INFLAMMATORY AND IMMUNE DISEASE

difference in outcomes (1 month was similar to 3 months) and that steroid dose made no difference. The VA increased by three lines in one third of surgery patients, half of steroid-treated patients, and half of untreated patients.

National Acute Spinal Cord Injury Study (NASCIS), a doubleblind randomized clinical trial, found that early high-dose steroids may be neuroprotective for spinal cord lesions. Whether this data apply to optic nerve trauma is unknown, but many clinicians treat TON with high-dose steroids if VA is LP or worse.

TRAUMATIC OPTIC NERVE EVULSION OR TRANSECTION Usually from countrecoup injury; even with apparently minor trauma, the nerve is easy to tear, as CNS tissue has the consistency of warm butter. Characterized by immediate NLP with variable hemorrhage over disk and CRAO-like presentation. May not see avulsion on CT with an intact ON sheath. If not directly transected by trauma, evulsion may be aided by increased IOP that ‘‘pushes’’ ON out of scleral canal or increased intraorbital pressure pushes globe anteriorly, stretching the nerve. If transected posterior in the orbit, the patient may have intact retinal circulation.

Inflammatory and Immune Disease

ANTERIOR OPTIC NEURITIS Monocular vision loss of insidious onset (nadir 7 to 10 days) with gradual recovery in 80% of cases. Typically, patients have pain with eye movement (90% of subjects in Optic Neuritis Treatment Trial [ONTT]—see below; caused by the dural attachment of the SR and MR to the ON sheath), decreased VA (especially contrast and color vision from the PMB fibers), and APD, with or without disk edema (30% of ONTT subjects). Symptoms may increase with increased body temperature or exercise (Uhthoff ’s sign). Usual age is <50 years old; in adults, is often from multiple sclerosis (60% of optic neuritis progesses to MS), and in children, is usually postviral. FA is normal, and periventricular plaques may be seen on MRI if patient has MS.

Atypical presentation: painless or sign or symptoms of systemic disease or inflammation such as vitritis, then consider sarcoidosis, syphilis, Lyme disease, bartonellosis, vasculitis, or toxoplasmosis. If patient is not getting better, suspect compressive lesion (e.g., ON sheath meningioma), Leber’s optic atrophy, or ischemic etiology.

Treatment: for acute disease, based on the ONTT, consider treatment with IV methylprednisolone 1000 mg qd (250 mg every 6 hours) for 3 days followed by oral prednisone taper 1 mg/kg for 11 days. (Because oral prednisone is 85% absorbed, the oral equivalent for initial treatment is 1200 mg divided qid.) In children, dose 2 mg/kg IV with slow taper.

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acute unilateral optic neuritis presumably secondary to demyelinating disease (seen mostly in young female patients without a diagnosis of MS).

Visual recovery begins within 2 weeks in most optic neuritis patients without any treatment, and improvement continues for up to 1 year. Although most patients recover to 20/20 VA, many still have symptomatic deficits in vision.

Oral prednisone was ineffective in speeding recovery or in improving the visual outcome after optic neuritis, and actually increased a patient’s risk for future attacks in either the affected or fellow eye (27% vs. 15% for placebo patients).

Treatment with high-dose, intravenous corticosteroids followed by oral corticosteroids accelerated visual recovery but provided no long-term benefit to vision. The IV steroids also provided a shortterm reduction in the rate of development of MS, particularly in patients with brain MRI changes consistent with demyelination. By 3 years of follow-up, however, this treatment effect had subsided.

Brain MRI is a powerful predictor of the early risk of MS after optic neuritis (especially if it shows >2 demyelinating lesions).

In optic neuritis patients with no brain MRI lesions, the following features of the optic neuritis are associated with a low 5-year risk of MS: lack of pain, optic disk edema (particularly if severe), peripapillary hemorrhage, retinal exudates, and mild visual loss.

The probability of a recurrence of optic neuritis in either eye within 5 years is 28%.

Controlled High-Risk Avonex Multiple Sclerosis Prevention Study (CHAMPS): INF-beta-1-alpha (Avonex) is protective for MS and decreases MS severity with a rapid sustained effect if two or more T2weighted MRI lesions >3 mm are present. Thus, image patients after their first episode of optic neuritis to rule out MS.

EATON-LAMBERT SYNDROME Autoimmune disease of the neuromuscular junction similar to myasthenia gravis, with muscle weakness and fatigue; less likely to be ocular than MG.

vous system, often with antecedent viral illness. Patients may need ventilator support for several months until it resolves.

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Miller Fisher syndrome: bulbar variant. ‘‘Guillain-Barre´ of the head and neck,’’ with ophthalmoplegia and descending paralysis; also has CSF dissociation.

Acute ophthalmoparesis (AO): forme fruste of Guillain-Barre´, affecting only the EOM; positive anti-GQ1B Ab against peripheral nerves.

MULTIPLE SCLEROSIS (MS), CLINICALLY DEFINITE MULTIPLE SCLEROSIS (CDMS) Autoimmune demyelinating disease that presents with optic neuritis in 18%, intranuclear ophthalmoplegia (INO) and horizontal diplopia, nystagmus (oscillopia), and atypical VF (inferior altitudinal, arcuate, cecocentral, or basically any VF defect). Also ask about fatigue, paresthesias, paresis, incontinence, and electric sensation down neck/arms with neck flexion (Lhermitte’s sign). Uncommon presentations include chiasmal neuritis with bitemporal hemianopsia (aggressive chiasmitis), CN III, IV, and VI nuclear dysfunction, skew deviation (supranuclear vertical gaze dysfunction), and intermediate uveitis. See Anterior Optic Neuritis above for evaluation and management.

Immunologic disease: chronic inflammatory demyelinating. Characterized by T-cell activation from myelin breakdown (possible viral beginning). T-cells are then exposed to an antigen that seems ‘‘foreign’’ or through molecular mimicry learns to attack the myelin sheath and migrate into the CNS. As T cells attack the myelinated axons, other antigens are uncovered (epitope spread). At some point, suppressor T cells take over, and the acute episode remits.

Risks for developing MS: genetic history, young, female, northern latitude (Caucasian, Scandinavian), and increased socioeconomic status

Two courses and etiologies: primary progressive (15%) and relapsing– remitting (85%), which may progress to secondary or chronic progressive (after 10 years, 40–45% are secondary-progressive). Treatment is aimed to decrease the rate that patients go on to secondary or chronic disease. The progressive form represents actual axonal loss, whereas the relapsing–remitting form is demyelinating attacks.

Causes of decreased VA that are more prevalent in MS patients: optic neuritis, intermediate uveitis with CME, chiasmitis (transverse myelitis, also known as Devic’s syndrome), optic tract plaques, and iritis.

Diagnosis with clinical findings plus lumbar puncture (increased IgG/ oligoclonal Ab) and MRI. MRI often shows white matter demyelinating plaques (especially periventricular, also known as Dawson’s fingers) that reach maximum size at 4 weeks after relapse; enhancing lesion in the corpus callosum is pathognomonic.

Treatment for relapsing–remitting disease: ‘‘ABC’’ drugs reduce the number of attacks, and many clinicians suggest that all three drugs work well as first-line therapy.

Avonex (interferon beta-1-alpha): per CHAMPS study, was effective in delaying the onset of the next attack.

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326NEUROLOGIC

Betaserone (interferon beta-1-beta)

Copaxone (copolymer glatiramer acetate): improves disability and

cognition.

Treatment for progressive MS: treat early to decrease disability and long-term axonal injury sequelae.

Mitoxantrone: myelin basic protein that is a chemotherapy drug, like Adriamycin, that may cause a dose-dependent vacuolar cardiomyopathy. Two-year maximum use recommended, or use occasionally as a rescue drug; turns patient blue after injection. MIMS (Mitoxantrone in Multiple Sclerosis) study showed that it increased T-suppressor cells.

May also try IV steroids and adrenocorticotropic hormone (ACTH).

MYASTHENIA GRAVIS (MG) Chronic autoimmune neuromuscular junction disorder with weakness and fatigability. Characterized by variable weakness of voluntary muscles, often EOM and limb muscles, which is made worse by use and improves with rest. Eighty to 90% of patients present with ocular findings: primary sign is ptosis (present in 75% of patients with ocular involvement) that may be unilateral or bilateral and worsens with fatigue. Ptotic lid may twitch when patient looks from down to up (Cogan’s lid twitch), or the opposite lid droops when the ptotic lid is raised (Schatz lid sign; like Herring’s effect). The second most common is strabismus (although diplopia is the main reported symptom), affecting MR > IR > SO; may have paresis of upgaze and an apparent INO. Eye movements are characterized by hypometric (lazy) large saccades and hypermetric small saccades (supernormal saccadic velocities). Also fatigable ophthalmoplegia, uncommonly nystagmus (weak muscles not central origin), orbicularis weakness, peak sign (lids do not close completely). Pupillary and accommodation problems reported but uncommon (for examinations, the pupils are not involved); also, risk of thymic hyperplasia or thymoma.

Pathogenesis: acquired ‘‘autoimmune’’ antibodies to motor end plates (thus decreased available acetylcholine receptors) and impaired synaptic transmission. Considered neuromuscular junction pathology, not cranial nerve palsy. Acetylcholine receptor usually regenerates every 7 to 10 days, but in MG is 1 day. Similar to Eaton-Lambert syndrome. Patients have increased risk of other autoimmune diseases, such as SLE, RA, and hyperthyroidism.

May be infantile, juvenile, or adult onset. F:M ¼ 3:2. Average female age of onset is 28 years old; average male onset is 43 years old. Fifty percent of patients have purely ocular MG, and 10% of cases remit spontaneously, usually after 1 year. Of the 40% that remain an ocular disease, 50% will develop generalized symptoms usually within 2 years. If a patient has purely ocular MG >2 years, there is <20% chance of

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systemic involvement. Ocular variant has decreased Ab titers and decreased thymoma incidence compared with systemic MG.

Diagnosis: clinical presentation, proving fatigability and the fleeting, varied, and recurrent presentation.

Tensilon (edrophonium chloride) testing: must have objective measure (e.g., millimeters of ptosis) to compare before and after the IV injection of Tensilon. Drug inhibits acetylcholinesterase, thus prolonging the effect of acetylcholine at the synaptic cleft. It has an onset within 60 seconds and lasts about 10 minutes. In children, use neostigmine IM (30 minute duration). Consider monitoring cardiac function during testing; because the drug stimulates muscarinic and nicotinic receptors, it may cause a cholinergic crisis (sweating, nausea, vomiting, salivation, fever). Have atropine available to reverse its effects.

Also may use ice testing on the ptotic lid for 2 minutes, which suggests the diagnosis of MG if at least 2 mm of lid improvement is seen (may also be false-positive as a result of the lid resting).

Check acetylcholine Ab, which is present in 60% of MG patients, and schedule thyroid function tests, as dysthyroidism is more common. Obtain a chest CT to rule out thymoma (potentially fatal). Also, single-fiber electromyography of the orbicularis muscle may be used for diagnosis.

Treatment: usually treated by neurologist, using pyridostigmine bromide (Mestinon) or neostigmine (Prostigmin) or chronic immunosuppression. Too much Mestinon floods receptors and may potentiate MG. Ninety-six percent of cases improve with cyclosporine. Consider thymectomy.

PERINEURITIS Disk edema from inflammation of the nerve sheath, with normal imaging and lumbar puncture; usually from sarcoidosis, syphilis, or

Bartonella henselae.

PSEUDOTUMOR CEREBRI (PTC), IDIOPATHIC INTRACRANIAL HYPERTENSION Usually seen in young, 20to 40-year-old, obese females who present with headache and papilledema. Vision disturbances include TVO, VF defects, postural bilateral amaurosis fugax, and horizontal diplopia (CN VI palsy). Also, most patients complain of tinnitus.

Diagnosis of exclusion: must do neuroimaging that shows no mass or dural sinus thrombosis. MRI is 90% predictive of PTC (however, up to 20% have ‘‘empty sella,’’ 80% have flattening of the posterior sclera).

Lumbar puncture shows increased opening pressure (>20 cm H20) but otherwise normal CSF studies.

Fifty percent are idiopathic and 50% are associated with known causes. Pathogenesis is likely hormonal imbalance, as PTC is associated with females, obesity, and exacerbated by pregnancy. May be precipitated by

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