Neurological Evaluation

Preoperative evaluation for DBS normally begins with assessment by a neurologist with specific expertise in the management of movement disorders. The neurological evaluation, possibly performed by a movement disorders specialist, should be focused on establishing that one of the diagnoses amenable to DBS treatment has been made properly. The diagnoses currently approved in the United States and widely accepted for DBS therapy throughout the world are essential tremor (ET), Parkinson’s disease (PD), and dystonia. Other tremors (i.e., midbrain, cerebellar, and orthostatic tremor), tics, and choreas (Huntington’s chorea and neuroacanthocytosis) have also been targeted with DBS in more experimental settings. Table 76-1 summarizes movement disorders in which DBS is currently indicated.

TABLE 76-1 Movement Disorders for Which Deep Brain Stimulation Is Currently Indicated

In addition, a movement disorder expert should review the medical management to make sure that all reasonable pharmacologic therapies have been properly attempted. This can be a very controversial point because opinions on what constitutes the “minimal” medication therapy to be attempted before DBS surgery vary greatly. When a patient with PD is being considered for DBS, examination both “off” and “on” medications should be performed because determination of benefit from levodopa has well-documented diagnostic and prognostic implications. In addition to neurological and motor deficits, functional disability should be documented by using an accepted objective rating scale that is specific to the patient’s diagnosis. Videotaped examinations are also of great value for clinical documentation and monitoring of long-term outcome.

The value of the initial neurological visit does not end with the selection process. It also establishes a clinical baseline for the best postoperative management and provides an opportunity to educate patients and caregivers on the proper risks and expectations with respect to outcome. The initial programming and subsequent setting and medication adjustments may represent quite a challenge when the patient is unknown to the treating physician. Patient expectations must be realistic and discussed early in the process. False expectations by patients or family members are common reasons for “DBS failures.”^1–3 DBS management represents a significant commitment of time, and consequently the patient and family must be motivated to undergo the challenges associated with the procedure.³ The role of the initial neurological evaluation extends to the surgical date in DBS centers that have the team neurologist present in the operating room; this person is an important source of clinical information to the surgeon and may be a calming influence on the patient during the implantation procedure.

Neurosurgical Evaluation

If the neurologist determines that the diagnosis is correct and that reasonable medical strategies have not provided acceptable benefit, the patient is referred to a functional neurosurgeon for further evaluation. During this meeting, the surgeon discusses with the patient the remainder of the preoperative process and the surgical options, including the available targets and methodologies (e.g., frame versus frameless) and a detailed review of the risks and realistic goals of DBS.

A fundamental task for the neurosurgeon is to define whether the risk-to-benefit ratio of the surgical procedure is acceptable to the patient. The most fearsome risk associated with a DBS procedure is the occurrence of intracerebral hemorrhage, which may cause contralateral weakness or other neurological deficits, including death in the most severe cases.⁴ The risk for hemorrhage may vary from center to center, based on the experience of the functional surgeon, but it is never null. In addition, there are device-related risks of system failure and infection, which can occur in 20% to 25% of patients in the best centers.^5,6 Patients are also reminded that battery replacement, requiring minor surgery, will be necessary after 2 to 5 years, depending on the current drain associated with therapeutic stimulation.

In addition, general contraindications to surgery should be explored. Patients with uncontrolled hypertension or diabetes, coronary artery disease, cardiac pacemakers, liver or kidney failure, seizure disorders, or coagulopathies may be poor candidates, although the risk-benefit ratio of DBS surgery should be assessed individually in every case.⁷ If the patient is a good surgical candidate and agrees to surgery, a tentative date for surgery is scheduled and the remainder of the preoperative evaluation is completed. If there is disagreement about the proper surgical target or treatment modality, the patient’s case should be reviewed at a multidisciplinary conference to arrive at a consensus.

Neurocognitive and Psychiatric Evaluation

A neuropsychologist and a psychiatrist are essential members of a good DBS program because proper cognitive assessment and psychiatric screening are fundamental steps in patient selection, in particular for subthalamic nucleus (STN) DBS for PD. Little or no data are available on patients with premorbid psychiatric or cognitive symptoms undergoing DBS of the globus pallidus (pars) interna (GPi) or ventral intermediate (VIM) nucleus of the thalamus.⁸

The prevalence of dementia is high in patients with PD,⁹ and preoperative dementia is a risk factor for permanent cognitive decline after DBS.^10,11 Because of insufficient evidence on the predictive validity of any given neuropsychological assessment, interview, or cognitive test,⁸ several test batteries are used for the selection of surgical candidates, with the goal of excluding those with dementia or severe deficits in executive function.¹² No consensus guidelines or “gold standards” are available, and detailed comparative data have not been published. In designing a neuropsychological battery for DBS candidates, it is important to cover the major neurocognitive domains for both patient selection and follow-up (Table 76-2); at the same time, the battery should not be excessively long because patients with PD fatigue easily. Moreover, many PD patients who are DBS candidates have severe medication-related “on-off fluctuations” and can sometimes experience significant cognitive disturbance during the “off” cycle and yet perform relatively normally during the “on period.”^8,13,14 Unfortunately, neuropsychological testing is not universally performed before DBS, potentially leading to negative postsurgical outcomes.¹

TABLE 76-2 Neuropsychological Evaluation of Patients with Parkinson’s Disease for Deep Brain Stimulation Surgery

Parkinson’s Disease

Diagnosis

DBS therapy should be considered only for patients with a confirmed diagnosis of advanced idiopathic PD, as defined by the presence of bradykinesia associated with at least one of the three following conditions: rigidity, resting tremor, and postural instability.²¹ It is important to differentiate idiopathic PD from the atypical parkinsonian disorders, which generally have an earlier onset and a more rapidly progressive course, including early dysautonomia, bulbar dysfunction, respiratory compromise, spasticity, ataxia, and apraxia.²² The most frequent atypical parkinsonian syndromes that can be misdiagnosed for idiopathic PD are PSP, MSA, Lewy body dementia (LBD), and corticobasal ganglionic degeneration (CBGD).²¹

Patients with atypical parkinsonian syndromes should not be selected for DBS therapy. Several case reports have demonstrated the ineffectiveness of DBS for MSA using either STN^23–26 or GPi targets,²⁷ even when the patient is responsive to levodopa. Although patients with levodopa-responsive bradykinesia, rigidity, or dystonia may show transient improvement,²⁴ speech, swallowing, and gait usually deteriorate, motor fluctuations do not improve, and the levodopa dose remains unchanged.^23,25 Clinical experience with DBS for other types of atypical parkinsonism, including CBGD and PSP, is extremely limited.²⁸

Disease Severity and Duration

Although it is not considered a predictor of DBS outcome, the duration of PD should be taken into consideration when ruling out atypical parkinsonism.^8,29 Typically, PD motor disability progresses slowly, so patients with advanced symptoms less than 5 years after onset should be evaluated further for atypical parkinsonism before being considered for DBS. At the same time, DBS should not be offered too late, when severe motor complications have resulted in marked loss of quality of life. Currently, DBS is performed after an average PD duration of 11 to 14 years. However, investigational studies offering DBS therapy at an early stage of the disease (7 years after initial motor symptoms) have yielded positive results, thus suggesting that DBS should be considered a therapeutic option earlier in the course of PD, when quality of life is still maintained.³⁰ Indeed, there is little consensus on what defines advanced, medication-refractory PD and therefore candidacy for DBS. Severe PD disability generally coincides with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of around 30 (out of a maximum of 108), and this would be a reasonable severity cutoff.⁷ Available experience with STN or GPi DBS has mostly been with levodopa-responsive patients having off-period UPDRS motor scores higher than 40 or 50.⁸ An ideal PD surgical candidate should be severely disabled when off levodopa while doing well, often with associated dyskinesias, on medications.

Response to Levodopa

A sustained preoperative response to levodopa not only provides support for the diagnosis of idiopathic PD but is also considered the best predictor of outcome after DBS.^8,29 Levodopa responsiveness should ideally be assessed in each patient being considered for DBS⁸ with a dose sufficient to reproduce the patient’s best on response after a medication-free interval of 12 hours (usually overnight). It is particularly important to assess whether gait difficulties (in particular, freezing and imbalance) are sensitive to levodopa before offering DBS.

Levodopa response is normally defined as a 30% improvement in UPDRS motor scores (part III) over the off state,^8,29 although there is no consensus on what constitutes an appropriate challenge dose of levodopa. A suprathreshold dose has been defined variably: use of the normal first dose of the day,³¹ a fixed 200-mg test dose,³² or even apomorphine³³ has been proposed. In the experience of our group and others, however, patients with well-defined idiopathic PD can benefit from DBS even when their motor response is indeterminate because of intolerance to levodopa³⁴ or when the most disabling symptom is a dopa-refractory tremor.²

Age

The role of age as an outcome predictor for DBS is somewhat controversial.^28,35 Some authors consider advanced age (in particular, age older than 70 years) a poor outcome predictor if not a contraindication to DBS surgery^20,29 because it has been correlated with negative outcomes such as cognitive decline¹¹ and gait instability.³⁵ Nonetheless, given that the average age at the onset of PD is 60 years and that the mean duration of illness is 10 to 15 years at the time of surgery, a large proportion of potential DBS candidates are 70 years or older. In reality, no specific age cutoff has been defined for DBS candidates with advanced PD.⁸ Decisions for or against DBS in the elderly population should be individualized by taking into account the grade of disability, risk factors for complications, general life expectancy, and the patient’s motivation. Unilateral procedures could be an option in some patients who are otherwise at too high a risk for a bilateral procedure. Alternative targets, such as thalamic and pallidal implants, may be considered in an older PD candidate when deteriorating cognition is an issue.^36,37

Cognitive Status

Normal cognitive status should be established with an appropriate battery of neuropsychological testing.¹² Preoperative dementia is considered a risk factor for permanent cognitive decline after DBS, independent of the target, even though the risk for cognitive decline after GPi DBS may be less than that after STN DBS.^36,38 Older age and severe preoperative cognitive impairment might be associated with poorer neurobehavioral outcomes.^39–44

Cognitive decline in PD is characterized by impaired executive function, visuospatial abnormalities, impaired memory, and language deficits.⁴⁵ An appropriate scale that reliably incorporates executive function (e.g., frontal assessment battery and other practical tests of executive function) should be included in screening tests for PD dementia. However, in PD patients it may be difficult to assess impairment in domains other than memory.⁸ No studies have yet evaluated the sensitivity, specificity, and negative or positive predictive value of any disease, demographic, or test score variable in predicting which patients might experience such clinically meaningful cognitive declines.

Psychiatric Comorbid Conditions

A psychiatric evaluation should be performed to assess the presence of untreated depression, anxiety, apathy, dopaminergic dysregulation syndrome, medication-induced hypomania/mania, psychotic symptoms, and suicide risk because all have been related to some extent to STN DBS.⁸ Postoperative depression has been reported in 1% to 25% of patients,^{36,41,42,46–48} but preoperative assessment for depression is not always documented. Two studies focusing on whether preoperative depression was a risk factor for postoperative depression found conflicting results.^42,47 In particular, neither study differentiated between postoperative depression and dopaminergic withdrawal symptoms.

The relationships among postoperative depression and preoperative depression, stimulation, medication changes, disease factors, and psychosocial factors has not been completely elucidated. A number of tools can be used, including the Beck Depression Inventory,⁴⁹ Hamilton Depression Rating Scale,⁵⁰ and Montgomery-Asberg Depression Rating Scale.⁵¹ Other scales, such as the Geriatric Depression Scale⁵² and Zung Self-Rating Depression Scale,⁵³ have not been formally validated in patients with PD. Further research is required to determine the best (i.e., sensitive, specific, but also practical for clinicians to administer rapidly) depression screening tool for PD patients.

In a study focusing on behavioral symptoms, postoperative hypomania developed in one of two patients with preoperative hypomania.⁴² No associations between postoperative mania and preoperative mania have otherwise been reported; however, the adequacy of the preoperative assessment for behavioral disorders is not always known.

Psychosis in PD patients is characterized by visual hallucinations and delusions (often paranoid).⁵⁴ Screening tools for psychosis should be sensitive to hallucinations, as well as other psychotic features such as delusions. Only one study evaluated the Parkinson Psychosis Rating Scale (PPRS), which may be appropriate for patients with PD.⁵⁵ However, to determine its specificity, the PPRS needs to be evaluated in both nonpsychotic and psychotic PD patients. Criteria for psychosis from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) have not been validated in PD. Likewise, there are insufficient data to draw conclusions about whether a preoperative history of medication-induced psychiatric symptoms or features of dopamine dysregulation syndrome worsen after surgery.

In uncontrolled series, suicide attempts and suicides have been documented in 0.5% to 2.9% of patients.^42,56–58 A multicenter study of 450 STN DBS patients reported a postoperative suicide rate of 0.5%.⁵⁷ In contrast, a study of 120 patients who underwent DBS (including patients with PD, dystonia, and ET) documented a postoperative suicide rate of 2.9% in PD patients who had undergone STN DBS.⁵⁸ The authors suggested that young male patients with a history of multiple surgeries may be at greater risk for such outcomes. However, given the nature of the study as a small uncontrolled retrospective cohort from a single center, conclusions from this study are limited.

Ventral Intermediate Thalamus

The first reports of DBS for the treatment of PD used thalamic stimulation. In a series of 80 PD patients treated by either unilateral or bilateral VIM DBS, 88% achieved complete or nearly complete relief of tremor on the Fahn-Tolosa-Marín scale at 6 months to 8 years postoperatively.⁵⁹ The effects of VIM DBS on other symptoms of PD, however, such as rigidity, bradykinesia, or drug-induced dyskinesias, were either short lasting or nonexistent. Currently, the role of VIM DBS for PD is limited to patients with tremor-predominant symptoms.

Globus Pallidus Interna

A number of studies have shown that bilateral GPi stimulation is safe and effective for the management of PD symptoms.^60–62 Based on previous experience with pallidotomy,⁶³ the ideal target for DBS is thought to be the most ventral-posterolateral area of the pallidum. In PD patients, GPi DBS improves tremor, rigidity, and bradykinesia in the off-medication state, as well as drug-induced dyskinesia, and results in overall improvement in UPDRS motor scores.^64–66 The most pronounced and long-lasting effect is a reduction in on-medication dyskinesias,⁶⁷ and PD patients suffering mainly from motor fluctuations and dyskinesias might be good candidates for GPi DBS. Unlike STN DBS, however, GPi DBS does not lead to a reduction in the patient’s levodopa requirement.⁶⁸

Subthalamic Nucleus

The clinical efficacy of STN DBS in reducing PD symptoms has been reported by numerous investigators and validated in prospective, randomized trials.^69–71 Long-term follow-up results show sustained improvement in tremor, rigidity, and akinesia in the off-medication state and a reduction in dopaminergic medication requirements 5 years after implantation.^56,72–77 A reduction in levodopa dosage is usually achieved and leads indirectly to improvement in levodopa-induced dyskinesias.^78,79 Initial improvements in gait, however, are not always sustained in the long term.^56,69,80

Selection Criteria

Dystonia is a movement disorder characterized by sustained, involuntary muscle contractions generating twisting and repetitive movements or abnormal postures.⁸¹ Different muscle groups can be involved to a variable extent and severity can range from intermittent contractions limited to a single body region (focal dystonia) to generalized dystonia involving the axial and limb muscles. Dystonia may be classified by age at onset (early versus late), anatomic distribution (focal, segmental, multifocal, and generalized), and etiology. Etiologic classification of dystonia includes two broad categories: primary, or idiopathic, and secondary, or symptomatic.⁸¹ There is a bimodal distribution in the age at onset of primary dystonia, with modes at 9 years (early onset) and 45 years (late onset).⁸² The majority of early-onset cases begin with leg or arm dystonia that progresses to involve more than one limb, and in about 50% the dystonia eventually generalizes. Late-onset primary dystonia commonly affects the neck or cranial muscles and tends to remain localized as focal or segmental dystonia. With cloning of the DYT1 gene,⁸³ it is now possible to diagnose a leading cause of generalized primary dystonia.

Secondary forms of dystonia can result from an assortment of lesions, many involving the basal ganglia or dopamine synthesis, that are either inherited (e.g., dopamine-responsive dystonia [DRD], Wilson’s disease, gangliosidoses) or due to exogenous factors (e.g., perinatal injury, infections, neuroleptic medications). Clinical abnormalities other than dystonia (e.g., parkinsonism, dementia, ataxia, optic atrophy) are frequently present in patients with symptomatic dystonia, imaging studies often reveal changes involving the basal ganglia, and other laboratory findings usually help in the diagnosis.

For the great majority of patients with dystonia, treatment is aimed at controlling symptoms rather than addressing the underlying cause. Pharmacologic therapies can be further subdivided into focal therapies such as intramuscular injections of botulinum toxin and systemic administration of medications that affect the central nervous system. Many medications have been reported to be of some benefit to selected dystonia patients, including anticholinergic, dopaminergic, and GABAergic (γ-aminobutyric acid agonists) agents, but no single therapy has been found to consistently produce improvement. Botulinum toxin is considered the treatment of choice for many focal dystonias.⁸⁴

With the notable exception of DRD, pharmacologic treatment of primary generalized dystonia is mostly unsatisfactory. As a consequence, surgical attempts to relieve dystonic spasm have become progressively more relevant for the treatment of dystonia. Chronic stimulation of the GPi is currently considered a safe and effective treatment of advanced, disabling dystonia.^85,86 Selection of appropriate patients for DBS is a prominent issue for neurologists and neurosurgeons who treat patients with movement disorders (Table 76-4). In determining an individual patient’s risk-benefit ratio, several variables need to be taken into consideration, including the patient’s motor, cognitive, overall medical, and psychological status.⁸⁷ The best candidates are patients with primary generalized, segmental, or cervical dystonia or hemidystonia who have not responded to medications or botulinum toxin injections and have progressed to profound disability as a result of motor impairment or pain.⁸⁷

TABLE 76-4 Specific Deep Brain Stimulation Selection Criteria for Dystonia

Selection Criteria

ET is a progressive neurological disease characterized by a postural or kinetic tremor affecting mainly the arms, but also the head, jaw, and voice, as well as other body regions.¹¹² Tremor usually begins in the arms and then spreads to other regions in some patients. Essential head tremor is more likely to develop in women than in men.¹¹³ Other types of tremor may also occur, including occasionally rest tremor in the arms.¹¹⁴ In some patients, gait and balance difficulties, anxiety and depressive symptoms, and cognitive difficulty may also develop.^115,116

ET is a common neurological disease, with a prevalence of approximately 4% in persons 40 years and older and considerably higher in the elderly population.¹¹⁴ ET is often mild and is occasionally defined as “benign essential tremor” or “familial tremor” because of the fact that approximately half the cases are transmitted with a pattern of inheritance most consistent with autosomal dominant transmission. However, no genes have as yet been identified.

Patients with severe tremor have difficulty performing many of their routine activities of daily living and require pharmacologic or surgical therapy.^114,117 Before considering surgery, patients should undergo an adequate trial of first-line drugs alone and in combination, including propranolol (60 to 320 mg/day) and primidone (300 to 750 mg/day). If patients fail first-line therapy, trials of second-line (clonazepam, alprazolam, and topiramate) and third-line (clonidine, acetazolamide, flunarizine, and theophylline) drugs may be administered; however, these medications rarely result in marked improvement, and surgery should not be delayed unnecessarily.¹¹⁴ In general, oral medications tend to be more helpful for limb tremor than for head or voice tremor, which may benefit from botulinum toxin injections.

DBS is indicated for ET patients refractory to medications when tremor severity and distribution cause unacceptable impairment of activities of daily living.^59,118–129 Table 76-5 summarizes current DBS selection criteria for ET. The most widely accepted scale for evaluating the severity of ET is the Fahn-Tolosa-Marín rating scale for tremor.¹³⁰

TABLE 76-5 Specific Deep Brain Stimulation Selection Criteria for Essential Tremor

DBS, deep brain stimulation; ET, essential tremor; VIM, ventral intermediate nucleus of the thalamus.

Few reports have addressed cognitive function in patients with ET to document abnormalities that would suggest systematic neuropsychological testing before DBS surgery.^131–136 However, no standardized cognitive screening has consistently been advocated to test ET patients before DBS implants. Quality of life can be investigated with the Quality of Life in Essential Tremor Questionnaire (QUEST); although still partially validated, this scale is the only one available to assess impairment of daily living activities in patients with ET.¹³⁷

Target Selection

At present, the VIM nucleus of the thalamus is the most commonly targeted site for DBS in patients with ET.^{120,138–141} In addition, there is limited yet positive evidence that stimulation of the STN can also produce satisfactory tremor control in ET patents.¹⁴² Unilateral VIM stimulation results in marked short- and long-term improvement in contralateral action and postural tremor and in some cases may have a mild ipsilateral effect.^122,141,143 There is, however, a decreasing effect over time, most noticeable with tremor of action.¹⁴⁴

Because voice tremor is not reliably improved by unilateral VIM stimulation,^125,145,146 it should not be a primary indication for DBS. Head tremor has also shown inconsistent or unpredictable improvement with unilateral and bilateral stimulation.^{3,122,125,139,147}

Selection Criteria

The efficacy of thalamic DBS as a therapy for medically intractable ET and PD tremor has spurred much interest in its application to other types of less common and more complex tremor syndromes, such as cerebellar tremor in multiple sclerosis (MS), Holmes’ tremor (HT), thalamic tremor (TT), and orthostatic tremor (OT).

Target Selection

DBS has been shown to be beneficial for several atypical tremor syndromes, although fewer cases have been reported and the benefit is less remarkable and less consistent than that reported for ET.¹⁴¹ Most studies of DBS for MS tremor targeted the thalamus and the VIM nucleus in particular.^162,163 Other successful targets include the ventralis oralis posterior (VOP) nucleus of the thalamus and the zona incerta. Stimulation of these alternative targets produced a 64% improvement in postural tremor and a 36% improvement in intention tremor.¹⁶⁴ Dual-electrode stimulation to simultaneously target the VIM/VOP border and the VOA/VOP border also provided significant reduction of tremor in one MS patient.¹⁶⁵ Because DBS of the thalamic VIM nucleus produces often inconsistent and short-term benefits, further research is necessary to determine the most effective target for MS-associated tremor.

With the exception of one patient treated by GPi DBS,¹⁶⁶ the thalamic VIM nucleus is also the most frequent target for successful DBS treatment of atypical tremors (mostly TT and HT) resulting from posttraumatic and vascular lesions.^{165,167–176} The youngest patient who underwent implantation, a 14-year-old girl, showed remarkable improvement (90%) with VIM DBS up to 2.5 years.¹⁵³ Successful VIM DBS has also been reported in three patients suffering from OT.^160,177

The caudal (motor) zona incerta has also been used as an alternative target for DBS treatment of atypical tremor, with reported improvement in all components of tremor affecting both the distal and proximal ends of limbs, as well as the axial musculature.¹⁷⁸ Two patients with dystonic tremor and one with neuropathic-related tremor responded well to unilateral stimulation of the posterior subthalamic area.¹⁷⁹ Subthalamic-thalamic stimulation achieved suppression of tremor related to spinocerebellar ataxia type 2.¹⁸⁰

Multiple targets have also been used to improve HT symptoms. Simultaneous placement of two DBS electrodes at the VIM/VOP border and at the VOA/VOP border resulted in excellent reduction of symptoms in three patients.¹⁶⁵ In one patient, combined STN-VIM stimulation but not stimulation of the STN or VIM nucleus alone produced global relief of tremor without adverse events.¹⁷⁰

Selection Criteria

Tourette’s syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics that wax and wane over time, often associated with behavioral disorders.¹⁸¹ The motor tics are stereotyped repetitive and involuntary movements that generally affect the face, head, and upper part of the body, whereas vocal tics are sounds usually represented by shouting, barking, sniffing, or grunting. Comorbid conditions include attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and self-injurious behavior. Symptoms often disappear before or during early adulthood or may be controlled with medication.¹⁸¹ Some patients, however, may have medically resistant severe and disabling tics that persist or worsen in adulthood.

To be considered a surgical candidate, TS patients need to be refractory to medical treatment and be severely disabled by the condition.¹⁸² A multidisciplinary approach that includes neurological and psychiatric evaluation is strongly recommended. The main scale used to evaluate the severity of symptoms is the Yale Global Tic Severity Scale.¹⁸³

The Dutch-Flemish Tourette Surgery Study Group has established guidelines for DBS in patients with TS,¹⁸⁴ and the Movement Disorders Society has published the recommendations of the Tourette Syndrome Association.¹⁸² The proposed selection criteria include the following:

TS patients should be excluded from neurosurgical treatment if they have a tic disorder other than TS, severe psychiatric comorbid conditions (other than associated behavioral disorders), or mental deficiency. Patients with active suicidal ideation are not good candidates for DBS.

Target Selection

The choice of target in TS is still controversial inasmuch as good outcomes have been reported with both thalamic and GPi DBS. To date, five targets have been used for DBS in patients with TS: (1) the medial portion of the thalamus at the cross point of the centromedian nucleus/substantia periventricularis/VOA nucleus,^187–190 (2) the medial portion of the thalamus at the centromedian nucleus and parafascicular nucleus,¹⁸³ (3) the posteroventrolateral GPi,¹⁹¹ (4) the anteromedial GPi,¹⁸³ and (5) the nucleus accumbens and anterior limb of the internal capsule.^192,193

A direct comparison among targets to determine whether the particular patient or symptoms could receive the best benefit is not possible because of the limited number of patients operated on.

Selection Criteria

Two types of chorea have been considered for treatment with DBS: Huntington’s disease (HD) and neuroacanthocytosis (NA). HD is a progressive hereditary neurodegenerative disease manifested by chorea and other hyperkinetic (dystonia, myoclonus, tics) and hypokinetic (parkinsonism) movement disorders. In addition, a variety of psychiatric and behavioral symptoms, along with cognitive decline, contribute significantly to the patient’s disability. No effective neuroprotective or disease-modifying therapy for HD is available.¹⁹⁴ NA includes combined features of chorea, orofacial tics, dystonia, amyotrophy, and elevated serum creatine kinase levels, with a peculiar finding of spiked red blood cells (acanthocytosis) in the blood smear. NA has been described most commonly as an autosomal recessive hereditary gene defect located on chromosome 9, but it also occurs as an autosomal dominant disorder and as part of an X-linked disorder called McLeod’s syndrome.¹⁹⁵ In most cases, the neurological disability caused by chorea is progressive.

Clinical assessment of patients with chorea can be standardized with the UHDRS¹⁹⁶ or the Abnormal Involuntary Movement Scale.¹⁹⁷ The functional status of HD patients is commonly assessed with the Total Functional Capacity Scale and the Independence Scale, both of which are incorporated into the UHDRS.

Medical therapy for chorea is fairly limited and restricted to symptomatic relief. Numerous medications have been used to improve chorea, including typical and atypical neuroleptics, dopamine depleters, antidepressants, antiglutamatergic drugs, GABA agonists, antiepileptic medications, acetylcholinesterase inhibitors, and botulinum toxin.¹⁹⁶

Target Selection

Thalamic and pallidal targets have been used for DBS therapy in patients with chorea. Bilateral GPi DBS in HD was first used for the treatment of a 43-year-old patient who had genetically confirmed HD, rapidly progressive disabling chorea despite medical treatment (tetrabenazine, haloperidol, amantadine), and no psychiatric symptoms.¹⁹⁸

Positive results of bilateral GPi DBS were reported in a second HD patient with debilitating choreoathetoid movements refractory to medical management (tetrabenazine, neuroleptics, minocycline) but no psychiatric comorbid conditions.¹⁹⁹ The effects were maintained at 1 year, but progressive hypokinetic symptoms eventually developed. Combined thalamic (VOP) and pallidal (GPi) stimulation proved effective in controlling abnormal movements in one case of intractable senile chorea.²⁰⁰

A slightly larger experience is available for NA. Bilateral high-frequency stimulation (160 Hz) of the VOP nucleus of the thalamus improved trunk spasms in one patient with NA, with stable clinical benefit for 1 year, although no clear effect on dysarthria was observed.²⁰¹ Interestingly, high-frequency stimulation of the GPi failed to improve²⁰² or even worsened NA-related chorea,²⁰³ whereas the best results were obtained with low-frequency (40 Hz) bilateral pallidal DBS using monopolar stimulation on two adjacent contacts.²⁰³