Long-term results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness
Cristina V. Torres, Rafael G. Sola, Jesús Pastor, Manuel Pedrosa, Marta Navas, Eduardo García-Navarrete, Elena Ezquiaga, Eduardo García-Camba, J Neurosurg. 2013 Aug;119(2):277-87. doi: 10.3171/2013.4.JNS121639.
Context:
Erethism is severe aggressiveness, including destructive behavior and self aggressivness often accompanied by hyperkinesia. Stemming from many causes, including epilepsy, trauma, perinatal insults… etc. It is often resistant to conventional medical treatment and through the years several procedures have been developed for the treatment of erethism. Amongst them is deep brain stimulation (DBS) of the posteriomedial hypothalamus (PMH). There are few studies on the matter of PMH-DBS in erethism and the authors of this case series endeavor to answer more questions on the efficacy and safety of DBS in patients with erethism.
Materials and Methods:
Records for 6 treated patients (age range=17-48) with a post surgical time ranging from 6-82 months were analyzed. All patients had been diagnosed by two different psychiatrist, prior to surgery, with refractory erethism. All patients had adjoining, but varying, symptoms and the effect of PMH-DBS on these symptoms, including hyperactivity, hyperphagia, polydipsia, seizures, and sleep disturbance was assessed.
DBS insertion was 2mm lateral to the third ventricle at the mid-commisural point and 2 mm inferior to the anterior-posterior commissure line at the PMH.
ICAP scores were measured pre-operatively and during post-operative follow ups as a measure of procedural outcome on erethism.
Statistical analysis of data was done via a paired student t-test where the data was normative and via Mann-Whitney-U where it was not.
DBS settings at last follow up ranged from patient to patient. Frequency ranged from (15-185), pulse width from 60-450, voltage from 1.3-2.5, density from 3.0-12.2, and charge from 11.0-61.4.
Results:
Two of the six patients died during the post-operative follow up period of causes independent of the DBS procedure/stimulation .
Five out of the six patients PMH-DBS did a reduce patient aggressiveness. Specifically statistically significant changes were measures in the self-aggressiveness (from -44.0+/-5.8 to -19.5+/-7.5, p<0.05) and heteroaggressivness (-43.2+/-3.2 to -25.3+/-6.1, p<0.05) categories of ICAP, but for the asocial behavior category (-25.3+/-4.6 to -22.3+/-4.8) no significant change was measured. One patient of these only experienced improvement in the self-aggression component.
DBS insertion also resulted in improvement of sleep pattern, sociability, and a decreased need of restraint. Of the three patients who suffered from seizures prior to surgery, one noticed a 30% reduction in seizures. One had a reduction in hyperphagia and polydipsia and three had a reduction in hyperactivity.
As far as post-surgical complications, one patient experienced an increase in cluster headaches, which were present prior to surgery, although these were treated well with medications. Additionally patients, on average gained a statistically insignificant increase in weight (78.3 +/- 7.8kg to 86.8 +/- 10.5 kg).
Changes in DBS settings did not appear to result in clinically significant changes.
Conclusion:
Despite finding that the procedure did result in improvement, the group was unable to determine the efficacy of differing DBS settings . Additional they were unable to definitively conclude that outcome was due to stimulation as opposed to insertion affects.
In consideration of outcome it is important to note that, even though asocial behavior was not affected by stimulation, this was expected as patients had pervasive developmental disorders, which confounded the measure of procedural outcome on asocial behavior. Additionally in the case of the one patient who did not benefit from stimulation at all, it is important to note that he had a temporal lesion. In Franzini et al’s case series, one of their patients with bi-frontal brain damage also did not respond to stimulation. As such it has been postulated that lesions to different limbic system structures may result in varying levels of responsiveness to DBS.
Procedural affects on seizures are not limited to this specific study. Frnzini et al saw a 50% reduction in one of their two patients seizures and a disappearance of generalized seizures in another and persistence of complex seizures. Treatment of seizures via DBS has been postulated and studied in previous studies. Rijckevorsel et al described a relation of the mammillary bodies and mammilothalamic tract to seizures and their potential targeting for seizure reduction. Duprez et al described the successful stimulation of 3 patients in their mammillary bodies and the safety and efficacy.
The efficacy of PMH-DBS on sleep and hyperphagia is thought to be due to the relation of the PMH to the reticular activating system and lateral hypothalamus, structures involved in wakefulness and hunger respectively.
Ideal criteria for patient selection, including stimulation parameters, and long term outcome remain uncertain, due to the small number of existing studies/reports on the topic of PMH-DBS in erethism. A large RCCT should be conducted to resolve this issue.
Erethism is severe aggressiveness, including destructive behavior and self aggressivness often accompanied by hyperkinesia. Stemming from many causes, including epilepsy, trauma, perinatal insults… etc. It is often resistant to conventional medical treatment and through the years several procedures have been developed for the treatment of erethism. Amongst them is deep brain stimulation (DBS) of the posteriomedial hypothalamus (PMH). There are few studies on the matter of PMH-DBS in erethism and the authors of this case series endeavor to answer more questions on the efficacy and safety of DBS in patients with erethism.
Materials and Methods:
Records for 6 treated patients (age range=17-48) with a post surgical time ranging from 6-82 months were analyzed. All patients had been diagnosed by two different psychiatrist, prior to surgery, with refractory erethism. All patients had adjoining, but varying, symptoms and the effect of PMH-DBS on these symptoms, including hyperactivity, hyperphagia, polydipsia, seizures, and sleep disturbance was assessed.
DBS insertion was 2mm lateral to the third ventricle at the mid-commisural point and 2 mm inferior to the anterior-posterior commissure line at the PMH.
ICAP scores were measured pre-operatively and during post-operative follow ups as a measure of procedural outcome on erethism.
Statistical analysis of data was done via a paired student t-test where the data was normative and via Mann-Whitney-U where it was not.
DBS settings at last follow up ranged from patient to patient. Frequency ranged from (15-185), pulse width from 60-450, voltage from 1.3-2.5, density from 3.0-12.2, and charge from 11.0-61.4.
Results:
Two of the six patients died during the post-operative follow up period of causes independent of the DBS procedure/stimulation .
Five out of the six patients PMH-DBS did a reduce patient aggressiveness. Specifically statistically significant changes were measures in the self-aggressiveness (from -44.0+/-5.8 to -19.5+/-7.5, p<0.05) and heteroaggressivness (-43.2+/-3.2 to -25.3+/-6.1, p<0.05) categories of ICAP, but for the asocial behavior category (-25.3+/-4.6 to -22.3+/-4.8) no significant change was measured. One patient of these only experienced improvement in the self-aggression component.
DBS insertion also resulted in improvement of sleep pattern, sociability, and a decreased need of restraint. Of the three patients who suffered from seizures prior to surgery, one noticed a 30% reduction in seizures. One had a reduction in hyperphagia and polydipsia and three had a reduction in hyperactivity.
As far as post-surgical complications, one patient experienced an increase in cluster headaches, which were present prior to surgery, although these were treated well with medications. Additionally patients, on average gained a statistically insignificant increase in weight (78.3 +/- 7.8kg to 86.8 +/- 10.5 kg).
Changes in DBS settings did not appear to result in clinically significant changes.
Conclusion:
Despite finding that the procedure did result in improvement, the group was unable to determine the efficacy of differing DBS settings . Additional they were unable to definitively conclude that outcome was due to stimulation as opposed to insertion affects.
In consideration of outcome it is important to note that, even though asocial behavior was not affected by stimulation, this was expected as patients had pervasive developmental disorders, which confounded the measure of procedural outcome on asocial behavior. Additionally in the case of the one patient who did not benefit from stimulation at all, it is important to note that he had a temporal lesion. In Franzini et al’s case series, one of their patients with bi-frontal brain damage also did not respond to stimulation. As such it has been postulated that lesions to different limbic system structures may result in varying levels of responsiveness to DBS.
Procedural affects on seizures are not limited to this specific study. Frnzini et al saw a 50% reduction in one of their two patients seizures and a disappearance of generalized seizures in another and persistence of complex seizures. Treatment of seizures via DBS has been postulated and studied in previous studies. Rijckevorsel et al described a relation of the mammillary bodies and mammilothalamic tract to seizures and their potential targeting for seizure reduction. Duprez et al described the successful stimulation of 3 patients in their mammillary bodies and the safety and efficacy.
The efficacy of PMH-DBS on sleep and hyperphagia is thought to be due to the relation of the PMH to the reticular activating system and lateral hypothalamus, structures involved in wakefulness and hunger respectively.
Ideal criteria for patient selection, including stimulation parameters, and long term outcome remain uncertain, due to the small number of existing studies/reports on the topic of PMH-DBS in erethism. A large RCCT should be conducted to resolve this issue.
Ask the expert
