Classification

Previously, dystonia had been classified according to involved body region(s), etiology, age of onset, and whether other neurologic features accompanied dystonia.¹⁷¹ When there were no accompanying neurologic features (other than tremor) and no underlying cause of the patient’s dystonia could be determined or the dystonia was from a known DYT1 or DYT6 mutation, then the dystonia was considered primary.¹⁷¹ Dystonia as the result of a known cause or underlying brain injury was referred to as secondary.¹⁷¹ (See Table 2.8 for examples of secondary dystonia.) If myoclonus, parkinsonism, or dysautonomia accompanied dystonia, it was classified as dystonia-plus.¹⁷¹

Recently, a new dystonia classification system has been proposed based on a subset of clinical characteristics and etiology.¹⁷⁰ Clinical characteristic subcategories include age of onset, body distribution, temporal pattern of occurrence, associated clinical features present with dystonia (no: isolated dystonia; yes: combined dystonia), if there is presence of neurodegeneration, and if the dystonia was inherited or acquired.¹⁷⁰ (See Table 2.9 for details of the new classification system.) Almost all previous studies reported results based upon the older classification system. Here we attempt, where possible, to describe dystonia patients using the new classification system as well.

Clarification of diagnosis

Dystonia patients referred for DBS treatment should undergo a detailed history of illness and physical examination in order to classify the type of dystonia. The age of onset, body distribution, temporal pattern, associated features, evidence of degeneration, and mode of acquisition can all help unveil a particular diagnosis or etiology. This is relevant, because certain types of dystonia will have better or worse DBS outcomes.

Most clinical trials have studied patients with isolated idiopathic/inherited (primary) generalized dystonia,^{173–178,204} but there is also a growing literature for the use of DBS in refractory isolated idiopathic/inherited (primary) focal and segmental dystonia.^{179–186,204}

To help confirm whether a patient has isolated idiopathic/inherited (primary) or combined acquired/inherited (secondary) dystonia, brain imaging (MRI if possible) should be performed to assess for structural abnormalities underlying acquired (secondary) causes. In cases of childhood or adolescence-onset generalized dystonia, the diagnosis of dopa-responsive dystonia (DYT5 dystonia, also called Segawa’s disease) should be excluded with a trial of levodopa, as this disorder can mimic idiopathic generalized dystonia and is exquisitely responsive to treatment with levodopa, obviating the need for DBS.

Documentation of dystonia

Before undergoing DBS surgery, a detailed videotaped clinical evaluation should be performed that includes standardized dystonia rating scales, if possible. Establishing a clear baseline of symptom distribution and severity is important. The most commonly used rating scale to measure the severity and disability from generalized dystonia is the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) (Appendix I).^193,194 This scale is composed of a movement scale (based on objective motor exam) and a disability scale (based on patient interview). The 120-point movement scale rates the severity of dystonia in nine body regions, taking into account both the severity and frequency of the dystonic movements. This scale has shown excellent inter-rater reliability and has emerged as a preferred rating scale for generalized dystonia.^193,194 The most commonly used rating scale for cervical dystonia is the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS),¹⁹⁵ an 85-point scale with subscores for dystonia severity, functional disability, and pain (Appendix J). For both scales, a higher score indicates more severe dystonia. Although these rating scales result in objective outcome measures, they are limited in measuring fixed versus mobile dystonia and complex movements. Performing videotaped exams is also helpful to provide clear documentation of the dystonia.

Assessment of disability

It is generally agreed that patients undergoing DBS for dystonia should be experiencing some level of functional impairment or disability from their dystonia. The degree of impairment may vary across patients and may be related to compromised movements, pain, social isolation, or often a combination of all of these factors. Both the BFMDRS and the TWSTRS have disability subscales that are helpful in documenting the level of disability, which may help to support moving forward with DBS treatment.

Status of pharmacological treatment

As with PD or ET, it is important that patients are offered DBS only after they have failed reasonable medical management. Patients with isolated idiopathic/inherited (primary) generalized dystonia should have tried treatment with anticholinergic, antiepileptic, and benzodiazepine medications, as well as baclofen. Dystonia of this type, however, is typically not very responsive to oral pharmacotherapy, and medications often produce intolerable adverse effects. Childhood or adolescence-onset dystonia is an exception, though, as patients with this disorder can respond favorably to anti-cholinergic medications and tend to tolerate such treatment. In patients with focal or segmental dystonia, treatment failure with similar medications should be reviewed. As previously mentioned, all childhood or adolescence-onset isolated idiopathic/inherited (primary) generalized dystonia should undergo an adequate trial of levodopa. Additionally, if patients fail to achieve adequate symptom relief after botulinum toxin injections with appropriate muscle selection and dosing, DBS should be considered.

Predictive factors

In recent years, more has been learned about what might be predictive of a better outcome with GPi DBS in dystonia. Studies of patients with isolated idiopathic/inherited (primary) dystonia with longer disease duration, older age at surgery, and fixed skeletal deformities at time of surgery tend to have worse outcomes.^196–198 Gender, baseline severity by BFMDRS, and the presence of phasic versus tonic movements are not predictive of outcome.^196–198 This remains independent of DYT1 gene mutation status.^196,197

Disease duration does not appear to be correlated with outcomes in late adulthood-onset isolated focal dystonia of the neck (cervical dystonia).¹⁹⁹ In one study, presence of lateral shift was negatively correlated with TWSTRS severity subscores following treatment with DBS, but not with post-DBS outcomes reflected in the total score, disability subscore, or pain subscore.¹⁹⁹ Cervical degenerative disease was not well-characterized and underlying skeletal deformities may have explained the association.¹⁹⁹

Neuropsychological and psychiatric assessments

Little is known about the impact of cognitive status, mood, and psychotic symptoms in dystonia patients and how much these factors should weigh in determining candidacy for DBS. Most patients with primary dystonia will not have significant cognitive dysfunction or psychotic symptoms; however, it is not uncommon to see significant depression or anxiety in this patient population. Having a neuropsychologist or psychiatrist evaluate the patient and identify significant mood symptoms to treat before surgery is generally recommended.

Target choice

Traditionally, dystonia has been treated with DBS of the GPi. Most dystonia DBS outcome studies, including all those previously cited, reflect patients treated with DBS at the GPi target. Patients who are appropriate candidates for treatment with DBS who have isolated idiopathic/inherited (primary) dystonia realize excellent outcomes with this target. Globus pallidus internus DBS, however, may be complicated by stimulation-induced bradykinesia in previously non-dystonic limbs²⁰⁰ and high total electrical energy requirements to achieve efficacy.

The subthalamic nucleus has been studied as an alternative surgical target in dystonia with increasing evidence for its efficacy.^201–203 More studies are needed, but it appears to be a promising alternative target for DBS in dystonia, with similar outcomes to those with GPi DBS. Unlike GPi DBS, patients do not develop stimulation-induced bradykinesia, but can experience transient stimulation-induced dyskinesia, which can make programming this target more challenging in some patients.²⁰²

Counseling patients on expected DBS outcome

Once a dystonia patient has been properly evaluated and screened for DBS, it is important to counsel the patient on the degree of expected improvement with DBS and the time course for benefit, which can be protracted. Patients with childhood/juvenile-onset primary generalized dystonia generally have the best outcome, with improvements of 40–90% as measured by the BFMDRS movement score commonly achieved. Although not as well-studied, adult-onset cranial/cervical and tardive dystonia patients can expect to improve similarly as measured by standardized dystonia scales. Secondary dystonia, other than tardive dystonia, typically responds more modestly (5–35% reduction in dystonia scores), although this level of improvement can be clinically meaningful.¹⁷² These estimates should only be used as a general guide, and the emphasis in counseling should be on the wide range of outcomes after DBS treatment in patients with dystonia (Table 2.10).

Surgical risk

The two most important risks of surgery are hemorrhagic stroke and device-related infection.^206,207 In large surgical series, the risk of symptomatic hemorrhage complicating DBS lead insertion is 1.5–3.0% per lead implant. The risk of a hemorrhage resulting in permanently increased morbidity is 0.5–1.0% per lead. This risk is increased in the setting of untreated hypertension, coagulopathy, or evidence on MRI of significant small vessel ischemic disease or extensive cerebral atrophy. Most clinicians require that a preoperative screening MRI of the brain be obtained, if not recently accomplished already, prior to making a final determination about surgical candidacy. The risk of serious infection of a newly implanted device, defined as an infection requiring reoperation to remove all or part of the implanted hardware, is 2–10% per patient. Conditions that increase this risk, such as long-standing severe diabetes or need for chronic immunosuppression, are relative contraindications for device implantation. Such patients may be more appropriate candidates for a unilateral ablative procedure.

Type of DBS neurostimulator

There are several commercially available DBS neurostimulators, each with different physical specifications and features. Determining which device to implant is based on patient diagnosis, body weight, device attributes, the need for unilateral or bilateral stimulation, and other factors. Availability of rechargeable neurostimulators will require additional candidate screening. Key factors in determining if a patient is a candidate for a rechargeable device are listed in Table 2.11.

Patient expectations and social support

Candidates for DBS should demonstrate a clear understanding of the procedures entailed in their treatment, potential risks of surgery, and realistic expectations about what can be achieved with DBS. Patients need to understand that DBS will not “cure” their disease or likely alter disease progression, and that the goal of DBS is suppression of motor symptoms and optimization of motor function and quality of life. Patients need to understand that the benefits of DBS will take time to accrue, as a number of visits may be required to optimize stimulator settings and the concomitant medication regimen. Patients and their families should be committed to working closely with the clinical team in the postoperative management of their DBS therapy, both in the early postoperative period and over time.

Interdisciplinary and multidisciplinary consensus

An effective method for arriving at decisions regarding the candidacy of patients for treatment with DBS is to collect the required data for each patient and then convene a conference in which these details are discussed by the interprofessional/multidisciplinary team. This team is typically comprised of neurologists, neurosurgeons, psychiatrists, nurses, neuropsychologists, and others who work together to evaluate and educate patients and their families. It is extremely useful to review together the medical history, motor testing scores, neurocognitive and psychiatric data, neuroimaging findings, and general clinical impressions. This process fosters a cohesive treatment approach and allows a consensus decision to be reached on each patient’s candidacy, surgical target, and surgical approach.

The determination of patient candidacy for DBS treatment in movement disorders is still evolving. As surgical techniques advance and DBS devices evolve, the risk associated with the implant surgery will likely decrease. This may lead some physicians and patients in the future to consider DBS treatment earlier in the course of the disease. However, for the present time, DBS is indicated for patients having a clear movement disorder diagnosis known to improve with DBS who are experiencing meaningful impairment from their symptoms, despite pharmacological management, in whom the potential risk associated with undergoing the implant surgery is deemed to be acceptable.