1. Brain Tumors Emergencies
Daniela Bota, MD PhD
Neuro-oncologist
UC Irvine

2. Classification of Brain Tumors: - high grade vs
Classification of Brain Tumors: - high grade vs. low grade and primary vs. secondary -
Low-Grade
WHO grade I:
low proliferative potential
frequently discrete nature
possibility of cure after surgical resection alone
WHO grade II:
generally infiltrating and low in mitotic activity
frequently recur
some types tend to progress to higher grades.
High Grade
WHO grade III: histologic evidence of malignancy
mitotic activity
clearly expressed infiltrative capabilities
anaplasia.
WHO grade IV:
mitotically active
necrosis-prone
associated with a rapid preoperative and postoperative evolution of disease.
Kleihues P and Cavenee WK 2000,
Kleihues et al. 2002

3. Primary CNS Tumors: Malignant Gliomas
the most common primary neoplasms of the brain
affects approximately 10,000 people every year in the United States
very aggressive tumors with a historical survival of less the one year, which has changed little over the last two decades
high heterogeneity in pts response to treatment, disease free survival, and overall survival (OS), which cannot be accurately predicted at the time of diagnosis

4. Glioblastoma Multiforme (WHO Grade IV) Anaplastic Astrocytoma
(WHO Grade III)
OK, for the non-neuro-oncologists in the audience, this is the tumor I will focus on.
Primary not secondary
Incidence
Two main types
Devastating course
Malignant glioma is the most common primary brain tumor affecting adults with about 18,000 cases diagnosed in the US each year.
Among malignant glioma, glioblastoma multiforme, WHO grade 4 tumors, is by far and away the most common malignant glioma, with the grade 3 tumors, including anaplastic astrocytoma, the next most common type.
These tumors have a devastating impact on our patients. As one might expect from the gross pathology and MRI images depicted here, the aggressive infiltrating nature of these tumors produces progressive and profound physical and mental disability leading to death in nearly all cases.
18,000 cases primary CNS tumors/year
15,000 deaths/year
2nd leading cancer death in young adults
Overall 5th and 6th leading causes of cancer death in men and women respectively
Uniformly fatal tumors

5. Secondary Neoplasms of the Central Nervous System
100, ,000 cases in the United States every year
Median survival rates between 2.9 and 3.4 months
Most common primary tumors are:
Lung carcinoma (27%)
Melanoma (22%)
Breast Carcinoma (15%)
Location:
Cerebrum (80%)
Cerebellum (16%)
Brainstem (3%)

6. Brain Tumor Diagnosis Initial Presentation: Headache: most common
Mental Status Changes
“Acute tumor attack” 5-10% of the patients: seizures, stroke- like symptoms
Imaging: MRI is superior to the CT
More accurate detection of multiple lesions
Better diagnosis of smaller lesions (under 2 cm)
No bone artifacts
Surgery is required for diagnostic, followed by combined treatment modalities (radiation, chemotherapy).

7. Brain Tumors – Acute Presentation
General impairment of cerebral function, headaches, seizures
Increased intracranial pressure
Specific localizing syndromes

8. Neurologic Manifestations of Brain Tumors
Primary effects
Direct effects
Compression of adjacent structures
Secondary effects
Edema
Hydrocephalus
Increased intracranial pressure
Paraneoplastic syndromes

9. Neurologic Manifestations of Brain Tumors
Positive symptoms seizures, headaches
Negative symptoms sensory loss aphasia hemiparesis

10. Headache First symptom in 35% of the patients with brain tumors
Eventually present in 70% of the patients

11. Headache Characteristics in BT
Morning headaches or those that awaken patient from sleep
Headaches that increase in frequency or severity over weeks or months
Headaches that differ from patient’s usual chronic headaches
Headaches associated with papilledema or focal signs

12. Pain - distortion of intracranial pain sensitive structures
dura
venous sinuses
cerebral arteries
cranial nerves
It usually responds to neuropathic pain medication (such as Gabapentin), or to opioids- but the cause needs to be identified.

13. Headache Location Frontal – supratentorial
Nuchal and occipital - posterior fossa

14. Nausea and Vomiting Increased intracranial pressure or hydrocephalus
When projectile, involvement of chemoreceptor trigger zone in medulla
Always consider the possibilities of tumor growth (progression) vs. intracranial bleeding (bleeding in the tumor) vs chemotherapy side-effects
Always obtain a head CT without contrast in a patient with HA’s and a known brain tumor

15. Facial Pain secondary to Brain Tumors
Distribution of trigeminal nerve
Common for the tumors at base of skull or nasopharynx

16. Facial Pain with BT compression vs. Trigeminal Neuralgia
Longer lasting
Less likely to be lancinating
May have sensory loss (facial numbness)

17. Temporal or Auricular Pain
If cancer-related, is most commonly due to thoracic malignancies
referred pain from irritation of vagus nerve in the chest

18. Brain Tumors and Plateau waves
Abrupt elevation of the intracranial pressure by as much as 100 mm Hg (normal 20 mm Hg)
May be sustained for minutes or hours
Clinical manifestation include:
Headache
Nausea
Vomiting
Leg weakness
Symptoms of incipient herniation

19. Plateau Wave Triggers Infections Anesthetics REM sleep
common factor - cerebral vasodilatation by events that lower arterial blood pressure

20. Cushing Reflex - severe increased ICP
Rising blood pressure
Bradycardia
Immediately consider means to lower ICP medically and call neurosurgery stat

21. Seizures and Brain Tumors
First symptom in 30% of the patients with brain tumors (every new seizure patient needs to have a brain MRI with contrast)
Present at some time in 70% of the diagnosed patients (consider tumor progression, intracranial bleeding secondary to chemotherapy such as Avastin, medication interaction with chemotherapy and non-compliance)
5% of patients with first time- seizure are diagnosed with brain tumors
Age increase the risk of epilepsy being caused by a tumor, especially over 45 years of age

22. The causes of a first seizure in adults 15 years of age and older
Cause Number of patients (%)
Idiopathic 27 (27.6)
Cerebral infarction 23 (23.5)
Alcohol withdrawal (11.2)
CNS infection (9.2)
Tumor (8.2)
Vascular malformation (6.1)
Trauma (4.1)
Drug toxicity (3.1)
Subdural hematoma (2.0)
Hyperglycemia (2.0)
Uremia (1.0)
Hyponatremia (1.0)
Cerebral malformation (1.0)
Adapted from Brain Tumors: an Encyclopedic Approach. Eds. Kaye AH, Laws E. 2nd edition. 2003

23. The causes of a first seizure based upon age distribution
Cause Number of patients (%)
<45 yrs >45 yrs
Idiopathic (45) (15.5)
Cerebral infarction (2.5) (37.9)
Alcohol related (15.0) (8.6)
CNS infection (17.5) (3.4)
Tumor (2.5) (12.0)
Vascular malformation (7.5) (5.2)
Trauma (7.5) (1.7)
Drug toxicity (0) (5.2)
Subdural hematoma (0) (3.4)
Hyperglycemia (0) (3.4)
Uremia (0) (1.7)
Hyponatremia (2.5) (0)
Cerebral malformation (0) (1.7)
Adapted from Brain Tumors: an Encyclopedic Approach. Eds. Kaye AH, Laws E. 2nd edition. 2003

24. Type of Tumor and Seizures
Seizures are more common with relatively slow-growing tumors (low-grade glioma are twice more frequent associated with seizures then glioblastoma)
Gangliogliomas, dysembrioplastic neuroepithelial tumors and hamartomas commonly present with epilepsy
Tumors originating from the meninges and vascular structures may also cause seizures, at a rate less then gliomas

25. Seizure Type and Location
Temporal Lobe
Simple olfactory hallucinations
Feelings of fear (anxiety attacks)
Complex partial seizures
Occipital Lobe
Occasionally visual seizures

26. Symptomatic Anticonvulsivant Therapy
Prophylactic AED treatment is not recommended
Symptomatic treatment is often difficult, with low rate of seizure-free patients
The AED’s proposed mechanisms of action cover only a few of the mechanisms involved in BT related seizures.
The morphologic changes, altered receptor distribution, changes in the cytokines expression cannot be altered by the current AED

27. AED’s, Brain Tumors and Multidrug Resistance
AEDs levels are hard to maintain in patients with BT due to the interactions with current medication (chemotherapy) and patient compliance issues
The multidrug resistance protein, glycoprotein P (P-gp) in increased in the brain of pt with neoplasms, as well as with intractable epilepsy, and is associated with the exotransport (elimination) of AED and chemotherapy drugs
Consider AED drugs that are not eliminated through the liver (such as Keppra and Topamax).

28. Thromboembolisms: DVT and PE
Patients with brain tumors develop much more common then the general population thromboembolic complications such as deep venous thrombosis and pulmonary embolisms
Newly-developed chemotherapy (anti-angiogenesis agents-Avastin) increases the risk of thrombosis
Work-up of the brain tumor patients presenting to the ER with leg pain or SOA should always include an US of the lower extremities and a spiral chest CT
Before starting the heparin/lovenox- a head CT needs to be obtained to r/o bleeding.

29. Conclusions
Most acute BT patient presentations are potentially life-threatening
Good medical management and prompt call to neurosurgical services when in doubt can save lifes
As our patients prognosis improve, more long-term complications are seen