- Email: [email protected]
ES158 GAIT disorders
Educational Sem#~ars
Thursday, 9 June 2005, 08.00 09.15, Room 36
ES145 Degenerative ataxias Chair: Thomas Klockgether, Bonn, Germany
Co-Chair: Massimo PandolJb, Brussels, Belgium
97
vohintary from involuntary abnormal movements. Only the combination of clfifical and neurophysiological investigations may often lead to a correct diagnosis which is the prerequisite for a rational treatment. The main topics of this educational seminar will be physiology, pathophysiology and diagnostic criteria in common and uncommon tremors as well as in dystonia.
Course description: The course will provide an overview of clinical characteristics, brain imaging findings and medical management of sporadic adult-onset ataxias.
Thursday, 9 June 2005, 08.00-09.15, Room 40
•
Non-hereditary adult-onset ataxias Z Klockgether*
*Borm, Germany Tile degenerative cerebellar ataxias comprise a wide spectrum of disorders with atmxia as the leading symptom. In most o f these disorders, ataxia is clue to degeneration of tile cerebellar cortex and its afferent or efferent fibre connections. Principally, it is distinguished between the hereditary and non-hereditary atmxias. The non-hereditary atmxias can be further subdivided into the acquired ataxias which are clue to defined exogenous or endogenous non-genetic causes. In contrast, the underlying cause of the sporadic degenerative ataxias is not known. There are two major categories: In approximately one third of the sporadic adult-onset atmxias, multiple system atrophy (MSA) is tile underlying brain disease. These patients typically suffer from accompanying autonomic failure and are known to have apoor prognosis. Tile remaining group has been tentatively named sporadic adult-onset ataxia of unknown origin (SAOA). Own studies show that SAOA patients usually have a pure cerebdlar atrophy and a more favourable prognosis than MSA. Objectives: Objectives of this teaching course are to present the diagnostic procedures required to correctly diagnose sporadic non-hereditary adult-onset ataxias. In addition, clinical characteristics, typical imaging findings and management of these disorders are discussed.
•
Degenerative ataxia: The inherited ataxias M. Pandolfo*
ES157 How to cope with complications of advanced Parkinson's disease and algorithms approach Chair: Daniel Truong, Fountain Valley, CA, USA
Co-Chair: ~lfi'ied Kuhn, Schweinfurt, Germany Course description: The thculty will discuss both motor and non-motor complications. Using short video clip tile audience will become familiar with different types of motor and non-motor fluctuations, such as changes in speech and vision. The faculty will also discuss treatment approach using different algorithms for different scenarios. Special attention will be given to tile use of newly approved medications and surgery to solve these complications.
Target audience: Residents in training and physicians interested in the treatment of Parkinson's Disease. Objectives: The objective of the course is to define complication of Par!dnson's Disease in its late stage.
Thursday, 9 June 2005, 08.00-09.15, Room 32
ES158 GAIT d i s o r d e r s Chair: Alan Crossman, Mancheste~ United Kingdom
Co-Chair: Nit Giladi, Tel Aviv, Israel
*Brussels, Belgium The goal of this presentation will be to provide up-to-date information to orient neurologists in the diagnosis and management of these rare and complex diseases, as well as to inform on tile progress of research on pathogensis and treatment. An overview of the inherited degenerative ataxias will be provided. The clinical presentation of the most common forms of recessive and dominant atmxia will be reviewed, with emphasis on specific elements that may help orienting the diagnosis. A diagnostic worknp will be proposed, and the use of genetic tests will be discussed. Some pathogenic mechanisms will then be reviewed. Current approaches for tile management of these disorders will be presented. Finally, possible new therapeutic approaches will be discussed.
Thursday, 9 June 2005, 08.00 09.15, Room 37
ES156 Neurophysiological investigations in movement d i s o r d e r s Chair: Carl Hermann Lilt'king, Freiburg, Germany
Co-Chair: Reiner Benecke, Restock, Germany Movement disorders are mainly caracterized and classified by using clinical criteria. Clinical neurophysiology is often regarded as an extension of neurological examination. Neurophysiological investigation can contribute to a better understanding of tile physiology of normal movements and the pathophysiology of movement disorders. It can also help to differentiate
•
Basal ganglia pathophysiology in movement disorders A. Crossman*
*Mand~ester, UnitedKingdom Two conceptual models o f movement disorders in basal ganglia disease are generally accepted. One attempts to explain the pathophysiology of parkinsonism and the other accounts for the occurrence of abnormal involuntary movements (dyskinesias). These models are in many respects only crude approximations; in particular they do not fully reflect the complexities of the nenroanatomy, nenrophysiology and neurochemistry of the basal ganglia. They are, nevertheless, valuable models in that they have some predictive capacity and have been used to devise new treatments, both surgical and medical, for movement disorders. Tile basal ganglia consist of the (neo)striatum and the globns pallidus (GP). The subthalamic nucleus (STN), substaTnia nigra (SN) and some ventral thalamic nuclei are often included because of their close relationship with tile basal ganglia. The striatum is composed of the caudate nucleus and the putamen. The globns pallidus consists of an external segment (GPe) and an internal segment (GPi) which have different afferent and efferent connections. The striatum receives most of tile afferent connections to the b anal ganglia. These include the dopaminergic nigrostriatal pathway, from the pars compacta of the substantia nigra (SNc), and glutamatergic projections from the cerebral cortex and intralaminar thalamic nuclei. Striatal cells project to two main targets - the globns pallidns and substantia nigra, pars reticnlata (SNr). MI these neurones use the inhibitory transmitter, garnma-aminobutyric acid
98
Educational Sem#~ars
(GABA). Striaotopallidal fibres terminating in tile GPe are referred to as tile "indirect" pathway and those terminating in GPe are referred to as tile "direct" pathway. Tile neurones of tile indirect pathway also synthesise enkephalin, whilst those of the direct pathway synthesise substance P and dynorphin. Tile GPe thus receives a GABAergic/enkephalinergic projection from the striatum (the origin of the indirect pathway). Cells of the GPe project axons through tile internal capsule to the subthalamic nucleus and also establish connections between the two pallidal segments. All of these pathways are GABAergic. The subthalamic nucleus is tile major termination of GPe efferents. It also receives input from the cerebral cortex and intralaminar thalamic nuclei. Its efferent projections are to the GP (both segrnents) and SNr. STN efferents are excitatory and mediated by glutamate. The GPi is regarded (together with the pars reticnlata of the substantia nigra) as the principal output of the basal ganglia, since tile majority of fibres projecting to other levels of the neuraxis originate there. Its principal afferent connections are the direct pathway from the striatum and the subthalamopallidal pathway. GPi efferent fibres are GABAergic. The largest efferent projection from GPi is to the ventral anterior (VA), ventral lateral (VL) and intralarninar nuclei o f tile thalamus. Tile VA and VL project to motor cortical regions of the frontal lobe. GPi also sends a projection to tile pedunculopontine nucleus (PPN) of tile caudal midbrain. This is to some extent co-extensive with the physiologically characterised mesencephic locomotor region, from which progressive movements can be elicited by electrical stimulation. The PPN in turn projects to brain stem reticular areas. These basal gax~glia com~ections constitute one of several parallel drcuits which intercom~ect striatal, thalamic, cortical and brain stem levels. Activity in the indirect pathway, transmitted through the GPeSTN GPi circuit, is thought to be responsible for inhibiting unwanted or inappropriate movements or behaviours. Activity in the direct pathway is thought to t'acilitate and reinforce behaviourally relevant motor activity. Dopamine appears to have a dual action in the striatum, with opposite effects upon tile cells of origin of tile direct and indirect pathways. Tilus, dopamine is inhibitory upon striatal nenrones which project to the GPe and excitatory upon those which project to the GPi. In Parkinson's disease, loss of striatal depamine leads to abnormal overactivity of the indirect pathway. This causes excessive inhibition of GPe and relief of inhibition of STN. Overactivity of STN ensues and, because of the excitatory nature of the subthalamopallidal projection, this in turn causes overactivity of GPi arm SNr output neurones. It remains unclear as to which output pathways mediate which parkinsonian symptoms or, indeed, whether such segregation exists. It is logical to assume that axial movements and postural control are mediated primarily through descending brain stenl and spinal mechanisms, whilst more distal movements, including skilled movements of the limbs,
depend more upon thalamocortical projections. Recent studies have indeed suggested that aldnesia and locomotor difficulties in experimental par!dnsonism are associated wittt dysfunction at the level of the pedunculopontine nucleus. A central feature of dyskinesias is abnormal nnderactivity of both tile subthalamic nucleus and tile medial globus pallides. These appear to be common features in L-DOPA-induced dyskinesia, chorea and ballism. Limb dysldnesia in these conditions can be alleviated by interruption of thalamocortical circuitry.
~ T h e
clinical aspects of gait disturbances in Parkinson's disease
N. Giladi* *Tel Avis, Israel Gait disturbances can be observed at the initial stage of the disease mainly as slowing in locomotion, shuffling gait and decreased arms swing but usually these symptoms are having only minor functional importance. As the disease progress, gait disturbances are becoming a major and frequently the most significant motor problem with major impact on independency and institutionalization. Tile continuous gait disorders are forcing the patient to change his/her motor behavior like adjusting timetable and being more secured. However, clue to their chronic and slowly progressive nature, patients are adjusting themselves and can maintain function and independency with or without a walking aid. In contrast, tile episodic problems like freezing, festination and sudden dis-equilibrium are major causes for falls, fear of falling and significant complications. Only part of tile gait disturbances are responding to depaminergic therapy and some can even be worsened by it. It is of great significance to be sure about tile relationships between each symptom and the depaminergic treatnlent in order to avoid therapeutic induced gait disturbances and falls. MAOB inllibition has recently been shown to be effective for the treatment of freezing of gait while depamine agonists have shown the opposite. This difference will be discussed. In addition to drugs a special attention will be given to the effect of STN DBS on gait and to physical and mental interventions like cueing that can be of great significance.
Thm'sday, 9 June 2005, 08.00-09.15, Room 39
ES159 A2 antagonists Chair: Peter Jenner, London, United Kingdom
Thursday, 9 June 2005, 08.00 09.15, Room 36
ES145 Degenerative ataxias Chair: Thomas Klockgether, Bonn, Germany
Co-Chair: Massimo PandolJb, Brussels, Belgium
97
vohintary from involuntary abnormal movements. Only the combination of clfifical and neurophysiological investigations may often lead to a correct diagnosis which is the prerequisite for a rational treatment. The main topics of this educational seminar will be physiology, pathophysiology and diagnostic criteria in common and uncommon tremors as well as in dystonia.
Course description: The course will provide an overview of clinical characteristics, brain imaging findings and medical management of sporadic adult-onset ataxias.
Thursday, 9 June 2005, 08.00-09.15, Room 40
•
Non-hereditary adult-onset ataxias Z Klockgether*
*Borm, Germany Tile degenerative cerebellar ataxias comprise a wide spectrum of disorders with atmxia as the leading symptom. In most o f these disorders, ataxia is clue to degeneration of tile cerebellar cortex and its afferent or efferent fibre connections. Principally, it is distinguished between the hereditary and non-hereditary atmxias. The non-hereditary atmxias can be further subdivided into the acquired ataxias which are clue to defined exogenous or endogenous non-genetic causes. In contrast, the underlying cause of the sporadic degenerative ataxias is not known. There are two major categories: In approximately one third of the sporadic adult-onset atmxias, multiple system atrophy (MSA) is tile underlying brain disease. These patients typically suffer from accompanying autonomic failure and are known to have apoor prognosis. Tile remaining group has been tentatively named sporadic adult-onset ataxia of unknown origin (SAOA). Own studies show that SAOA patients usually have a pure cerebdlar atrophy and a more favourable prognosis than MSA. Objectives: Objectives of this teaching course are to present the diagnostic procedures required to correctly diagnose sporadic non-hereditary adult-onset ataxias. In addition, clinical characteristics, typical imaging findings and management of these disorders are discussed.
•
Degenerative ataxia: The inherited ataxias M. Pandolfo*
ES157 How to cope with complications of advanced Parkinson's disease and algorithms approach Chair: Daniel Truong, Fountain Valley, CA, USA
Co-Chair: ~lfi'ied Kuhn, Schweinfurt, Germany Course description: The thculty will discuss both motor and non-motor complications. Using short video clip tile audience will become familiar with different types of motor and non-motor fluctuations, such as changes in speech and vision. The faculty will also discuss treatment approach using different algorithms for different scenarios. Special attention will be given to tile use of newly approved medications and surgery to solve these complications.
Target audience: Residents in training and physicians interested in the treatment of Parkinson's Disease. Objectives: The objective of the course is to define complication of Par!dnson's Disease in its late stage.
Thursday, 9 June 2005, 08.00-09.15, Room 32
ES158 GAIT d i s o r d e r s Chair: Alan Crossman, Mancheste~ United Kingdom
Co-Chair: Nit Giladi, Tel Aviv, Israel
*Brussels, Belgium The goal of this presentation will be to provide up-to-date information to orient neurologists in the diagnosis and management of these rare and complex diseases, as well as to inform on tile progress of research on pathogensis and treatment. An overview of the inherited degenerative ataxias will be provided. The clinical presentation of the most common forms of recessive and dominant atmxia will be reviewed, with emphasis on specific elements that may help orienting the diagnosis. A diagnostic worknp will be proposed, and the use of genetic tests will be discussed. Some pathogenic mechanisms will then be reviewed. Current approaches for tile management of these disorders will be presented. Finally, possible new therapeutic approaches will be discussed.
Thursday, 9 June 2005, 08.00 09.15, Room 37
ES156 Neurophysiological investigations in movement d i s o r d e r s Chair: Carl Hermann Lilt'king, Freiburg, Germany
Co-Chair: Reiner Benecke, Restock, Germany Movement disorders are mainly caracterized and classified by using clinical criteria. Clinical neurophysiology is often regarded as an extension of neurological examination. Neurophysiological investigation can contribute to a better understanding of tile physiology of normal movements and the pathophysiology of movement disorders. It can also help to differentiate
•
Basal ganglia pathophysiology in movement disorders A. Crossman*
*Mand~ester, UnitedKingdom Two conceptual models o f movement disorders in basal ganglia disease are generally accepted. One attempts to explain the pathophysiology of parkinsonism and the other accounts for the occurrence of abnormal involuntary movements (dyskinesias). These models are in many respects only crude approximations; in particular they do not fully reflect the complexities of the nenroanatomy, nenrophysiology and neurochemistry of the basal ganglia. They are, nevertheless, valuable models in that they have some predictive capacity and have been used to devise new treatments, both surgical and medical, for movement disorders. Tile basal ganglia consist of the (neo)striatum and the globns pallidus (GP). The subthalamic nucleus (STN), substaTnia nigra (SN) and some ventral thalamic nuclei are often included because of their close relationship with tile basal ganglia. The striatum is composed of the caudate nucleus and the putamen. The globns pallidus consists of an external segment (GPe) and an internal segment (GPi) which have different afferent and efferent connections. The striatum receives most of tile afferent connections to the b anal ganglia. These include the dopaminergic nigrostriatal pathway, from the pars compacta of the substantia nigra (SNc), and glutamatergic projections from the cerebral cortex and intralaminar thalamic nuclei. Striatal cells project to two main targets - the globns pallidns and substantia nigra, pars reticnlata (SNr). MI these neurones use the inhibitory transmitter, garnma-aminobutyric acid
98
Educational Sem#~ars
(GABA). Striaotopallidal fibres terminating in tile GPe are referred to as tile "indirect" pathway and those terminating in GPe are referred to as tile "direct" pathway. Tile neurones of tile indirect pathway also synthesise enkephalin, whilst those of the direct pathway synthesise substance P and dynorphin. Tile GPe thus receives a GABAergic/enkephalinergic projection from the striatum (the origin of the indirect pathway). Cells of the GPe project axons through tile internal capsule to the subthalamic nucleus and also establish connections between the two pallidal segments. All of these pathways are GABAergic. The subthalamic nucleus is tile major termination of GPe efferents. It also receives input from the cerebral cortex and intralaminar thalamic nuclei. Its efferent projections are to the GP (both segrnents) and SNr. STN efferents are excitatory and mediated by glutamate. The GPi is regarded (together with the pars reticnlata of the substantia nigra) as the principal output of the basal ganglia, since tile majority of fibres projecting to other levels of the neuraxis originate there. Its principal afferent connections are the direct pathway from the striatum and the subthalamopallidal pathway. GPi efferent fibres are GABAergic. The largest efferent projection from GPi is to the ventral anterior (VA), ventral lateral (VL) and intralarninar nuclei o f tile thalamus. Tile VA and VL project to motor cortical regions of the frontal lobe. GPi also sends a projection to tile pedunculopontine nucleus (PPN) of tile caudal midbrain. This is to some extent co-extensive with the physiologically characterised mesencephic locomotor region, from which progressive movements can be elicited by electrical stimulation. The PPN in turn projects to brain stem reticular areas. These basal gax~glia com~ections constitute one of several parallel drcuits which intercom~ect striatal, thalamic, cortical and brain stem levels. Activity in the indirect pathway, transmitted through the GPeSTN GPi circuit, is thought to be responsible for inhibiting unwanted or inappropriate movements or behaviours. Activity in the direct pathway is thought to t'acilitate and reinforce behaviourally relevant motor activity. Dopamine appears to have a dual action in the striatum, with opposite effects upon tile cells of origin of tile direct and indirect pathways. Tilus, dopamine is inhibitory upon striatal nenrones which project to the GPe and excitatory upon those which project to the GPi. In Parkinson's disease, loss of striatal depamine leads to abnormal overactivity of the indirect pathway. This causes excessive inhibition of GPe and relief of inhibition of STN. Overactivity of STN ensues and, because of the excitatory nature of the subthalamopallidal projection, this in turn causes overactivity of GPi arm SNr output neurones. It remains unclear as to which output pathways mediate which parkinsonian symptoms or, indeed, whether such segregation exists. It is logical to assume that axial movements and postural control are mediated primarily through descending brain stenl and spinal mechanisms, whilst more distal movements, including skilled movements of the limbs,
depend more upon thalamocortical projections. Recent studies have indeed suggested that aldnesia and locomotor difficulties in experimental par!dnsonism are associated wittt dysfunction at the level of the pedunculopontine nucleus. A central feature of dyskinesias is abnormal nnderactivity of both tile subthalamic nucleus and tile medial globus pallides. These appear to be common features in L-DOPA-induced dyskinesia, chorea and ballism. Limb dysldnesia in these conditions can be alleviated by interruption of thalamocortical circuitry.
~ T h e
clinical aspects of gait disturbances in Parkinson's disease
N. Giladi* *Tel Avis, Israel Gait disturbances can be observed at the initial stage of the disease mainly as slowing in locomotion, shuffling gait and decreased arms swing but usually these symptoms are having only minor functional importance. As the disease progress, gait disturbances are becoming a major and frequently the most significant motor problem with major impact on independency and institutionalization. Tile continuous gait disorders are forcing the patient to change his/her motor behavior like adjusting timetable and being more secured. However, clue to their chronic and slowly progressive nature, patients are adjusting themselves and can maintain function and independency with or without a walking aid. In contrast, tile episodic problems like freezing, festination and sudden dis-equilibrium are major causes for falls, fear of falling and significant complications. Only part of tile gait disturbances are responding to depaminergic therapy and some can even be worsened by it. It is of great significance to be sure about tile relationships between each symptom and the depaminergic treatnlent in order to avoid therapeutic induced gait disturbances and falls. MAOB inllibition has recently been shown to be effective for the treatment of freezing of gait while depamine agonists have shown the opposite. This difference will be discussed. In addition to drugs a special attention will be given to the effect of STN DBS on gait and to physical and mental interventions like cueing that can be of great significance.
Thm'sday, 9 June 2005, 08.00-09.15, Room 39
ES159 A2 antagonists Chair: Peter Jenner, London, United Kingdom