1. Dr. Zana A. Mohammed
M.B.Ch.B., F.I.B.M.S. Neurology
Faculty of medical science
School of medicine
University of Sulaimaniah

2. Brain compartments

4. Brain tumor
A brain tumor is a localized intracranial lesion which occupies space within the skull.

5. Incidence of primary brain tumors (benign or malignant) 12.8/100,000
10%–15% of cancer patients develop brain metastases
Second leading cause of death from a neurological cause after stroke

6. Often unknown Risk factors: Genetic changes Family history
Errors in fetal development
Ionizing radiation
Environmental hazards (including diet)
Viruses
Injury or immunosuppression

7. Primary ( benign and malignant). secondary (metastatic)
35% - lung
20% - breast
10% - kidney
5% - gastrointestinal tract
Location ( intra-axial and extra-axial)

8. Clinical features
There are three groups of symptoms and signs resulting from brain tumors:
Raised intracranial pressure
Epilepsy
Evolving focal neurological deficit.

9. Raised intracranial pressure
The cardinal features of raised intracranial pressure are:
• Headache
• Vomiting
• Papilledema
• False localizing signs
• Depression of conscious level
• Signs of tentorial herniation and coning.

10. Headaches of raised intracranial pressure tend not to be
extremely severe, they are usually generalized throughout the head, and they tend to be worse in the mornings when the patient wakes. They sometimes wake the patient earlier than his normal waking time.
papilledema: The patient may report transient blurring or loss of vision. Such visual obscurations should stimulate urgent investigation and treatment.

11. False localizing signs
We have seen that a mass lesion in one compartment of the brain can induce shift and compression in parts of the brain remote from the primary lesion producing false localizing signs.
• The descent of the brainstem may stretch the 6th cranial nerve
to produce a non-localizing lateral rectus palsy:
• The ventricular dilatation above midline CSF obstructive lesions, or above posterior fossa lesions may produce:
—intellectual and behavioral changes suggestive of primary frontal pathology;
—an interference with vertical eye movements (upper midbrain) because of the dilatation of the posterior part of the 3rd ventricle and aqueduct

13. Epilepsy
Focal epilepsy, focal epilepsy progressing on to a generalized tonic–clonic seizure, tonic–clonic seizures with post-ictal focal neurological signs, and tonic–clonic epilepsy without any apparent focal features may all indicate the presence of a tumor in the cerebrum.
Epilepsy is not a feature of posterior fossa tumors.
Epilepsy is not commonly caused by tumors, and less than 50% of cerebral tumors produce epilepsy, but the occurrence of epilepsy in adult life should prompt the possibility of a brain tumor in the doctor’s mind.

14. Focal neurological deficit
The presence of a tumor impairs the function of the part of the brain in which it resides. The nature of the evolving focal neurological deficit clearly depends on the site of the lesion.
Tumors near the midline and in the posterior fossa may produce marked features of raised intracranial pressure before there are many localizing signs.

18. Gliomas Oligodendroglioma Ependymomas Medulloblastoma CNS Lymphoma
Astrocytoma (Grades I & II)
Anaplastic Astrocytoma
Glioblastoma Multiforme
Oligodendroglioma
Ependymomas
Medulloblastoma
CNS Lymphoma
Intra-axial gliomas originate from glial cells; they affect brain by invasion and infiltration.
Gliomas
Low Grade Glioma (WHO – grade I)
?? Nonenhancing
?? Benign – 5–7 years – dedifferentiate – more aggressive
Astrocytoma (WHO – grade II)
?? Nonenhancing, infiltrative
?? 5–7 years – dedifferentiates – more aggressive
Anaplstic Astrocytoma (WHO – grade III)
?? Enhancing
?? Survival 18–24 months
Glioblastoma Multiforme (WHO – grade IV)
?? Enhancing, necrotic center
?? Survival 8–10 months
Ependymomas
?? Arises from lining of ventricle
?? Benign tumor – causes obstruction of CSF
Medulloblastoma
?? Malignant tissue – infra-tentorial
?? May “seed” spinal cord
CNS Lymphoma
?? Common in immunocompromised patients (e.g., transplant/AIDS)
?? Radiation/decadron or chemotherapy (radiation & chemo effective)
?? Survival 1–4 years

19. Gliomas are seen to appear in both the benign and malignant groups of tumors.
Astrocytomas are by far the most common glial tumor; derived from oligodendrocytes, ependyma, neurons, primitive neuroectodermal or other tissues are much rarer.
Gliomas are classified histologically from grade 1 (benign) to grade 4
(the highly malignant glioblastoma multiforme).
Benign gliomas are, unfortunately, much less common than malignant ones and have a tendency to become more malignant with time.

20. Grade I
Non-infiltrating

21. Grade II Infiltrating Slow growing

22. Grade III
Infiltrating
Aggressive

23. Grade IV
Highly infiltrative
Rapidly growing
Areas of necrosis

24. Grades II-IV Mixed astro/glio

25. Slow growing Benign HCP/ICP Surgery, RT, Chemo

26. Small cell embryonal neoplasms Malignant HCP/ICP

27. Primary CNS lymphoma
B lymphocytes
Increased ICP
Brain destruction

28. Acoustic neuromas (Schwannoma) Pituitary adenoma Neurofibroma
Meningioma
Metastatic
Acoustic neuromas (Schwannoma)
Pituitary adenoma
Neurofibroma
Extra-axial originate from supporting structures of CNS.
Meningioma
• Slow-growing, attached to meninges
• Usually benign
Metastatic
?? Usually from lung, breast, kidney and GI
?? Enhancing – necrotic center, peritumoral edema, occurs in gray matter
Acoustic neuroma
• Cranial nerve VIII
• Benign
Pituitary adenoma
?? Classification by hormone secretion
?? Classification by location – adenohypophysis – anterior pituitary
Prolactin-secreting – serum prolactin >500 mU/L
a. Microadenoma
- hyperprolactinemia, galactorrhea, amenorrhea
- infertility; males – impotence
b. Macroadenoma
- mild hyperprolactinemia due to disruption of pituitary stalk
Growth hormone – deficiency
a. Childhood
- dwarfism, slow/absent growth
- absent/delayed sexual development, cephalofacial disproportion
b. Adulthood
- increased body fat, decreased muscle mass
- decreased bone density – increased risk of fractures, impaired glucose tolerance
Neurofibroma
?? Genetic because of autosomal dominant mendelian trait; firm, encapsulated lesions
?? Attach to nerve
?? Benign
?? Occur late in childhood/early adolescence
?? Treated with surgery, radiation

29. Meningioma Nearly always benign.
They may arise from any part of the meninges, over the surface of the brain, from the falx, or from the tentorium.
There is a plane of cleavage between tumor and brain tissue which makes total removal a definite possibility.

30. Usually benign
Slow growing
Well circumscribed
Easily excisable

31. Benign tumors of the Schwann cells
Located in CP angle and the internal auditory meatus in the petrous temporal bone.
produce progressive unilateral nerve deafness, associated 5th and 7th nerve dysfunction, unilateral cerebellar signs and evidence of raised intracranial pressure.
Early diagnosis is critical
•Arises from the meninges
•Slightly higher incidence in women
•Very bloody
•Benign

32. Benign
Anterior pituitary
Endocrine dysfunction
chiasmatic compression
Bitemporal hemianopia

33. Pituitary adenomas Space-occupying effects:
suprasellar extension to compress optic nerves/chiasm/tracts. Bitemporal hemianopia resulting from chiasmal compression. so monocular blindness due to optic nerve compression and homonymous hemianopia from optic tract compression according to location of pituitary gland.
Lateral expansion may compress structures on the lateral wall of the cavernous sinus (cranial nerves, 3, 4, 5a and 6), producing double vision and forehead numbness.
Forward and downward expansion of the adenoma results in enormous expansion of the pituitary fossa and occasional erosion through bone into the sphenoidal air sinus.

34. 2. The endocrine disturbances that accompany the development of a pituitary adenoma are:
Positive if the tumor cells are secretory (prolactin, growth hormone, etc.)
Negative if the tumor is preventing normal secretion by the rest of the pituitary gland (varying degrees of pan hypopituitarism).

35. Cystic tumor coming from remnant of Rathke’s pouch
Hypothalamic-pituitary axis dysfunction

36. Peritumoral edema Necrotic center
Most common site is breast and lung
•Seed to brain by lymphatic system or blood vessels

37. 80% of metastases occur supratentorially and 20% infratentorially (distribution of cerebral blood supply)
Up to 75% of patients have neuroimaging evidence of multiple metastases at presentation
Lung cancer and melanoma are most likely to produce multiple metastases
Renal cell carcinoma, breast cancer, and colon cancer are most likely to produce single brain metastasis
Retroperitoneal, pelvic, gastrointestinal primary tumors have predilection for posterior fossa

38. Metastasis occurs with hematogenous spread and typically land at gray matter white matter junction because of abrupt change in blood vessel caliber.
Except for certain neoplasms such as malignant melanomas that can penetrate arterial (arteriolar) walls and are often hemorrhagic, most tumors usually penetrate capillary beds to arrive at their destination

39. Radiological Imaging LP/CSF analysis Pathology
Computed Tomography scan (CT scan) with/without contrast
Magnetic Resonance Imaging (MRI) with/without contrast
Plain films
Myelography
Positron Emission Tomography scan (PET scan)
LP/CSF analysis
Pathology
Diagnostic Procedures
Computed Tomography (CT) Scan
?? Evaluate bony lesions, hemorrhages with enhancement – enhancing tumors
?? May miss smaller parenchymal lesions
Magnetic Resonance Imaging (MRI)
?? Structures shown in three planes
?? With and without contrast – enhancing lesions
?? Document smaller parenchymal lesions
?? MRI technology variations
MRI angiography – visualization of vascular structures
MR spectroscopy – documents chemical composition, brain metabolites, increased
choline peak, tumor lactate peak
- tumor necrosis diagnostic and prognostic tool
Positron Emission Tomography scan (PET scan)
?? F-18 fluorodeoxyglucose (FDG)
?? Measures tissue metabolism
?? Differentiates treatment-related necrosis vs. tumor necrosis

40. Resection Craniotomy Stereotaxis Surgery Biopsy Transsphenoidal
?? Brain surgery, partial resection, resection of tumor
Steriotactic Surgery
??MRI–CT guided surgery to remove small superficial tumor
Biopsy
?? To remove piece of tumor to determine type of tumor
Transsphenoidal
??Approach through nasal passage to remove pituitary tumor

41. Drug therapy – Palliative
Done for symptom treatment and to prevent complications
NSAIDs
Analgesics
Steroids (Decadron, medrols, prednisone)
Anti-seizure medications (phenytoin)
Histamine blockers
Anti-emetics
Muscle relaxers (for spasms)
Mannitol for ICP –New Hypertonic saline

42. Wound infection
Seizures
CSF leak
Edema
Increased ICP
Hematoma
Hypovolemic shock
Hydrocephalus
Atelectasis
Pulmonary edema
Meningitis
Fluid and electrolyte imbalances (ADH)

43. Damages DNA of rapidly dividing cells 4000–6000 Gy total dose
Duration of 4–8 weeks
Radiation is sensitive to cells that rapidly divide (e.g., brain tumors) and normal tissue too.
Low-grade radiation
Daily radiation doses of 150–200 Gy … goes +2 cm margin beyond tumor bed
Types of Radiation
??External beam radiation
??Stereotactic radiosurgery (gamma, linac, cyberknife)
??Interstitial brachytherapy – isotopes inserted into tumor bed, removed in 4–5 days
Considerations
•Skin burns are a big concern and reddened skin from beam of radiation.
•Corticosteroids are given during radiation to control cerebral edema
•Radiation necrosis may occur after treatments are completed; may need to be surgically
removed.

44. Slows cell growth Cytotoxic drugs
CCNU, BCNU, PCV, Cisplatin, Etoposide, Vincristine, Temozolomide (Temodar)
Cancer cells are rapidly dividing cells.
A combination of drugs is sometimes used.
Chemotherapeutic drugs are administered by the PO, IV or intrathecal routes
Acute side effects include the following:
•Oral mucositis: Provide mouth care on regular basis
•Check for bone marrow suppression: WBC with differential; Neurtrophils >1500
•Fatigue: Rest, check hemoglobin >10, platelets >10,000
•Hair loss: Encourage patients to wear scarves and use makeup; review cause of hair
loss and that it will regrow
•Nausea/vomiting: Antiemetics
•Anxiety: Reassure positive attitude
•Peripheral neuropathy: Non-narcotics, opioids, adjuvant (e.g., antidepressants,
anticonvulsants, anxiolytics)

45. A patient is being directly admitted to the medical-surgical unit for evaluation of a brain mass seen in the frontal lobe on a diagnostic CT scan. Which of the following signs and symptoms would the patient most likely present with?
Personality changes
Visual field cuts
Difficulty hearing
Difficulty swallowing

46. Case 1
A 65-year-old widow presents with a 6-month history of unsteadiness. She has started to veer to the left. She has been well prior to this, apart from a longstanding hearing problem and surgery for colon cancer 5 years ago. On examination she has an ataxic gait, slight leftwards nystagmus, an absent left corneal reflex and marked left-sided deafness. There is no papilledema.
a. What do you think is the cause of her symptoms?

47. Case 2
A 45-year-old oil company executive returns from secondment in Nigeria because of ill health. Over the last 3 months he has become slow and erratic, making frequent mistakes at work and getting lost on his way home. His memory has become poor and he has had difficulty in finding his words. His appetite has faded and he has lost weight. In the last 2 weeks he has become unsteady on his feet and incontinent of urine.
On examination he is thin. He has no fever but his axillary and inguinal lymph nodes are slightly enlarged. He is drowsy. He had bilateral papilledema. He has difficulty cooperating with a neurological examination and becomes increasingly irritated when you persist.
a. What do you think is the cause of his symptoms?

48. Thanks