Headache, Lethargy, and a History of Breast Cancer: Case Presentation

A 52-year-old woman presents complaining of 5 days of headaches and lethargy. Immediately, you notice her pupils (shown). The patient appears sleepy and is a poor historian, but a family member states that the patient developed a throbbing headache 5 days before presentation and has become increasingly lethargic. The patient also complains of nausea without vomiting or abdominal pain, difficulty walking, blurry vision, and confusion.

Which of the following conditions are associated with anisocoria?

A. Third nerve palsy
B. Horner syndrome
C. Uncal herniation
D. Normal variant for some patients
E. All of the above
F. None of the above

Image courtesy of Wikipedia Commons

Answer: E. All of the above

The patient had stage III right-sided inflammatory breast cancer and a subsequent modified radical mastectomy 1 year ago, with doxorubicin and cyclosporine chemotherapy. She is currently taking tamoxifen and has no known allergies. Blood pressure is 114/80 mmHg, pulse is 80 bpm, respiratory rate is 14, and temperature is 99°F. The patient was initially able to follow simple commands but soon deteriorated. She only opens her eyes to painful stimuli and makes incomprehensible noises. She moves all four extremities to painful stimuli only and has a Glasgow Coma Scale score of 8. The above laboratory examinations were performed emergently.

The patient's funduscopic examination is shown above. No facial asymmetry is noted, and the patient has normal deep tendon reflexes. Examination of the chest is significant for a right mastectomy scar; no palpable lymphadenopathy or masses are present. The heart is regular, without murmurs, and auscultation of the lungs is unremarkable. The abdomen is soft and without masses.

What is the finding highlighted by the blue arrows in the above image?

A. Flame hemorrhages
B. Cherry red fovea
C. Blurred optic disc edges
D. Normal funduscopic examination

Answer: C. Blurred optic disc edges

An emergent computed tomography (CT) scan of the head is performed. Subsequent to this, the patient receives an emergent procedure followed by a repeat CT (shown).

What was the diagnosis and the procedure performed?

A. Subarachnoid hemorrhage, hemicraniectomy
B. Subarachnoid hemorrhage, right frontal ventriculostomy
C. Metastasis with edema, hemicraniectomy
D. Obstructive hydrocephalus, right frontal ventriculostomy
E. Metastasis with edema, right frontal ventriculostomy

Answer: D. Obstructive hydrocephalus, right frontal ventriculostomy

The CT and magnetic resonance imaging (MRI) scans show enlargement of the third and lateral ventricle; the red arrow indicates the dilated ventricles. Hydrocephalus can be defined broadly as a disturbance of the formation, flow, or absorption of cerebrospinal fluid (CSF) that leads to an increase in the volume occupied by this fluid in the central nervous system (CNS).

This MRI indicates the cause of the obstructive hydrocephalus to be multiple metastases, as shown in the posterior fossa. Normally, CSF is produced in the choroid plexus, and flows through the CNS by the following route: choroid plexus to the lateral ventricle, through the interventricular foramen of Monro into the third ventricle, through the cerebral aqueduct of Sylvius into the fourth ventricle, through the 2 lateral foramina of Luschka and the single medial foramen of Magendie, and finally into the subarachnoid space. In the subarachnoid space, the CSF is absorbed by the arachnoid granulations into the dural sinus and drains into the venous system.

Hydrocephalus is categorized as obstructive (shown) or nonobstructive (communicating) hydrocephalus.^[1] Obstructive hydrocephalus occurs when there is ventricular enlargement under tension as a result of an obstruction of the flow of CSF anywhere in the pathway. Hydrocephalus can be further classified as acute (occurring over days), subacute (occurring over weeks), and chronic (typically present for months to years).

The most common causes of hydrocephalus are shown. Although the primary site for breast metastasis is bone, the next most common sites for metastasis are the leptomeninges and the brain parenchyma. Congenital malformations are the most common cause of obstructive hydrocephalus in children. Other congenital abnormalities, such as congenital aqueduct stenosis, can remain asymptomatic until adulthood.^[1]

Symptoms of obstructive hydrocephalus are shown. Presentations vary according to patient age and the obstruction's etiology. Adults frequently complain of headaches that are worse in the morning and that are relieved by sitting up; however, they become continuous as the condition progresses. Adult patients may have failure of upward gaze (Parinaud sign or dorsal midbrain syndrome; shown), papilledema, truncal and limb ataxia, and/or a unilateral or bilateral sixth nerve palsy. Accumulation of CSF can cause elevated intracranial pressure, resulting in tonsillar herniation, compression of the brain stem, and subsequent respiratory arrest. If hydrocephalus is left untreated, death may occur.

Although a lumbar puncture is useful in diagnosing and treating nonobstructive hydrocephalus (shown), the procedure is contraindicated in obstructive hydrocephalus. The sudden loss of CSF in the spinal column could potentially create a negative pressure gradient and exacerbate tonsillar herniation.

Obstructive hydrocephalus generally requires surgical treatment, although medical therapy (shown) may be used as a temporizing measure until surgery is performed. Medications can be used in cases that are expected to resolve, such as with meningitis. A medical course of therapy aims to either reduce CSF production, increase CSF absorption, or decrease cerebral edema. Patients with rapidly declining mental status can also be intubated and hyperventilated to elicit a transient drop in intracranial pressure, although this is thought to be short lived. If patients present with seizures, anticonvulsant medications should be given. The role of prophylactic anticonvulsants is controversial.^[2]

This MRI sagittal image demonstrates dilatation of lateral ventricles (red arrow) and dilatation of the fourth ventricle (blue arrow). Implantation of a surgical shunt is the preferred mode of treatment, usually ventriculoperitoneal (VP). Complications include infection of the valve and catheter (which can cause ventriculitis and bacteremia), inguinal hernias, perforation of abdominal organs, intestinal obstruction, volvulus, and CSF ascites. Another surgical option aims to reduce CSF production by choroid plexectomy, choroid plexus thrombosis, or third ventriculostomy, in which a hole is made in the third ventricle floor, creating a detour and allowing the CSF to circulate and be absorbed.

In this case, neurosurgeons were consulted and the patient received an emergent ventriculostomy. Upon admission, the patient was also found to have a urinary tract infection, which was treated with ciprofloxacin. Following treatment of the urinary tract infection, she received whole brain radiation in an attempt to decrease the size of the metastases (surgical resection was not possible given their location). The patient improved considerably after VP shunt placement (shown) and she was discharged. Unfortunately, the patient was lost to follow-up and the further management of her metastatic disease and ultimate outcome is unknown.