- Email: [email protected]
IN22-TU-02 Thrombolysis in the area of limited resources
19th World Congress of Neurology, Invited Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S5–S56
by mask or pressure bag and dexamethasone are effective HACE treatments. If mild HACE is treated promptly most cases resolve over several days. Once in coma, death is likely. Retinal haemorrhages: Altitude-related symptomless retinal haemorrhages were described in the 1970s. Occasionally, a florid retinopathy develops with visual loss. Stroke: Transient hemiparesis is sometimes seen with papilledema during HACE. Thrombotic infarction is presumed to cause more substantial hemiparesis: polycythemia, dehydration and cold probably contribute. Seizures, syncope, migraine, TIAs and funny turns: Occasionally an isolated seizure occurs when going high, but people whose epilepsy is well-controlled rarely have problems. In HACE, seizures are unusual. Syncope and near syncope are common during AMS. AMS can begin with a classical migraine. Transient aphasia has been noted. Other “funny turns”, some probably non-epileptic attacks, are common. Other phenomena: Over 10 million people live around 4000 m with few ill-effects. Chronic Mountain Sickness is fatigue/headache with polycythemia seen in high altitude residents. Permanent habitation is impossible above 6000 m. Deterioration is the steady decline in energy above 6500 m. Cognitive changes are common. Confusion and hallucinations occur above 8000 m. IN21-TU-03 Space neurology and the transfer of research results in the clinical praxis I.B. Kozlovskaya. Neurophysiology, Institute of Biomedical Problems, Moscow, Russian Federation Purpose: It was shown in space flight and on ground simulation studies that a trigger for development of all set of weightlessness negative effects, including muscular detraining, motor control disorders, orthostatic insufficiency and others is the elimination of support stimulation which is followed by essential decrease of tonic system activity. A wide spectrum of means for activation of tonic mechanisms in microgravity such as axial loading suit, mechanical stimulator of sole support zones and low-frequency myostimulator have been developed and used successfully for preventing development of hypokinetic disorders in space flights. Method: Taking into account the similarities of the nature of sensorymotor disturbances caused by microgravity and those, mediated by pathological processes, a wide program of works directed to implement, preventive measures of hypokinetic syndrome, in practice of rehabilitation of patients, suffering heavy motor disturbances, caused by perinatal encephalopathy, ICP, ischemic stroke, traumatic brain injury and other diseases. Results: Space medical technologies adapted for clinical practice showed their high efficacy in rehabilitation practice. Axial loading suit became the main mean of rehabilitation in patients with ICP and was successfully used more than in 70 Russian Centers. The new clinical type of this suit was suggested for rehabilitation of patients with an ischemic stroke, Parkinson’s disease and traumatic brain injury. There was confirmed also a high efficacy of other implemented means such as pneumatic stimulator of sole support zones, low-frequency myoelectricstimulator and dry immersion tank. Conclusion: Reducing the depth of sensorymotor disturbances, new rehabilitation means help faster recovery of health and motor activity of patients and to increase the possibilities of social adaptation, improving the quality of patients life.
S19
IN22 – Stroke 5: treatment in stroke IN22-TU-01 Current status of carotid artery stenting (CAS) N. Sakai, H. Adachi, Y. Ueno, T. Kunieda, C. Sakai, H. Yamagami, H. Imamura, M. Koyanagi, K. Todo, S. Yamamoto, Y. Kuramoto, N. Kohara, H. Kikuchi. Neurosurgery and Stroke Center, Kobe City General Hospital Neuroendovascular Therapy, Institute for Biomedical Research and Innovation, Kobe, Japan Carotid artery stenting (CAS) is increasingly being used for treatment of symptomatic and asymptomatic carotid artery diseases. We have been doing CAS since 1997 with several divices, and Prexise/Angioguard XP have been used since approved in 2007. To report our experience and current Japanese status about CAS. In my experience of 909 patients, 993 CAS procedures had been performed with cerebral protection, except for initial 75 cases with balloon expandable stent. Current standard procedure of CAS is as follows: under local anesthesia, trans-femoral approach, using 8F guiding catheter, cross the lesion with Angioguard XP, open the filter, pre-dilation with low profile 3.5–4.0mm PTA balloon, deploy self-expanding stent(Precise) followed by post-PTA and aspirate blood if necessary. Finally, capure Angioguard XP, if filter device is not indicated fro embolic protection, distal balloon or proximal protection will be used. Embolic events were checked by TCD and MRI/DWI. The stroke and death rate within 30 days was 2.1% and 0.4% respectively, and reversible ischemic neurologic symptoms occurred in 3.5%. In-stent-restenosis rate is 6.7%, and no ipsilateral stroke, related to carotid diseases, occurred after 120 days of CAS. However, another stroke, cardiovascular events and malignant diseases occurred in over 30% of patients. On the basis of our series, the use of cerebral protection devices appears to reduce thromboembolic complications during CAS, and management of cardiovascular events and medical condition by cardiologist is essential for successful treatment of carotid diseases. IN22-TU-02 Thrombolysis in the area of limited resources N.C. Suwanwela. Department of Medicine, Chulalongkorn University, Bangkok, Thailand Eighty-seven percent of stroke mortality occurs in the lower and middle income population. It is projected that within the next 10–12 years, the incidence of stroke will be much greater in this particular class of population than those with higher income. Intravenous thrombolytic therapy has been recommended as a standard treatment for acute ischemic stroke in most clinical practice guidelines. However, in countries with limited resources, the uptake of evidence into clinical practice is very slow. The major obstacles behind are the short therapeutic window and the limited knowledge/experience of physicians. Moreover, the cost associated with this treatment is a main factor determining its utilization in many hospitals. In Thailand, we started by setting up a stroke fast track program at a tertiary care hospital to use as a model. After the establishment of the treatment efficacy in the tertiary care hospital, the neurological association, the stroke society together with other medical professional societies were able to convince the government funding agency to adopt the program and expand the treatment to regional hospitals. Top up payment for the cost of medication and program setup, as well as special training was provided for participated hospital. We also have campaigns to increase public awareness about stroke. With this setting, the number of thrombolytic cases in Thailand has rapidly increased more than double during the past year and more patients in the rural area received the treatment. In conclusion, in countries with limited resources, the use of intravenous thrombolysis in acute ischemic stroke is still not widely applied. This is partly due to high cost for the hospital infrastructure setup as well as the cost of medications. Therefore, collaboration between stroke
S20
19th World Congress of Neurology, Invited Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S5–S56
physicians, emergency medical service team, stroke unit personnel, professional societies, policy makers and the health care funding agencies are the key to success. IN22-TU-03 Stroke units – how to organize stroke care services M. Brainin. Center Clinical Neurosciences, Danube University, Krems, Austria A stroke unit is hospital department that provides organized care exclusively for patients suffering from stroke. This is characterized by coordinated multidisciplinary care directed at emergency handling of stroke patients, performing prompt clinical and imaging diagnosis and providing available therapy immediately. Continuous monitoring, preventing complications, treating comorbidity, and early mobilisation are crucial components. Preclinical efforts are directed at shortening admission times and avoiding in-hospital delays. Several such stroke units have been recommended in international guidelines which include in a step down fashion comprehensive (tertiary care) stroke units, stroke units with basic care, and general hospital care using stroke pathways. While not all these components have been tested in randomized trials it has been widely accepted that such care systems are very effective and many stroke registries show the extremely good performances in terms of effectiveness and reaching best possible outcomes. In Austria, for example, a system of such acute care units has been established which has transport times mostly under 45 minutes and a thrombolysis rate, which has improved between 2003 to 2008 from 4 to 13% of all admissions. The percentage of eligible thrombolysis patients reaching stroke units within 2 hours of stroke onset has now reached a thrombolysis rate of more than 50%. Systematic care for acute stroke can be established by means of acute stroke units directed at avoiding in-hospital delays and offering best possible acute therapy, preventing complications and early mobilisation.
IN23 – Child neurology 1 IN23-TU-01 Myopathy: update in diagnosis and treatment – focusing on metabolic myopathies I. Nishino. Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan Among various muscle diseases, metabolic myopathies are probably one of the most important topics as many of these conditions are treatable. I will discuss metabolic myopathies and focus on Pompe disease and lipid dysmetabolism. Pompe disease is the only hereditary muscle disease for which curative treatment is available, as enzyme replacement therapy (ERT) has recently become available. Pompe disease can be classified into three forms: infantile, childhood and adult-onset. Patients with infantile form present with muscle hypotonia and hypertrophic cardiomyopathy. Most patients die within 1 year after birth without treatment, but with ERT, survival rate has been significantly improved. Muscle pathology shows marked vacuolar changes with glycogen accumulation and high acid phosphatase activity. The childhood and adult-onset forms are relatively milder, whereby patients exhibit limb-girdle muscle weakness and atrophy but usually do not show cardiomyopathy. In adult-onset cases the findings in muscle pathology can sometimes be minimal, thus many cases are probably overlooked. There are two major myopathic conditions due to lipid dysmetabolism. One condition is rhabdomyolysis. Determining the cause of rhabdomyolysis is often not easy as clinical and pathological features are usually nonspecific. Of note, however, very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency, which is probably the most common b-oxidation defect,
may be diagnosed by immunohistochemistry. The other myopathy due to lipid dysmetabolism is lipid storage myopathy, a condition diagnosed by its characteristic finding on muscle pathology. In our study, 3/4 of cases had no mutations in any of known causative genes, indicating that cause is still unknown in majority of cases. Nevertheless, treatment is available for carnitine deficiency and some cases of multiple acyl-CoA dehydrogenase deficiency, thus knowledge about these genetically identifiable and potentially treatable diseases are of relevance. IN23-TU-02 Interventional therapy for epilepsy A. Ikeda. Departments of Brain Pathophysiology and Neurology, Kyoto University School of Medicine, Kyoto, Japan IN23-TU-03 Genes and pathways implicated in malformations of cortical development H. Cross. Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom
IN24 – Multiple sclerosis 2 IN24-TU-01 Immunological and neurobiological interactions in multiple sclerosis R. Hohlfeld. Ludwig Maximilians University of Munich, Munich, Germany Multiple Sclerosis (MS) is the most frequently occurring inflammatory disease of the central nervous system. Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of the disease. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of tissue-infiltrating T and B cells. Novel candidate auto-antigens, including B-cell antigens, have been identified. Several promising immunological “biomarkers” with possible prognostic, diagnostic and therapeutic relevance have recently been described. One of these markers, antibody against aquaporin-4, has been suggested as a marker for a subtype of MS characterized by optico-spinal involvement. Much progress has also been made in understanding the milieu factors that make the CNS a very special and conducive environment for interactions between cells of the immune system and nervous system. Chemokines guide the migration of immune cells into MS lesions, and survival factors such as BAFF foster the long-term persistence of certain types of immune cells in the CNS environment. Intriguingly, tissue-infiltrating immune cells secrete neurotrophic factors, which might support the survival of some neuronal and glial cells. Altogether, these discoveries have shed new light on the immuno-pathogenesis of MS, and will make a strong impact on the development of novel therapies for this still incurable disease. IN24-TU-02 Aquaporin-4 autoimmunity T. Misu. Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan Recently, the disease-specific antibody was found in the serum from neuromyelitis optica (NMO) patients, and its target antigen was identified as aquaporin-4 (AQP4), mainly expressed in astroglial foot processes. However, the pathogenic role of AQP4 antibody in NMO has not been fully elucidated. In our immunohistochemical studies, the loss of AQP4 was evident in about 90% of NMO lesions, especially in perivascular areas of acute inflammatory lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) was also weak or lost in
by mask or pressure bag and dexamethasone are effective HACE treatments. If mild HACE is treated promptly most cases resolve over several days. Once in coma, death is likely. Retinal haemorrhages: Altitude-related symptomless retinal haemorrhages were described in the 1970s. Occasionally, a florid retinopathy develops with visual loss. Stroke: Transient hemiparesis is sometimes seen with papilledema during HACE. Thrombotic infarction is presumed to cause more substantial hemiparesis: polycythemia, dehydration and cold probably contribute. Seizures, syncope, migraine, TIAs and funny turns: Occasionally an isolated seizure occurs when going high, but people whose epilepsy is well-controlled rarely have problems. In HACE, seizures are unusual. Syncope and near syncope are common during AMS. AMS can begin with a classical migraine. Transient aphasia has been noted. Other “funny turns”, some probably non-epileptic attacks, are common. Other phenomena: Over 10 million people live around 4000 m with few ill-effects. Chronic Mountain Sickness is fatigue/headache with polycythemia seen in high altitude residents. Permanent habitation is impossible above 6000 m. Deterioration is the steady decline in energy above 6500 m. Cognitive changes are common. Confusion and hallucinations occur above 8000 m. IN21-TU-03 Space neurology and the transfer of research results in the clinical praxis I.B. Kozlovskaya. Neurophysiology, Institute of Biomedical Problems, Moscow, Russian Federation Purpose: It was shown in space flight and on ground simulation studies that a trigger for development of all set of weightlessness negative effects, including muscular detraining, motor control disorders, orthostatic insufficiency and others is the elimination of support stimulation which is followed by essential decrease of tonic system activity. A wide spectrum of means for activation of tonic mechanisms in microgravity such as axial loading suit, mechanical stimulator of sole support zones and low-frequency myostimulator have been developed and used successfully for preventing development of hypokinetic disorders in space flights. Method: Taking into account the similarities of the nature of sensorymotor disturbances caused by microgravity and those, mediated by pathological processes, a wide program of works directed to implement, preventive measures of hypokinetic syndrome, in practice of rehabilitation of patients, suffering heavy motor disturbances, caused by perinatal encephalopathy, ICP, ischemic stroke, traumatic brain injury and other diseases. Results: Space medical technologies adapted for clinical practice showed their high efficacy in rehabilitation practice. Axial loading suit became the main mean of rehabilitation in patients with ICP and was successfully used more than in 70 Russian Centers. The new clinical type of this suit was suggested for rehabilitation of patients with an ischemic stroke, Parkinson’s disease and traumatic brain injury. There was confirmed also a high efficacy of other implemented means such as pneumatic stimulator of sole support zones, low-frequency myoelectricstimulator and dry immersion tank. Conclusion: Reducing the depth of sensorymotor disturbances, new rehabilitation means help faster recovery of health and motor activity of patients and to increase the possibilities of social adaptation, improving the quality of patients life.
S19
IN22 – Stroke 5: treatment in stroke IN22-TU-01 Current status of carotid artery stenting (CAS) N. Sakai, H. Adachi, Y. Ueno, T. Kunieda, C. Sakai, H. Yamagami, H. Imamura, M. Koyanagi, K. Todo, S. Yamamoto, Y. Kuramoto, N. Kohara, H. Kikuchi. Neurosurgery and Stroke Center, Kobe City General Hospital Neuroendovascular Therapy, Institute for Biomedical Research and Innovation, Kobe, Japan Carotid artery stenting (CAS) is increasingly being used for treatment of symptomatic and asymptomatic carotid artery diseases. We have been doing CAS since 1997 with several divices, and Prexise/Angioguard XP have been used since approved in 2007. To report our experience and current Japanese status about CAS. In my experience of 909 patients, 993 CAS procedures had been performed with cerebral protection, except for initial 75 cases with balloon expandable stent. Current standard procedure of CAS is as follows: under local anesthesia, trans-femoral approach, using 8F guiding catheter, cross the lesion with Angioguard XP, open the filter, pre-dilation with low profile 3.5–4.0mm PTA balloon, deploy self-expanding stent(Precise) followed by post-PTA and aspirate blood if necessary. Finally, capure Angioguard XP, if filter device is not indicated fro embolic protection, distal balloon or proximal protection will be used. Embolic events were checked by TCD and MRI/DWI. The stroke and death rate within 30 days was 2.1% and 0.4% respectively, and reversible ischemic neurologic symptoms occurred in 3.5%. In-stent-restenosis rate is 6.7%, and no ipsilateral stroke, related to carotid diseases, occurred after 120 days of CAS. However, another stroke, cardiovascular events and malignant diseases occurred in over 30% of patients. On the basis of our series, the use of cerebral protection devices appears to reduce thromboembolic complications during CAS, and management of cardiovascular events and medical condition by cardiologist is essential for successful treatment of carotid diseases. IN22-TU-02 Thrombolysis in the area of limited resources N.C. Suwanwela. Department of Medicine, Chulalongkorn University, Bangkok, Thailand Eighty-seven percent of stroke mortality occurs in the lower and middle income population. It is projected that within the next 10–12 years, the incidence of stroke will be much greater in this particular class of population than those with higher income. Intravenous thrombolytic therapy has been recommended as a standard treatment for acute ischemic stroke in most clinical practice guidelines. However, in countries with limited resources, the uptake of evidence into clinical practice is very slow. The major obstacles behind are the short therapeutic window and the limited knowledge/experience of physicians. Moreover, the cost associated with this treatment is a main factor determining its utilization in many hospitals. In Thailand, we started by setting up a stroke fast track program at a tertiary care hospital to use as a model. After the establishment of the treatment efficacy in the tertiary care hospital, the neurological association, the stroke society together with other medical professional societies were able to convince the government funding agency to adopt the program and expand the treatment to regional hospitals. Top up payment for the cost of medication and program setup, as well as special training was provided for participated hospital. We also have campaigns to increase public awareness about stroke. With this setting, the number of thrombolytic cases in Thailand has rapidly increased more than double during the past year and more patients in the rural area received the treatment. In conclusion, in countries with limited resources, the use of intravenous thrombolysis in acute ischemic stroke is still not widely applied. This is partly due to high cost for the hospital infrastructure setup as well as the cost of medications. Therefore, collaboration between stroke
S20
19th World Congress of Neurology, Invited Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S5–S56
physicians, emergency medical service team, stroke unit personnel, professional societies, policy makers and the health care funding agencies are the key to success. IN22-TU-03 Stroke units – how to organize stroke care services M. Brainin. Center Clinical Neurosciences, Danube University, Krems, Austria A stroke unit is hospital department that provides organized care exclusively for patients suffering from stroke. This is characterized by coordinated multidisciplinary care directed at emergency handling of stroke patients, performing prompt clinical and imaging diagnosis and providing available therapy immediately. Continuous monitoring, preventing complications, treating comorbidity, and early mobilisation are crucial components. Preclinical efforts are directed at shortening admission times and avoiding in-hospital delays. Several such stroke units have been recommended in international guidelines which include in a step down fashion comprehensive (tertiary care) stroke units, stroke units with basic care, and general hospital care using stroke pathways. While not all these components have been tested in randomized trials it has been widely accepted that such care systems are very effective and many stroke registries show the extremely good performances in terms of effectiveness and reaching best possible outcomes. In Austria, for example, a system of such acute care units has been established which has transport times mostly under 45 minutes and a thrombolysis rate, which has improved between 2003 to 2008 from 4 to 13% of all admissions. The percentage of eligible thrombolysis patients reaching stroke units within 2 hours of stroke onset has now reached a thrombolysis rate of more than 50%. Systematic care for acute stroke can be established by means of acute stroke units directed at avoiding in-hospital delays and offering best possible acute therapy, preventing complications and early mobilisation.
IN23 – Child neurology 1 IN23-TU-01 Myopathy: update in diagnosis and treatment – focusing on metabolic myopathies I. Nishino. Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan Among various muscle diseases, metabolic myopathies are probably one of the most important topics as many of these conditions are treatable. I will discuss metabolic myopathies and focus on Pompe disease and lipid dysmetabolism. Pompe disease is the only hereditary muscle disease for which curative treatment is available, as enzyme replacement therapy (ERT) has recently become available. Pompe disease can be classified into three forms: infantile, childhood and adult-onset. Patients with infantile form present with muscle hypotonia and hypertrophic cardiomyopathy. Most patients die within 1 year after birth without treatment, but with ERT, survival rate has been significantly improved. Muscle pathology shows marked vacuolar changes with glycogen accumulation and high acid phosphatase activity. The childhood and adult-onset forms are relatively milder, whereby patients exhibit limb-girdle muscle weakness and atrophy but usually do not show cardiomyopathy. In adult-onset cases the findings in muscle pathology can sometimes be minimal, thus many cases are probably overlooked. There are two major myopathic conditions due to lipid dysmetabolism. One condition is rhabdomyolysis. Determining the cause of rhabdomyolysis is often not easy as clinical and pathological features are usually nonspecific. Of note, however, very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency, which is probably the most common b-oxidation defect,
may be diagnosed by immunohistochemistry. The other myopathy due to lipid dysmetabolism is lipid storage myopathy, a condition diagnosed by its characteristic finding on muscle pathology. In our study, 3/4 of cases had no mutations in any of known causative genes, indicating that cause is still unknown in majority of cases. Nevertheless, treatment is available for carnitine deficiency and some cases of multiple acyl-CoA dehydrogenase deficiency, thus knowledge about these genetically identifiable and potentially treatable diseases are of relevance. IN23-TU-02 Interventional therapy for epilepsy A. Ikeda. Departments of Brain Pathophysiology and Neurology, Kyoto University School of Medicine, Kyoto, Japan IN23-TU-03 Genes and pathways implicated in malformations of cortical development H. Cross. Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom
IN24 – Multiple sclerosis 2 IN24-TU-01 Immunological and neurobiological interactions in multiple sclerosis R. Hohlfeld. Ludwig Maximilians University of Munich, Munich, Germany Multiple Sclerosis (MS) is the most frequently occurring inflammatory disease of the central nervous system. Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of the disease. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of tissue-infiltrating T and B cells. Novel candidate auto-antigens, including B-cell antigens, have been identified. Several promising immunological “biomarkers” with possible prognostic, diagnostic and therapeutic relevance have recently been described. One of these markers, antibody against aquaporin-4, has been suggested as a marker for a subtype of MS characterized by optico-spinal involvement. Much progress has also been made in understanding the milieu factors that make the CNS a very special and conducive environment for interactions between cells of the immune system and nervous system. Chemokines guide the migration of immune cells into MS lesions, and survival factors such as BAFF foster the long-term persistence of certain types of immune cells in the CNS environment. Intriguingly, tissue-infiltrating immune cells secrete neurotrophic factors, which might support the survival of some neuronal and glial cells. Altogether, these discoveries have shed new light on the immuno-pathogenesis of MS, and will make a strong impact on the development of novel therapies for this still incurable disease. IN24-TU-02 Aquaporin-4 autoimmunity T. Misu. Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan Recently, the disease-specific antibody was found in the serum from neuromyelitis optica (NMO) patients, and its target antigen was identified as aquaporin-4 (AQP4), mainly expressed in astroglial foot processes. However, the pathogenic role of AQP4 antibody in NMO has not been fully elucidated. In our immunohistochemical studies, the loss of AQP4 was evident in about 90% of NMO lesions, especially in perivascular areas of acute inflammatory lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) was also weak or lost in