Dystonia

Classification

Dystonias are defined as syndromes of sustained muscle contractions, usually agonists and antagonists, leading to twisting, repetitive movements, or abnormal postures. They can be grouped into primary dystonias, dystonia-plus syndromes, heredodegenerative dystonias, and secondary forms. The classification scheme is important for defining the cause of the dystonia (i.e., genetic vs. pharmacologically-induced), and potentially for prognostic reasons.

Primary dystonias are those in which dystonia is the only phenotypic manifestation (except that tremor may be present as well), and for which no environmental agent or prior insult appears responsible. These include hereditary dystonias such as early limb-onset (Oppenheim's) dystonia, which is associated with a 3-base-pair deletion in the DYT1 gene, which maps to chromosome 9q34. The DYT 6 and DYT 7 genes are also associated with familial dystonias.

Dystonia-plus syndromes are those with manifestations of dystonia and other movement disorders (such as dystonia with parkinsonism, or dystonia with myoclonus).

Neurodegenerative diseases that produce dystonia among their manifestations are classified as heredodegenerative dystonias. Genetic disorders such as spinocer-ebellar degeneration or Wilson's disease fall into this classification scheme when dystonia is a component of their symptomatology.

Secondary dystonias are those that develop as a result of environmental insults to the nervous system. These can include perinatal cerebral injuries, focal or diffuse craniocerebral, spinal cord, or peripheral nerve lesions from trauma or other causes, pharmacologically- or toxicologically-induced dystonia, such as those related to dopamine D2 receptor blocking actions, ergotism, or levodopa-induced dystonia.

General Principles of Treatment

Pharmacological treatments for dystonia currently include levodopa, benzodiaz-epines, dopamine antagonists, baclofen, muscle relaxants, and, for focal dystonias, botulinum toxin injections into the affected muscles. Botulinum toxin therapy generally requires repetition every few months, and some patients develop antibodies to the toxin, rendering the treatment ineffective.

Because most forms of dystonia, with the exception of dopa-responsive dystonias, respond poorly to medical therapy, a number of surgical therapies have

arisen. These can be grouped as peripheral or central approaches to treatment. Peripheral surgical therapies include sectioning of affected muscles, or sectioning of the nerves to affected muscles. Most commonly, this involves division of the accessory nerve for spasmotic torticollis.

Central approaches include lesioning or stimulation of regions of the CNS involved in the higher-order processing of motor output. As with most movement disorders, the optimal CNS target for the surgical treatment of dystonia remains controversial. Some benefit has been demonstrated with lesioning of either the ventrolateral thalamus (Hassler's ventralis intermedius (Vim)) or the posteroventral globus pallidus interna (GPi). Deep brain stimulation with leads placed in the GPi or the subthalamic nucleus (STN) has also shown some success in early reports. MR-based targeting is often used to localize these targets.

Thalamotomy and GPi Pallidotomy

The creation of lesions in either the GPi or in the Vim nucleus of the thalamus entails the same technical approach. The standard target coordinates are modified based on direct targeting to the MRI. A guide tube is introduced through a burr hole at the coronal suture, with the entry point chosen so as to approximate the parasaggittal plane with respect to the target, and to avoid the ventricle. A micro-electrode is advanced through the guide tube, and the depths are recorded at which the electrophysiological signatures characteristic of the cells of the relevant nuclei are found. This map is then superimposed on a scaled atlas of the basal ganglia, and used to confirm the site prior to placement of the lesion.

The lesion is generated using a radiofrequency lesion generator. The resulting current produces thermal coagulation of tissue in regions that fall within the 45°C isotherm. Unpredictable factors such as tissue inhomogeneities and proximity to bone or the ventricular system can produce variations in lesion size and geometry. For this reason the procedures are performed in awake patients whose sensory, motor and visual functions are tested during the procedure.

Deep Brain Stimulation

The techniques employed for deep brain stimulation of the GPi, STN, or Vim are similar to those used for lesioning. Once the target is identified, a lead with 4 distal contacts is placed. The electrode is attached to a temporary pulse generator, and stimulation is performed using voltages from 0 to 10 microvolts, pulse widths of 90 microseconds, and frequencies of 180 Hz, while the patient is tested for motor, sensory, or visual phenomena. The adequacy of the lead position is based upon the results of macrostimulation (Table 5).

When an adequate lead position has been confirmed, the leads are tunnelled subcutaneously to and connected to the pulse generator, which is placed in a subcutaneous pocket below the ipsilateral clavicle and above the clavipectoral fascia. The pulse generator is activated transcutaneously 1 to 6 weeks following the procedure, using a handheld magnetic probe. During any changes in stimulation parameters, careful attention is paid to the patients motor, sensory and visual responses. Commonly used stimulation parameters are provided in Table 6.

Table 5. Effects of microelectrode stimulation in vicinity of DBS targets

Side Effect

Subthalamic Nucleus

Globus Pallidus Interna

Low-voltage persistent paresthesias Low-voltage dysarthria Low-voltage tonic contractions Low-voltage diplopia Dyskinesia Depression

No effect at high voltage

Low-voltage dysarthria Low-voltage tonic contractions Visual phenomenon at any voltage No effect at high voltage

Likely Position of Contact

Too posterior or medial

Too lateral Too lateral

Too anteromedial Just right Too inferior

Too Superior or anterior

Too posteromedial Too posteromedial

Close to optic tract

Too superior, anterior, or lateral

Table 6. Common DBS pulse generator settings

Variable Common Settings (bipolar stimulation)

Frequency 185 Hz (both targets)

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