Medical  therapy is symptomatic and usually involves the use of steroids, and anticonvulsant medication in addition to analgesics, and antiemetics. Side effects of steroids can be significant, and all patients should be treated with an H₂-receptor blocker. The dose of steroids should be tailored for each patient and assessed on a regular basis. It is better to avoid late-night dosing if possible, as it can lead to sleep disturbances and behavioral problems.

The typical dexamethasone  dose employed by most physicians preoperatively is 4 mg (po/IV) every 6 hours, and the dose is tapered postoperatively. Patients need to be followed closely during the tapering period.

Antiepileptic drug practice has historically been dependent on the neurosurgeon's preference, and most patients are started on prophylactic anticonvulsants. It is recommended that prophylactic anticonvulsants is not required in newly diagnosed brain tumor patients who have never had a seizure. he patients who have had seizure need to continue the anticonvulsants post operatively.

 Surgery continues to be its basic therapy and plays a central role in interdisciplinary glioma management.

Rickman Godlee performed the first surgery for a glioma in 1884.

Cushing, Dandy, and Krause redefined the neurosurgical principles in the early 90s.

Today's surgeon has a battery of tools in imaging and surgery.

The principles and techniques of surgery and adjuvant therapy are the same for all intrinsic brain tumors.

The sites and types of tumor may necessitate minor modifications, and are discussed elsewhere.

Various surgical options are available, and the surgical approach should be carefully chosen to maximize tumor resection while preserving vital brain structures and minimizing the risk of postoperative neurologic deficits.

The choice of operative approach depends on the location, size, gross characteristics (extent of demarcation, consistency, and vascularity), probable histology, and radio sensitivity of the tumor, as well as on the neurological status and general condition of the patient, and, of course, the surgeon's technical ability, and available tools.

Open Surgery: 

A meticulous preoperative planning is mandatory. The planning starts at bedside.

Intrinsic tumors, generally, is confined to sulcal boundaries, and do not cross pial barriers.

A proper history and clinical examination, obtained at the bedside, may give a 'clue' about the exact site where the tumor started, and help in tumor excision. A tumor, which  appears to be a fronto-parietal on CT/MRI, may be actually a frontal tumor starting in the frontal lobe and growing backwards pushing the central sulcus backwards, and will have significant motor deficit with no sensory deficit at examination. Hence a generous excision may be planned, and will not damage the motor strip.

A thorough pre operative study of all radiological imaging must be reviewed, with special attention to tumor location and neighborhood 'eloquent areas', vascular channels, central sulcus, sylvian fissure ,widened sulci overlying the tumor, and other safe corridors; special reference to be made to the preferred position of the patient at surgery, and aim of the surgery.

"The brain floats in a sea of CSF, with rivers of CSF which allows access to its interior", says Yasergil.

Recent advances in neuroimaging with MRI, MR/CT angiogram, MR spectroscopy, and functional MRI have greatly helped the surgeon decide on the so called 'safe corridors'.

Preoperative corticosteroids provide rapid, often dramatic, symptomatic improvement. Therapeutic effect of steroids is limited to 6-8 weeks.  The daily standard dose is 16 to 24 mg for dexamethasone and 80 to 120 mg for methylprednisolone. Dose-related symptomatic improvement with minimal side effects has been shown for up to 96 mg of dexamethasone and 500 mg of methylprednisolone daily.  The effects of corticosteroids include, reduction of tumor mass, reduction of peritumoral edema, decrease in permeability of the blood-brain barrier, and increase in cell cycle time.

All patients with a history of seizures should receive anticonvulsants.

The prophylactic use of anticonvulsants is controversial similar to the use pre operative antibiotics.

Position of the patient at surgery is most important.

The site of lesion, the familiarity of the surgeon should be taken into account.

Osmodiuretic therapy is very useful in both an emergency and a peri-operative situation.                    

A surface marking of sagittal sinus, central sulcus and sylvian fissure will help in their protection at surgery.

Sylvian fissure      - a line drawn from nasion to lambda (approximately corresponds to EOP).

Rolandic fissure    - a line perpendicular to the midpoint of a line drawn from outer margin of the eyebrow and the tragus.

It is then possible to outline the frontal, parietal, and the temporal lobes.

Posterior to a line from the lambda to the posterior mastoid is the occipital lobe.

Individual variations is the rule.

The scalp incision should provide sufficient exposure of the relevant cranium, maintain adequate blood supply to the scalp flap and minimize cosmetic deformity. Traditionally, various classical flaps have been described.

Infiltration of 2% xylocaine and adrenaline (1:200,000) mixture, if permitted by the anesthetist, in the connective tissue overlying the galea helps in dissection as well as controlling the blood loss.

Bone removal should preserve blood supply to the bone plate, avoid air sinuses, remove sufficient bone to permit identification of cranial and parenchymal landmarks, achieve brain retraction without compression, and avoid extensive exposure of uninvolved cortex. Most surgeons advise a generous craniotomy for gliomas.

In the author's experience, a generous craniotomy do not add to benefits.

A dural flap is turned towards the venous sinus closest to the exposure, taking precautions to avoid the cortical veins.

Use of a quality microscope in tumor removal from this stage is the order of the day.

Neuroendoscope assisted microsurgery is becoming popular, and helps in exploring the corners with minimal brain retraction.

'En bloc resection' may be achieved in a surface (lobar) tumor an area that is either clinically silent or already non-functional. Technical refinements in surgery with subpial dissection or transsulcal approaches with brain mapping and awake craniotomy has helped for tumors at eloquent areas.

In lesions over the sulci, the transit vessels must be preserved as they may be supplying the normal brain.

A subcortical tumor can be identified by distortion of neuroanatomical landmarks.

The overlying gyri may be flattened and  pale  due to paucity of vascularity.

Gentle palpation and /or needling with a brain cannula may help in the absence of surface changes.

A glioblastoma is softer, whereas a low grade glioma would be firmer with respect to the surrounding parenchyma.

Alternatively, delineation of the subcortical dimensions by real-time B-mode ultrasonography, or performing a cortical incision under stereotactic guidance, if available, may be carried out.

Overlying cortex may be removed in 'non eloquent' areas and the tumor may be debulked from inside out.

Piecemeal excision is preferred. The common oncologic principles of surgical excision cannot be applied to brain tumors; clearance margin of 1.5 to 5 cms around the tumor margin cannot be given in most brain tumors in view of risk of severe morbidity. The surgeon is forced to enter the tumor and debulk it before excising the capsule.

The site of the cortical incision and the angle and depth of the transparenchymal approach are determined by the location and shape of the tumor with respect to eloquent cortex, major fiber tracts and deep nuclei as well as bone prominences, dural septa, vascular structures and ventricles. 

Intratumoral bleeding may be a problem, and will stop only with tumor excision.

Intratumoral resection is needed to avoid eloquent areas such as, Pre and Postcentral gyrus,

                                                                                               Calcarine gyri bilaterally

                                                                                               Dominant posterior inferior frontal gyrus,

                                                                                               Posterior superior temporal gyrus, Inferior parietal lobule,

                                                                                               and Nondominant superior parietal lobule.

In the rare instance in which an eloquent gyrus must be incised, the incision should be made transversely to its axis. 

The tumor is facilitated by suction, bipolar coagulation and microscissors, and , if available by, ultrasonic aspiration, and laser. Disruption of uninvolved tracts of white matter, or opening the ventricle must be avoided.

The goal is maximal tumor removal without creation of new neurological deficits. 

Recent advances have made removal of a strategically located tumor possible.

Successful excision of deep seated (thalamus and basal ganglia) gliomas through trans sylvian-trans insular approach, trans callosal approach, and  trans cortical-trans ventricular approach, have been reported with image guided surgery.

Lobectomy in addition to gross total tumor excision, may be useful for large temporal and frontotemporal tumors.

Lobectomy with partial tumor excision has no benefit.

Associated hydrocephalus may need a drainage procedure.

Postoperative CT scan or MRI scan with and without contrast material within 48 hours after surgery is recommended to study the residual tumor, if any. After 48 hours, post operative changes may mask the residual tumor mass in a scan.  

Reoperation:

Advances in surgical glioma management suggest that reoperation of malignant tumors may be justified by the palliative effect of tumor mass reduction, which in turn enhances the cytotoxic effect of adjuvant therapy.

Reoperation should be considered when a substantial mass of tumor can be removed and the patient’s age, response to earlier surgery, and performance status suggest the potential for improvement of quality of life.

The rationale for reoperation is the same as for the original operation (confirmation of tumor histology and reduction of tumor mass).

Tumor Biopsy:

Biopsy is performed when open surgery is not planned any reason. Blind burrhole biopsy is outdated.

Stereotactic frames provide a rigid, three-dimensional (3D) coordinate system for accurate targeting of brain lesions identified on CT or MRI scans. Stereotaxy is particularly well-suited for obtaining tissue for biopsy from tumors located in deep structures, such as the thalamus, basal ganglia, and brainstem, or in other sites where aggressive tissue removal would produce unacceptable neurologic deficits . A limitation of stereotactic biopsy is that small volumes of tissue are obtained, and tissue sampling errors may result in failure to reach a correct diagnosis. Stereotactic biopsy may be nondiagnostic in about 10 of cases and has a surgical morbidity of approximately 5%.

Controversies  exist in the timing and nature of Glioma surgery.

Patient's age and general condition, neurological status, and location and presumed nature of the tumor are the deciding factors.

Surgery is widely recommended, when the tumor is associated with raised ICP, and progressive neurological deficit, or intractable epilepsy. Easily accessible tumors in the 'non eloquent' areas may be excised.

The controversy is in a radiologically low grade tumor in an eloquent area, with no raised ICT or neurological deficit.

When to operate?

Infiltrative nature of most gliomas, multifocality of gliomas, varied biological behavior of the tumors, potential deficits and complications related to surgery, and the widely accepted, though controversial, view that interventions may provoke progression to a higher grade, are the arguments against surgery. Additionally, it has been claimed that this line of treatment leaves ample time for the toxic effects of radiotherapy and chemotherapy to manifest.

The patients are offered only symptomatic treatment with or without a biopsy. However, theses patients need regular follow ups.

The advocates of early surgery argue that CT and MRI, despite recent advances, do not give an accurate pathological diagnosis. The surgeon is better equipped with a tissue diagnosis to arrange for further therapy. Contrast enhancement is not reliable, and these days of medico legal problems, a tissue diagnosis is a must.

How much to remove?

Most studies, all of which are retrospective, suggest that a gross total excision of a low grade glioma and incomplete excision followed by radiotherapy prolong the survival. Moreover, it has been suggested that extent of surgery is an important factor in predicting recurrence, and that the recurrent tumors show higher grade. The advocates for radical surgery claim that extensive surgery may favorably influence the recurrence rates, modify tumor behavior, and ultimately prolong the survival.  Gross total excision may control the seizures. Large tumor tissue avoids sampling error as in stereotactic biopsy, and helps in molecular study. Some gliomas ( pilocytic astrocytomas) are 'curable' by surgery alone. These studies are not randomized or even case controlled trials.

Another group of surgeons feel total resection, given the infiltrative and multifocal nature of these gliomas, do not provide any additional benefit. They recommend a tissue diagnosis and appropriate radiotherapy and chemotherapy.

The author recommends that the decision has to be individualized, taking into account of the patient condition and the surgeon's surgical skills, and that radiotherapy may be with held after gross total excision in low grade tumors.

Deep seated radiologically high grade gliomas with no significant raised ICP or neurological deficit, surgery may not be recommended despite all the surgical advances. A stereotactic biopsy and appropriate radiotherapy and chemotherapy is widely practiced. The tumor cells infiltrate far beyond the visible tumor margins, and the radiology may reveal only about 505 to 60% of the tumor, it has been suggested. Even lobectomy has not shown any survival benefit is high grade tumors.

Some surgeons have reported longer survival times with total excision. They consider a gross total resection to be more beneficial than a partial resection or biopsy. Some others found no correlation between the degree of cytoreductive surgery and survival.

This issue has never been investigated in a prospective randomized manner.

Radical resection, in addition to establishing the histological diagnosis, provides immediate palliation, reestablishes the  intracranial CSF dynamics, reactivates immunological self defence, enhances the effect of adjuvant therapy by removing resistant cells, and moving cells into more vulnerable phases of the cell cycle, and also by reducing the target (tumor) load.

It has been generally agreed that > 98 % resection results in prolonged survival, and < 94 % resection is only diagnostic & symptomatic benefit, but no statistical survival benefit.

The author recommends gross total excision for all radiologically high grade tumors in non eloquent areas, provided the patient's age and general condition permits. Tumors in eloquent areas with neurological deficits, may also be excised, as it will improve the existing neurological deficit, and the quality of life, though temporarily.

Photodynamic therapy:

Photodynamic (Photoradiation) therapy has been in use for certain cases of cancer of the esophagus and non-small cell lung cancer, and  most recently, to treat actinic keratosis, a precancerous skin condition. It is a form of treatment that depends on the selective retention of a photosenstizer followed by laser treatment with light of an appropriate wavelength. The theoretical advantage is that it is a two component or binary system which generates singlet oxygen capable of selectively killing tumor cells only when combined together, presumably avoiding significant damage to normal tissues. It has long been known that hematoporphyrin has a propensity to localize in tumor tissue. This accumulation has been linked to the degree of vascularity, the number of low density lipoprotein receptors on the tumor plasma membrane, the decreasing extracellular pH, and uptake by non-viable cells in necrotic regions.

Irradiation of a cell incorporating a photosenstizer, such as hematoporphyrin derivatives, by low power visible light induces photochemical reactions which lead to cell death. HpDs1, and in particular, a purified component called Photofrin (HpD-II), are currently being used in clinical trials. The blood brain barrier (BBB) is not permeable for hematoporphrin, thus normal brain does not take up HpD-II and there is selective killing of tumor cells, that are not resected at surgery.

Following tumor excision, the tumor bed is cleared off hematoma and hemostatic agents, and filled with photosenstizer uniformly. The laser beam, as calculated, is applied for about 30 to 60 minutes. The usual post operative management is carried out in a dark room. The radiotherapy is started after four weeks, as HpDs1 may remain for some time in small vessels.

The safety and effectiveness of this therapy need further studies.  

 Radiotherapy   is discussed elsewhere.

 Adjuvant Therapy:

At the time of diagnosis most glioblastomas have a tumor mass of approximately 100g with an estimated cell content of 10^11.  After surgery and radiotherapy 10² or 10³ cells will remain.  The immune system is able to cope with 10^5.

The remaining 10²³ cells are the goal of adjunctive therapies, in order to control local tumor growth.

Chemotherapy: Chemotherapy is the only established adjuvant treatment, but still many questions concerning clinical effectiveness exist.  In pediatric brain tumor treatment chemotherapy has found wider application. 

As an attempt to avoid the effects of radiotherapy in those under 3 years of age, preirradiation chemotherapy is being tried.

It is indicated for high-grade malignant gliomas as an adjuvant to surgery and radiotherapy or surgery in recurrent tumors. Reports suggest that the median survival time (MST) with surgery alone is 14 weeks, and with radiotherapy it is 36 weeks, and that single agent chemotherapy improves MST to 51-73 weeks.  It is discussed elsewhere.

In recent years, minimizing the side effects of chemotherapy, and radiotherapy is an important consideration. A better understanding of the molecular events leading to tumor development has provided an opportunity to intervene with experimental modalities, such as, genetherapy, immunotherapy, and angiostatic therapy.

In addition, other investigatory agents include,