bubble_chart Overview

Gliomas, also known as glial cell tumors or simply gliomas, are tumors originating from the neuroectoderm, hence they are also referred to as neuroectodermal tumors or neuroepithelial tumors. These tumors arise from neural interstitial cells, including glial cells, ependymal cells, choroid plexus epithelial cells, and neuronal parenchymal cells, i.e., neurons. Most tumors originate from various types of glial cells, but based on histogenetic origin and similar biological characteristics, tumors arising from the neuroectoderm are generally termed gliomas.

bubble_chart Epidemiology

Glioma is the most common among various intracranial tumors. Among gliomas, astrocytoma is the most frequent, followed by glioblastoma multiforme, with ependymoma ranking third. According to statistics from Xuanwu Hospital in Beijing and the Affiliated Hospital of Tianjin Medical College, among 2573 cases of glioma, they accounted for 39.1%, 25.8%, and 18.2%, respectively.

Males are more commonly affected, particularly in glioblastoma multiforme and medulloblastoma, where males significantly outnumber females. The age of onset is mostly between 20 and 50 years, peaking at 30–40 years, with another smaller peak occurring in children around 10 years old.

Each type of glioma has its own predilection for specific age groups. For example, astrocytoma is more common in adults, glioblastoma multiforme in middle-aged individuals, ependymoma in children and young adults, and medulloblastoma predominantly occurs in children. The preferred locations of different gliomas also vary. Astrocytoma often arises in the cerebral hemispheres of adults, while in children, it is more frequently found in the cerebellum. Glioblastoma multiforme almost exclusively occurs in the cerebral hemispheres. Ependymoma is commonly seen in the fourth ventricle, oligodendroglioma predominantly arises in the cerebral hemispheres, and medulloblastoma is almost always located in the cerebellar vermis.

bubble_chart Pathogenesis

As the tumor gradually enlarges, it forms an intracranial space-occupying lesion, often accompanied by surrounding cerebral edema. When this exceeds compensatory limits, it leads to increased intracranial pressure. If the tumor obstructs cerebrospinal fluid circulation or compresses veins, impairing venous return, intracranial pressure rises further. Hemorrhage, necrosis, or cyst formation within the tumor can accelerate this process. When intracranial pressure reaches a critical point, even a slight increase in intracranial volume will cause a rapid rise in pressure. If intracranial pressure monitoring is performed, plateau waves appear when pressure reaches 6.67–13.3 kPa (mercury column). Repeated and prolonged plateau waves are clinical signs. When intracranial pressure equals the {|###|}stirred pulse{|###|} pressure, cerebral vasoparalysis occurs, cerebral blood flow ceases, blood pressure drops, and the patient will soon die.

As the tumor grows, local intracranial pressure becomes highest, creating pressure gradients between intracranial compartments and causing brain displacement. If this worsens progressively, brain herniation occurs. Supratentorial hemispheric tumors can lead to subfalcine herniation, where the cingulate gyrus shifts across the midline, potentially causing wedge-shaped necrosis. The {|###|}stirred pulse{|###|} of the pericallosal artery may also be compressed and displaced, and in severe cases, infarction in its supply area can occur. More critically, transtentorial herniation (uncal herniation) occurs when the medial temporal lobe (uncus) herniates through the tentorial notch into the posterior fossa. The ipsilateral oculomotor nerve is compressed and paralyzed, leading to pupillary dilation and loss of light reflex. Compression of the cerebral peduncle in the midbrain causes contralateral hemiplegia. Sometimes, the contralateral cerebral peduncle is compressed against the tentorial edge or bone, resulting in ipsilateral hemiplegia. The posterior {|###|}stirred pulse{|###|} of the choroid membrane and the posterior cerebral artery may also be compressed, leading to ischemic necrosis. Finally, brainstem compression can cause downward axial displacement, resulting in midbrain and upper pontine infarction and hemorrhage. The patient becomes unconscious, blood pressure rises, pulse slows, and breathing becomes deep and irregular, possibly progressing to decerebrate rigidity. Eventually, respiration stops, blood pressure drops, and cardiac arrest leads to death. Infratentorial posterior fossa tumors can cause {|###|}occipital bone{|###|} foramen magnum herniation, where the cerebellar tonsils herniate downward through the foramen magnum. In severe cases, the ventral medulla is compressed against the anterior edge of the foramen magnum. Supratentorial tumors may also accompany foramen magnum herniation, leading to medullary ischemia. The patient becomes unconscious, blood pressure rises, pulse slows but remains strong, and breathing becomes deep and irregular. Subsequently, respiration ceases, blood pressure falls, pulse becomes rapid and weak, and death ultimately ensues.

bubble_chart Clinical Manifestations

The course of glioma varies depending on its pathological type and location, with the time from symptom onset to medical consultation typically ranging from several weeks to months, and in rare cases, extending to years. Highly malignant tumors and those in the posterior cranial fossa often have a shorter history, while more benign tumors or those located in so-called silent areas tend to have a longer history. If the tumor causes hemorrhage or cyst formation, the progression of symptoms may accelerate, sometimes even resembling the course of cerebrovascular disease.

Symptoms primarily manifest in two aspects. One is increased intracranial pressure and other general symptoms, such as headache, vomiting, visual impairment, diplopia, epileptic seizures, and psychiatric symptoms. The other is local symptoms caused by the tumor's compression, infiltration, or destruction of brain tissue, leading to neurological deficits.

Headache is mostly due to increased intracranial pressure. As the tumor grows, intracranial pressure gradually rises, compressing or stretching pain-sensitive structures such as blood vessels, the dura mater, and certain cranial nerves, resulting in headache. It is often throbbing or distending in nature, typically localized to the frontal, temporal, or occipital regions. For superficial tumors in one cerebral hemisphere, the headache may predominantly occur on the affected side. Initially intermittent, headaches often occur in the early morning and worsen over time as the tumor progresses, with the duration of pain extending.

Vomiting is caused by stimulation of the medullary vomiting center or the vagus nerve and may occur without preceding nausea, often being projectile. In children, due to cranial suture separation, headache may not be prominent, and since posterior fossa tumors are more common, vomiting is more pronounced.

Increased intracranial pressure can lead to papilledema, which, if prolonged, may cause secondary optic atrophy and vision loss. Tumors compressing the optic nerve can result in primary optic atrophy, also leading to vision loss. The abducens nerve is prone to compression or stretching, often causing paralysis and diplopia.

Some patients with tumors experience epileptic symptoms, which may even be early manifestations. Epilepsy onset in adulthood is generally symptomatic, often due to brain tumors. Cases where seizures are difficult to control with medication or where the nature of seizures changes should raise suspicion of a brain tumor. Tumors near the cortex are more likely to cause epilepsy, while deep-seated tumors rarely do. Focal epilepsy has localizing significance.

Some tumors, particularly those in the frontal lobe, may gradually lead to psychiatric symptoms such as personality changes, apathy, reduced speech and activity, poor concentration, memory decline, indifference to surroundings, and neglect of personal hygiene.

Local symptoms depend on the tumor's location and progressively worsen. This is especially true for malignant gliomas, which grow rapidly, infiltrate and destroy brain tissue, and are accompanied by significant peritumoral edema, resulting in more pronounced and rapidly progressing local symptoms. Tumors in the ventricles or silent areas may initially lack local symptoms. In contrast, tumors in critical areas like the brainstem may present with local symptoms early, with increased intracranial pressure appearing much later. Some slow-growing tumors, due to compensatory mechanisms, may only show signs of increased intracranial pressure at an advanced stage.

bubble_chart Diagnosis

The diagnosis is made based on factors such as age, gender, location, and clinical course, and the pathological type is estimated. In addition to medical history and neurological examinations, auxiliary tests are required to aid in localization and qualitative diagnosis.

(1) Cerebrospinal fluid (CSF) examination: Lumbar puncture often reveals increased pressure. In tumors located on the brain surface or within the ventricles, CSF protein levels may be elevated, and white blood cell counts may also increase, with some cases showing tumor cells. However, in cases of significantly elevated intracranial pressure, lumbar puncture carries the risk of inducing brain herniation. Therefore, it is generally performed only when necessary, such as to differentiate from inflammation or hemorrhage. For cases with markedly increased pressure, the procedure should be conducted cautiously, avoiding excessive CSF drainage. Postoperative mannitol infusion and close observation are recommended.

(2) Ultrasound examination: This helps determine lateralization and detect hydrocephalus. In infants, B-mode ultrasound scanning through the anterior fontanelle can reveal tumor images and other pathological changes.

(3) Electroencephalography (EEG): The EEG changes in gliomas include localized alterations in brain waves at the tumor site, as well as generalized changes in frequency and amplitude. These are influenced by tumor size, invasiveness, degree of brain edema, and elevated intracranial pressure. Superficial tumors are more likely to exhibit localized abnormalities, while deep-seated tumors show fewer localized changes. Benign tumors like astrocytomas and oligodendrogliomas primarily manifest as localized delta waves, sometimes accompanied by epileptiform waves such as spikes or sharp waves. Larger glioblastomas may show widespread delta waves, sometimes only allowing lateralization.

(4) Radioisotope scanning (gamma encephalography): Faster-growing, highly vascularized tumors with increased blood-brain barrier permeability exhibit higher isotope uptake. For example, glioblastomas show concentrated isotope images, possibly with low-density areas due to necrosis or cyst formation, requiring differentiation from metastatic tumors based on shape and multiplicity. Benign gliomas like astrocytomas show lower concentrations, slightly higher than surrounding brain tissue, with less clear images, and some may yield negative findings.

(5) Radiological examinations: These include skull X-rays, ventriculography, and computed tomography (CT) scans. Skull X-rays may reveal signs of increased intracranial pressure, tumor calcification, or pineal gland calcification displacement. Ventriculography can show cerebral vascular displacement and tumor vasculature. These abnormalities vary by tumor location and type, aiding in localization and sometimes even qualitative diagnosis. CT scans, especially with contrast enhancement, offer the highest diagnostic value, with nearly 100% accuracy in localization and over 90% accuracy in qualitative diagnosis. They display tumor location, extent, shape, brain tissue reaction, and ventricular displacement. However, clinical correlation remains essential for definitive diagnosis.

(6) Magnetic resonance imaging (MRI): MRI is more accurate than CT in diagnosing brain tumors, providing clearer images and detecting微小 tumors not visible on CT.

Positron emission tomography (PET) produces images similar to CT and can assess tumor metabolic activity, helping differentiate benign from malignant tumors.

bubble_chart Treatment Measures

The treatment of gliomas primarily involves surgical intervention. However, due to the infiltrative growth of the tumor and the lack of a clear boundary between the tumor and brain tissue, complete resection is often difficult to achieve, except in cases where the tumor is small and located in an accessible area during the early stages. Comprehensive treatment is generally recommended, which includes postoperative radiotherapy and chemotherapy, to delay recurrence and prolong survival. Early diagnosis and timely treatment should be prioritized to improve therapeutic outcomes. In the {|###|}advanced stage, surgery becomes not only more challenging and risky but also often leaves behind neurological deficits. Particularly for highly malignant tumors, recurrence is common within a short period.

(1) Surgical treatment: The principle is to remove the tumor as much as possible while preserving neurological function. For small early-stage tumors, complete resection should be attempted. Superficial tumors can be approached by incising the cortex around the tumor, while tumors within the white matter should be accessed through cortical incisions that avoid critical functional areas. During tumor dissection, a safe distance should be maintained from the tumor, operating within normal brain tissue rather than adhering closely to the tumor. This approach yields better outcomes, especially for relatively benign tumors such as astrocytomas or oligodendrogliomas located in the frontal or temporal lobes or the cerebellar hemisphere.

For larger tumors in the frontal or temporal lobes, a lobectomy can be performed to remove the tumor along with the affected lobe. In the frontal lobe, the posterior margin of the incision should be at least 2 cm anterior to the precentral gyrus, and in the dominant hemisphere, care should be taken to avoid the motor speech area. In the temporal lobe, the posterior margin should be anterior to the inferior anastomotic vein, and injury to the vessels of the lateral fissure should be avoided. A few tumors located in the occipital lobe may also be treated with lobectomy, though this may result in hemianopia. For extensive frontal or temporal lobe tumors that cannot be completely resected, maximal tumor resection combined with frontal or temporal pole resection for internal decompression can prolong the time to recurrence.

For tumors involving more than two lobes of a cerebral hemisphere with existing hemiplegia but without invasion of the basal ganglia, thalamus, or contralateral side, a hemispherectomy may be considered.

For tumors located in motor or speech areas without significant hemiplegia or aphasia, care should be taken to preserve neurological function while resecting the tumor appropriately to avoid severe sequelae. Subtemporal or decompressive craniectomy may be performed simultaneously. Alternatively, a biopsy followed by decompression may suffice. For thalamic tumors compressing or obstructing the third ventricle, a shunt procedure may be performed; otherwise, decompression may be considered.

Intraventricular tumors can be approached by incising the brain tissue from non-critical functional areas to enter the ventricle, with the goal of removing as much tumor as possible to relieve ventricular obstruction. Care must be taken to avoid injury to adjacent structures such as the hypothalamus or brainstem to prevent complications. For brainstem tumors, small nodular or cystic lesions may be resected, while those causing increased intracranial pressure may be treated with shunt procedures. Tumors of the superior vermis that are difficult to resect may also be managed with shunting.

In emergency cases, supratentorial tumors should first be treated with dehydrating agents while diagnostic tests are expedited, followed by surgical intervention. For posterior fossa tumors, ventricular drainage may be performed initially, with definitive surgery delayed for 2–3 days until the patient's condition stabilizes.

(2) Radiotherapy: External radiation sources include high-voltage X-ray machines, {|###|}60Co units, and electron accelerators. The latter two deliver high-energy radiation with strong penetration, low skin dose, minimal bone absorption, and reduced lateral scatter. Accelerators concentrate the dose at the intended depth, with a sharp drop-off beyond this point, sparing normal brain tissue behind the lesion. Radiotherapy should ideally begin as soon as the patient's general condition permits postoperatively. The typical dose for gliomas is 5000–6000 cGy, delivered over 5–6 weeks. For highly radiosensitive tumors with large fields, such as medulloblastomas, 4000–5000 cGy may be administered.

The sensitivity of various types of gliomas to radiotherapy varies. Generally, poorly differentiated tumors are considered more sensitive than well-differentiated ones. Medulloblastoma is the most sensitive to radiotherapy, followed by ependymoblastoma, while glioblastoma multiforme is only sensitive at grade II. Astrocytoma, oligodendroglioma, and pineocytoma are even less sensitive. For medulloblastoma and ependymoma, due to their tendency to spread via cerebrospinal fluid, irradiation should include the entire spinal canal.

(3) Chemotherapy: Highly liposoluble chemotherapeutic drugs that can cross the blood-brain barrier are suitable for brain gliomas. In grade III–IV astrocytomas, the blood-brain barrier is disrupted due to edema, allowing large water-soluble molecules to pass through. Therefore, some believe that the selection of drugs can be expanded to include many water-soluble molecules. However, in reality, the disruption of the blood-brain barrier is not severe in the densely proliferating cell areas around the tumor. Hence, liposoluble drugs should still be the primary choice. Below is a focused introduction to the currently preferred drugs.

① Teniposide: Its chemical name is 4'-demethyl-epipodophyllotoxin-β-D-thenylidene glucoside, and its trade name is Vumon (Teniposide, VM26). It is a semi-synthetic derivative of podophyllotoxin with a molecular weight of 656.7. It has a broad antitumor spectrum, high liposolubility, and can cross the blood-brain barrier. As a cell-cycle-specific drug, it damages DNA and blocks the G2 (late stage of DNA synthesis [third stage]) and M (mitotic phase) phases. VM26 exhibits the highest toxicity to tumor cells (70–98%) and the lowest toxicity to normal cells (only 28–38%). VM ₂₆ The usual dose for adults is 120–200 mg/m ² daily for 2–6 days. When combined with CCNU, the dose may be reduced to 60 mg/m ² daily, administered intravenously in 250 mL of 10% glucose solution over approximately 1.5 hours for 2 days, followed by oral CCNU on days 3 and 4, totaling 4 days per treatment cycle. The cycle is repeated every 6 weeks. Side effects: Bone marrow suppression is relatively mild, and toxicity is low; cardiovascular reactions manifest as hypotension, so blood pressure should be monitored during IV infusion.

② Lomustine (CCNU): This drug has been used clinically for many years. It is a cell-cycle-nonspecific drug that acts on all phases of proliferating cells, including the resting phase. It is highly liposoluble and can cross the blood-brain barrier, making it suitable for treating malignant brain gliomas. However, its toxic reactions are significant, primarily manifesting as delayed bone marrow suppression and cumulative effects, which severely limit its use. After 4–5 treatment cycles, white blood cell and platelet counts often drop sharply, forcing treatment delays or even discontinuation, leading to relapse. Additionally, gastrointestinal reactions are severe, with high rates of nausea, vomiting, and abdominal pain after administration. The liver and lungs may also be affected. The usual dose for adults is 100–130 mg/m ² orally daily for 1–2 days, repeated every 4–6 days. When combined with VM ₂₆ , the dose may be reduced to 60 mg/m ² daily.

③ Semustine (MeCCNU): The dosage is 170–225 mg/m ² . The administration method is the same as CCNU, but its toxicity is lower.

Chemotherapy for gliomas tends to involve combination drug therapy. Based on cell kinetics and the specificity of drugs to the cell cycle, two or more drugs—sometimes even multiple drugs—are used in combination to enhance efficacy. Zhang Tianxi from Shanghai has applied a sequential chemotherapy regimen of teniposide (VM₂₆) and lomustine (CCNU), achieving significant therapeutic effects, which is highly recommended. The method and steps are as follows: Each treatment cycle lasts 4 days. **Days 1 and 2:** VM₂₆ 100mg is added to 250ml of 10% glucose solution for intravenous drip over 1.5–2 hours, administered for 2 consecutive days. Rapid infusion or direct intravenous injection of VM₂₆ may cause a sudden drop in blood pressure and must be avoided. Blood pressure should be monitored during the infusion to prevent accidents. If blood pressure falls below 10 kPa, the medication should be discontinued immediately. Since VM²⁶ tends to lose efficacy if diluted and left at room temperature for over 4 hours, it should be prepared and used immediately. **Days 3 and 4:** CC-NU 80mg is taken orally each day. An antiemetic such as domperidone should be administered 30 minutes before taking the medication to reduce gastrointestinal reactions. After completing one cycle, the next cycle is repeated every 6 weeks. Generally, the peak effect of CCNU occurs in the fourth week after administration. Therefore, routine re-examination of white blood cell (WBC) and platelet counts should be conducted by the end of the fifth week. If WBC counts fall below 3×10⁹/L or platelet counts below 90×10₉/L, chemotherapy should be postponed until blood counts recover before starting the next cycle. Due to the cumulative toxicity of CCNU, blood counts often become difficult to maintain after 4–5 cycles, necessitating extended intervals between cycles. Alternatively, VM{|113|}26{|114|} may be used alone as a transitional measure until blood counts improve, after which the two-drug combination can be resumed. During this period, supportive therapies such as DNA and batyl alcohol may be routinely administered. If the patient tolerates the treatment well, it may continue for 10–15 cycles or more. If CT scans show no signs of recurrence and clinical outcomes are satisfactory, the treatment may eventually be discontinued, followed by follow-up monitoring.

(4) Immunotherapy: Immunotherapy is still in the trial stage, and its efficacy is not yet certain, requiring further research.

(5) Other drug treatments: For malignant gliomas, hormone therapy can be administered first, with dexamethasone being the most effective. In addition to reducing cerebral edema, it also has the effect of inhibiting tumor cell growth. This can alleviate symptoms before proceeding with surgical treatment.

For patients with epileptic seizures, anti-epileptic drugs should be administered before and after surgery.