Control of movement cerebral cortex thalamus basal ganglia

Control of movement cerebral cortex thalamus basal ganglia cerebellum brain stem spinal cord muscles: movement receptors

Neuromuscular transmission Cl- channel dihydropyridine rec. ryanodine rec.

Diseases of neuromuscular transmission Autoimmune myasthenia gravis acquired, antibodies against subunit of N receptor (immunogenic region) Congenital forms of myasthenia gravis heterogeneous origin: • deficit of Ach-esterase • slow-channel syndrome (ion channel of N receptor) Lambert-Eaton syndrome antibodies against Ca 2+ channel

Diseases of muscle excitability Myotonia myotonic muscular dystrophy, myotonia congenita, paramyotonia congenita: Cl- channel Periodic paralyses normo- hyper- hypokalemia hyperkalemic: Na+ channels (noninactivating) Malignant hyperthermia ryanodine receptor

Myopathies Muscular dystrophies: Duchenne, Becker: X linked recessive, Xp 21, dystrophin Limb girdle dystrophies: autosomal, sarcoglycans Congenital muscular dystrophy: laminin (merosin) Myopathies associated with inborn errors of metabolism (lipid, glykogen, oxidative phosphorylation) Acquired myopathies: inflammatory endocrine toxic

Lower motor neuron alpha-motor neurons various etiology • neuronopathies (soma) • radiculopathies (spinal root) • neuropathies (nerve) paresis-plegia hypotonia of affected muscles hyporeflexia of muscle stretch reflexes atrophy of affected muscles fasciculations, fibrillation potentials (EMG)

Upper motor neuron descending motor tracts cerebral cortex-spinal cord various etiology paresis-plegia spasticity of affected muscles hyperreflexia of muscle stretch reflexes positive Babinski sign response no atrophy

The Basal ganglia thalamus nc. caudatus putamen e. i. globus pallidus: ext. , int. nc. subthalamicus c. r. substantia nigra: pars compacta, reticulata

Internal loops cerebral cortex GABA/Enk g. pallidus ext. GABA striatum (Ach) GABA/P Glu nc. subtalamicus Glu D 1 Dopamin D 2 s. nigra comp. g. pallidus int. / s. nigra ret. Indirect: decrease of cortical excitability Nigro-striatal: decrease Glu GABA thalamus Glu cerebral cortex Direct: increase of cortical excitability Nigro-striatal: increase

Hypokinetic disorders • akinesia (initiation of movements) • bradykinesia (slowness of movements) • rigidity • flexed posture • resting tremor (acral parts) • vegetative signs (increase of salivation, sweating) Loss of influence of the nigro-striatal pathway: • overactivity in the indirect pathway (inhibitory) • relative increase of ACh over DA in the striatum Parkinson´s disease: idiopathic neurodegenerative disease Parkinsonlike states: vascular, viral, anoxia

Hyperkinetic disorders • dyskinesias: athetosis, chorea, ballism, dystonia • hypotonia Huntington´s chorea autosomal dominant (trinucleotid disease) chromosome 4, huntingtin CAG (glutamine), normal < 40, affected > 40 cholinergic and GABAergic cells : striatum cerebral cortex (dementia)

Cerebellar disorders ataxia: stance, gait, balance asynergia: coordination during multi-joint movements dysdiadochokinezia: alternating movements dysmetria: reaching of targets action tremor hypotonia central part: (axial and proximal limb muscles) stance, gait, balance, asynergia lateral part: (distal limb muscles) dysmetria, dysdiadochokinezia, action tremor, hypotonia

Spinal ataxia dorsal columns pathways tactile and proprioceptive sensation depends on the eye control loss of conscious perception of position Vestibular ataxia vestibular system depends on the head position depends on the eye control Apraxia learned voluntary movement motor associative areas prefrontal, posterior parietal