The trigemino-cardiac reflex (TCR) is a well-established neurogenic reflex that is mainly investigated in neurosurgical patients (1–6). This unique brainstem reflex is incited by the stimulation of the fifth nerve and produces adverse cardiorespiratory changes including bradycardia, asystole, and apnea. Interestingly, the TCR phenomenon reported in the literature mainly reveals the acute as well as transient nature of this reflex that is considered as a mild physiological response in most of the cases (3, 6). Also, the general management of such situations is the removal of stimuli (3, 6, 7). This relatively high prevalence of detection of the TCR occurrences and the relatively often benign course of the phenomenon is owing to the pre-, peri-, and postoperative presence of the anesthetists (1–9).

However, the chronic nature of TCR event is largely underestimated and underreported in the current literature. This may be partly due to the persistent yet vague nature of symptoms (opposite to the acute TCR episode) that make the diagnosis very difficult. An extrapolation of the prevalence from acute to chronic cases suggests that there might also be a substantial number of chronic cases (10). Therefore, this article aims to provide the comprehensive understanding of the chronic form of TCR, its manifestations, and management by literature search. Also, this paper would certainly impart a better diagnosis and understanding of TCR phenomenon by knowing the relatively less common form of a chronic TCR.

We searched PubMed for following terms in various combination including (“prolonged” OR “chronic” OR “persistent” OR “delayed”) AND (“oculocardiac reflex” OR “trigeminal cardiac reflex” OR “trigeminocardiac reflex”) from January 1, 1970, to August 31, 2016.

Total of 140 articles were searched through applying the terms. Out of 140, 93 articles met the language and human subject restrictions. Out of 93, only 6 articles finally met the inclusion criteria and further reviewed. Total of six patients included in the final analysis (Table 1). Out of six, 50% were pediatric patients. Strikingly, all the six reported patients were male. Further analysis revealed that the five out of six patients were related to peripheral TCR group and remaining one showed central TCR phenomenon. The timing of presentation of the chronic TCR varied from 29 h to several years. The description of cases is given below.

The TCR is one of the most investigated brainstem reflexes that manifests commonly as adverse hemodynamic changes during the stimulation of any of the sensory branch of the trigeminal nerve. This phenomenon has been reported in various surgical conditions as well as in neurosurgical interventions and mainly illustrates the acute nature of this reflex that persists during the surgical and other chemical/physical/electrical stimuli (1–10). The afferent nerve fibers carry the stimulus via the trigeminal nerve and efferent fibers through the vagus nerve. The TCR is broadly classified as the peripheral and the central type depending upon the stimulation of anatomical location. Depending upon the three sensory divisions of the trigeminal nerve, the peripheral type is further divided into OCR and MCR (9). After reviewing the literature, one can infer that the TCR is a mild transient physiological response and gets abolished after the removal of the inciting stimulus. However, as mentioned in the above-described cases, it can be clearly seen that this phenomenon also has a chronic type and that has far more impact in overall symptomatology and clinical decision-making. We have now gone outside the OR and open the window from a strict cause-effect relationship within a few seconds to a wider variance of reactions (10, 17). Our previous definition work is based on acute cases. We have to look now if these works are also available for the chronic cases. Another point is the connection of chronic TCR to the oxygen-conserving reflex (8). Again, we have no cases of cerebral ischemia undermining a strong correlation between these two phenomena.

Trigemino-cardiac reflex versus vasovagal: the vasovagal response (VVR) can also be postulated as the one of the mechanisms responsible for the similar autonomic manifestations. This reflex mainly controlled through two pathways (18). One is the central VVR that involves cortico-hypothalmic and medullary cardiac centers and second is the peripheral VVR that included heart directly. The VVR is commonly incited by intense emotion, prolonged standing, instrumentation, and severe pain responses (18, 19). This is a transient phenomenon, which improves quickly on lying down, and is usually found in healthy individuals. In described cases, none of the above mentioned inciting factors were present exclusively. In addition, these autonomic manifestations were improved after the surgical interventions, thereby, clearly describes the cause-effect relationship of TCR phenomenon.

There are three significant findings in this review about chronic TCR (11–16). First, the peripheral TCR was the commonest type, and the OCR was the most common subtype associated with the chronic form of TCR. Whether or not the ophthalmic division of the fifth nerve is more prone to the chronic form of TCR is a matter of further investigation. However, considering the present findings of this review, it seems plausible. Also, the first branch of the fifth nerve is also the shortest and pure sensory branch that may be a factor of more incidence of peripheral TCR episodes. Second, besides bradycardia, nausea was the commonest presenting symptom. It is apparent that because of vague symptoms (nausea, vomiting, etc.), the diagnosing the chronic TCR is very challenging. Therefore, it could be another reason for the underreported incidence of chronic TCR cases. Therefore, we want to emphasize here that the TCR should also be included in the differential diagnosis of the patient, if he/she presents with vague symptoms such as nausea, vomiting, dizziness, etc. and had a history of injury (even trivial) including eye, orbit, or any other structure supplied by the fifth nerve. Thirdly, in all the cases, the surgery was the definitive cure for all the symptoms related to the TCR. This important finding suggests that the chronic form of TCR seems more like a pathological rather than a physiological entity, and has a negative impact on the overall health of the patient. Here, it should be noted that the indication of surgery/intervention was mainly due to the on-going symptoms rather than an absolute pathological or surgical cause. Therefore, for the entire medical community, it is imperative to understand the phenomenon of chronic TCR that is not limited to any particular specialty. This will help thousands and thousands of patients who are still in the phase of diagnosis and are suffering from those vague symptoms daily.

In the paucity of substantial evidence, these case reports should only be interpreted as an informative tool for understanding the concept of chronic TCR. These cases do exhibit a sound cause and effect relationship and therefore support our hypothesis. All cases were found in males. It may be a simple reflection of injury pattern that is more common in the male gender (20). Whether or not peripheral TCR is common in males is a matter of further research.

The chronic form of TCR is an underreported entity and certainly has a substantial impact on the patient health. With the knowledge of the chronic TCR, we can be certainly able to diagnose more and more patients and impart better management in such cases. Further research is warranted to elucidate the exact mechanism of chronic TCR.

TC helped in developing the concept, designing, data collection, data interpretation, and writing the manuscript. BS gave substantial inputs in developing the concept and writing the manuscript. Both the authors accepted the final version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.