Decreased Dopamine Concentrations in the Frontal Cortex After Ablative Surgeries in Patients Exhibiting Self-Injurious Behavior: A Microdialysis Study

This study included four male patients with severe mental retardation and SIB, from 16 to 27 years of age (mean, 19 years). They all presented with a history of frequently beating their head or banging their forehead against a wall for 6–20 years (mean, 12 years). Three patients also occasionally exhibited physically violent outbursts toward their family. They were diagnosed with mental retardation because of low intelligence. They all were repeatedly hospitalized in a psychiatric hospital for SIB, and their current medications included haloperidol, risperidone, clozapine, valproate, and clonazepam. Importantly, all these efforts failed to result in adequate alleviation of their dangerous behaviors. MRI and CT scans failed to find any brain abnormalities for these patients. Brain [¹⁸F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) was performed in two patients under anesthesia, and the results showed low baseline metabolism in their left frontal lobe.

All four patients underwent combined stereotactic bilateral amygdalotomies and cingulotomies. Before the surgery, each patient’s case was submitted to our institution’s bioethics committee. Each surgery was undertaken only after careful review and approval by this committee. The patient’s parents were fully informed about the risks and possible benefits of the surgery, and a written consent form was obtained. Details regarding the target and the surgical techniques in general can be found elsewhere.¹ There were two steps for microdialysis. First, the microdialysis cannula (CMA 70; CMA Microdialysis, Solna, Sweden) was inserted into the left frontal cortex of each patient before making the lesions. Microdialysis was performed using Ringer’s solution in the operating theater (flow rate, 0.3 μL/min) using a microdialysis pump (CMA 106; CMA Microdialysis). Samples were collected for 180 minutes, and the microvials were changed approximately every 60 minutes. The samples were stored at −80°C. Second, after surgery, the microdialysis cannula was kept in the same place, and the patient was transferred to a neurointensive care unit. Microdialysis was performed continuously in all four patients using the same procedures for at least 36 hours. The collected samples were analyzed by high-performance liquid chromatography as described previously.⁶ After each surgery, a brain CT scan was carried out to identify the location of the cannula tip. The microdialysis cannulae were removed from the patients at different time points.

After surgery, one patient had a “taming effect” following surgery, and during the 4-year follow-up period, no episode of SIB was reported. Two patients had short-term relief of SIB and resumed as before the operation. The fourth patient, the oldest among the four patients, had no benefit of the surgery during the 3-year follow-up period.

The average concentrations of dopamine, norepinephrine, 5-hydroxyindoleacetic acid, GABA, and glutamine in the left cortex at different times after the operations were analyzed. Only the dopamine concentration showed significant decreases during the 36-hour observation period. Compared with the baseline concentration, dopamine concentrations at 15–36 hours postoperatively were significant lower (Figure 1).