Elektroschwache und Kosmische Strings Move and improve - Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Elektroschwache und Kosmische Strings Move and improve - how coordinative training helps ataxia Ludger Schöls Department of Neurology and Hertie-Institute for Clinical Brain Research University of Tübingen Bevor ich mit dem eigentlichen Vortrag beginne, möchte ich noch kurz das Projekt vorstellen, in das meine Arbeiten eingebettet sind: Markus Quandt San Antonio, 16.03.2012 Carsten Schulz-Key

Physikalische Eigenschaften Presenter disclosures Ludger Schöls has no relationships to disclose or list

Outline Cerebellum and motor learning Does physiotherapy help in ataxias? Which physiotherapy concept is successful? A flash in the pan or longterm effects?

Cerebellum is the place of motor learning Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Cerebellum is the place of motor learning Marr (1969) & Albus (1971): Cerebellum is the „motor learning machine“ Examples: Motor use of new tools (Imamizu et al., 2000) Fast recalibration of internal motor programs - e.g. saccadic adptation (Barash et al., 1999) - e.g. adaptation to new force fields (Maschke et al, 2004) - e.g. adaptation of anticipated motor prediction Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Carsten Schulz-Key

Cerebellar degeneration in ataxias Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Cerebellar degeneration in ataxias Regeneration of cerebellar function after focal lesions is well established: e.g. after tumor or stroke limited regeneration if cerebellar nuclei are affected Ataxias are degenerative diseases Degeneration is a generalized rather than a focal process No healthy regions left that can take over for affected parts Doubts that the cerebellum can still learn motor functions with a degenerative ataxia This matches with the experiences of some patients that physiotherapy was not particular helpful to them Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Carsten Schulz-Key

Which physiotherapy? But: Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Which physiotherapy? But: Does that proof physiotherapy ot be ineffective? If a pain killer does not help against high glucose levels this does not mean that drugs are ineffective in diabetes So: Which physiotherapy did not help? Vojta? Bobath? Isometric training? Massage / relaxation? Balance? Coordinative training? Which physiotherapy concepts do help? No physiotherapy concept had been evaluated in ataxia !!! Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Carsten Schulz-Key

Active coordinative training Neurology 2009; 73:1823-1830 Concept of Doris Brötz (Tübingen): Active release of „fixed“ movement patterns Traning of static balance Training of dynamic balance Whole body movements Falling strategies and Steps to prevent falling Movements to treat and prevent contractures Rather few exercises but frequent repetitions

Study design Physio Intrinsic control Follow up Longterm V1 V2 V3 V4 Intervention: 4 week course with 3 physiotherapy sessions a week = 12 x physiotherapy per patient

Read out Goal attainment score (Patient) Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Read out Goal attainment score (Patient) Berg balance score (Physiotherapist) Ataxia rating scale (Neurologist) Movement analysis (Computer) Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Carsten Schulz-Key

Goal attainment score (GAS) Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Goal attainment score (GAS) GAS addresses indivudal goals in daily life selected by the patient 0: Stage at entry of study 1: Less than expected 2: Expected outcome 3: Better outcome than expected 4: Much better than expected 1 2 3 4 Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Kiresuk et. al., 1994; Lawrence Erlbaum Associates Inc. Carsten Schulz-Key

Berg balance score (BBS) Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 Berg balance score (BBS) The BBS rates balance in a physiotherapeutic examination 14 items addressed Sitting Stance Gait Timed movements Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Berg et. al., 1989; Physiotherapy Canada Carsten Schulz-Key

SARA Scale for the assessment and rating of ataxia (SARA) Objektorientierte Partitionierungsstrategien und Architekturbewertung ... 19.04.2017 16:23:45 SARA Scale for the assessment and rating of ataxia (SARA) Higher scores indicate more severe problems 8 items, maximum sum score: 40 Item 1: Gait (8 points) Item 2 Stance (6 points) Item 3: Sitting (4 points) Item 4: Speech (6 points) Item 5: Finger chase (4 points) Item 6: Finger pointing (4 points) Item 7: Diadochokinesia (4 points) Item 8: Heel-shin slide (4 points) Stadium 1: basaler Neocortex fronantal, temporal und occipital Stadium 2: Phases of [beta]-amyloidosis. Phase 1 is characterized by exclusively neocortical A[beta] deposits (Neocortex: black). Phase 2 shows additional allocortical A[beta] deposits (red arrows), phase 3 additional A[beta] deposits in diencephalic nuclei (red arrows) and the striatum (not shown), phase 4 additional A[beta] deposits in distinct brainstem nuclei (substantia nigra, red nucleus, central gray, superior and inferior collicle, inferior olivary nucleus, and intermediate reticular zone) (red arrows), and phase 5 in the cerebellum and additional brainstem nuclei (pontine nuclei, locus coeruleus, parabrachial nuclei, reticulo-tegmental nucleus, dorsal tegmental nucleus, and oral and central raphe nuclei) (red arrows). Schmitz-Hübsch et. al., 2006; Neurology Carsten Schulz-Key

Computerized movement analysis Registration of three-dimensional movement trajectories by 41 reflecting markers using a VICON motion capture system with 10 infrared cameras Analysis of complex whole body movmements for variability in room and time Stance: sway is assessed as path length of the center of gravity while standing with feet together Gait: Analysis of intra-limb coordination by the angle-angle plots of the hip and knee joints  temporal variability measure: vbt Dynamic balance on a treadmill with sudden backward move

Results Improvement after training: - 5.2 SARA points ~ progression of 2 – 4 years Goal attainment: 2.5 = more than expected Gait velocity, intra-limb coordination, static and dynamic balance all improved More benefit with cerebellar rather than afferent ataxia Persistent effects after 8 weeks but better with regular training at home: - 0.4 vs +1.0 Ilg et al, Neurology 2009

Case S.T. - stance 48 year old kindergarten teacher Pre Idiopathic cerebellar ataxia Disease duration 1.5 years Physiotherapy before the study: Stabilisation exercises Isometric training Pre Post

Case S.T. - gait Pre 48 year old kindergarten teacher Idiopathic cerebellar ataxia Disease duration 1.5 years Physiotherapy before the study: Stabilisation exercises Isometric training Pre Post

Case S.T. – complex movements 48 year old kindergarten teacher Idiopathic cerebellar ataxia Disease duration 1.5 years Physiotherapy before the study: Stabilisation exercises Isometric training Pre Post

Case S.T. – stairs Pre 48 year old kindergarten teacher Idiopathic cerebellar ataxia Disease duration 1.5 years Physiotherapy before the study: Stabilisation exercises Isometric training Pre Post Goal attainment score 0: Climbing stairs only with banister 1: Intermittend use of the banister 2: No banister required for 2 steps in both directions 3: Staircase upwards without banister 4: Staircase up and down without banister

Longterm effects Even after 1 year SARA was better than baseline especially in the cerebellar group Goal attainment: After 1 year still better than expected Improvement in intra-limb coordination persisted over 1 year in the cerebellar Patients performing continuous exercises were doing better than those without training Ilg et al, Mov Disord 2010

Conclusions Move and improve! Physiotherapy is able to improve ataxia even in cerebellar degeneration Active, coordinative training is a successful physiotherapy concept in ataxia Effects are visible not only as a group mean but also on an individual basis Effects persist over long term especially if a continuous training is performed Patients with afferent ataxia do profit but cerebellar ataxia is likely to respond even better Improvements meet individual goals in every day life Move and improve!

Thank you … … and the dream team! Matthis Synofzik Winfried Ilg Doris Brötz