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617: Efficacy of conservative treatment, fludrocortisone, and domperidone for symptomatic orthostatic hypotension in Parkinson’s disease
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Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040
enables anticipatory monitoring for disease complications and identifies therapeutic options for affected children. A regional variant with predominant facial, neck and arm weakness without sensory loss has been reported in adults but only very rarely described in childhood. We report clinical and neurophysiologic findings in two children with the pharyngeal-cervical-brachial form of Guillain-Barre´ syndrome. These are the youngest cases of this uncommon disorder reported to date. doi:10.1016/j.jocn.2007.02.045
615: A study on stem cell function in the ischemia-damaged area after stroke Aria Omrani; NanoMedical Studies Group, Iran Studies in neonatal mice show that if neural stem cells (NSCs) are seeded on synthetic extracellular matrix and implanted into an ischemia-damaged area, then new parenchyma composed of neurons and glia is formed and becomes vascularized. Findings by Eriksson et al indicated neurogenesis from precursors in the subventricular zone (SVZ) in vivo in humans, and precursors capable of forming neurons in human subcortical white matter. For efficient repair after stroke it may be necessary to provide NSCs with a platform so that they can reform appropriate brain structure and connections. However, NSCs are concentrated along the subventricular zone, and their migration to the zone of infarction is limited by a long migratory pathway. Bone marrow cells, being distributed throughout all tissues by the bloodstream, have easy access to the zone of infarction. Brain injury, specifically cerebral ischemia, enhances bone marrow plasticity and provides an environment that supports the differentiation of bone marrow-derived cells into endothelial cells and neurons. Neovascularization of the peripheral and coronary vasculature can be enhanced by the exogenous delivery of bone marrowderived endothelial progenitor cells (EPCs). Some animal studies indicate intrastriatal and intravenous delivery of marrow stromal cells results in a small percentage of these cells expressing neuronal markers in ischemic brain. Considering the differentiation of bone marrow-derived progenitor cells into endothelial cells and NeuN-expressing cells , the utility of bone marrow–derived cells offers a novel potential treatment for stroke. The type of functional recovery after stroke depends on the site of implantation. Some studies report no recovery of sensorimotor function in rats with intraventricular grafts, whereas animals with intraparenchymal grafts either ipsilateral or contralateral to the lesion have shown reduced sensorimotor asymmetry. doi:10.1016/j.jocn.2007.02.046
616: Axonal excitability properties in hemifacial spasm Arun V. Krishnan a, Michael Hayes b, Matthew C. Kiernan a; a Prince of Wales Medical Research Institute and Prince of Wales Hospital; b Concord Hospital Introduction: Hemifacial spasm (HFS) is characterised by involuntary, irregular contractions of muscles innervated by the facial nerve. Whether the facial nerve has a relative predisposition for ectopic activity has not been clarified, nor has the process through which these abnormal responses are generated. Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, may provide further insights into the pathophysiology of HFS. Method: The excitability properties of the facial nerve were initially measured in a group of control subjects looking for biophysical differences that may predispose the facial nerve to ectopic activity. In a second series of studies, patients with HFS were investigated. In total, compound muscle action potentials were recorded from nasalis in 12 controls and 9 HFS patients following stimulation of the facial nerve anterior to the earlobe. Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100-ms polarizing currents, a current threshold relationship and the recovery of excitability following supramaximal stimulation were recorded on both affected and unaffected sides in HFS patients. Results: When compared to normative data from the upper (median nerve) and lower limbs (tibial nerve), there was ‘fanning-in’ of threshold electrotonus, reduced superexcitability and increased subexcitability in facial nerve studies (P < 0.05), consistent with relative axonal depolarisation. In subsequent studies in HFS patients, there were no significant differences in distal facial nerve excitability properties from the affected side in HFS patients when compared either to the unaffected side or to normative facial nerve data. Conclusion: A relative depolarisation of the facial nerve in control studies may suggest a propensity for this nerve to develop ectopic impulse activity. Peripheral facial nerve studies in HFS patients suggest that ectopic impulse generation arises from a more proximal or central location such as the facial nerve nucleus. doi:10.1016/j.jocn.2007.02.047
617: Efficacy of conservative treatment, fludrocortisone, and domperidone for symptomatic orthostatic hypotension in Parkinson’s disease Kerrie L. Schoffer, John D. O’Sullivan, Karen O’Maley, Robert Henderson; Royal Brisbane and Women’s Hospital Purpose: Orthostatic hypotension (OH) is the most frequently reported autonomic feature of Idiopathic Parkin-
Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040
son’s Disease (IPD), and contributes to cognitive decline, morbidity, and overall mortality. There is no scientific evidence demonstrating efficacy of any antihypotensive therapies in this patient group. In this study, we sought to investigate three treatments (conservative therapy, fludrocortisone, and domperidone) for symptomatic OH in IPD. Methods: Phase I assessed patient compliance and overall efficacy of conservative measures. Phase II was a double-blind randomized controlled trial of domperidone and fludrocortisone in a crossover design, with primary outcome measures consisting of two previously validated questionnaires, a clinical global impression of change (CGI), and tilt table testing in our autonomic laboratory. Results: 17 patients with IPD were studied. Conservative therapy did not significantly alter any of the outcome measures, although patients found compliance difficult. There was a statistically significant improvement in scoring on the orthostatic component of the Autonomic Symptom Profile questionnaire for both fludrocortisone and domperidone, with fludrocortisone having greater effect. CGI scores improved on both medications and there was nonsignificant trend towards reduced systolic and diastolic blood pressure drop on tilt table testing, with domperidone trending towards a greater effect. Conclusions: Efficacy and compliance with conservative therapy in IPD patients may be limited by disease related factors. Both fludrocortisone and domperidone are efficacious in the treatment of orthostatic hypotension in IPD, resulting in a significant change in patients’ subjective symptomatology, as well as a trend towards improvement on autonomic parameters. doi:10.1016/j.jocn.2007.02.048
618: Is there a role for peripheral C nociceptors in pathopysiology and treatment of neuropathic pain after spinal cord injury – a case report Gunnar L. Wasner a, Dennis Naleschinski b, Ralf b a Baron ; University of New South Wales; b University of Schleswig-Holstein, Germany Chronic neuropathic pain following spinal cord injury (SCI) due to lesions of nervous tissue occurs in about 30% of the patients. Treatment of neuropathic pain is inadequate, because the underlying mechanisms are not well understood. Based on animal experiments it is generally thought that pain originates at the spinal level of injury without any influence from the periphery. Here we present the case of a SCI patient with evidence for contribution of peripheral C nociceptors to his neuropathic pain. A 54-year-old male had suffered from severe ongoing burning pain at both medial aspects of his distal thighs
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for three years after an incomplete lesion of the spinal cord at T 12 level (ASIA C). Quantitative sensory testing in the painful area revealed mechanical dynamic and pinprick hyperalgesia and a loss of any cold and heat pain perception within the range of 0–50 °C. However, topical application of capsaicin (which activates and sensitises heat sensitive C nociceptors) induced continuous burning pain of considerable magnitude, an increase in dynamic hyperalgesia and a drop in heat pain threshold to 35.4 °C, i.e. heat hyperalgesia. Topical application of locally acting lidocaine patches (5%) within the painful area for 7 days reduced both ongoing pain and mechanical allodynia by 43%. The initial finding of an absence of thermal pain perception would indicate severe denervation of peripheral C nociceptors. In this case, mechanical allodynia is suggested to be due to central sensitisation at spinal level to the input of preserved A fibre afferents. However, the pain-enhancing effect of capsaicin which activates peripheral C nociceptors and the pain-relieving effect of topical lidocaine which inhibits C fibre activity indicates a crucial role for peripheral C nociceptors in pain generation in this patient. Supported by the Alexander von Humboldt-Foundation and the Spinal Injuries Research Centre (SIRC) of the Prince of Wales Medical Research Institute. doi:10.1016/j.jocn.2007.02.049
619: Preserved cognition and functional independence after a large right PCA infarct: longitudinal clinical and neuropathological findings Olivier Piguet a, Hayley P. Bennett a, Louise M. Waite b, Jillian J. Kril b, Helen Creasey b, G. Anthony Broe a, Glenda M. Halliday a; a Prince of Wales Medical, Research Institute and The University of New South Wales; b University of Sydney BVR was a 77-year-old gentleman who sustained a large infarct in the territory of the posterior cerebral (PCA) artery. Medical and neurological examination, cognitive assessment and evaluation of functional independence were collected on four occasions over a 10-year period. The initial examination performed 2 years poststroke revealed only a mild gait abnormality and a left homonymous hemianopia but no functional or cognitive deficits. BVR showed no signs of visual neglect, no memory deficit, no evidence of prosopagnosia or spatial disorientation. Over the next 6 years, neurological signs became progressively more pronounced (impaired hand coordination and postural instability) accompanied by a mild increase in apathy. Functional independence and cognition were maintained. It is only at the age of 87 years and after two other strokes that BVR’s level of independence and cognitive functioning became
Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040
enables anticipatory monitoring for disease complications and identifies therapeutic options for affected children. A regional variant with predominant facial, neck and arm weakness without sensory loss has been reported in adults but only very rarely described in childhood. We report clinical and neurophysiologic findings in two children with the pharyngeal-cervical-brachial form of Guillain-Barre´ syndrome. These are the youngest cases of this uncommon disorder reported to date. doi:10.1016/j.jocn.2007.02.045
615: A study on stem cell function in the ischemia-damaged area after stroke Aria Omrani; NanoMedical Studies Group, Iran Studies in neonatal mice show that if neural stem cells (NSCs) are seeded on synthetic extracellular matrix and implanted into an ischemia-damaged area, then new parenchyma composed of neurons and glia is formed and becomes vascularized. Findings by Eriksson et al indicated neurogenesis from precursors in the subventricular zone (SVZ) in vivo in humans, and precursors capable of forming neurons in human subcortical white matter. For efficient repair after stroke it may be necessary to provide NSCs with a platform so that they can reform appropriate brain structure and connections. However, NSCs are concentrated along the subventricular zone, and their migration to the zone of infarction is limited by a long migratory pathway. Bone marrow cells, being distributed throughout all tissues by the bloodstream, have easy access to the zone of infarction. Brain injury, specifically cerebral ischemia, enhances bone marrow plasticity and provides an environment that supports the differentiation of bone marrow-derived cells into endothelial cells and neurons. Neovascularization of the peripheral and coronary vasculature can be enhanced by the exogenous delivery of bone marrowderived endothelial progenitor cells (EPCs). Some animal studies indicate intrastriatal and intravenous delivery of marrow stromal cells results in a small percentage of these cells expressing neuronal markers in ischemic brain. Considering the differentiation of bone marrow-derived progenitor cells into endothelial cells and NeuN-expressing cells , the utility of bone marrow–derived cells offers a novel potential treatment for stroke. The type of functional recovery after stroke depends on the site of implantation. Some studies report no recovery of sensorimotor function in rats with intraventricular grafts, whereas animals with intraparenchymal grafts either ipsilateral or contralateral to the lesion have shown reduced sensorimotor asymmetry. doi:10.1016/j.jocn.2007.02.046
616: Axonal excitability properties in hemifacial spasm Arun V. Krishnan a, Michael Hayes b, Matthew C. Kiernan a; a Prince of Wales Medical Research Institute and Prince of Wales Hospital; b Concord Hospital Introduction: Hemifacial spasm (HFS) is characterised by involuntary, irregular contractions of muscles innervated by the facial nerve. Whether the facial nerve has a relative predisposition for ectopic activity has not been clarified, nor has the process through which these abnormal responses are generated. Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, may provide further insights into the pathophysiology of HFS. Method: The excitability properties of the facial nerve were initially measured in a group of control subjects looking for biophysical differences that may predispose the facial nerve to ectopic activity. In a second series of studies, patients with HFS were investigated. In total, compound muscle action potentials were recorded from nasalis in 12 controls and 9 HFS patients following stimulation of the facial nerve anterior to the earlobe. Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100-ms polarizing currents, a current threshold relationship and the recovery of excitability following supramaximal stimulation were recorded on both affected and unaffected sides in HFS patients. Results: When compared to normative data from the upper (median nerve) and lower limbs (tibial nerve), there was ‘fanning-in’ of threshold electrotonus, reduced superexcitability and increased subexcitability in facial nerve studies (P < 0.05), consistent with relative axonal depolarisation. In subsequent studies in HFS patients, there were no significant differences in distal facial nerve excitability properties from the affected side in HFS patients when compared either to the unaffected side or to normative facial nerve data. Conclusion: A relative depolarisation of the facial nerve in control studies may suggest a propensity for this nerve to develop ectopic impulse activity. Peripheral facial nerve studies in HFS patients suggest that ectopic impulse generation arises from a more proximal or central location such as the facial nerve nucleus. doi:10.1016/j.jocn.2007.02.047
617: Efficacy of conservative treatment, fludrocortisone, and domperidone for symptomatic orthostatic hypotension in Parkinson’s disease Kerrie L. Schoffer, John D. O’Sullivan, Karen O’Maley, Robert Henderson; Royal Brisbane and Women’s Hospital Purpose: Orthostatic hypotension (OH) is the most frequently reported autonomic feature of Idiopathic Parkin-
Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040
son’s Disease (IPD), and contributes to cognitive decline, morbidity, and overall mortality. There is no scientific evidence demonstrating efficacy of any antihypotensive therapies in this patient group. In this study, we sought to investigate three treatments (conservative therapy, fludrocortisone, and domperidone) for symptomatic OH in IPD. Methods: Phase I assessed patient compliance and overall efficacy of conservative measures. Phase II was a double-blind randomized controlled trial of domperidone and fludrocortisone in a crossover design, with primary outcome measures consisting of two previously validated questionnaires, a clinical global impression of change (CGI), and tilt table testing in our autonomic laboratory. Results: 17 patients with IPD were studied. Conservative therapy did not significantly alter any of the outcome measures, although patients found compliance difficult. There was a statistically significant improvement in scoring on the orthostatic component of the Autonomic Symptom Profile questionnaire for both fludrocortisone and domperidone, with fludrocortisone having greater effect. CGI scores improved on both medications and there was nonsignificant trend towards reduced systolic and diastolic blood pressure drop on tilt table testing, with domperidone trending towards a greater effect. Conclusions: Efficacy and compliance with conservative therapy in IPD patients may be limited by disease related factors. Both fludrocortisone and domperidone are efficacious in the treatment of orthostatic hypotension in IPD, resulting in a significant change in patients’ subjective symptomatology, as well as a trend towards improvement on autonomic parameters. doi:10.1016/j.jocn.2007.02.048
618: Is there a role for peripheral C nociceptors in pathopysiology and treatment of neuropathic pain after spinal cord injury – a case report Gunnar L. Wasner a, Dennis Naleschinski b, Ralf b a Baron ; University of New South Wales; b University of Schleswig-Holstein, Germany Chronic neuropathic pain following spinal cord injury (SCI) due to lesions of nervous tissue occurs in about 30% of the patients. Treatment of neuropathic pain is inadequate, because the underlying mechanisms are not well understood. Based on animal experiments it is generally thought that pain originates at the spinal level of injury without any influence from the periphery. Here we present the case of a SCI patient with evidence for contribution of peripheral C nociceptors to his neuropathic pain. A 54-year-old male had suffered from severe ongoing burning pain at both medial aspects of his distal thighs
1023
for three years after an incomplete lesion of the spinal cord at T 12 level (ASIA C). Quantitative sensory testing in the painful area revealed mechanical dynamic and pinprick hyperalgesia and a loss of any cold and heat pain perception within the range of 0–50 °C. However, topical application of capsaicin (which activates and sensitises heat sensitive C nociceptors) induced continuous burning pain of considerable magnitude, an increase in dynamic hyperalgesia and a drop in heat pain threshold to 35.4 °C, i.e. heat hyperalgesia. Topical application of locally acting lidocaine patches (5%) within the painful area for 7 days reduced both ongoing pain and mechanical allodynia by 43%. The initial finding of an absence of thermal pain perception would indicate severe denervation of peripheral C nociceptors. In this case, mechanical allodynia is suggested to be due to central sensitisation at spinal level to the input of preserved A fibre afferents. However, the pain-enhancing effect of capsaicin which activates peripheral C nociceptors and the pain-relieving effect of topical lidocaine which inhibits C fibre activity indicates a crucial role for peripheral C nociceptors in pain generation in this patient. Supported by the Alexander von Humboldt-Foundation and the Spinal Injuries Research Centre (SIRC) of the Prince of Wales Medical Research Institute. doi:10.1016/j.jocn.2007.02.049
619: Preserved cognition and functional independence after a large right PCA infarct: longitudinal clinical and neuropathological findings Olivier Piguet a, Hayley P. Bennett a, Louise M. Waite b, Jillian J. Kril b, Helen Creasey b, G. Anthony Broe a, Glenda M. Halliday a; a Prince of Wales Medical, Research Institute and The University of New South Wales; b University of Sydney BVR was a 77-year-old gentleman who sustained a large infarct in the territory of the posterior cerebral (PCA) artery. Medical and neurological examination, cognitive assessment and evaluation of functional independence were collected on four occasions over a 10-year period. The initial examination performed 2 years poststroke revealed only a mild gait abnormality and a left homonymous hemianopia but no functional or cognitive deficits. BVR showed no signs of visual neglect, no memory deficit, no evidence of prosopagnosia or spatial disorientation. Over the next 6 years, neurological signs became progressively more pronounced (impaired hand coordination and postural instability) accompanied by a mild increase in apathy. Functional independence and cognition were maintained. It is only at the age of 87 years and after two other strokes that BVR’s level of independence and cognitive functioning became