Neurocritical Care

12. Deterioration from Brain Metastasis

A 64-year-old man with history of smoking was admitted after having recurrent episodes of loss of consciousness over the last 2 days. For the previous 3–4 weeks he had been having more problems with concentration and worsening gait balance. He also noticed that he was not seeing well on the right side and had difficulties with left hand movements. Upon evaluation in our emergency department he was fully awake but his answers were slow. He had a right visual field deficit and left-sided ataxia. A CT scan showed masses in the left cerebellar hemisphere and the left parietooccipital region surrounded by fairly extensive edema. He was started on dexamethasone. Anticipating decline despite administration of corticosteroids and the possibility of an urgent neurosurgical debulking, he was admitted to our NICU for close observation. Twelve hours after arrival his condition declined. On examination he is difficult to awaken and has developed left facial and abducens nerve palsies.

What do you do now?

Malignancies may present anywhere in the brain and cause rapid decline even before the pathology is known. Patients with a primary malignant brain tumor may worsen quickly from growth of the tumor size, but the most common causes for decline are increasing edema and new hemorrhage (Table 12.1). The more aggressive the tumor, the higher is the likelihood of these two complications. Highly malignant tumors secrete angiogenic factors, which promote the rapid formation of intratumoral vessels. The lack of efficient tight junctions in these vessels produces a disruption of the blood brain barrier, which results in the formation of vasogenic edema. These vessels are also immature and thus fragile and prone to rupture.

Patients with malignant brain tumors may also deteriorate as a result of exacerbating factors that disturb ongoing compensatory mechanisms. For instance, seizures can produce hypoventilation and hypercapnia from a reduced respiratory drive, which in turn can lead to increased cerebral blood volume and worsening tissue shift in patients with exhausted intracranial compliance. Incremental administration of opiates for excruciating headaches can have similar consequences. Severe hyponatremia, sometimes related to inadequate secretion of antidiuretic hormone, as a paraneoplastic disorder or due to hydrocephalus, can worsen cerebral edema. Radiation therapy, although useful for the reduction of mass effect in the longer term, is characteristically associated with worsening inflammatory edema in the early phase.

So what options do we have for our patient? Corticosteroids are very useful for the treatment of peritumoral vasogenic edema and often high doses are necessary. We adjust the dose depending on the severity of the edema. In patients with preserved alertness and no substantial brain tissue shift the usual dose of 10 mg of dexamethasone may suffice. However, we administer intravenous bolus doses of 20–100 mg in severe and extreme cases. Maintenance doses then range from 4 to 10 mg every 4 to 6 hours. When using high-dose steroids it is essential to minimize the risks and to initiate preventive measures (Table 12.2). Even if administered early, intravenous dexamethasone may take hours to reach its maximum effect and patients may deteriorate before that time. Other anti-edema medical treatments (mannitol or hypertonic saline) only have a role in emergency situations and often are used as a bridge towards surgery.

TABLE 12.1 Causes of Neurological Deterioration in Patients with Malignant Brain Tumors

Worsening of vasogenic peritumoral edema*

Intratumoral hemorrhage*

Seizures with prolonged recovery of aphasia or hemiparesis

Obstructive hydrocephalus

Venous infarction from extension of the tumor to the dural sinus

Arterial infarction from vessel invasion or compression by the tumor

*By far the two most common

Surgical treatment is the most effective. If complete resection is not possible, debulking should be considered. Patients who present with rapid clinical worsening and signs of brainstem displacement, those with large intratumoral hemorrhages, and those failing increasing doses of glucocorticosteroids necessitate urgent surgery. Often the decision to operate will have to be made without knowing the primary pathology and thus the prognosis. Biopsies should be generally discouraged in patients with large masses and no space to expand. Even minor postoperative bleeding—a relatively frequent occurrence- can put patients at considerable further risk if the mass effect is not reduced during surgery. As illustrated by our case, cerebellar masses require surgery more often than supratentorial ones. Occasionally, the acute neurological decline may be due to superimposed obstructive hydrocephalus, and in these cases ventricular drainage can be a minimally invasive temporary solution.

TABLE 12.2 Short-Term Side Effects and Preventive Measures Related to High-Dose Glucocorticosteroids

Side effect

Preventive measure

Hyperglycemia

Frequent glucose monitoringInsulin scale or continuous infusion

Increased susceptibility to infections (especially by Pneumocystis jiroveci)

Double-strength trimetroprim sulfamethoxazole 3 times per week

Psychosis

Antidopaminergics

Mood swings

Mood stabilizers (e.g., valproic acid)

Peptic ulcers*

H2 blockers or proton pump inhibitors

High blood pressure

Monitoring and treatment as necessary

Myopathy

Minimize immobilization

Hypokalemia

Potassium monitoring and replacement

*Risk may only be increased with high doses, when there is severe stress, and after recent use of nonsteroidal anti-inflammatory agents.

Whether patients with known malignant primary brain tumors need urgent or emergent surgery is a complex decision. The previous functional status of the patient, his or her previously stated wishes, the possibility of effective future tumor treatment, and, most important, the potential for recovery of quality of life after surgery have to be carefully considered. The major ethical question in some patients reaching this stage is whether a neurosurgical procedure is justified in a situation that may be hopeless and in which surgery may afford only minimal gain in survival with poor quality of life. Some families are unable to decide, others may have a better perspective and may turn to palliative care.

Our patient had been given 20 mg of dexamethasone and 2,000 mg of levetiracetam (for suspected previous seizures) in the emergency department. When he worsened in the ICU we gave 20 mg more of dexamethasone along with 1 g/kg of 20% mannitol. A repeat CT scan—showed that he had developed obstructive hydrocephalus from aqueductal compression. He underwent urgent surgery for excision of the cerebellar mass (Figure 12.1.) His hydrocephalus resolved and his neurological condition improved. He continued receiving dexamethasone 6 mg every 6 hours with subsequent taper. His CT scan of the chest showed a nodular mass. Lung biopsy and brain pathology showed non–small cell carcinoma. He underwent further treatment and had a good functional status 6 months later.

All patients with a neurosurgical procedure for metastasis from a highly malignant tumor or recurrent brain malignancy will succumb in a short time period. Yet, after aggressive treatment of the brain mass, the quality of life during most of that time can be quite acceptable in some patients.

graphic001001.eps

FIGURE 12.1 A) Head CT scan showing a left cerebellar mass with associated edema producing effacement of the 4th ventricle. B) At a higher level, a second mass is seen in the left parietooccipital area. Note the dilatation of the third ventricle. C) After surgical excision of the cerebellar mass, the CT scan shows persistent edema with mass effect but less prominent than before and reappearance of a visible 4th ventricle.

KEY POINTS TO REMEMBER REGARDING DETERIORATION FROM BRAIN METASTASIS

· Acute neurological decline from brain metastasis or malignant brain tumor is most frequently due to worsening vasogenic edema or hemorrhage.

· Precipitating causes (such as seizures, hypoventilation, and hyponatremia) need to be recognized and treated without delay.

· Glucocorticosteroids are the best medical treatment for vasogenic edema.

· Surgical treatment (tumor removal or debulking) becomes urgent or emergent in rapidly deteriorating patients, presence of a large hemorrhage, and patients refractory to medical treatments. When offering surgery as a life-saving intervention, the future prognosis and wishes of the patient need to be discussed in detail.

Further Reading

Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Paleologos NA, Patchell RA, Ryken TC, Kalkanis SN. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010; 96:45–68.

Qureshi AI, Geocadin RG, Suarez JI et al. Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions. Crit Care Med 2000; 28:1556–1564.

Ranjan T, Abrey LE. Current management of metastatic brain disease. Neurotherapeutics. 2009;6:598–603.

Ryken TC, McDermott M, Robinson PD et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010; 96:103–114.

Silbergeld DL, Rostomily RC, Alvord EC Jr. The cause of death in patients with glioblastoma is multifactorial: clinical factors and autopsy findings in 117 cases of supratentorial glioblastoma in adults. J Neurooncol 1991; 10:179–185.

Stiver SI. Angiogenesis and its role in the behavior of astrocytic brain tumors. Front Biosci 2004; 9:3105–3123.

Wen PY, Schiff D, Kesari S, Drappatz J, Gigas DC, Doherty L. Medical management of patients with brain tumors. J Neurooncol 2006; 80:313–332.