Elevated ICP occurs in a variety of settings including: congenitally; with intracranial neoplasm or other mass; infection (meningitis, encephalitis); or subdural or subarachnoid hemorrhage. Often no cause is identified (idiopathic intracranial hypertension or pseudotumor cerebri; see below).

Symptoms

Initially asymptomatic, visual loss, and dyschromatopsia occur with chronic papilledema; may have headache, nausea, emesis, transient visual obscurations (lasting seconds), diplopia, altered mental status, or other neurologic deficits.

Signs

Normal or decreased visual acuity and color vision, red desaturation, enlarged blind spot proportional to degree of edema, bilateral (rarely unilateral) optic disc edema with blurred disc margins, disc hyperemia, reduced physiologic cup, thickened nerve fiber layer obscuring retinal vessels, peripapillary nerve fiber layer hemorrhages, cotton-wool spots, exudates, retinal folds (Paton’s lines), and absent venous pulsations (absent in 20% of normal individuals); may have cranial nerve VI palsy, vascular attenuation, visual field defects, decreased visual acuity and optic atrophy (occurs late with axonal loss). Foster–Kennedy syndrome refers to the finding of unilateral papilledema with contralateral optic atrophy and anosmia, due to an olfactory groove meningioma resulting in compression on one side (atrophy) and elevated ICP causing edema of the other disc.

Figure 11-1 Papilledema due to an intracranial tumor. There is marked edema of the nerve head with blurring of the disc margins 360° and two flame-shaped hemorrhages.

Differential Diagnosis

Optic disc edema without elevated ICP is due to malignant hypertension, diabetic papillitis, anemia, central retinal vein occlusion, neuroretinitis, uveitis, optic neuritis, anterior ischemic optic neuropathy, Leber’s optic neuropathy, hypotony, infiltration (lymphoma, leukemia), optic nerve mass, pseudopapilledema (e.g., optic nerve drusen).

Evaluation

• Complete ophthalmic history, neurologic exam, and eye exam with attention to visual acuity, color vision, pupils, and ophthalmoscopy.

• Check visual fields.

• Emergent neuroimaging: Head and orbital magnetic resonance imaging (MRI) (or CT scan if MRI not available) to rule out intracranial processes; consider venography (MRV) to look for venous sinus thrombosis.

• Lumbar puncture (after MRI) to check opening pressure and composition of cerebrospinal fluid.

• Lab tests: To identify etiology of disc edema if ICP is not elevated on LP. Fasting blood sugar, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), angiotensin converting enzyme (ACE).

• Check blood pressure.

• Neurology consultation.

Management

• Treat underlying etiology.

Prognosis

Depends on etiology.

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

Definition

Disorder of unknown etiology that meets the following criteria: (1) signs and symptoms of increased intracranial pressure, (2) high cerebrospinal fluid pressure (> 200 mmH₂O in nonobese and > 250 mmH₂O in obese patients) with normal composition, (3) normal neuroimaging studies, (4) normal neurologic examination findings (except papilledema or cranial nerve VI palsy), and (5) no identifiable cause, such as an inciting medication (modified Dandy criteria).

Etiology

Idiopathic; may be associated with vitamin A, tetracycline, oral contraceptive pills (due to hypercoagulability and dural sinus thrombosis), nalidixic acid, lithium, or steroid use or withdrawal; also associated with dural sinus thrombosis, radical neck surgery, middle ear disease (which may cause dural sinus thrombosis), recent weight gain, chronic obstructive pulmonary disease, and pregnancy. Idiopathic intracranial hypertension is a diagnosis of exclusion.

Epidemiology

Usually occurs in obese 20–45-year-old females (2 : 1).

Symptoms

Asymptomatic; may have headache, transient visual obscurations (lasting seconds), intracranial noises (whooshing), diplopia, pulsatile tinnitus, dizziness, nausea, and emesis.

Signs

Normal or decreased visual acuity, color vision, and contrast sensitivity; bilateral optic disc edema; may have cranial nerve VI palsy (30%) or visual field defect.

Figure 11-2 Idiopathic intracranial hypertension demonstrating papilledema.

Differential Diagnosis

Rule out other causes of papilledema and optic disc edema (see Papilledema section).

Evaluation

• Complete ophthalmic history, neurologic exam, and eye exam with attention to visual acuity, color vision, pupils, motility, and ophthalmoscopy.

• Check visual fields (enlarged blind spot, generalized constriction).

• Emergent neuroimaging: Head and orbital MRI (or CT scan if MRI not available) to rule out intracranial processes; consider venography (MRV) to look for venous sinus thrombosis.

• Lumbar puncture (after MRI) to check opening pressure and composition of cerebrospinal fluid.

• Check blood pressure.

• Neurology consultation.

Management

• If the patient is obese, initiate a weight-loss program.

• Discontinue vitamin A, tetracycline, oral contraceptive pills, nalidixic acid, lithium, or steroid use.

• No further treatment recommended unless patient exhibits progressive visual loss, visual field defects, or intractable headaches.

• Systemic acetazolamide (Diamox) 500–2000 mg po qd.

• Consider systemic diuretics (furosemide [Lasix] 60–120 mg po divided q6h); follow visual field, visual acuity, and color vision.

• Oral steroids (prednisone 60–100 mg po qd) are controversial; check purified protein derivative (PPD) and controls, blood glucose, and chest radiographs before starting systemic steroids.

• Add H₂-blocker (ranitidine [Zantac] 150 mg po bid) or proton pump inhibitor when administering systemic steroids.

• Consider surgery for progressive visual loss despite maximal medical therapy (optic nerve sheath fenestration, lumboperitoneal shunt).

Prognosis

Usually self-limited over 6–12 months; variable if visual loss has occurred.

Optic Neuritis

Definition

The term optic neuritis refers to inflammation of the optic nerve.

Papillitis

Inflammation is anterior, optic disc swelling present.

Retrobulbar

Inflammation is behind the globe, no optic disc swelling; more common.

Devic’s Syndrome

Bilateral optic neuritis with transverse myelitis.

Etiology

Demyelination is the most common cause; others include vasculitic, infectious, and autoimmune.

Epidemiology

Demyelinative optic neuritis usually occurs in 15–45-year-old females. The majority of patients with multiple sclerosis (MS) have evidence of optic neuritis; this approaches 100% in postmortem pathologic studies; optic neuritis is the initial diagnosis in 20% of MS cases; conversely, roughly 50–60% of patients with isolated optic neuritis will eventually develop MS. Note: optic neuritis in children is usually bilateral, postviral (i.e., mumps, measles), and less likely to be associated with MS.

Symptoms

Subacute visual loss (usually progresses for 1–2 weeks followed by recovery over the following 3 months), pain on eye movement, dyschromatopsia, diminished sense of brightness; may have previous viral syndrome, or phosphenes (light flashes) on eye movement or with loud noises.

Signs

Decreased visual acuity ranging from 20/ 20 to no light perception, visual field defect (most often central or paracentral scotoma, but any pattern of field loss can occur), decreased color vision and contrast sensitivity, relative afferent pupillary defect (RAPD); may have optic disc swelling (35%), mild vitritis, altered depth perception (Pulfrich’s phenomenon), and increased latency and decreased amplitude of visual evoked response.

Differential Diagnosis

Intraocular inflammation, malignant hypertension, diabetes mellitus, cat-scratch disease, optic perineuritis, sarcoidosis, syphilis, tuberculosis, collagen vascular disease, Leber’s optic neuropathy, optic nerve glioma, orbital tumor, anterior ischemic optic neuropathy, central serous retinopathy, multiple evanescent white dot syndrome, acute idiopathic blind spot enlargement syndrome.

Evaluation

• Complete ophthalmic history, neurologic exam, and eye exam with attention to visual acuity, color vision, Amsler grid, contrast sensitivity, pupils, motility, and ophthalmoscopy.

• Check visual fields.

• If patient does not carry the diagnosis of MS, then obtain an MRI of the head and orbits to evaluate periventricular white matter for demyelinating lesions or plaques (best predictor of future development of MS).

• Lab tests: Unnecessary for typical case of optic neuritis. When atypical features exist: ANA, ACE, Venereal Disease Research Laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test, ESR; consider Bartonella henselae if optic nerve is swollen and exposure to kittens.

• Check blood pressure.

• Consider lumbar puncture to rule out intracranial processes.

• Neuro-ophthalmology consultation.

Management

• If MRI is positive, consider systemic steroids (methylprednisolone 250 mg IV q6h for 3 days, followed by prednisone 1 mg /kg /day for 11 days and rapid taper 20 mg /day on day 12 and 10 mg /day on days 13–15). The Optic Neuritis Treatment Trial (ONTT) showed that this regimen led to visual recovery 2 weeks faster than other treatments; however, no difference in final visual acuity, and a decreased incidence of MS over the ensuing 2 years but no difference after 3 years. Note: Do not use oral steroids alone, because this led to an increased risk of recurrent optic neuritis (ONTT conclusion).

• Check PPD and controls, blood glucose, and chest radiographs before starting systemic steroids.

• Add H₂-blocker (ranitidine [Zantac] 150 mg po bid) or proton pump inhibitor when administering systemic steroids.

• The CHAMPS study group showed that patients receiving weekly intramuscular interferon β-1a (Avonex) following steroid therapy for a first episode of optic neuritis associated with at least two lesions on MRI greater than 3 mm had a reduction in onset of clinical MS over 3 years and improvement or less worsening of MRI lesions.

Prognosis

Good in cases of demyelination; visual acuity improves over months; final acuity depends on severity of initial visual loss; 70% of patients will recover 20 / 20 vision. Permanent subtle color vision and contrast sensitivity deficits are common; even after recovery, patient may have blurred vision with increased body temperature or exercise (Uhthoff’s phenomenon or symptom). Approximately 30% will have another attack in either eye, and 30–50% of patients with isolated optic neuritis will develop MS over 5–10 years.

Anterior Ischemic Optic Neuropathy

Definition

Ischemic infarction of anterior optic nerve due to occlusion of the posterior ciliary circulation just behind the lamina cribrosa.

Etiology

Optic nerve infarction is encountered in different settings, but is often divided into two categories:

Arteritic

Occurs in the setting of giant cell arteritis (GCA; temporal arteritis).

Nonarteritic

Occurs in several settings but is most often “spontaneous” without an identified precipitating factor.

Epidemiology

Arteritic

Usually occurs in patients > 55 years old (mostly over 70), the fellow eye is involved in 75% of cases within 2 weeks without treatment; associated with polymyalgia rheumatica.

Nonarteritic

Usually occurs in middle-aged patients; fellow eye is involved in up to 40% of cases. Associated with hypertension (40%), diabetes mellitus (30%), ischemic heart disease (20%), hypercholesterolemia (70%), and smoking (50%); arteriosclerotic changes are found in optic disc vessels.

Symptoms

Acute, unilateral, painless visual loss (arteritic > nonarteritic) and dyschromatopsia.

Arteritic

May also have headache, fever, malaise, weight loss, scalp tenderness, jaw claudication, amaurosis fugax, diplopia, polymyalgia rheumatica symptoms (joint pain), and eye pain.

Signs

Normal or decreased visual acuity, decreased color vision, RAPD, central or altitudinal visual field defect (usually inferior and large), swollen optic disc (pallor or atrophy after 6–8 weeks), fellow nerve often crowded with a small or absent cup, fellow nerve may be pale from prior episode (pseudo Foster–Kennedy syndrome; more common than true Foster–Kennedy [see above]).

Arteritic

May also have swollen, tender, temporal artery, cotton-wool spots, branch or central retinal artery occlusion, ophthalmic artery occlusion, anterior segment ischemia, cranial nerve palsy (especially cranial nerve VI); optic disc cupping occurs late; choroidal infarcts can be seen on fluorescein angiogram.

Figure 11-3 Anterior ischemic optic neuropathy with disc edema and flame hemorrhages.

Figure 11-4 Anterior ischemic optic neuropathy with (A) disc edema and (B) late leakage on fluorescein angiogram.

Differential Diagnosis

Malignant hypertension, diabetes mellitus, retinal vascular occlusion, compressive lesion, collagen vascular disease, syphilis, herpes zoster; also migraine, postoperative, massive blood loss, normal (low)-tension glaucoma.

Evaluation

• Complete ophthalmic history with attention to erectile dysfunction drugs, amiodarone, and obstructive sleep apnea.

• Complete eye exam with attention to visual acuity, color vision, Amsler grid, pupils, and ophthalmoscopy.

• Check visual fields.

• Lab tests: STAT ESR (to rule out arteritic form; ESR > [age/ 2] in men and > [(age 10)/2] in women is abnormal), CBC (low hematocrit, high platelets), fasting blood glucose, C-reactive protein (CRP), VDRL, FTA-ABS, ANA.

• Check blood pressure.

• Arteritic: Consider temporal artery biopsy (beware: can get false-negative results from skip lesions); will remain positive up to 2 weeks after starting corticosteroids.

• Consider fluorescein angiogram; choroidal nonperfusion in arteritic form.

• Medical consultation.

Management

ARTERITIC

• Systemic steroids (methylprednisolone 1 g IV qd in divided doses for 3 days, then prednisone 60–100 mg po qd with a slow taper; decrease by no more than 2.5–5.0 mg / wk) started before results of biopsy are known to prevent ischemic optic neuropathy in fellow eye; follow ESR, CRP, and symptoms carefully.

• Check PPD and controls, blood glucose, and chest radiographs before starting systemic steroids.

• Add H₂-blocker (ranitidine [Zantac] 150 mg po bid) or proton pump inhibitor when administering systemic steroids.

NONARTERITIC

• Consider daily aspirin.

Prognosis

Worse for the arteritic form associated with GCA in which visual recovery is rare. Roughly 10% with the nonarteritic form will progress and slightly more than 42% will improve (≥ 3 Snellen lines, but some of this perceived improvement may represent learning to scan with the remaining visual field as opposed to true axonal recovery).

Traumatic Optic Neuropathy

Definition

Damage to the optic nerve (intraocular, intraorbital, or intracranial) from direct or indirect trauma.

Etiology

Direct Injuries

Orbital or cerebral trauma that transgresses normal tissue planes to disrupt the anatomic integrity of the optic nerve (e.g., penetrating injury or bone fragment).

Indirect Injuries

Forces transmitted at a distance from the optic nerve; the mechanism of injury may involve transmission of energy through the cranium, resulting in elastic deformation of the sphenoid bone, and thus a direct transfer of force to the canalicular portion of the nerve.

Optic Nerve Avulsion

Dislocation of the nerve at its point of attachment with the globe; usually occurs with deceleration injuries causing anterior displacement of the globe.

Epidemiology

Occurs in 3% of patients with severe head trauma and 2.5% of patients with midfacial fractures.

Symptoms

Acute visual loss, dyschromatopsia, pain from associated injuries.

Signs

Decreased visual acuity ranging from 20 / 20 to no light perception, RAPD, decreased color vision, visual field defect; optic nerve usually appears normal acutely with optic atrophy developing later; may have other signs of ocular trauma. Hemorrhage at the location of the optic disc occurs with optic nerve avulsion.

Figure 11-5 Traumatic optic nerve avulsion.

Figure 11-6 Traumatic avulsion of the globe: the entire globe is extruded from the orbit but still attached to the optic nerve.

Differential Diagnosis

Commotio, open globe, retinal detachment, Terson’s syndrome, Purtscher’s retinopathy, macular hole, vitreous hemorrhage.

Evaluation

• Check for associated life-threatening injuries.

• Complete ophthalmic history, neurologic exam, and eye exam with attention to mechanism of injury, visual acuity, color vision, pupils, motility, tonometry, anterior segment, and ophthalmoscopy.

• Orbital CT scan with thin coronal images through the canal to assess location and extent of damage, mechanism of injury, and associated trauma.

• Check visual fields.

• Medical or neurology consultation may be required for associated injuries.

Management

• Consider megadose systemic steroids (methylprednisolone 30 mg / kg IV initial dose, then starting 2 hours later 15 mg / kg every 6 hours for 1–3 days); controversial because dosage, length of treatment, and efficacy are unproved.

• Consider surgical decompression if there is no improvement or there is radiographic evidence of optic canal fracture.

Prognosis

Usually poor, depends on degree of optic nerve damage; 20–35% improve spontaneously.

Other Optic Neuropathies

Definition

Variety of processes that cause unilateral or bilateral optic nerve damage and subsequent optic atrophy. Atrophy of axons with resultant disc pallor occurs 6–8 weeks after injury anterior to the lateral geniculate nucleus.

Figure 11-7 Optic atrophy demonstrating pale nerve: the optic nerve pallor is most striking in the inferotemporal region of the disc (arrowhead).

Etiology

Compressive

Neoplasm (orbit, suprasellar), thyroid-related ophthalmopathy, hematoma.

Hereditary

Isolated

Leber’s hereditary optic neuropathy

Typically occurs in 10- to 30-year-old males (9 : 1). Rapid, severe visual loss that starts unilaterally, but sequentially involves fellow eye usually within 1 year but can be within days to weeks. Optic nerve hyperemia and swollen nerve fiber layer with small, peripapillary, telangiectatic blood vessels that do not leak on fluorescein angiography (optic nerve also does not stain). Mitochondrial DNA mutation – mothers transmit defect to all sons (50% affected) and all daughters are carriers (10% affected). Three common mutations in the mitochondrial genome at nucleotide positions 3460, 11778, and 14484 have been identified.

Dominant optic atrophy (Kjer or juvenile optic atrophy)

Most common hereditary optic neuropathy, prevalence of 1 : 12,000 to 1 : 50,000; highly variable age of onset (mean around 4 to 6 years of age). Mild, insidious loss of vision (ranging from 20 / 20 to 20 / 800), tritanopic dyschromatopsia; slight progression; nystagmus rare; a wedge of pallor is seen on the temporal aspect of the disc (temporal excavation). Mapped to chromosomes 3q28-q29 (OPA1 gene), 18q12.2-q12.3 (OPA4 gene), and 22q12-q13 (OPA5 gene).