Cristina V. Torres, Rafael G. Sola, Jesús Pastor, Manuel Pedrosa, Marta Navas, Eduardo García-Navarrete, Elena Ezquiaga and Eduardo García-Camba
Erethism describes severe cases of unprovoked aggressive behavior, usually associated with some degree of mental impairment and gross brain damage. The etiology can be epileptic, postencephalitic, or posttraumatic, or the condition can be caused by brain malformations or perinatal insults. Erethism is often refractory to medication, and patients must often be interned in institutions, where they are managed with major restraining measures. The hypothalamus is a crucial group of nuclei that coordinate behavioral and autonomic responses and play a central role in the control of aggressive behavior. Deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) has been proposed as a treatment for resistant erethism, although experience with this treatment around the world is scarce. The objective of this study was to examine the long-term outcome of PMH DBS in 6 patients with severe erethism treated at the authors' institution.
Medical records of 6 patients treated with PMH DBS for intractable aggressiveness were reviewed. The therapeutic effect on behavior was assessed by the Inventory for Client and Agency Planning preoperatively and at the last follow-up visit.
Two patients died during the follow-up period due to causes unrelated to the neurosurgical treatment. Five of 6 patients experienced a significant reduction in aggressiveness (the mean Inventory for Client and Agency Planning general aggressiveness score was −47 at baseline and −25 at the last follow-up; mean follow-up 3.5 years). Similar responses were obtained with low- and high-frequency stimulation. In 4 cases, the patients' sleep patterns became more regular, and in 1 case, binge eating and polydipsia ceased. One of the 3 patients who had epilepsy noticed a 30% reduction in seizure frequency. Another patient experienced a marked sympathetic response with high-frequency stimulation during the first stimulation trial, but this subsided when stimulation was set at low frequency. A worsening of a previous headache was noted by 1 patient. There were no other side effects.
In this case series, 5 of 6 patients with pathological aggressiveness had a reduction of their outbursts of violence after PMH DBS, without significant adverse effects. Prospective controlled studies with a larger number of patients are needed to confirm these results.
Vengalathur Ganesan Ramesh
Juan Delgado-Fernández, Maria Ángeles García-Pallero, Rafael Manzanares-Soler, Pilar Martín-Plasencia, Guillermo Blasco, Natalia Frade-Porto, Marta Navas-García, Paloma Pulido, Rafael G. Sola and Cristina V. Torres
Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance.
The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres.
Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024).
The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.
Cristina V. Torres, Guillermo Blasco, Marta Navas García, Elena Ezquiaga, Jesús Pastor, Lorena Vega-Zelaya, Paloma Pulido Rivas, Silvia Pérez Rodrigo and Rafael Manzanares
Initial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors’ objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders.
This was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation.
The series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field.
In this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.