Astrocytoma of the spinal cord

If a malignant or benign tumor develops from astrocytes - star-shaped neuroglial cells - the neoplasm is called an astrocytoma. The main function of astrocytes is to regulate the chemical environment of the brain and to form a physiologic barrier between the circulatory system and the CNS. Astrocytoma of the spinal cord is about 9 times less common than brain tumors and affects mostly adults. In most cases, benign astrocytomas become malignant - this occurs in about 70% of patients. [1]

Epidemiology

Astrocytoma is the most common variant of glioma, a glial cell tumor. In general, pathology can develop in any of the departments of the brain, as well as in the cerebellum, spinal cord. In childhood, the optic nerve is often affected.

In seven out of ten patients, benign astrocytoma becomes malignant.

In children, tumors of the brain or spinal cord are the second most common type of malignancy after leukemia. In the United States alone, more than 4,000 new cases of central nervous system tumors are diagnosed each year. Approximately 50% of brain tumors in children are gliomas or astrocytomas. They develop from glial cells that make up the accessory brain tissue. Astrocytomas are benign or malignant and can appear in different parts of the spinal cord.

In children, astrocytomas are much more common (by almost 20%), and among adult patients, men are about one and a half times more common than women. There are more than a dozen brain tumor lesions per spinal cord astrocytoma. [2]

Causes of the spinal cord astrocytomas

To date, the exact causes of spinal cord astrocytoma formation are unknown. There are theories of possible hereditary predisposition, exposure to oncogenic viruses, external factors, occupational hazards, etc.

The appearance of astrocytoma may be due to such causes:

• radiation exposure to the body;
• severe or prolonged ultraviolet exposure;
• unfavorable environmental situation;
• prolonged stay in close proximity to high-voltage lines;
• Exposure to chemicals, hazardous waste (including nuclear waste);
• smoking;
• genetic defects;
• Frequent consumption of foods containing carcinogenic and other dangerous components;
• unfavorable family history.

Regular and severe stress, psycho-emotional imbalance play a certain role in the development of pathology. Specific causes include Hippel-Lindau disease, Li-Fraumeni syndrome, hereditary neurofibromatosis type I, tuberous sclerosis.

Risk factors

The main factor that can trigger the development of astrocytoma is genetic predisposition. Other potential factors include:

• unfavorable environmental situation in the region of residence;
• regular stay in conditions of occupational hazards, work with chemicals (especially dangerous are considered formalin, nitrosamine);
• viral infectious diseases - in particular herpes-6, cytomegalovirus infection, paliomavirus (SV40);
• frequent or deep stress, depressive states, psycho-emotional shocks;
• a sudden or profound drop in immunity;
• age-related changes.

Radiation exposure (including radiation therapy) increases the risk of astrocytoma.

Pathogenesis

Astrocytes are the best known type of glial structures. The cells are star-shaped, and their presumed function is to clear the extracellular space of "unnecessary" ions and mediators, which helps to get rid of chemical barriers to the binding mechanisms operating on neuronal surfaces. It is likely that astrocytes also help neurons by transporting glucose to the most active cells and by playing a role in the transmission of some impulses necessary for the normal regulation of synapse function. It has been found that after brain damage, astrocytes take part in its repair by "mopping up" necrotic particles of the neuron, possibly affecting the non-proliferation of toxic components and preventing intoxication.

Up to 5% of astrocytomas are associated with congenital pathologies with autosomal dominant inheritance (e.g. Neurofibromatosis). In the vast majority of cases, primary astrocytoma tumors develop without a clear cause, i.e. Sporadically.

Diffuse growth with invasive invasion of surrounding tissues is typical for tumor processes of the spinal cord. On the degree of malignancy depends on how quickly the astrocytoma will develop. Thus, especially malignant tumors appear within a few months, and benign and weak malignancy can develop for years without revealing any distinct symptomatology. In some cases, pathology may be associated with dysembryogenetic processes (minor developmental anomalies). [3]

Symptoms of the spinal cord astrocytomas

Symptomatology in spinal cord astrocytoma is nonspecific and extensive, depending on the size of the tumor and its localization. The first signs appear only when the neoplasm begins to press on nearby tissues and structures. Most often, patients complain of headaches (more often attack-like, up to vomiting), the appearance of problems with digestion and urinary function, disorders in walking. The acute course of the disease is very rare: in most cases, the problem increases gradually. [4]

In the initial stages of development, astrocytoma is almost always hidden, without distinct symptoms. Pathological picture appears only from the stage of active tumor development. The following signs are noted:

• severe head pain, sometimes to the point of vomiting (vomiting brings relief);
• increased body temperature in the area of the lesion (up to 38.5°C on average);
• changes in pain sensitivity, paresthesias;
• The appearance of pain in the area of the affected part of the spinal cord;
• weakness of the limb muscles, numbness, paralysis of the legs;
• deterioration and loss of function of internal organs (more often pelvic organs).

Stages

The sequence of development of astrocytoma, like all intramedullary tumors of the spinal cord, follows three stages:

• segmental stage;
• complete transverse spinal cord lesion;
• the radicular pain stage.

The segmental stage is associated with the occurrence of dissociated segmental disorders of superficial sensitivity according to the level of neoplasm localization.

Complete transverse lesion of the spinal cord starts from the moment the tumor process grows into the white matter. Segmental sensory disturbances are replaced by conductive ones, motor and trophic changes appear, the functionality of pelvic organs is affected.

The stage of radicular pain begins from the moment the tumor process goes beyond the spinal limits. Since the neoplasm affects the nerve endings, radicular pain syndrome appears. [5]

Forms

Astrocytoma develops from the astrocytic area of glia and is represented by astrocyte cells. In addition to the spinal cord, the tumor can be located in the large cerebral hemispheres, cerebellum, and brain stem.

Distinguish between astrocytoma with low and high malignancy:

• low malignancy - Grade I-II;
• elevated malignancy - Grade III-IV.

Depending on the presence of the IDH 1-2 defect, mutational and non-mutational astrocytomas are distinguished. In the absence of a mutation, a "wild type" or wt (wild type) is said to be present.

List of tumor processes by degrees of malignancy:

• Grades I-II are represented by piloid pilocytic astrocytoma and low-stage diffuse astrocytoma. Such neoplasms are characterized by delayed development, which starts at a young age.
• Grades III-IV are represented by anaplastic astrocytoma and glioblastoma multiforme. These neoplasms grow rapidly, rapidly spreading to nearby structures.

A classic variation of piloid astrocytoma is said to be a classic variation of piloid astrocytoma if MRI shows a T1-mode hypodense and T2-mode hyperdense neoplasm, which in most cases accumulates contrast agent well and completely. Sometimes it may contain a cystic component.

Piloid astrocytoma of the spinal cord is more common in children and young adults.

Diffuse astrocytoma of the spinal cord belongs to gliomas of low malignancy, as well as pleomorphic xanthoastrocytoma, oligodendroglioma, oligoastrocytoma. This is a morphologically, diagnostically and clinically heterogeneous category of neoplasms. Classification features have a significant impact on therapeutic tactics, determine the course and prognosis of the pathology. [6]

Complications and consequences

Intramedullary tumors, which include astrocytoma, are rare, occurring in only 2% of all tumors of the central nervous system. Many neoplasms in this category are benign, but even in this case, complete removal of the tumor is mandatory. Radiotherapy in this case is inappropriate, since such astrocytomas are radiosensitive, and therapy damages the spinal cord due to increased radiation exposure. Nevertheless, when using combined techniques, such treatment is still performed. For example, they combine radiation therapy with chemotherapy, or hyperthermia, or other available methods.

Astrocytoma of the spinal cord most often begins with the appearance of pain syndrome in the affected area. Then there are changes in sensitivity, weakening of muscles in the limbs. Diffuse tumor growth with infiltration into normal nerve tissue is possible. In the absence of treatment in the corresponding area, the spinal cord is affected completely, which entails disorders of the function of organs at the level and below the pathology zone.

There is also data on the occurrence of complications after the removal of astrocytoma. During surgery, the surgeon decompresses the spinal cord, removes the neoplasm completely and tries to do everything possible to prevent the subsequent development of neurological failure. However, it is not always possible to carry out the intervention smoothly: many tumors are strongly spread to the surrounding tissue, or are located in places that are difficult to access. This leads to the likelihood of intra- and postoperative complications. Thus, patients may have aggravation or appearance of new sensorimotor disorders, formation of tetraparesis or tetraplegia. The list of the most frequent complications of astrocytoma is as follows:

• neurological disorders;
• spinal edema;
• infectious postoperative complications, purulent meningitis, myelitis, meningoencephalitis);
• postoperative liquorrhea;
• spinal canal hematomas;
• formation of liquor cysts (pseudo-myeloradiculocele);
• air embolisms, thromboembolisms;
• septic and trophic complications;
• intestinal paresis;
• orthopedic implications, kyphosis, scoliosis, functional instability.

According to observations, the majority of complications developed in the early postoperative stage - approximately 30% of cases, and in the overwhelming number of patients (more than 90% of cases) such complications were categorized as mild. Complicated and severe complications leading to patient death were observed in only 1% of cases.

Can an astrocytoma reappear or metastasize after its removal? Theoretically, the reoccurrence of the neoplasm can occur in any part of the spinal cord, but there are no statistical data on this. Metastasis to the spinal cord is possible in piloid astrocytoma of the brain, lung cancer and so on. Here it is important to note that the spinal cord astrocytoma itself I degree usually does not give metastases, however, starting with the II degree of pathology, the neoplasm is already able to metastasize. In the III-IV degree of the disease, metastases are almost always present: such tumors grow rapidly and require urgent and active treatment. [7]

Diagnostics of the spinal cord astrocytomas

Diagnostic measures in case of suspected astrocytoma are performed in neurological or neurosurgical institutions. First, the patient's general condition, pain intensity, neurological and orthopedic status are assessed.

Laboratory diagnosis is nonspecific. Assign general urine and blood tests, blood biochemistry with determination of glucose, total protein, bilirubin and albumin levels, creatinitis and urea, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase. Examine markers as indicated, microelemental composition of blood, expanded coagulogram.

The first-priority instrumental diagnosis in astrocytoma should be represented by magnetic resonance imaging of the corresponding part of the spinal column with or without contrast agent injection. If indicated, the area of examination can be expanded up to the neuroaxis.

MRI is performed with a recommended device magnetic field strength of 1.5-3 Tesla. On the resulting image, astrocytomas are most often eccentrically localized, sometimes have an exophytic component and do not accumulate contrast agent, or show heterogeneous accumulation, or a single zone of accumulation is present. [8]

In patients requiring clarification of the diagnosis of spinal cord astrocytoma, CT perfusion study is additionally performed as part of the differential diagnosis.

Differential diagnosis

A differential diagnosis between tumor and non-tumor processes is recommended. CT perfusion is becoming a crucial procedure to identify intramedullary spinal cord tumors. This method evaluates the blood flow velocity in spinal tissues, which helps to differentiate between cerebrospinal tumor and demyelinating pathology. The study is also indicated for the differentiation of glioma, ependymoma and hemangioblastoma.

If MRI reveals intense hyperperfusion in the area of the pathologic focus, intramedullary hemangioblastoma is diagnosed. It is recommended to perform additional MRI or CT-angiography to clarify the vascular anatomy of the neoplasm.

In addition, differential diagnosis should be aimed at excluding the most similar pathologies of the spinal cord - in particular, we can talk about discogenic myelopathy, syringomyelia, myelitis, arteriovenous aneurysm, funicular myelosis, amyotrophic lateral sclerosis, tuberculoma, echinococcosis and cysticercosis, foci of tertiary syphilis, hematomyelia, circulatory disorders in the cerebrospinal vessels.

Treatment of the spinal cord astrocytomas

The main method of treatment of astrocytoma is its removal through surgery. Surgery is scheduled after the patient has undergone all diagnostic measures. The choice of treatment tactics takes into account the type and location of the neoplasm, its prevalence and aggressiveness, as well as the age of the patient. For example, radiation therapy is rarely used in pediatric practice due to the high risk of side effects. [9]

Some of the most common treatments include the following:

• Surgical intervention - allows to remove as many tumor cells as possible. Surgery can be used as a stand-alone procedure for first-degree astrocytoma, but for tumors with other degrees of malignancy it is combined with other therapeutic procedures.
• Chemotherapy - can be used as an adjunct to surgery or as the main treatment. In infants, chemotherapy is used as a temporary replacement for radiation therapy until the baby grows up. Chemotherapy may include the use of drugs such as Carboplatin, Vincristine, Vinblastine, Thioguanine, Procarbazine, and Lomustine. But chemotherapy alone does not cure even a low malignant astrocytoma of the spinal cord. In addition, surgical intervention is used.
• Radiation therapy is a standard adjunct to surgery designed to destroy the remaining tumor structures.
• Targeted treatment involves the use of drugs that block the development and spread of malignant cells by affecting specific molecules involved in the growth of the neoplasm. The essence of targeting therapy is in the targeted attack of astrocytoma cells, as a result of which the tumor becomes vulnerable and weak. Unlike chemotherapy, targeted therapy is selective and acts only on malignant cells without damaging healthy structures.
  • Inhibitors such as Vemurafenib and Dabrafenib are used for neoplasms with a change in the BRAF V600 gene.
  • In cases of BRAF fusion or duplication or low malignancy astrocytomas, MEK inhibitors such as Selumetinib or Trametinib may be used.
  • In low malignancy astrocytomas, Sirolimus and Everolimus may have a sufficient effect.
• Immunotherapy involves using your own immune system to recognize tumor cells and further attack them. The drugs of choice are so-called checkpoint inhibitors. They block signals from malignant structures, which create a defense against immune action.

Anticonvulsants and steroids are used as symptomatic treatment. If necessary, consultations with an endocrinologist, ophthalmologist, rehabilitation specialist and psychologist are prescribed.

Postoperative treatment may include medications such as these:

• A course of chemoradiation therapy according to the appropriate program at the linear gas pedal (radical single focal dose 2 Gy, total focal dose 60 Gy).
• Mustofaran (Fotemustine) 208 mg once every 7 days. The prepared solution should be protected from light and immediately after preparation placed in an opaque cover. Children and pregnant women are not prescribed the drug. Hematologic parameters are necessarily monitored during treatment.
• Temozolamide 100-250 mg according to the individualized scheme. Capsules do not open, use carefully, avoiding contact of the drug with the skin. Take on an empty stomach, wash down with a glass of water. If vomiting occurs after taking it, the drug is no longer taken that day. In children Temozolamide is prescribed from 3 years of age.
• Bevacizumab 5-15 mg/kg once every 14-21 days, long-term. Among possible side effects: gastrointestinal and pulmonary hemorrhages, arterial thromboembolism, arrhythmias, thrombosis, hypertension.

Every 3-6 months, a diagnostic MRI with contrast is performed, after which treatment is adjusted as indicated.

Physiotherapy treatment

Questions about the possibility of using physiotherapy in patients with spinal cord astrocytoma arise quite often. Traditionally, such therapy is considered a contraindication, but this is not always true. Currently, specialists have the following information:

• Drug electrophoresis can be used for tumor processes - including spinal cord astrocytoma - if necessary.
• The use of pulsed currents - such as electrosleep, electric anesthesia, diadynamic therapy, sinus-modulated therapy, and fluctuating currents - has no effect on the growth of the neoplasm and the spread of metastases. Moreover, pulsed currents are indicated for the elimination of edema.
• The application of magnetic fields has a slowing effect on tumor growth, has some antiblastic properties.
• Ultrasound is not contraindicated in patients with astrocytoma.
• Electromagnetic rays of the EHF range improve the performance of the main treatment (surgery, chemotherapy and radiotherapy), support hematopoiesis and immune defense, reduce pain.

Procedures such as ultraviolet irradiation, laser therapy, heat therapy and therapeutic baths (radon, turpentine, hydrogen sulfide, silica), massage and manual therapy are prohibited in spinal cord astrocytoma.

After surgical intervention, it is recommended to refer patients to a sanatorium and resort treatment within a year or so as part of rehabilitation. The possibility of using hirudotherapy in astrocytoma has not been studied.

Herbal treatment

Phytotherapy cannot be used in cancer patients instead of the main treatment. However, medicinal plants are quite successfully used to stimulate the body's defenses, to relieve pain syndrome. Competent use of herbs helps to improve the quality of life of patients suffering from spinal cord astrocytoma.

Many plants contain specific antitumor substances. In addition, plant products provide additional protection against cancer by maintaining a normal acid-alkaline balance in the body.

Herbs are used dried or fresh. They are used to prepare extracts, decoctions, infusions and tinctures. Among the most popular plants that can improve the condition of patients with astrocytoma are the following:

• Nettle is a well-known herb that can improve liver function, normalize blood sugar levels, eliminate swelling, destroy bacteria and stop the growth of tumor cells. Experts recommend brewing an infusion of nettle and use it 3-4 times a day. Contraindication: tendency to thrombosis.
• Cinnamon (not to be confused with cassia) is a popular spice that contains many beneficial components, including carvacrol and coumarin. To obtain an anticancer effect, ½ tsp. Of cinnamon powder should be consumed daily.
• Ginger root is a medicinal spice containing natural antioxidants that provide strong anti-tumor activity. Ginger can be added to drinks, first and second dishes, desserts. However, ginger tea, which should be drunk 3-4 times a day, is considered the main therapeutic remedy.
• Oregano, or oregano, is a well-known herb with a specific flavor. It contains active phenolic acids and flavonoids, as well as quercitin, which limits the growth of malignant cells. Crushed herb can be brewed as an infusion, and also added to meat, fish dishes, salads, casseroles.

Doctors warn: do not expect miracles from herbal treatment of spinal cord astrocytoma. Phytotherapy is used only as an auxiliary link, in combination with conservative and surgical methods.

Surgical treatment

Radiosurgery is the optimal method of eliminating spinal cord astrocytomas. Non-contact surgery is effective in relation to tumors of different location and distribution, and is a good substitute for conventional surgery. The use of the so-called Cyberknife is associated with the delivery of ionizing doses of ionizing rays destructive for malignant structures into the tissues. Healthy surrounding tissues are not affected.

At the preparatory stage, the patient undergoes diagnostic CT and MRI, after which a digital three-dimensional model of mutual localization of the neoplasm and unchanged normal tissues is determined. Then the specialist draws up a scheme of radiosurgical intervention with the formation of the irradiation dose that the astrocytoma should receive to block all biological reactions in it.

On average, radiotherapy is broken down into 2-3 stages (fractions).

Surgery involves removing as much of the tumor as possible. Tumors of the second degree or more are treated by surgery in combination with chemotherapy and radiation therapy. A comprehensive approach should prevent further spread of the tumor process.

In each case, the degree of surgical intervention is determined by the immediate characteristics of the spinal cord astrocytoma. Treatment tactics are formed by several specialists at once: neurosurgeon, radiation oncologist, medical physicist, oncologist-chemotherapist.

Prevention

Leading a healthy lifestyle will help maintain a healthy spinal cord and strengthen the body as a whole. Important criteria for astrocytoma prevention include:

• a full healthy diet with quality products;
• adequate physical activity, regular walks in the fresh air;
• adequate rest and sleep periods;
• development of stress resistance, application of various techniques to relieve stress.

It is important to see a general practitioner regularly, especially for patients with chronic pathologies and those who have undergone cancer and radiation or systemic chemotherapy.

Among other recommendations:

• add more plant foods (especially vegetables and greens) and less synthetic foods and fast foods to your diet;
• add as little animal fat as possible to your meals, and it is advisable to eliminate margarines altogether;
• control your body weight, keep physically active;
• Stop smoking and drinking strong alcoholic beverages;
• Do not overload your back, dose and distribute the load correctly.

A healthy lifestyle and regular consultations and check-ups with your GP are key to keeping your body functional for years to come.

Forecast

Astrocytoma is a type of tumor process that has an unfavorable prognosis. Pathology can occur in patients of any age, including children. Treatment of the disease is mandatory, regardless of the degree of malignancy and anatomical spread. Therapeutic tactics are selected after all diagnostic measures. Surgical treatment, radio and radiation therapy, chemotherapy may be recommended. Often it is necessary to combine several therapeutic methods at once.

If initially benign, treatment in 70% leads to complete recovery and elimination of neurological symptoms. The recovery period lasts from several months to two years. In more complex cases, the outcome of the disease is disability - loss of ability to work, with the inability to fully restore the functions of the body. The number of fatal outcomes after surgical removal of neoplasm is estimated at about 1.5%. [10] Lack of treatment and malignancy indicate an unfavorable prognosis. Neglected astrocytoma of the spinal cord, associated with the inexpediency or impossibility of surgery, is treated with the use of palliative techniques.