Fig. 15.1
MRI slices showing the typical lesions of capsulotomy, NAcc lesion, and cingulotomy. a Axial view of capsulotomy. b Coronal view of capsulotomy. c Axial view of NAcc lesion. d Coronal view of NAcc lesion. e Axial view of cingulotomy. f Coronal view of cingulotomy
15.4.2 Deep Brain Stimulation
Deep brain stimulation (DBS) has been considered as an effective treatment for a variety of neurological and psychotic disorders refractory to normal therapy, including Parkinson’s disease (PD), dystonia, tremor, and obsessive-compulsive disorder (OCD) [56–59]. Deep brain stimulation (DBS) is a neurosurgical treatment involving implantation of electrodes that send electrical impulses to specific locations in the brain. Unlike ablative procedures, DBS is a reversible intervention that causes less damage to neural tissue. Furthermore, most side effects are reversible and can be managed by adjusting stimulation parameters.
DBS is an innovative and promising approach for the treatment of patients with treatment-refractory reward-related psychiatric disorders , DBS targets, such as the NAcc, the ventral capsule/ventral striatum (VC/VS ), and SCC, have been used in the treatment of OCD, addiction, MDD, and AN. We demonstrated the efficacy of DBS for AN, as DBS targeting the NAcc reduced excessive hypermetabolism in the frontal lobe, hippocampus, and lentiform nucleus. These findings suggest that DBS can reduce maladaptive activity and connectivity in the stimulated region and restore diseased neural networks to a healthy state [31].
To date, there are few publications regarding the effects of DBS on AN. The first study (a case series) of DBS in AN was conducted by Wu et al. [55] in Shanghai. Four adolescent patients with AN treated with DBS of the NAcc exhibited an average 65 % increase in body weight (average baseline BMI: 11.9 kg/m2; average follow-up BMI: 19.6 kg/m2) at a 38-month follow-up examination, and menstrual cycles were restored within 11 months for all these patients. At the final follow up, where DBS systems are explanted 1 year after the battery has fully discharged, no recurrence of symptoms was observed; thus patients were in remission according to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Wang et al. [60] report that ablation (6 AN patients) or DBS (2 patients) of the NAcc resulted in restoration of menstruation within 9 months of surgery, and a recovery in BMI to within a normal range (>18 kg/m2) within 12 months. These two preliminary studies demonstrate that DBS is a viable option for weight restoration in AN.
Recently, Lipsman et al. [32] published the results of a phase 1 pilot trial of subcallosal cingulate (ACC) DBS in 6 adult patients with treatment-refractory AN. They observed that DBS was relatively safe in this population and resulted in improvements in mood, anxiety, affective regulation, and anorexia-related obsessions and compulsions in 4 patients. At 9-month follow-up examinations, only 3 patients exhibited improved BMI’s relative to estimated historical baselines; menstruation status was not noted.
Given the similarities in symptomatology and associated neurocircuitry between OCD and AN, and the established efficacy of DBS for OCD [50, 51], we hypothesize that DBS of the NAcc and other areas associated with reward, might be effective in patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvements in core AN symptoms and associated comorbidities and complications.
15.4.3 Ablative Procedures
As mentioned previously, not all treatment-refractory AN patients experience beneficial effects from DBS, especially the binging-purging subtype, and those with long term (>10 years) AN. In these cases, lesion procedures, such as capsulotomy and cingulotomy , should be considered, as discussed below.
15.4.3.1 Anterior Capsulotomy
Anterior capsulotomy is a stereotactic ablative procedure that involves specific lesions to disconnect limbic circuits involved in different psychiatric disorders , such as OCD, MDD, and addiction. Most patients exhibit relief of certain symptoms and improved cognitive function, without experiencing alterations in personality [61–64].
Anterior capsulotomy involves ablation of the anterior limb of the internal capsule to disconnect the prefrontal cortex and subcortical nuclei (including the dorsomedial thalamus), and is a widely used psychosurgical procedure. Ablations are performed by thermal coagulation or focal gamma radiation guided by computed tomography (CT) or magnetic resonance imaging (MRI ). MRI is considered the best modality for locating the anterior capsule because of the large inter-individual differences in this structure. Targets are first identified by visualization of the internal capsule on stereotactic MRIs. Two bilateral trepanations are then performed immediately behind the coronal suture and a lesion is created by thermo-coagulation using radiofrequency probes reaching 80 °C for approximately 60 s. Lesions are typically 4 mm in diameter and 10 mm in length along the contoured target.
A recent study reported the results of 1 patient with OCD comorbid with AN who received bilateral anterior capsulotomy. The patient experienced significant weight gain and improvement in OCD symptoms at a 3 month follow-up examination [53]. In our institution, of the 150 patients who underwent capsulotomies during October 2005 to December 2013, 85 % experienced an improvement in symptoms, and menstruation resumed in all female patients. The results suggest that this is a very promising procedure for treatment of AN. In contrast to DBS, bilateral capsulotomy can cause short-term side effects including incontinence, disorientation, sleep-disorders, and refeeding syndrome. These symptoms usually resolve within 1 month of the operation. A few patients (<5 %) experience long-term side effects including memory loss, fatigue, excessive weight gain, and personality changes.
15.4.3.2 Anterior Cingulotomy
Anterior cingulotomy is one of the most popular psychosurgical procedures currently performed in the US [65, 66]. Clinicians based at Massachusetts General Hospital have significant experience with cingulotomies for treatment of OCD or MDD, and report very positive outcomes [66, 67]. Typically lesions are created by thermo-coagulation through radiofrequency probes reaching 80–85 °C for 90 s. The electrode is then withdrawn by 1.0 cm and the lesion is enlarged superiorly using the same lesion parameters. These steps are repeated for the opposite hemisphere. This produces symmetrical bilateral lesions of the ACC.
Cingulotomy is a relatively safe procedure with a lower incidence of adverse events than anterior capsulotomy . Immediate, transient symptoms include headache, confusion, and urinary incontinence. In our institution, anterior cingulotomies are performed on AN patients only after a bilateral capsulotomy has failed for at least 1 year, and approximately half of these patients experience positive clinical outcomes with this procedure.
15.4.3.3 Lesioning of the Nucleus Accumbens
Dysfunctions of the primary reward system are a central feature of AN. The NAcc is a key component of this reward system, and may be important for progression of AN. NAcc DBS has been successfully used for treatment of OCD, drug addiction , MDD, and AN. Wang et al. [60] reported the results of 6 AN patients treated with NAcc lesioning. One year after the operation patients exhibited improved basic vital signs and BMI, restoration of menstruation, and improvements in the symptoms of depression, anxiety, and OCD. Although data were obtained from a limited number of cases, considering the successful reports of NAcc DBS, lesioning of the NAcc should be considered as a potential procedure for treatment of refractory AN.
15.4.3.4 Combined Surgical Procedures
As stated above, the majority of AN patients present with psychiatric comorbidities including OCD, MDD, or anxiety disorders. Personality disorders and alcohol or substance abuse may also be present among those with the binging-purging subtype of AN. These parallel symptoms indicate that there is a considerable overlap in reward system neurocircuitry between these psychiatric disorders and eating disorders. For some chronic, refractory AN patients, if the first surgical procedure has failed, a second surgery targeting areas including the NAcc, the anterior internal capsule, and the ACC, should be considered, which can lead to improvements in both core AN symptoms and associated comorbidities and complications.
NAcc DBS Combined with Anterior Capsulotomy
Animal experiments suggest that DBS of the NAcc is a potential treatment option for AN either alone or in combination with an anterior capsulotomy [68]. In our first series, of 15 AN patients treated with NAcc DBS, 12 cases experienced treatment failure and thus bilateral anterior capsulotomies were performed at a second surgery. All these patients achieved a significant improvement in both eating behaviors and psychiatric symptoms [54]. NAcc DBS combined with a bilateral or unilateral anterior capsulotomy is therefore a viable treatment option for severe, treatment-refractory AN patients.
Anterior Capsulotomy Combined with Anterior Cingulotomy
Given the successful results of anterior cingulotomy in OCD and anxiety, this procedure should be considered as a potential second surgery for AN patients experiencing symptoms of OCD, depression, or anxiety, following failure of the initial bilateral anterior capsulotomy. Notably, of 12 patients at our institution in whom bilateral anterior capsulotomies failed, an additional anterior cingulotomy resulted in further improvements in about half of these patients.
15.5 Grading of Anorexia Nervosa and Surgical Options
Patients with AN have elevated rates of lifetime diagnoses of anxiety disorders, MDD, OCD, personality disorders, and substance abuse disorders. Severe comorbidities and longer disease duration contribute to less favorable outcomes for AN. Based on data obtained from 180 cases of surgical treatment for AN, we categorize AN into 4 grades depending on clinical characteristics, which in turn guide the selection of treatment options.
15.5.1 Grading of AN According to Clinical Features
Grade I: Dieting and/or excessive exercise.
Grade II: Dieting and at least one psychiatric symptom such as OCD, anxiety, or depression.
Grade III: Binge-eating and/or purging behaviors (self-induced vomiting or the misuse of laxatives, diuretics), accompanied by psychiatric symptoms including OCD, anxiety, or depression.
Grade IV: Binge-eating and/or purging behaviors, accompanied by at least one of the following severe psychiatric disorders : substance abuse, kleptomania, promiscuity, self-injurious behavior, or a personality disorder.
Note that if AN disease duration is longer than 6 years, the patient will be graded one level higher.
15.5.2 Selection of Surgical Treatment
Patient treatment options depend on the grade of AN, as follows.
Grade I: Psychotherapeutic interventions and pharmacological therapies.
Grade II: Psychotherapeutic interventions/pharmacological therapies or/and bilateral NAcc DBS.
Grade III: Bilateral anterior capsulotomy or bilateral NAcc ablation .
Grade IV: Bilateral anterior capsulotomy combined with bilateral anterior cingulotomy .
15.6 Indications and Patient Selection Criteria
Since there are few publications regarding patient selection criteria and limited data are available, there are no definite guidelines on AN patient selection criteria. However, the general consensus regarding selection criteria for surgery in our institution is as follows:
1.
Patients must exhibit a consistent diagnosis of AN, either the restricting or binge-purging subtype, as defined by DSM-IV criteria and based on a psychiatric interview.
2.
Patients must be confirmed as treatment-refractory AN. In our center, treatment-refractory AN is defined as follows. Firstly, patients must have been treated with an appropriate therapy for more than 3 years. Secondly, at least two types of therapy (including pharmacological treatment, behavioral therapy, and psychotherapy) must have been applied with no response. Lastly, patients must have experienced a rapid decrease in body weight over a short time period, which could be life threatening without effective intervention.
3.
AN must be of disabling severity with substantial functional impairment according to DSM-IV criterion C, and patients must exhibit a global assessment of functioning (GAF) score of 45 or less for at least 2 years.
4.
Patient weight must be <85 % of ideal body weight (and/or BMI < 17.5).
5.
Patients or their representatives must be willing to give informed consent for treatment and any subsequent follow-up study.
Exclusion criteria are as follows:
1.
Unstable physical condition (severe electrolyte disturbances, cardiac failure, or other physical contraindications for surgery/anesthesia).
2.
Patients with obvious encephalotrophy caused by Alzheimer’s disease, tumor, or trauma, as confirmed by MRI.
3.
Patients with any contraindication to MRI (pregnancy, pacemakers, or metal implants contraindicated for MRI, not including the DBS implant and the stimulator itself).
4.
Patients with severe heart disease or other organic problems contraindicated for neurosurgery.
5.
Patients younger than 14 years.
6.
Refusal to sign the patient information and consent form.
15.7 Perioperative Patient Management
Considering the wide range of physiological abnormalities observed in AN, careful perioperative management is required.
15.7.1 Preoperative Management
As a result of long-term malnutrition, most AN patients have an unstable physical condition which is contraindicated for surgery or anesthesia. These conditions include severe electrolyte disturbances, cardiac failure, abnormal liver function, and coagulation abnormalities, amongst others. Therefore, more detailed preoperative screening examinations such as electrocardiograms and appropriate blood tests (disseminated intravascular coagulation tests, blood biochemical examinations, routine blood tests, blood glucose tests) are essential to assess potential medical risks.
According to our experiences, hypokalemia and hypoalbuminemia are the most common electrolyte disorders, which should be restored to normal conditions before surgery. In addition, most patients with AN exhibit comorbidities such as OCD, depression, and anxiety. The mental status of AN patients is often unstable and patients frequently present with irritation and deep depression. Thus, patients must be closely monitored throughout the entire procedure.
15.7.2 Intraoperative Management
Local anesthesia is recommended during the lesioning procedure to avoid hypervolemia and excessive dilution of electrolytes. For AN patients receiving DBS treatment, local and general anesthesia are required. Considering the potential anesthetic complications, a thorough preoperative anesthetic assessment and evaluation is required. In addition, doses of most (anesthetic) drugs should be adjusted for weight, and during the operation, electrocardiographic changes and potassium levels should be monitored carefully to minimize the risk of arrhythmias.
Specific caution must be taken during the burr hole procedure because the skull of AN patients is usually very thin; excessive pressure to the dura may cause epidural hematomas. To avoid cerebrospinal fluid overflow during the operation, fibrin glue should be applied immediately after opening the dura. Furthermore, a warm air blower is necessary during the operation to maintain normal body temperature. Lastly, the operation should be completed in a timely manner and appropriate soft mats should be applied to avoid bedsores.
15.7.3 Postoperative Management
Since patients with AN exhibit a very low body weight, strict control of rehydration fluids should be observed after surgery. According to our experience, mannitol should not be administered considering the risk of intracranial hemorrhage. Blood tests should also be monitored closely to avoid fluid and electrolyte disturbances. Pharmacological therapies should be administered on the second day after surgery, but dosage should be adjusted based on the patients’ symptoms; psychotherapeutic interventions can be initiated 2 weeks after surgery.
15.8 Adverse Events Associated with Surgery for Anorexia Nervosa
Complications of stereotactic surgery in AN patients can be classified into the following subtypes.
15.8.1 Operative Complications
Intracranial hematomas are a severe complication of stereotactic surgery . In 216 cases of stereotactic surgery at our institution, four cases of epidural hematoma were observed; three recovered after surgery and 1 patient died as a result of disseminated intravascular coagulation. Hematomas occur more frequently in AN patients than in other disorders treated with stereotactic surgery , such as Parkinson’s disease, dystonia, OCD, and others, likely as a result of the serious condition of patients with AN.
Related posts:
DBS in Psychiatry and the Pendulum of History
Deep Brain Stimulation for the Management of Treatment-Refractory Major Depressive Disorder
Deep Brain Stimulation for Tourette Syndrome
Neuroimaging in Psychiatry
Ablative Surgery for Depression
High-angular diffusion MRI in reward-based psychiatric disorders
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