Several systemic diseases that are associated with raised CSF protein concentration have given rise to a pseudotumor syndrome, including the Guillain-Barré syndrome, systemic lupus, and spinal tumors, particularly oligodendroglioma. Elevated spinal fluid pressure has been attributed to a blockage of CSF absorption by the proteinaceous fluid in Guillain-Barré syndrome, but this mechanism has never been validated and fails to explain those few instances in which pseudotumor syndromes has been associated with a near-normal protein content of the CSF. This explanation is even less compelling if one recalls that the protein concentration of the fluid in the cerebral spaces is considerably lower than in the spinal ones. Also, as we have pointed out, when calculated correctly, neither the resistance to CSF absorption nor the colloid osmotic effect attributable to an increased protein content in the spinal fluid is adequate to explain the pressure elevation (Ropper and Marmarou). The mechanism of this type of pseudotumor syndrome is presently unknown.
In addition to mechanical factors, a number of toxic and metabolic disturbances may give rise to a pseudotumor syndrome. In children, as chronic corticosteroid therapy is withdrawn, there may be a period of headache, papilledema, and elevated ICP with little or no enlargement of the lateral ventricles. Lead toxicity in children may be marked by brain swelling and papilledema. Excessive doses of tetracycline (particularly outdated medication) and vitamin A (particularly in the form of isotretinoin, an oral vitamin A derivative used in the treatment of severe acne) also have been shown to cause intracranial hypertension in children and adolescents. Ingestion of large quantities of bear liver by hunters is another curious source of intoxication with vitamin A underlying pseudotumor. Isolated instances of hypoor hyperadrenalism, myxedema, and hypoparathyroidism have been associated with increased CSF pressure and papilledema, and occasionally the administration of estrogens, phenothiazines, lithium, the antiarrhythmic drug amiodarone, and quinolone antibiotics has the same effect, for reasons not known.
The first step in differential diagnosis is to exclude an underlying tumor or the nontumorous causes of raised ICP, mainly dural venous occlusion, and meningeal inflammation. This can be accomplished by CT and MRI, although it should be borne in mind that certain chronic meningeal reactions (e.g., those caused by sarcoidosis or to tuberculous or carcinomatous meningitis), which give rise to headache and papilledema, may sometimes elude detection by these imaging procedures. In these cases, however, lumbar puncture will disclose the diagnosis. It should be emphasized that the diagnosis of idiopathic pseudotumor cerebri should not be accepted when the CSF content is abnormal.
Careful evaluations of the visual fields and of visual acuity is required soon after the diagnosis of idiopathic pseudotumor is established. Repeated examination of visual function, preferably in collaboration with an ophthalmologist, is essential in detecting early and potentially reversible visual loss. At the same time, it must be acknowledged that measurements of visual acuity (and of confrontation fields) are relatively insensitive means of detecting early visual loss and that abnormalities in these tests indicate that damage to the optic nerve head has already occurred. Quantitative perimetry, using the kinetic Goldmann technique, has been more informative than other methods. The neurologist probably is advised to refer the patient for perimetry as an adjunctive test. Fundus photographs are also a reasonable means of assessing the course of papilledema. A reduction in previously normal acuity to less than 20/20 corrected, enlargement of the blind spot, or the appearance of sector field defects, usually inferonasal, are indications for prompt treatment of raised ICP.