Hypothalamic hamartoma is a rare benign hypothalamic tumor that resembles a gangliocytoma in histological characteristics. Etiological factors are not precisely established. The neoplasm is manifested by epileptic seizures, a decrease in cognitive abilities, and an advance in the pace of puberty. To diagnose hypothalamic neoplasia, electroencephalography and cerebral MR scanning are required. Treatment includes anticonvulsants, transcranial physical methods of exposure (magnetic stimulation, micropolarization), neurosurgical operations.
D33 Benign neoplasm of the brain and other parts of the central nervous system
Congenital hypothalamic hamartomas are extremely rare in clinical neurology: about 1 case per 200 thousand live-born children. No gender and racial differences in morbidity were found. According to the classification of CNS neoplasms (WHO, 1993), pathology belongs to the category of “cysts and tumor-like lesions”. The high urgency of the problem is associated with the nonspecific nature of symptoms, the difficulty of timely diagnosis, which creates obstacles to adequate treatment of the tumor.
Hypothalamic hamartoma are included in the category of embryonic benign formations formed in children during early intrauterine development (first trimester of pregnancy). Until now, there is no generally accepted concept of the appearance of neoplasia in pediatric neurology. It is believed that they arise spontaneously under the influence of risk factors, which are grouped into the following groups:
- Genetic disorders. Point gene mutations remain one of the main causes of abnormalities in the development of the central nervous system, but their detailed study is difficult due to the wide variety of pathologies, polymorphism of the clinical picture.
- Teratogenic factors. Hypothalamus damage is often caused by neuroinfections (toxoplasmosis, rubella, herpes simplex viruses), physical hazards (ionizing radiation), chemical toxins (some medications, household chemicals, agricultural poisons).
- Pathology of pregnancy. Hamartomas are more common in children born to mothers with extragenital diseases (cardiovascular insufficiency, endocrine disorders, liver and kidney diseases), as well as in complicated pregnancy (toxicosis, rhesus conflict).
The hypothalamus is the structure of the intermediate brain, it has 50 pairs of nuclei, each of which performs a specific function. The organ has neural connections with the cerebral cortex, cerebellum, brain stem and spinal cord, regulates vital functions (hunger, thirst, sleep and wakefulness), affects higher mental activity, secretes hormones that control the work of the endocrine glands.
With the formation of an embryonic tumor, all functions of the hypothalamus are disrupted, which is manifested by a variety of pathological symptoms. The degree of disorders depends on the size of the hamartoma: neoplasms slowly increase in size, squeeze the surrounding nerve tissue, causing an aggravation of symptoms. The hamartoma has the same histological structure as the healthy parts of the hypothalamus, but the cells differ in abnormal structure and immaturity.
Hypothalamic embryonic neoplasia according to morphological classification are gangliocytomas. They contain elements of sympathetic nerve nodes, the cells have a low proliferative potential, minimal nuclear atypia and a high degree of differentiation — signs indicating the benign nature of neoplasia.
Thanks to the improvement of MRI diagnostics of hypothalamic neoplasms in children, hamartomas were divided into 3 types according to anatomical localization, which is important for determining the leading symptoms and choosing treatment tactics. There are the following options for the location of the embryonic formation:
- Infrahypothalamic (peduncular). It is diagnosed in 67% of patients, characterized by the location of the hamartoma near the ventral hypothalamic surface.
- Suprahypothalamic. It is observed in 18.5% of cases, represented by tumor growth in the area of chiasmal recessus of the third ventricle.
- Intrahypothalamic (session). It is determined in 14.5% of sufferers of hypothalamic hamartomas. Neoplasia takes the place of a gray hillock and lies on a wide base to its ventral part.
The manifestation of the disease mainly occurs in young children, but cases of clinical manifestations of neoplasia in adolescents or adults are not excluded. The earlier the first signs of hamartoma appear, the larger the size of the neoplasm, and the more it disrupts the functioning of the hypothalamus. There are 3 main symptoms in the clinical picture: epileptic seizures (87.5% of patients), intellectual disabilities, signs of premature puberty (62.5%).
A distinctive feature of hypothalamic hamartoma are gelastic seizures — the rarest form of convulsive paroxysms, which occurs in 0.1% of patients with epilepsy. Convulsions in children are mainly represented by violent laughter attacks. Paroxysms are supplemented by vegetative disorders: dilation of the pupils, redness of the face, abdominal discomfort, urinary incontinence.
Premature puberty is diagnosed when secondary sexual characteristics appear in boys up to 9 years old and in girls up to 8 years old. In boys, the voice becomes rougher, the adam’s apple begins to loom, the linear dimensions of the testicles and penis increase. In girls, the mammary glands swell, hair appears in the armpits and on the pubis, menstruation begins. Acne, increased greasiness of the skin, a sharp smell of sweat are also typical.
Cognitive impairment of varying severity is observed in 100% of patients. At an early age, they manifest themselves in the form of delayed speech function, late development of sitting, standing, walking skills, lack of cognitive activity in children. As the child grows up, the symptoms are supplemented by disorders of the psycho-emotional sphere: mood instability, bouts of aggression, excessive isolation.
Mental retardation that occurs with hypothalamic hamartoma causes serious socialization disorders in children, creates problems during school education. The degree of intellectual disabilities varies from mild, in which the ability to learn is preserved, to severe, when the child has only elementary self-service skills, and speech abilities are limited to individual words.
With the progression of the hypothalamus tumor, there is a total lesion of the intermediate brain, manifested by generalized epilepsy. In the absence of treatment, children may develop an epileptic status — a life-threatening condition in which a series of convulsive seizures occurs without returning consciousness. Premature sexual development is fraught with early closure of bone growth zones, girls have a risk of polycystic ovary syndrome.
It is possible to suspect a hypothalamic hamartoma during a clinical examination by a pediatric neurologist for the presence of complaints of uncontrolled laughter attacks. During a physical examination, the degree of the child’s motor and mental development, the safety of reflex activity, and the functioning of the sensory organs are assessed. Instrumental methods are prescribed to verify the diagnosis:
- MRI of the brain. On the MRI images, a volumetric formation of a homogeneous structure with clear contours is visualized, which does not accumulate a contrast agent, has no signs of invasive growth. When examined in T1 mode, the focus is hypointensive, and in T2 mode it is variable hyperintensive.
- EEG. According to the results of the study, various variants of epileptic activity are determined: spikes, acute waves, pathological complexes “peak-slow wave”, “acute-slow wave”. To clarify the diagnosis, electroencephalography with photostimulation, hyperventilation is necessary.
Drug treatment of neoplasms in children is symptomatic. Anticonvulsants (valproates, benzodiazepines) are prescribed to correct gelastic paroxysms. Neurometabolic substances, vitamin and mineral complexes are used to improve the functional capabilities of the brain. Non-medicinal methods show high effectiveness in the treatment of epilepsy:
- Transcranial magnetic stimulation. With TMS, the hypothalamus region and other areas of the brain are affected by a low-intensity magnetic field to achieve the effect of inhibition, increase GABA production.
- Transcranial micropolarization. The essence of the method is the effect of a constant weak current on the scalp at certain points — the so-called neuromodulation technique, which corrects psychopathological manifestations, reduces neuronal interaction in the epileptic focus.
Neurosurgical operations on the hypothalamus are indicated for hamartoma sizes of more than 1.5 cm, pharmacoresistant epilepsy with generalized seizures or severe endocrine disorders in children. Taking into account the specifics of the localization of the tumor process, microsurgical resection, endoscopic access, and a modern method of radiosurgery are used. The effectiveness of surgical treatment is 54-90%.
Given the pronounced intellectual disorders, children with hypothalamic embryonic neoplasia need the help of correctional teachers. With a mild or moderate degree of mental retardation, it is possible to study in special classes, for the development of speech, a long program of classes with a children’s speech therapist is necessary. According to the indications, clinical psychologists are involved in rehabilitation.
Prognosis and prevention
Since hamartomas belong to benign tumors without the risk of malignancy, the prognosis is favorable if the disease is diagnosed early and the organic defect of the hypothalamus is eliminated in a timely manner. With large neoplasms located in areas of the brain that are difficult for neurosurgeons to access, the prognosis worsens. Given the ambiguity of the etiopathogenesis of hamartoma, primary prevention measures have not been developed.