysautonomia refers to any abnormality of autonomic function. Unfortunately, the use of such a generic label for a specific syndrome has caused additional confusion for a condition that many clinicians fail to recognize. For this reason, an international expert consensus group that I am chairing is promoting the use of the term paroxysmal sympathetic hyperactivity to identify the key clinical features of the condition.
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diagnosing Dysautonomia after acute traumatic brain injury evidence for overresponsiveness to afferent stimuli
Archives of Physical Medicine and Rehabilitation, 2009Co-Authors: Ian J Baguley, Roxana E Heriseanu, Shameran Slewayounan, Melissa Nott, Iain E PerkesAbstract:Abstract Baguley IJ, Nott MT, Slewa-Younan S, Heriseanu RE, Perkes IE. Diagnosing Dysautonomia after acute traumatic brain injury: evidence for overresponsiveness to afferent stimuli. Objective To differentiate between traumatic brain injury (TBI) subjects with normal and elevated autonomic activity by quantifying cardiac responsivity to nociceptive stimuli and to determine the utility of heart rate variability (HRV) and event-related heart rate changes in diagnosing Dysautonomia. Design Prospective cohort study. Setting Intensive care unit in a tertiary metropolitan trauma center. Participants Adults (N=27) with TBI recruited from 79 consecutive TBI admissions comprising 16 autonomically aroused and 11 control subjects matched by age, sex, and injury severity. Interventions None. Main Outcome Measures Immediate: pattern of autonomic changes indexed by HRV and event-related heart rate after nociceptive stimuli. Six months: length of stay, Glasgow Coma Scale, and Disability Rating Scale. Results Heart rate changes (for both HRV and event-related heart rate) were associated with the diagnostic group and 6-month outcome when evaluated pre- and poststimulus but not when evaluated at rest. When assessed on day 7 postinjury, the comparison of HRV and heart rate parameters suggested an overresponsivity to nociceptive stimuli in dysautonomic subjects. These subjects showed a 2-fold increase in mean heart rate relative to subjects with sympathetic arousal of short duration (16% vs 8%), and a 6-fold increase over nonaroused control subjects. Data suggest that post-TBI sympathetic arousal is a spectrum disorder comprising, at one end, a short-duration syndrome and, at the other end, a dramatic, severe sympathetic and motor overactivity syndrome that continued for many months postinjury and associated with a significantly worse 6-month outcome. These findings suggest that it is not the presence of reactivity per se but rather the failure of processes to control for overreactivity that contributes to dysautonomic storming. Conclusions This study provides empirical evidence that dysautonomic subjects show overresponsiveness to afferent stimuli. Findings from this study suggest an evidence-driven revision of diagnostic criteria and a simple clinical algorithm for the improved identification of cases.
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a critical review of the pathophysiology of Dysautonomia following traumatic brain injury
Neurocritical Care, 2008Co-Authors: Ian J Baguley, Roxana E Heriseanu, Ian D Cameron, Shameran Slewayounan, Melissa NottAbstract:The management of Dysautonomia following severe traumatic brain injury (TBI) remains problematic, primarily due to an inadequate understanding of the pathophysiology of the condition. While the original theories inferred an epileptogenic source, there is greater support for disconnection theories in the literature. Disconnection theories suggest that Dysautonomia follows the release of one or more excitatory centres from higher centre control. Conventional disconnection theories suggest excitatory centre/s located in the upper brainstem and diencephalon drive paroxysms. Another disconnection theory, the Excitatory:Inhibitory Ratio (EIR) Model, suggests the causative brainstem/diencephalic centres are inhibitory in nature, with damage releasing excitatory spinal cord processes. Review of the available data suggests that Dysautonomia follows structural and/or functional (for example raised intracerebral pressure or neurotransmitter blockade) abnormalities, with the tendency to develop Dysautonomic paroxysms being more closely associated with mesencephalic rather than diencephalic damage. Many reports suggest that paroxysmal episodes can be triggered by environmental events and minimised by various but predictable neurotransmitter effects. This article presents a critical review of the competing theories against the available observational, clinical and neurotransmitter evidence. Following this process, it is suggested that the EIR Model more readily explains pathophysiological and treatment data compared to conventional disconnection models. In particular, the EIR Model provides an explanatory model that encompasses other acute autonomic emergency syndromes, accommodates ‘triggering’ of paroxysms and provides a rationale for all known medication effects.
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gabapentin in the management of Dysautonomia following severe traumatic brain injury a case series
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: Ian J Baguley, Roxana E Heriseanu, Joseph A Gurka, Annette Nordenbo, Ian D CameronAbstract:The pharmacological management of Dysautonomia, otherwise known as autonomic storms, following acute neurological insults, is problematic and remains poorly researched. This paper presents six subjects with Dysautonomia following extremely severe traumatic brain injury where gabapentin controlled paroxysmal autonomic changes and posturing in the early post-acute phase following limited success with conventional medication regimens. In two subjects, other medications were reduced or ceased without a recurrence of symptoms. It is proposed that medications that can block or minimise abnormal afferent stimuli may represent a better option for Dysautonomia management than drugs which increase inhibition of efferent pathways. Potential mechanisms for these effects are discussed.
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Dysautonomia and heart rate variability following severe traumatic brain injury
Brain Injury, 2006Co-Authors: Ian J Baguley, Roxana E Heriseanu, Kim L Felmingham, Ian D CameronAbstract:Primary objective: To investigate disconnection theories postulated as the cause of Dysautonomia following severe traumatic brain injury (TBI) through analysis of heart rate variability (HRV).Methods and procedures: Data were collected on age-matched subjects with and without Dysautonomia (eight subjects in each group) and 16 non-injured controls. Data included injury details, continuous electrocardiograph recordings and rehabilitation outcome.Main outcomes and results: The TBI group revealed significant differences in HRV parameters both compared to controls and between dysautonomic and non-dysautonomic subjects. Additionally, HRV parameters for dysautonomic subjects showed evidence of an uncoupling of the normal relationship between heart rate and sympathetic/parasympathetic balance. HRV changes persisted for the Dysautonomia group for a mean of 14 months post-injury.Conclusions: Dysautonomic subjects revealed prolonged uncoupling of heart rate and HRV parameters compared to non-dysautonomic subjects an...
Felicia B Axelrod - One of the best experts on this subject based on the ideXlab platform.
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hereditary sensory autonomic neuropathy caused by a mutation in dystonin
Annals of Neurology, 2012Co-Authors: Simon Edvardson, Felicia B Axelrod, Channa Maayan, Yuval Cinnamon, Chaim Jalas, Avraham Shaag, Orly ElpelegAbstract:In 4 infants with a new lethal autonomic sensory neuropathy with clinical features similar to familial Dysautonomia as well as contractures, we identified a deleterious mutation in the DST gene, using homozygosity mapping followed by exome sequencing. DST encodes dystonin, a cytoskeleton linker protein, and the mutation results in an unstable transcript. Interestingly, dystonin is significantly more abundant in cells of familial Dysautonomia patients with IKBKAP (I-κ-B kinase complex-associated protein) mutation compared to fibroblasts of controls, suggesting that upregulation of dystonin is responsible for the milder course in familial Dysautonomia. Homozygosity mapping followed by exome sequencing is a successful approach to identify mutated genes in rare monogenic disorders.
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Neoplasia in Familial Dysautonomia: A 20-Year Review in a Young Patient Population
The Journal of pediatrics, 2009Co-Authors: Gabrielle Gold-von Simson, Eleny Romanos-sirakis, Channa Maayan, Felicia B AxelrodAbstract:We reviewed the charts of all patients with familial Dysautonomia (n = 631) and found that 2% had been diagnosed with tumors. We hypothesize that the IκB Kinase-associated protein gene mutation, which causes aberrant RNA splicing in patients with familial Dysautonomia, may contribute to tumorigenesis in this genetically homogenous patient population.
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familial Dysautonomia a review of the current pharmacological treatments
Expert Opinion on Pharmacotherapy, 2005Co-Authors: Felicia B AxelrodAbstract:Treatment of familial Dysautonomia, a genetic disorder affecting neuronal development and survival, has improved morbidity and survival for this disorder. Although this is primarily a neurological disorder causing sensory and autonomic dysfunction, there are secondary systemic perturbations affecting ophthalmological, gastrointestinal, respiratory, cardiovascular, orthopaedic and renal function. Penetrance is complete, but there is marked variability in expression. Preventative and supportive treatments have included measures to maintain eye moisture, fundoplication with gastrostomy, the use of central agents such as benzodiazepines and clonidine to control vomiting and the dysautonomic crisis, and fludrocortisone and midodrine to combat cardiovascular lability. With the identification of the familial Dysautonomia gene, it has been suggested that it may be possible to treat patients by modifying production and expression of the genetic product.
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Gastroesophageal reflux in familial Dysautonomia: correlation with crisis frequency and sensory dysfunction.
Journal of Pediatric Gastroenterology and Nutrition, 2005Co-Authors: Vinay Sundaram, Felicia B AxelrodAbstract:OBJECTIVES: Familial Dysautonomia (FD), a genetic disorder resulting in sensory and autonomic nervous system dysfunction, is associated with a high frequency of gastroesophageal reflux (GER). In this study the authors attempted to determine if GER prevalence correlated with dysautonomic crisis frequency and small fiber sensory dysfunction. METHODS: Of an initial population of 252 FD patients who had survived past their seventh year and were alive during the year of study from June 1, 2001 to June 1, 2002, 174 (69.0%) had sufficient data in their patient files to be included in this retrospective analysis. Subjects were stratified into three groups: those with no GER, those medically treated for GER and those surgically treated for GER with fundoplication. Data were obtained regarding frequency and severity of dysautonomic crises and sensory function including pain sensation, cold and warm thresholds and vibration perception. RESULTS: There were no significant differences among the three groups regarding age or severity of sensory dysfunction. However, dysautonomic crises were significantly more frequent in FD patients who were presumed to have more intractable GER, as they had required fundoplication (P < 0.05). CONCLUSIONS: The data confirm the high incidence of GER in the FD population and demonstrate that GER is independent of severity of sensory dysfunction. In addition, the authors demonstrate that fundoplication does not alleviate the central autonomic cause of retching, the dysautonomic crisis.
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Assessing microcirculation in familial Dysautonomia by laser Doppler flowmeter
Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 1998Co-Authors: M Weiser, Max-josef Hilz, Ludmila Bronfin, Felicia B AxelrodAbstract:Microcirculatory vasomotor responses to an α-adrenergic agonist and an antagonist were assessed in 11 familial Dysautonomia and nine control subjects by laser Doppler flowmetry. Using two iontophoresis machines, blood flow in the midclavicular areas was continuously monitored by two channel laser Doppler flowmeter. Simultaneously, the α-antagonist (0.5 mM phentolamine hydrochloride) and a control solution (0.9% saline) were iontophoresed at 200 μA for 15 min. The α-agonist (0.5 mM norepinephrine bitartrate) was then iontophoresed (20 μA) to both pretreated areas for progressively longer pulses separated by 3-min observation intervals (15, 30, 60, 90, 120 s). The familial Dysautonomia subject group had higher mean baseline perfusion with widely fluctuating baselines, especially on the phentolamine pretreated side (P=0.03). Saline iontophoresis significantly increased perfusion in the control group, but not in the familial Dysautonomia group (ANOVA:P=0.02 and 0.15, respectively). There was >100% increase in flow by the end of the saline observation period in seven of nine controls, but in only three of 11 familial Dysautonomia subjects. Phentolamine iontophoresis differentiated familial Dysautonomia subjects into responders and nonresponders by 7–8 min when all nine control subjects, but only five of 11 familial Dysautonomia subjects, had >200% increase in blood flow. Irrespective of pretreatment type, norepinephrine decreased blood flow in both familial Dysautonomia and control groups (ANOVA:P
Shameran Slewayounan - One of the best experts on this subject based on the ideXlab platform.
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diagnosing Dysautonomia after acute traumatic brain injury evidence for overresponsiveness to afferent stimuli
Archives of Physical Medicine and Rehabilitation, 2009Co-Authors: Ian J Baguley, Roxana E Heriseanu, Shameran Slewayounan, Melissa Nott, Iain E PerkesAbstract:Abstract Baguley IJ, Nott MT, Slewa-Younan S, Heriseanu RE, Perkes IE. Diagnosing Dysautonomia after acute traumatic brain injury: evidence for overresponsiveness to afferent stimuli. Objective To differentiate between traumatic brain injury (TBI) subjects with normal and elevated autonomic activity by quantifying cardiac responsivity to nociceptive stimuli and to determine the utility of heart rate variability (HRV) and event-related heart rate changes in diagnosing Dysautonomia. Design Prospective cohort study. Setting Intensive care unit in a tertiary metropolitan trauma center. Participants Adults (N=27) with TBI recruited from 79 consecutive TBI admissions comprising 16 autonomically aroused and 11 control subjects matched by age, sex, and injury severity. Interventions None. Main Outcome Measures Immediate: pattern of autonomic changes indexed by HRV and event-related heart rate after nociceptive stimuli. Six months: length of stay, Glasgow Coma Scale, and Disability Rating Scale. Results Heart rate changes (for both HRV and event-related heart rate) were associated with the diagnostic group and 6-month outcome when evaluated pre- and poststimulus but not when evaluated at rest. When assessed on day 7 postinjury, the comparison of HRV and heart rate parameters suggested an overresponsivity to nociceptive stimuli in dysautonomic subjects. These subjects showed a 2-fold increase in mean heart rate relative to subjects with sympathetic arousal of short duration (16% vs 8%), and a 6-fold increase over nonaroused control subjects. Data suggest that post-TBI sympathetic arousal is a spectrum disorder comprising, at one end, a short-duration syndrome and, at the other end, a dramatic, severe sympathetic and motor overactivity syndrome that continued for many months postinjury and associated with a significantly worse 6-month outcome. These findings suggest that it is not the presence of reactivity per se but rather the failure of processes to control for overreactivity that contributes to dysautonomic storming. Conclusions This study provides empirical evidence that dysautonomic subjects show overresponsiveness to afferent stimuli. Findings from this study suggest an evidence-driven revision of diagnostic criteria and a simple clinical algorithm for the improved identification of cases.
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a critical review of the pathophysiology of Dysautonomia following traumatic brain injury
Neurocritical Care, 2008Co-Authors: Ian J Baguley, Roxana E Heriseanu, Ian D Cameron, Shameran Slewayounan, Melissa NottAbstract:The management of Dysautonomia following severe traumatic brain injury (TBI) remains problematic, primarily due to an inadequate understanding of the pathophysiology of the condition. While the original theories inferred an epileptogenic source, there is greater support for disconnection theories in the literature. Disconnection theories suggest that Dysautonomia follows the release of one or more excitatory centres from higher centre control. Conventional disconnection theories suggest excitatory centre/s located in the upper brainstem and diencephalon drive paroxysms. Another disconnection theory, the Excitatory:Inhibitory Ratio (EIR) Model, suggests the causative brainstem/diencephalic centres are inhibitory in nature, with damage releasing excitatory spinal cord processes. Review of the available data suggests that Dysautonomia follows structural and/or functional (for example raised intracerebral pressure or neurotransmitter blockade) abnormalities, with the tendency to develop Dysautonomic paroxysms being more closely associated with mesencephalic rather than diencephalic damage. Many reports suggest that paroxysmal episodes can be triggered by environmental events and minimised by various but predictable neurotransmitter effects. This article presents a critical review of the competing theories against the available observational, clinical and neurotransmitter evidence. Following this process, it is suggested that the EIR Model more readily explains pathophysiological and treatment data compared to conventional disconnection models. In particular, the EIR Model provides an explanatory model that encompasses other acute autonomic emergency syndromes, accommodates ‘triggering’ of paroxysms and provides a rationale for all known medication effects.
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pharmacological management of Dysautonomia following traumatic brain injury
Brain Injury, 2004Co-Authors: Ian J Baguley, Ian D Cameron, Alisa Green, Shameran Slewayounan, Jeno E Marosszeky, Joseph A GurkaAbstract:Primary objective: To document and critically evaluate the likely effectiveness of pharmacological treatments used in a sample of patients with Dysautonomia and to link these findings to previously published literature. Research design: Retrospective case control chart review. Methods and procedures: Data were collected on age, sex and GCS matched subjects with and without Dysautonomia (35 cases and 35 controls). Data included demographic and injury details, physiological parameters, medication usage, clinical progress and rehabilitation outcome. Descriptive analyses were undertaken to characterize the timing and frequency of CNS active medications. Main outcomes and results: Dysautonomic patients were significantly more likely to receive neurologically active medications. A wide variety of drugs were utilised with the most frequent being morphine/midazolam and chlorpromazine. Cessation of morphine/midazolam produced significant increases in heart rate and respiratory rate but not temperature. Chlorpromaz...
David S. Goldstein - One of the best experts on this subject based on the ideXlab platform.
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Comprehensive Physiology - Dysautonomia in Parkinson Disease
Comprehensive Physiology, 2014Co-Authors: David S. GoldsteinAbstract:Dysautonomias are conditions in which altered function of one or more components of the autonomic nervous system (ANS) adversely affects health. This review updates knowledge about Dysautonomia in Parkinson disease (PD). Most PD patients have symptoms or signs of Dysautonomia; occasionally, the abnormalities dominate the clinical picture. Components of the ANS include the sympathetic noradrenergic system (SNS), the parasympathetic nervous system (PNS), the sympathetic cholinergic system (SCS), the sympathetic adrenomedullary system (SAS), and the enteric nervous system (ENS). Dysfunction of each component system produces characteristic manifestations. In PD, it is cardiovascular Dysautonomia that is best understood scientifically, mainly because of the variety of clinical laboratory tools available to assess functions of catecholamine systems. Most of this review focuses on this aspect of autonomic involvement in PD. PD features cardiac sympathetic denervation, which can precede the movement disorder. Loss of cardiac SNS innervation occurs independently of the loss of striatal dopaminergic innervation underlying the motor signs of PD and is associated with other nonmotor manifestations, including anosmia, REM behavior disorder, orthostatic hypotension (OH), and dementia. Autonomic dysfunction in PD is important not only in clinical management and in providing potential biomarkers but also for understanding disease mechanisms (e.g., autotoxicity exerted by catecholamine metabolites). Since Lewy bodies and Lewy neurites containing alpha-synuclein constitute neuropathologic hallmarks of the disease, and catecholamine depletion in the striatum and heart are characteristic neurochemical features, a key goal of future research is to understand better the link between alpha-synucleinopathy and loss of catecholamine neurons in PD.
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Dysautonomia in parkinson disease
Comprehensive Physiology, 2014Co-Authors: David S. GoldsteinAbstract:Dysautonomias are conditions in which altered function of one or more components of the autonomic nervous system (ANS) adversely affects health. This review updates knowledge about Dysautonomia in Parkinson disease (PD). Most PD patients have symptoms or signs of Dysautonomia; occasionally, the abnormalities dominate the clinical picture. Components of the ANS include the sympathetic noradrenergic system (SNS), the parasympathetic nervous system (PNS), the sympathetic cholinergic system (SCS), the sympathetic adrenomedullary system (SAS), and the enteric nervous system (ENS). Dysfunction of each component system produces characteristic manifestations. In PD, it is cardiovascular Dysautonomia that is best understood scientifically, mainly because of the variety of clinical laboratory tools available to assess functions of catecholamine systems. Most of this review focuses on this aspect of autonomic involvement in PD. PD features cardiac sympathetic denervation, which can precede the movement disorder. Loss of cardiac SNS innervation occurs independently of the loss of striatal dopaminergic innervation underlying the motor signs of PD and is associated with other nonmotor manifestations, including anosmia, REM behavior disorder, orthostatic hypotension (OH), and dementia. Autonomic dysfunction in PD is important not only in clinical management and in providing potential biomarkers but also for understanding disease mechanisms (e.g., autotoxicity exerted by catecholamine metabolites). Since Lewy bodies and Lewy neurites containing alpha-synuclein constitute neuropathologic hallmarks of the disease, and catecholamine depletion in the striatum and heart are characteristic neurochemical features, a key goal of future research is to understand better the link between alpha-synucleinopathy and loss of catecholamine neurons in PD.
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SYMPATHETIC CARDIONEUROPATHY IN DysautonomiaS
Advances in pharmacology (San Diego Calif.), 1998Co-Authors: David S. Goldstein, Courtney Holmes, Richard O. Cannon, Graeme Eisenhofer, Irwin J. KopinAbstract:Background The classification of Dysautonomias has been confusing, and the pathophysiology obscure. We examined sympathetic innervation of the heart in patients with acquired, idiopathic Dysautonomias using thoracic positron-emission tomography and assessments of the entry rate of the sympathetic neurotransmitter norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover). We related the laboratory findings to signs of sympathetic neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure responses associated with the Valsalva maneuver), central neural degeneration, and responsiveness to treatment with levodopa–carbidopa (Sinemet). Methods Cardiac scans were obtained after intravenous administration of 6-[18F]fluorodopamine in 26 patients with Dysautonomia. Fourteen had sympathetic neurocirculatory failure — three with no signs of central neurodegeneration (pure autonomic failure), two with parkinsonism responsive to treatment with levodopa–carbidopa, and nine wit...
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Sympathetic cardioneuropathy in Dysautonomias.
The New England journal of medicine, 1997Co-Authors: David S. Goldstein, Courtney Holmes, Richard O. Cannon, Graeme Eisenhofer, Irwin J. KopinAbstract:Background The classification of Dysautonomias has been confusing, and the pathophysiology obscure. We examined sympathetic innervation of the heart in patients with acquired, idiopathic Dysautonomias using thoracic positron-emission tomography and assessments of the entry rate of the sympathetic neurotransmitter norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover). We related the laboratory findings to signs of sympathetic neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure responses associated with the Valsalva maneuver), central neural degeneration, and responsiveness to treatment with levodopa-carbidopa (Sinemet). Methods Cardiac scans were obtained after intravenous administration of 6-[ 18 F]fluorodopamine in 26 patients with Dysautonomia. Fourteen had sympathetic neurocirculatory failure - three with no signs of central neurodegeneration (pure autonomic failure), two with parkinsonism responsive to treatment with levodopa-carbidopa, and nine with central neurodegeneration unresponsive to treatment with levodopa-carbidopa (the Shy-Drager syndrome). The rates of cardiac norepinephrine spillover were estimated on the basis of concentrations of intravenously infused [ 3 H]norepinephrine during catheterization of the right side of the heart. Results Patients with pure autonomic failure or parkinsonism and sympathetic neurocirculatory failure had no myocardial 6-[ 18 F]fluorodopamine-derived radioactivity or cardiac norepinephrine spillover, indicating loss of myocardial sympathetic-nerve terminals, whereas patients with the Shy-Drager syndrome had increased levels of 6-[ 18 F]fluorodopamine-derived radioactivity, indicating intact sympathetic terminals and absent nerve traffic. Patients with Dysautonomia who did not have sympathetic neurocirculatory failure had normal levels of 6-[ 18 F]fluorodopamine-derived radioactivity in myocardium and normal rates of cardiac norepinephrine spillover. Conclusions The results of 6-[ 18 F]fluorodopamine positron-emission tomography and neurochemical analyses support a new clinical pathophysiologic classification of Dysautonomias, based on the occurrence of sympathetic neurocirculatory failure, signs of central neurodegeneration, and responsiveness to levodopa-carbidopa.
Ian D Cameron - One of the best experts on this subject based on the ideXlab platform.
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a critical review of the pathophysiology of Dysautonomia following traumatic brain injury
Neurocritical Care, 2008Co-Authors: Ian J Baguley, Roxana E Heriseanu, Ian D Cameron, Shameran Slewayounan, Melissa NottAbstract:The management of Dysautonomia following severe traumatic brain injury (TBI) remains problematic, primarily due to an inadequate understanding of the pathophysiology of the condition. While the original theories inferred an epileptogenic source, there is greater support for disconnection theories in the literature. Disconnection theories suggest that Dysautonomia follows the release of one or more excitatory centres from higher centre control. Conventional disconnection theories suggest excitatory centre/s located in the upper brainstem and diencephalon drive paroxysms. Another disconnection theory, the Excitatory:Inhibitory Ratio (EIR) Model, suggests the causative brainstem/diencephalic centres are inhibitory in nature, with damage releasing excitatory spinal cord processes. Review of the available data suggests that Dysautonomia follows structural and/or functional (for example raised intracerebral pressure or neurotransmitter blockade) abnormalities, with the tendency to develop Dysautonomic paroxysms being more closely associated with mesencephalic rather than diencephalic damage. Many reports suggest that paroxysmal episodes can be triggered by environmental events and minimised by various but predictable neurotransmitter effects. This article presents a critical review of the competing theories against the available observational, clinical and neurotransmitter evidence. Following this process, it is suggested that the EIR Model more readily explains pathophysiological and treatment data compared to conventional disconnection models. In particular, the EIR Model provides an explanatory model that encompasses other acute autonomic emergency syndromes, accommodates ‘triggering’ of paroxysms and provides a rationale for all known medication effects.
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gabapentin in the management of Dysautonomia following severe traumatic brain injury a case series
Journal of Neurology Neurosurgery and Psychiatry, 2006Co-Authors: Ian J Baguley, Roxana E Heriseanu, Joseph A Gurka, Annette Nordenbo, Ian D CameronAbstract:The pharmacological management of Dysautonomia, otherwise known as autonomic storms, following acute neurological insults, is problematic and remains poorly researched. This paper presents six subjects with Dysautonomia following extremely severe traumatic brain injury where gabapentin controlled paroxysmal autonomic changes and posturing in the early post-acute phase following limited success with conventional medication regimens. In two subjects, other medications were reduced or ceased without a recurrence of symptoms. It is proposed that medications that can block or minimise abnormal afferent stimuli may represent a better option for Dysautonomia management than drugs which increase inhibition of efferent pathways. Potential mechanisms for these effects are discussed.
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Dysautonomia and heart rate variability following severe traumatic brain injury
Brain Injury, 2006Co-Authors: Ian J Baguley, Roxana E Heriseanu, Kim L Felmingham, Ian D CameronAbstract:Primary objective: To investigate disconnection theories postulated as the cause of Dysautonomia following severe traumatic brain injury (TBI) through analysis of heart rate variability (HRV).Methods and procedures: Data were collected on age-matched subjects with and without Dysautonomia (eight subjects in each group) and 16 non-injured controls. Data included injury details, continuous electrocardiograph recordings and rehabilitation outcome.Main outcomes and results: The TBI group revealed significant differences in HRV parameters both compared to controls and between dysautonomic and non-dysautonomic subjects. Additionally, HRV parameters for dysautonomic subjects showed evidence of an uncoupling of the normal relationship between heart rate and sympathetic/parasympathetic balance. HRV changes persisted for the Dysautonomia group for a mean of 14 months post-injury.Conclusions: Dysautonomic subjects revealed prolonged uncoupling of heart rate and HRV parameters compared to non-dysautonomic subjects an...
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pharmacological management of Dysautonomia following traumatic brain injury
Brain Injury, 2004Co-Authors: Ian J Baguley, Ian D Cameron, Alisa Green, Shameran Slewayounan, Jeno E Marosszeky, Joseph A GurkaAbstract:Primary objective: To document and critically evaluate the likely effectiveness of pharmacological treatments used in a sample of patients with Dysautonomia and to link these findings to previously published literature. Research design: Retrospective case control chart review. Methods and procedures: Data were collected on age, sex and GCS matched subjects with and without Dysautonomia (35 cases and 35 controls). Data included demographic and injury details, physiological parameters, medication usage, clinical progress and rehabilitation outcome. Descriptive analyses were undertaken to characterize the timing and frequency of CNS active medications. Main outcomes and results: Dysautonomic patients were significantly more likely to receive neurologically active medications. A wide variety of drugs were utilised with the most frequent being morphine/midazolam and chlorpromazine. Cessation of morphine/midazolam produced significant increases in heart rate and respiratory rate but not temperature. Chlorpromaz...
