Sympatholysis subsequent to intraoperative amygdalohippocampal stimulation: A report of three pediatric neurosurgical cases with literature review.

The existence of neural connection between the limbic system (hypothalamus, hippocampus, amygdala, and other adjacent areas) and the autonomic nervous system has been postulated to trigger severe hemodynamic responses. The hemodynamic consequences of stimulation of amygdala or hippocampus have been sporadically reported in animal studies and adult patients. However, the effect of this stimulation in pediatric patients is scarce. We present our experience of three cases of sympatholysis during intraoperative manipulation of amygdalohippocampus and review the pertinent literature.

Introduction

The limbic system governs a variety of functions including emotion, behavior, motivation, cognition, long-term memory, and olfaction.[1] Anatomically, it includes the hypothalamus, hippocampus, amygdala, and other adjacent areas. A variety of arrhythmias encountered in association with temporal lobe epilepsy also indicates the correlation between the limbic and autonomic nervous systems.[2] Intraoperative manipulation of amygdala or hippocampus can lead to autonomic disturbances which can have serious consequences. We encountered three cases of severe intraoperative bradycardia following stimulation of left amygdalohippocampal region and wished to report them and also review the relevant literature on this phenomenon.

Case Reports

Case report 1

A 12-year-old male child was posted for left pterional craniotomy and excision of meningioma of the left medial temporal lobe under general anesthesia. His baseline heart rate (HR) was 105–108 beats/min (sinus rhythm) and blood pressure (BP) was 100/56 mmHg. Following induction of anesthesia, the change in BP and HR was within 20% of the baseline and maintained as such thereafter. During surgical resection of the temporal lobe meningioma, there was an abrupt and precipitous fall of both HR (46 beats/min) and BP (40/24 mmHg) confirmed by manual palpation of pulse. The operating surgeon was immediately informed and questioned about the site of surgery at that precise moment. The surgeon confirmed that the amygdalohippocampal complex was being stimulated. Immediately, the stimulus was withdrawn. However, bradycardia and hypotension persisted and intravenous (IV) atropine 0.4 mg (in incremental doses of 0.1 mg) had to be administered, following which the HR and BP returned to near baseline values. Subsequent, surgery was completed uneventfully with complete resection of the medial temporal lobe.

Case report 2

A 5-year-old male child diagnosed with intractable complex partial seizures refractory to medical therapy was scheduled for left amygdalohippocampectomy. Intraoperatively, the hemodynamic parameters were stable when during manipulation of hippocampus, and HR dropped suddenly to 48 beats/min (confirmed manually) from a baseline of 110 to 115 beats/min. However, BP remained unchanged. The operating surgeon was promptly informed. Removal of the stimulus led to gradual restoration of HR without medical interventions. Rest of the surgery completed uneventfully.

Case report 3

An 8-year-old male child scheduled for surgical excision of suprasellar mass with parasellar extension by left pterional craniotomy approach under general anesthesia had one episode of severe intraoperative bradycardia (<50 beats/min) during the surgery from a baseline of 105 beats/min which was manually confirmed. The operating surgeon was notified immediately. As communicated by surgeon, the event occurred when he was operating in the lateral corridor and attempted to retract the left medial temporal lobe. Severe bradycardia was associated with slight decrease in BP (within 20% of the baseline). Removal of surgical stimulus led to gradual increase in HR (77–80 beats/min). On resumption of the surgery, the second episode of persistent bradycardia soon ensued (HR - 46/min) when the medial temporal lobe was retracted again. Removal of the stimulus followed by 0.6 mg IV atropine (in an incremental dose of 0.1 mg) resolved the crisis. Rest of the surgery was unremarkable.

Discussion

Amygdalohippocampal complex, an integral component of the limbic system, is the dominant site of origin of complex partial seizures and has shown to trigger variable hemodynamic responses on stimulation. These changes in cardiac rate and rhythm have been observed more often in adults.[34] In our case series involving stimulation of the amygdalohippocampal complex during pediatric neurosurgery, the most noticeable change observed was sinus bradycardia with or without BP alterations. Induction of anesthesia was with IV thiopentone in all cases. Maintenance of anesthesia was done with O2:air = 1:1 and sevoflurane (1–1.5%) along with top up doses of fentanyl and atracurium. Since in the postinduction phases and a considerable duration of intraoperative period, patients were hemodynamically stable with the same maintenance drugs used in all three cases, sudden bradycardia due to anesthetic drugs seems unlikely.

Other common causes of intraoperative bradycardia could have been trigeminocardiac reflex (TCR), raised intracranial pressure (ICP), or brainstem manipulation. However, TCR appears unlikely as by definition, it should occur secondary to stimulation of trigeminal nerve (either centrally or peripherally) which cannot be explained based on the anatomical areas of stimulation in these cases. As craniotomy had been done, dura was open, and in the absence of other manifestations, the possibility of raised ICP was also excluded. Since the surgeries involved supratentorial compartment, brainstem manipulation was again a very remote possibility. Moreover, bradycardia in all three cases was observed in temporal association with surgery being done at the level of hippocampus and amygdala. This reinforced the observations of existence of unfavorable effects of limbic system stimulation on the autonomic nervous system.

Haruta et al. observed an increase in mean arterial pressure (17% of baseline) and a decrease in HR (24% of baseline) after the intrahippocampal injection of neostigmine in anesthetized rats.[5] They postulated that the stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a hypertensive response with reflex bradycardia. Out of 61 episodes of complex partial seizures of the temporal lobe origin in twenty patients, Li et al. reported tachycardia (24/61) in the majority as noticeable changes in cardiac rhythm. Bradycardia was observed in only 5% (3/61) of the significant cardiac changes.[3] However, our findings were more consistent with the observations made by Cox et al., who witnessed bradycardia, hypotension, and hind limb vasodilatation in response to electrical stimulation of central nucleus of amygdala in anesthetized rabbit.[6] Similar observations (bradycardia, hypotension) were made after the electrical and chemical stimulation of hippocampal formation in the anesthetized and awake rats.[7] Sato et al. reported of six cases of severe bradycardia along with a decrease in systolic blood pressure during amygdalohippocampectomy for intractable epilepsy.[4] They made a clear observation that bradycardia occurred either when the amygdala or hippocampus was manipulated or when a bipolar coagulator was used.

There is scarcity of literature available pertaining to hemodynamic effects associated with intraoperative amygdalohippocampal stimulation in pediatric neurosurgeries. As of now, it is clear that the limbic system is neurally connected with the autonomic nervous system. However, the exact reason for predominance of parasympathetic outflow as in our cases cannot be explained clearly. In a recently published study conducted on thirty patients with intractable temporal lobe epilepsy, Ghchime et al. observed that the right cerebral hemisphere predominantly modulates sympathetic activity while the left cerebral hemisphere mainly modulates parasympathetic activity.[8] Their results are somewhat consistent with other previous investigations.[910] These findings also accentuate our observations of predominant sympatholytic activity on stimulation of left amygdala and/or hippocampus.

Conclusion

Occurrence of hemodynamic perturbations during surgeries involving limbic system should always be borne in mind. Appropriate monitoring in the intraoperative period along with timely intervention can prevent undue catastrophes.

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Conflicts of interest

There are no conflicts of interest.