Movement Disorders as a Subspecialty of Neurology and an Introduction to the Physiology of MovementCHAPTER 1

‘Movement disorders' is a growing subspecialty of neurology. It is of interest to consider what is responsible for this growth. Taking the broad view, a driving factor is the growth of medical knowledge and the progressive subdividing of medical expertise. Neurology is getting so large that it is difficult to be expert in all of it. This is leading to subspecialization. At present in the United States, this subspecialization is being formally recognized by the American Board of Psychiatry and Neurology and the United Council for Neurologic Subspecialties. Movement disorders began to develop with the interest in Parkinson disease, and in particular, with the development of treatment for Parkinson disease. At the outset movement disorders encompassed only disorders of the basal ganglia, and included, for example, dystonia and Huntington disease as well as Parkinson disease. A group of neurologists, colleagues and students of C. David Marsden and Stanley Fahn, began to talk about movement disorders rather than basal ganglia disorders. Other disorders involving movement were added to the field. Interest was always enhanced by the development of therapies, and, as another example, myoclonus became a more relevant topic after the discovery that it could be ameliorated by 5-hydroxytryptophan. The ataxias were added relatively late since interest in them focused on the cerebellum rather than the basal ganglia. Spasticity joined only very recently after the demonstration that botulinum toxin injections could be helpful.

Local interest groups on movement disorders began to spring up, and these were often called basal ganglia clubs at first (and some still retain that name). One activity that stimulated interest was patient discussions centered around showing videotapes of the patients. Marsden and Fahn initiated a dinner meeting at the American Academy of 4Neurology where they and the participants would bring videotapes of “unusual” movement disorders, and these discussions would go on well passed the designated closing time. On the international level, Fahn and Marsden started a society, the Movement Disorder Society (MODIS), with a journal called Movement Disorders. The journal had the novel feature of including videotapes to illustrate the articles. Reiner Benecke and Marsden had the idea for an international society to have meeting about movement disorders, and they called this the International Medical Society for Motor Disturbances (ISMD). MODIS joined ISMD for the meeting in Washington, DC in 1990 that was called the First International Congress on Movement Disorders. This was successful, and the two societies merged in the next two years to form a “new” society called the Movement Disorder Society (MDS). MDS has grown to be a very successful international society with an important journal and active yearly meetings.

Movement disorders encompass all neurologic disorders characterized by abnormal movements. While most practices are dominated by patients with Parkinson disease, the variety of patients is very broad. The prevalence of different movement disorders is in (Table 1.1).

Research in movement disorders is very active on multiple levels. Areas include the basic physiology of movement, the pathophysiology of disordered movement, genetics, cell biology, pharmacology, and clinical trials. Therapeutics is expanding and includes drugs, surgery, injectables such as botulinum toxin, and rehabilitation methods. Basic research encompasses mechanisms of neuro-degeneration and the potential use of stem cells. The rapid changes in therapeutic options make continuing medical education a necessity and a challenge.

Subsequent chapters in this book cover all areas of clinical movement disorders and the approach to the patient in detail. It is valuable at the onset to consider in broad terms how movement is generated (Fahn and Jankovic 2007).

Movement, whether voluntary or involuntary, is produced by the contraction of muscle. Muscle, in turn, is normally controlled entirely by the anterior horn cells or alpha motoneurons. Some involuntary movement disorders arise from muscle, alpha motoneuron axon, or the alpha motoneuron itself. As the sole controller of muscle, the alpha motoneuron is clearly important in understanding the genesis of movement. The influences upon the alpha motoneuron are many and complex, but have been extensively studied. Inputs onto the alpha motoneuron can be divided into the segmental inputs and the supraspinal inputs.

The main supraspinal control comes from the corticospinal tract. Approximately 30% of 5the corticospinal tract arises from the primary motor cortex, and other significant contributions come from premotor cortex and sensory cortex. Other cortical neurons project to basal ganglia, cerebellum and brainstem, and these structures can also originate spinal projections. Particularly important is the reticular formation that originates several reticulospinal tracts with different functions. The rubrospinal tract, originating in the magnocellular division of the red nucleus, while important in lower primates, is virtually absent in humans.

The basal ganglia circuitry and cerebellar circuitry both can be considered as subcortical loops that largely receive information from the cortex and return most of the output back to cortex via the thalamus. Both also have smaller directly descending projections. Although both loops utilize the thalamus, the relay nuclei are separate, and the loops remain largely separate.

The basal ganglia loop anatomy is complex with many connections, but a simplification has become popular that has some value. In this model there are two pathways that go from cortex and back to cortex again. The direct pathway is putamen, internal division of the globus pallidus (GPi), and thalamus (mainly the Vop nucleus). The indirect pathway is putamen, external division of the globus pallidus (GPe), subthalamic nucleus (STN), GPi, and thalamus. The substantia nigra, pars compacta, (SNc) is the source of the important nigro-striatal dopamine pathway and appears to modulate the loop, although not being in the loop itself. The contribution of the basal ganglia to movement remains controversial. One possibility is that they contribute to refining movement by working in a center-surround mechanism.

Basal ganglia disorders are characterized by a wide variety of movement signs and symptoms. Often they are divided into hypokinetic and hyperkinetic varieties, implying too little movement on the one hand and too much movement on the other.

The anatomy of the cerebellar pathways, like the basal ganglia pathways, is complex, but there are simplified models that aid thinking. The main cortico-cerebellar-cortical loop is frontal lobe, pontine nuclei, cerebellar cortex (via middle cerebellar peduncle), deep cerebellar nuclei, red nucleus and VL thalamus (via superior cerebellar peduncle), and motor cortex. The input fibers to the cerebellar cortex are the mossy fibers that synapse onto granule cells which in turn synapse onto the Purkinje cells. There is also extensive sensory input via spinocerebellar tracts, largely carried in the inferior cerebellar peduncle. A critical modulatory loop involves the inferior olivary nucleus. The inferior olive innervates both the cerebellar cortex and deep nuclei via the inferior cerebellar peduncle and the climbing fibers that synapse directly onto Purkinje cells. Feedback returns to the inferior olive by a dentate-olivary pathway that travels in the superior cerebellar peduncle, goes around the red nucleus and descends in the central tegmental tract. The cerebellum clearly involves the fine control of the timing of movement, and patients with cerebellar lesions have ataxia, disorganized, poorly coordinated or clumsy movement.

The primary motor cortex provides the principal output to the corticospinal tract. Thus, its inputs determine the brain's contribution to movement. The main inputs come from the premotor cortices, including the lateral premotor cortex, the supplementary 6motor area, and the caudal parts of the cingulate motor area. These areas in turn receive their input from wide areas of brain including the presupplementary motor area, rostral parts of the cingulate motor area, dorsolateral prefrontal cortex, and parietal areas. There has been considerable attention recently to the parietal-premotor connections, which are highly specific and appear to provide important links between sensory and motor function.

The apraxias are disorders of motor control, characterized by a loss of the motor program, not explicable by more elemental motor, sensory, coordination or language impairments. Idiomotor apraxia is present when there is knowledge of the task, but there are temporal and spatial errors in performance. It has long been suspected to be due to a disconnection between parietal and premotor areas.

There are many disorders where there is some confusion as to whether a movement is voluntary or involuntary. There is only limited understanding of the nature of voluntariness. Examples include tics in Tourette syndrome and psychogenic movement disorders.

As is apparent, movement disorders can arise almost anywhere in the central nervous system. This gives rise to the incredible diversity of symptoms and disorders, and makes differential diagnosis a challenge. This book will be a helpful guide for diagnosis and therapy.