Aggressive supportive care in patients with suspected MESCC is extremely important. Cord compression may present as a pain crisis [10]. Emergency pain control management prior to imaging is necessary to prevent movement artifact and to complete the diagnostic examination. Strategies for managing a pain crisis can be found in Chapter 2 of this book. High-dose corticosteroids, with initial intravenous bolus of dexamethasone dose ranging from 10 to 100 mg, followed by divided q 6 h dosages ranging from 16 to 96 mg daily should also be given when MESCC is suspected [11] and may produce significant clinical improvement even before definitive treatment starts.

Respond. Once an MESCC is confirmed, the choice of the treatment depends on a number of factors including the patient’s performance status and overall fitness, the presence or absence of significant spinal fluid flow block and bony vertebral lesions, the degree of spine instability, the primary tumor, the extent of the disease and metastases, and the presence of other complications or medical comorbidities [12]. If the MRI shows epidural disease without significant spinal block, urgent radiation therapy is the treatment of choice, as this provides highly effective palliation for bone pain and will prevent progression in most cases [13]. Highly radiosensitive tumors include lymphoma, myeloma, Ewing sarcoma, seminoma, and neuroblastoma; breast and prostate are less radiosensitive; kidney, colon, lung, and melanoma are relatively radioresistant. There is no general optimal dose and fractionation regimen for MESCC; often 30 Gy in 10 fractions is chosen. Results should start to be seen within a few days of starting radiotherapy. The high-dose corticosteroid therapy should be continued during treatment.

If the MRI shows significant spinal block with cord compression and spinal instability, and the patient is a surgical candidate, lesion-directed surgery and spine stabilization should be considered. Spinal instability is a potential cause of spinal cord damage in addition to the epidural mass and is not affected by radiation therapy. If the patient has a spinal block but is not a surgical candidate, emergency radiation therapy or spinal stereotactic radiosurgery is an option. Chemotherapy is a reasonable treatment option for MESCC when the underlying tumor is chemosensitive. It has been used for both Hodgkin’s and non-Hodgkin’s lymphoma, breast cancer, germ cell tumors, and neuroblastoma. Hormonal manipulation has also been used in hormone-naïve patient with MESCC from breast and prostate cancer following radiotherapy.

If comfort care is the goal and the patient is unable to undergo emergency radiation treatment or surgery, then corticosteroids and opioids via IV-PCA will be most effective for pain control. In patients with limited life expectancy, regional anesthesia with a continuous epidural spinal catheter or intrathecal pump may be an option.

Recover. If surgery is performed for metastatic MESCC, it is followed by radiation therapy. Several weeks of rehabilitation will also be required following treatment. The outcome depends mainly on two things—the type of cancer and how well it responds to treatment. Treatment of MESCC usually relieves pain, leg weakness, and loss of bladder or bowel control. Radiotherapy controls spinal pain in over 70% of cases [13]. When patients with only minor problems in walking start treatment, they are likely to recover their walking completely. In patients who were unable to walk at the time of surgery or initiating XRT, only 10–20% are likely to regain full mobility [14].

13.2.2 Elevated Intracranial Pressure

Elevated intracranial pressure (EICP) is another potentially devastating neurological complication of cancer, and can occur with both primary brain tumor and cerebral metastases. Intracranial pressure is normally ≤15 mm Hg in adults, and pathologic intracranial hypertension is present at pressures ≥20 mm Hg. Like MESCC, EICP may also present emergently, although this is a much rarer problem than MESCC even in a cancer center. Successful management of patients with EICP requires prompt recognition, therapy directed at both reducing EICP and reversing its underlying cause, and the judicious use of invasive monitoring.

Prepare. Brain metastases are more common cause of EICP than primary brain tumors. The incidence of brain metastases varies by primary tumor site: lung 50%, breast 15–20%, melanoma 10%, and less common with kidney, colorectal, lymphoma, and unknown primary. EICP is caused by vasogenic peritumoral edema and bleeding within necrotic tumor. The symptoms of EICP include headaches, cognitive dysfunction, focal weakness, and seizures, caused by cerebral edema disrupting synaptic transmission and altering neuronal excitability. Unchecked, EICP may result in brain herniation.

Plan. Clinical findings that suggest the need for urgent intervention include worsening headache, vomiting, altered mental status, increasing lethargy and the onset of stupor, unstable vital signs, focal signs such as fixed and dilated pupil(s), or decorticate or decerebrate posturing. Cushing’s triad of bradycardia, respiratory depression, and hypertension is an ominous finding, indicative of brainstem compression occurring. As with MESCC, the choice of the treatment of malignant EICP depends on a number of factors including: the patient’s performance status and overall fitness, the primary tumor, the extent of the disease and metastases, and the presence of other complications or medical comorbidities. If urgent aggressive intervention is indicated, optimal care requires collaboration between the hospitalist, intensivist, and the neurosurgeon. Brain metastases generally have a poor prognosis so treatment may not be warranted. In patients where the GOC is to allow a natural death, comfort care is the goal and it is reassuring that death from EICP is usually peaceful.

Mitigate. The best therapy for EICP is resection of the tumor. While a decision is being made to pursue this, reduction of intracranial pressure should be begun, and reduction of intracranial pressure and improvement in neurologic symptoms usually begins within hours of commencing glucocorticoids [15]. In patients with severe symptoms, the usual dexamethasone regimen consists of a 10 mg loading dose, followed by 4 mg 4 times/day or 8 mg twice daily. There is some evidence that lower doses (1–2 mg 4 times/day) may be as effective and less toxic in patients without impending herniation. Dexamethasone should be stopped in 72–96 h if there is no response. The role of steroids in patients with EICP for comfort care is more controversial. Steroids may have a role if the patient is very symptomatic, but run the risk of unnecessarily prolonging suffering. Opioids may be prescribed if there are bothersome headaches.

Respond. The emergent response to EICP when aggressive treatment is indicated includes resuscitation and reduction of the volume of the intracranial contents. Establishing a secure airway and close attention to blood pressure allow the clinician to identify and treat apnea and hypotension quickly. Standard resuscitation techniques should be instituted as soon as possible, including head elevation, and hyperventilation. In addition to steroids, critically ill patients with unstable vital signs should be given osmotic diuretics such as mannitol (1–1.5 g/kg IV). If appropriate, ventriculostomy is a rapid means of simultaneously diagnosing and treating elevated ICP.

Recover. Patients undergoing aggressive management with neurosurgery ± stereotactic radiosurgery may then go on to have whole brain XRT and/or chemotherapy. Inpatient rehabilitation may then be required for patients with a neurologic deficit. Where a more conservative approach to management has been chosen, keeping the patient sedated decreases ICP by reducing metabolic demand. Fever should be aggressively treated with Tylenol and mechanical cooling, as fever increases brain metabolism thereby increasing and aggravating EICP by increasing the volume of blood in the cranial vault. Seizures can both complicate and contribute to elevated ICP. Anticonvulsant therapy should be instituted if seizures are suspected; there are no randomized trials that have established the superiority of one agent over others. Prophylactic anticonvulsant treatment is generally not recommended for patients with a primary or metastatic brain tumor and without a history of antecedent seizure [16], but may be warranted in some cases which include high-risk mass lesions, such as those within supratentorial cortical locations or lesions adjacent to the cortex.

13.2.3 Status Epilepticus

Status epilepticus (SE), defined as continuous generalized tonic-clonic seizures lasting beyond 5 min without full recovery between seizures, is a life-threatening event and a neurologic emergency. Untreated, it causes multiple metabolic derangements which can produce permanent brain damage if prompt and vigorous treatment is not provided. Other medical complications of SE include aspiration, hypotension, cardiac arrhythmias, rhabdomyolysis, renal failure, hepatic failure, and intracranial hypertension. Immediate treatment with appropriate doses of medications is also critical since uncontrolled SE can become refractory and very difficult to control.

Prepare. Any type of seizure can evolve into SE. In adult palliative care patients, the main causes of SE are brain tumors (primary or metastatic), metabolic derangements (hypoglycemia and electrolyte imbalance), as well as hypoxia, low antiepileptic drug levels, acute cerebrovascular accidents, meningitis, encephalitis, and cerebral abscess. Other causes include global hypoxic–ischemic insult, drug and alcohol abuse or withdrawal, and head trauma. Stroke accounts for almost 50% of acute symptomatic causes of SE in adults and elderly. Primary or metastatic CNS tumors are commonly associated with epilepsy, and seizure is the first presenting symptom in 30–90% of cases. Generalized seizures may occur with a large mass producing increased intracranial pressure.

Plan. In settings where SE is common, such as in the Emergency Room or on the Neurology floor of a cancer center, there should be an algorithm for managing SE that staff members are trained in. If SE is diagnosed or suspected, an emergent neurology consult should be called and an interdisciplinary team including anesthesiology or ICU should be involved, to prepare for intubation and transfer to a neuromonitoring unit.

Mitigate. The diagnosis of generalized tonic-clonic SE is not difficult, and should be easy to differentiate from other conditions. Nonconvulsive (absence) SE may be harder to diagnose and is characterized by stupor, a confused state of altered consciousness and little or no motor activity. It is important to differentiate nonconvulsive SE from pseudostatus or drug-induced coma. Pseudostatus and drug-induced coma lack the typical pattern of EEG activity and evolution seen with SE. A controversial issue is whether all patients with brain metastases should be given anticonvulsants. Patients who present with seizures require anticonvulsants; however, prophylactic anticonvulsants did not protect against subsequent seizures. Furthermore, antiepileptics stimulate the cytochrome P450 enzyme, enhancing the metabolism of some chemotherapy agents, rendering them less effective. Anticonvulsants also enhance metabolism of corticosteroids, thus reducing control of cerebral edema. They also frequently cause drug interactions associated with life-threatening side effects such as Stevens–Johnson syndrome. Therefore, prophylactic anticonvulsants are not recommended for patients with underlying brain metastases or other structural brain lesions. Patients with brain metastases from melanoma may be an exception to the general recommendation against prophylactic anticonvulsants, given their higher prevalence of seizures.

Respond. Treatment should be begun immediately when diagnosing SE. Maintain airway, breathing, and circulation, obtain finger stick to assess for hypoglycemia, and give benzodiazepines. Maintain Airway patency by positioning patient’s head (backward head tilt with chin lifted up), Breathing by giving supplemental oxygen by nasal cannula or mask and Circulation by fluid support. Minimize injury by moving the patient to a safe environment to prevent falls or head injury. Obtain IV access and draw blood samples for serum chemistry, glucose level, hematology studies, toxicology screen and antiepileptic drug levels. Begin continuous vital signs and ECG monitoring. The Memorial Sloan Kettering Cancer (MSKCC) algorithm for managing SE is shown in Box 13.2.