Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death
Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1–2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS) and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s) of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN) and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking.
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KeywordsColloid cyst of the third ventricle Hypothalamus stimulation Contraction band necrosis Sudden death
Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle, accounting for 0.2-2% of all intracranial and approximately for 15–20% of intraventricular neoplasms, respectively. Colloid cysts are slow growing and the initial onset of symptoms is usually between 20 and 50 years of age, although they have been reported also in younger patients. Diagnosis during childhood is unusual and only 1-2% of all reported cases occurred during the patients’ first decade.Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s) of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts.
Here we present the death of a previously healthy young boy harboring a colloid cyst of the third ventricle. We investigated the possible mechanism of death through a careful histological examination of heart specimens in addition to gross and histological examination of the brain.
A 10 year – old boy at 8.00 p.m. complained a severe headache accompanied by vomiting attacks. An emergency physician visited him and advised him to rest for some hours. He lost consciousness in the early morning and was transported to the local hospital, where he was pronounced dead upon arrival. The medical history taken from the parents showed no significant signs and symptoms except for repeated mild attacks of leg weakness. Familial history was negative both for cardiovascular and neurological diseases and sudden death.
Toxicological analyses were negative.
In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN) and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death.
We observed two patterns of myocardial lesions. One corresponded to fragmentation of the whole myocell (pancellular lesion), which ranges from early breakdown in pathological bands to a total granular disruption (myofibrillar degeneration). The second pattern, associated with the previous one, is characterized by a unique band of 10 to 20 hyper-contracted sarcomeres close to the intercalated disc (paradiscal lesion). These lesions are typical of catecholamine myotoxicity and may express a sympathetic overstimulation.
As previously reported, in many conditions in which a sympathetic overtone is likely to be present, CBN is observed as a histological hallmark of an adrenergic storm. Such myocardial pathological pattern is also described in many brain diseases. In fact there is a strong evidence that overactivity of the sympathetic limb of the autonomic nervous system is the common phenomenon that links the cardiac alterations seen in neurological fatal events. These effects on the heart may contribute in a major way to the mortality rates of many primarily neurological conditions such as subarachnoid hemorrhage, cerebral infarction, status epilepticus, and head trauma, acute intracranial hypertension, and may also be important in the pathogenesis of sudden death in the context of intraventricular colloid cyst. Neurogenic cardiac stunning (due to hyperacute, intense, neuronal sympathetic activation) may represent the pathological cardiac event occurring in response to sudden increase in intracranial cerebral pressure (ICP) in third ventricle colloid cyst context. The cyst can fill the ventricle or obstruct the flow of CSF and lead to prominent hydrocephalus. Acute ventricular hydrocephalus with intracranial hypertension and brain herniation can result in cerebral compression, medullary (respiratory) compromise and death[7–10]. Sudden death has been also related to acute cyst swelling due to spontaneous intralesional bleeding that may cause acute obstructive hydrocephalus and intracranial hypertension due to rapid enlargement of the lesion itself[11–13].
In other words, “sympathotonic” prone individuals may have an “adrenergic crisis” any time a structural brain damage occurs, which explains the high variability among subjects of the same group. These pathological conditions may trigger a catecholamine myotoxicity and acting through free radical mediated lipid peroxidation with intramyocellular Ca2+ influx. In fact, we hypothesized that in the pathophysiology of CBN a role is played by the presence of reactive oxygen species (ROS). Exposure of normal myocardium to ROS-generating systems alters myocardial function through persistent cellular loss of K+, depletion of high-energy phosphates, elevated intracellular calcium concentration, loss of systolic force development, progressive diastolic tension, and depressed metabolic function[22, 23]. Catecholamines may induce oxidative damage through reactive intermediates resulting from their auto-oxidation, irrespective of their interaction with adrenergic receptors, thus representing an important factor in the pathogenesis of catecholamines-induced cardiotoxicity. In a previous paper we have described the effect of ROS on the catecholamine-mediated myocardial expressions of TNF-a (tumor necrosis factor-alpha), MCP-1 (monocyte chemotactic protein-1), interleukins IL6, IL8, IL10 and a significant apoptotic process randomly sparse in the damaged myocardium[25, 26]. The rise of the cardio-inhibitory cytokines may be interpreted as the adaptive response of jeopardized myocardium with respect to the cardiac dysfunction resulting from catecholamines effects.
The presented histological investigation can contribute to elucidate the link between cardiac damage and colloid cyst of the third ventricle and to understand the exact pathophysiologic mechanism causing the sudden death of these patients when acute hydrocephalus and brain herniaton are not present. Coagulative myocytolysis may represent the histological hallmark of the sympathetic imbalance due to hypothalamic centers reflex stimulation independently from the size of the cyst and the amount of hydrocephalus. Considering this intriguing hypothesis surgical removal of colloid cysts of the third ventricle, even if small and asymptomatic, is mandatory[3, 12, 27].
Written informed consent was obtained from the patient’s relatives for publication of this case report and any accompanying images.
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