Case 6.

[Alon]

You are beginning the night shift in the pediatric emergency department of a tertiary care hospital when you notice a tall, Caucasian adolescent girl being led by the hand, by her parents, into an examining room. She does not appear to be in any acute distress, but her cautious gait reminds you of a person walking in the dark. You pick up her chart and read that this 15-year-old has been referred for evaluation of visual changes.

The girl is calm and pleasant as you interview her. She tells you that she has had no problems with her health until two weeks ago, when she began experiencing headache that she describes as constant, diffuse, and with a pressure-like quality. Acetaminophen provided some relief at first, but the intensity of pain has become worse and the headache is now refractory to analgesics. She reports mild lower neck soreness but denies fever, chills, neck stiffness, aura, photophobia, phonophobia, or altered mental status.

Three days after the onset of headache, the girl began nonbilious, non-bloody emesis at least three times a day. She saw her primary care physician, who suspected gastroenteritis and prescribed an oral anti-emetic. She continued to vomit, however, including every time she tried to take the medication. Four days later, she returned to the physician's office and was told that she might have a urinary tract infection. She received an intramuscular injection of ceftriaxone and was given a follow-up appointment in one week.

Her symptoms became worse, however. Five days before she was brought to your ED, she noticed increasingly blurred vision. Her concerned parents took her to the emergency room of another hospital, where she was treated for vomiting and dehydration. She received IV hydration and an anti-emetic rectal suppository; the nausea and vomiting appeared to improve slightly. To her parents' dismay, she was discharged without an explanation for the blurred vision.

The girl's vision continued to deteriorate. At the follow-up office appointment, the physician was shocked to learn that, in one week, she had lost nearly all vision. She no longer distinguished colors and shapes, and perceived only shadows and motion. She had lost 12 pounds in two weeks because of persistent vomiting. She was immediately referred to your ED for evaluation.

On questioning, you learn that your patient has an unremarkable medical history. She has no known allergies. She has not been able to tolerate oral medications. She denies using vitamins, dietary supplements, or acne medications. The family history includes obesity, diabetes mellitus, and hypertension. She lives in a stable home with her mother, father, and three siblings.

The girl reports owning two cats and two hamsters that are kept in the house. There are horses, chickens, goats, and ducks on the family's property, but she denies close contact with those animals. She also denies recent travel, changes to her diet, any history of trauma, and use of tobacco, alcohol, or illicit drugs. She reports never having been sexually active; her last menstrual period was one month ago. She receives emotional support at home and declares that her mood is good.

On physical examination, you note marked obesity: The girl weighs nearly 150 kg and has a body mass index of 46 kg/m2. She is afebrile. Vital signs are normal: heart rate, 68/min; respiratory rate, 16/min; and blood pressure, 118/72 mm Hg. She is pleasant but appears tired; she speaks with a remarkably calm demeanor. As you examine the patient, you note that the left eye does not close fully and that the left side of the face droops.

The pupillary exam reveals symmetric, moderately dilated (4 to 5 mm), sluggishly reactive pupils with an intact consensual light reflex bilaterally. She has limited abduction of the right eye. Fundoscopic examination reveals florid papilledema; venous pulsation is absent.

Continuing with the neurologic examination, you cannot elicit deep tendon reflexes. Gait appears stable but cautious because of her inability to see. The rest of her physical examination is normal, including a lack of meningeal signs.

Your examination has detected several neurologic deficits:

* bilateral optic nerve (cranial nerve II) compromise with papilledema
* right abducens nerve (cranial nerve VI) palsy
* left facial nerve (cranial nerve VII) palsy

These findings, with a history of headache and vomiting, point to the presence of increased intracranial pressure (ICP).

As you begin the diagnostic workup, you consider the common causes of increased ICP (see the table). Most ominous is an intracranial mass lesion, such as tumor, abscess, or hemorrhage, causing a mass effect. An infectious cause, such as meningitis and encephalitis, increases cerebral blood flow and commonly elevates ICP. Also to be considered are hydrocephalus and pseudotumor cerebri. In a setting of trauma, drowning, cardiopulmonary arrest, or status epilepticus, hypoxic-ischemic encephalopathy can cause diffuse neuronal swelling. Cerebral edema can also be caused by rapid correction of diabetic ketoacidosis.

With that differential in mind, you begin the laboratory evaluation. You order blood and urine specimens to be collected, and then immediately send the patient to the radiology suite for a computed tomographic (CT) scan of the head, with and without contrast. A preliminary report reads "Normal." You review the images yourself, and agree: There is no evidence of intracranial mass, hydrocephalus, or any other abnormality.

By now, lab test results have come back. A CBC shows a white blood cell count of 14.6 x 103/μL, with a differential count of 70% neutrophils, 24% lymphocytes, and 5% monocytes; hemoglobin, 14.5 g/dL; and platelets, 316 x 103/μL. The erythrocyte sedimentation rate is 32 mm/hr. Electrolyte, blood urea nitrogen, creatinine, and glucose levels are all within normal limits. Urinalysis is normal. A urine pregnancy test is negative.

With clinical evidence of increased ICP and a normal CT scan, you now feel more confident with a provisional diagnosis of pseudotumor cerebri. As a young, obese woman, she meets the typical description of a person at risk of idiopathic intracranial hypertension. To finalize that diagnosis, you still need to order a lumbar puncture to measure opening pressure and a magnetic resonance imaging (MRI) scan of the brain to rule out other causes of ICP. Because of her large body habitus, you decide that lumbar puncture is best performed under fluoroscopic guidance. You admit her to the inpatient pediatric service and request the appropriate neurology, infectious disease, and ophthalmology consultations.

No rest for the weary Over the next few days on the pediatric floor, the young woman is kept busy with a series of diagnostic tests and therapeutic interventions to restore her eyesight. On her first hospital day, she undergoes MRI of the brain, with and without contrast, and lumbar puncture under fluoroscopy. As expected, the MRI scan is normal.

The lumbar puncture yields a surprising result, however: Opening pressure is 19 cm of water—high normal, and not as high as expected, given the clinical presentation. Other cerebrospinal fluid (CSF) chemistry test results are unremarkable: glucose, 58 mg/dL; protein, 37 mg/dL; RBC count, 4/mm3; and WBC count, 2/mm3 with a differential count of 96% lymphocytoid and 4% histiocytoid cells. These results add a wrinkle to the evaluation because opening pressure is insufficiently elevated to diagnose pseudotumor cerebri with certainty.

The neurology attending has now had a chance to review the history, examine the patient, and evaluate the workup. He refines and broadens the differential diagnosis in light of an apparently normal ICP. Intracranial mass lesion, hydrocephalus, and other structural abnormalities are ruled out with negative CT and MRI scanning of the head.

Other neurologic conditions to consider include demyelinating disease, such as acute disseminated encephalomyelitis, multiple sclerosis, and Fisher syndrome. Acute disseminated encephalomyelitis is an acute demyelinating condition that typically follows an acute viral illness, such as Epstein-Barr virus infection. It may present with headache and acute loss of vision, but would appear as areas of cortical demyelination on MRI. Likewise, hallmarks of multiple sclerosis are multiple neurologic deficits and MRI findings in different locations at different times of presentation. These central demyelinating disorders are unlikely, given that the CSF protein level is not elevated and the CSF IgG synthesis rate, myelin basic protein, and electrophoresis are normal.

Fisher syndrome, also known as a variant of Guillain-Barré syndrome, is characterized by ophthalmoplegia, ataxia, and areflexia. Blindness is not typically expected in this condition, but the results of the clinical examination, which documented palsy of the right abducens nerve, cautious gait, and absent deep-tendon reflexes, warrant further investigation. To this end, an electromyogram is performed; the test does not show evidence of a generalized demyelinating neuropathy. Furthermore, a serum anti-GQ1b antibody test, highly sensitive for Fisher syndrome, is negative.

Screening for rheumatologic disorders, such as systemic lupus erythematosus and sarcoidosis, is performed: Complement and angiotensin-converting enzyme levels are normal, and an antinuclear antibody test is negative. Endocrinopathies are also considered: Electrolyte values, thyroid function, and the hemoglobin A1c level are all normal.

Last, infectious causes remain part of the differential diagnosis but are much less likely in the absence of a history of fever and CSF abnormalities. Serum antibody titers for Bartonella henselae, Epstein-Barr virus, and West Nile virus are all negative. The serum IgM level for Mycoplasma pneumoniae is elevated but a CSF polymerase chain reaction assay is negative. Other CSF studies—for syphilis, West Nile virus and other arboviruses, mycobacteria, and fungi—are all negative.

With such an extensive (and expensive) diagnostic workup turning out negative, what could the diagnosis possibly be? Despite the normal opening pressure on lumbar puncture, the clinical examination still supports intracranial hypertension. In fact, the patient reports that her headache and neck pain have diminished since the lumbar puncture—a finding that is common in pseudotumor cerebri.

By this time, the ophthalmologist has evaluated the young woman's vision and is impressed by the severity of the papilledema. He, too, believes that the patient appears to have pseudotumor cerebri, but he also questions whether this could be an inflammatory process of the optic nerve. MRI of the orbits, with and without contrast, is ordered to elucidate this possibility; meantime, acetazolamide and high-dose dexamethasone are begun. (Acetazolamide, a carbonic anhydrase inhibitor, reduces intracranial pressure by decreasing production of CSF; a corticosteroid is adjunctive therapy for severe cases of papilledema when vision is threatened.

Everything in the workup seems to support a diagnosis of pseudotumor cerebri. Even the MRI scan of the orbits reveals enlargement of the subarachnoid space surrounding the optic nerves, indicative of increased ICP. The optic chiasm and optic tracts are unremarkable. The cavernous sinuses show no evidence of thrombosis, and there are no abnormal enhancing lesions anywhere on the scan. With all the evidence pointing to increased ICP, could the error be in the measurement of opening pressure?

The neurology attending contacts the radiologist who performed the initial lumbar puncture. He learns that, because of the patient's size, the procedure was technically difficult, and was performed with the patient turned prone; opening pressure was measured by recording the height of the CSF in the reservoir. But the radiologist failed to account for the length of the needle when recording the opening pressure! Repeat fluoroscopic-guided lumbar puncture is performed, and the opening pressure is 54 cm of water. The other CSF chemistry values remain similar to those of the first lumbar puncture.

To your great relief, the diagnosis of pseudotumor cerebri is now substantiated with the documentation of increased ICP. The ophthalmologist proceeds with bilateral optic nerve sheath fenestration to relieve pressure on the optic nerve and to reduce optic nerve edema—a procedure that stabilizes or improves visual function in most patients with pseudotumor cerebri and visual loss, although the long-term failure rate may be as high as 35%.

The patient tolerates surgery well. At discharge, she reports having recovered the ability to perceive colors and shapes. Seven months later, she continues to do well, although her vision has not returned to baseline (and may never). She reports decreased peripheral vision and myopia but, with corrective lenses, can function well and has returned to all of her usual daily activities. She has not required additional surgery and her headache has fully resolved.

Pseudotumor cerebri is sometimes referred to as benign intracranial hypertension. This name derives from the observation that fatal herniation does not occur when a lumbar puncture is performed in the face of high ICP. As this case illustrates, however, pseudotumor cerebri is not at all "benign": It causes significant morbidity from chronic headache and poses a real threat of visual loss. Some children require repeated lumbar puncture, and a few undergo placement of a lumboperitoneal shunt to relieve increased pressure for symptomatic relief.

Don't rest until you've shed light on the diagnosis! With early recognition and treatment, the long-term prognosis is good for a patient with pseudotumor cerebri. Maintain a high level of clinical suspicion when managing chronic headache, always perform a fundoscopic exam, and be persistent at every turn!

[Alon]

Initial differential for an elevated ICP

Intracranial tumor

* Sinus thrombosis
* Hemorrhage

Infection

* Meningitis
* Encephalitis
* Abscess

Hydrocephalus

Pseudotumor cerebri

Encephalopathy (hypoxic-ischemic)

* Cardiopulmonary arrest
* Drowning
* Trauma

Rapid correction of diabetic ketoacidosis

[Bella]

Случай очень поучительный. Спасибо.