Ординатура / Офтальмология / Английские материалы / Clinical Medicine in Optometric Practice_Muchnick_2007

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patients, 90% go on to more generalized weakness within 2 years.

The patient may complain of difficulty chewing and swallowing. Dramatic weakness of the normally powerful movements of the major muscles of the limbs is also present. In time, the respiratory muscles can become impaired. The condition is characterized by exacerbations and remissions. The symptoms of MG are worsened by pregnancy and underlying infection. Drugs such as propranolol, lithium, tetracycline, and aminoglycoside antibiotics worsen the myasthenic condition and should be avoided in these patients.

MG is caused by an immune-mediated disorder. In approximately 80% of MG patients, detectable antibodies to the postsynaptic acetylcholine (ACh) receptor are present. Loss of the receptor in the postsynaptic muscle membrane prevents depolarization of the postsynaptic muscle membrane resulting in muscle weakness and fatigue. An immune-mediated disorder is also suspected in the remaining 20% of patients who do not exhibit ACh-receptor antibodies.

The diagnosis of MG begins with the high degree of suspicion raised by the clinical signs and symptoms. The examiner can confirm involvement of the upper lids by asking the patient to sustain an upgaze posture and noting a worsening of the ptosis within 2 minutes.

Electromyography (EMG) is of significant diagnostic importance when evaluating a patient for MG. The classic electrodiagnostic pattern in MS is known as the electrodercremental response. Reduction in the action potential size is present and reverses to normal when edrophonium chloride (Tensilon) is administered to the patient.

Pharmacological testing for MG involves anticholinesterase drugs to demonstrate a temporary improvement in muscle power. The Tensilon test is conducted by the intravenous administration of 10 mg of edrophonium and the subsequent observation of approximately 5 minutes of muscular strength improvement. Tensilon is a acetylcholinesterase inhibitor.

An alternative to edrophonium is the intramuscular injection of neostigmine that in MG patients improves muscular strength for as long as 2 hours.

MG is often found associated with tumor of the thymus (in 15% of patients with MG), thyrotoxicosis, rheumatoid arthritis, and lupus erythematosus. These conditions should be excluded by a complete physical examination with laboratory testing and radioimaging studies.

The treatment of MG includes the use of surgery, medications, and plasmapheresis. Pyridostigmine is an anticholinesterase drug given at a dosage of 60 mg, four times daily orally, for symptomatic improvement.

If the patient is younger than 60 years and does not respond well to pyridostigmine, then a surgical thy-

mectomy may lead to slowly improving symptomatic relief. The mechanism by which thymectomy leads to symptomatic improvement is not yet understood. More than 60% of patients improve with thymectomy, but it is only offered to patients younger than 60 years.

If the patient responds poorly to pyridostigmine and thymectomy, then corticosteroids may be helpful. In fact, many think that corticosteroids are the first treatment of choice to induce remission of the autoimmune element of MG. Oral prednisone is administered, but the patient must be watched closely for transient respiratory difficulty. Steroids are effective in inducing remission of MG in 80% of cases.

If MG exacerbates despite these treatments, then azathioprine has been found to be helpful. The therapeutic benefits of azathioprine may take as long as a year from initiation.

Plasmapheresis, or plasma exchange, permits temporary improvement in cases of rapidly worsening MG or before surgery. This technique removes acetylcholine receptor antibodies from the blood and produces rapid but short-lived improvement in symptoms.

The majority of patients with MG achieve wellcontrolled tolerance of their muscle weakness with drug and surgical intervention. The mortality associated with MG is mostly related to aspiration pneumonia caused by respiratory weakness.

Muscular Dystrophies

This group of disorders is characterized by muscle weakness and muscle wasting (Table 17-1). These inherited disorders exhibit variations in age at onset, muscle involvement, rate of progression, and prognosis. Muscular dystrophies result in deformities of the musculoskeletal system and muscular contractures. Treatment of these myopathic disorders encompasses targeted physical therapy and orthopedic surgeries.

Ocular Dystrophy

This dystrophy is inherited as an autosomal dominant disorder that causes deletions in the DNA of the mitochondria. Most patients are affected when they are younger than 30 years. The earliest manifestation of ocular dystrophy is ptosis. Eventually, external ophthalmoplegia occurs with facial weakness. As the dystrophy slowly develops, the limb muscles may weaken. The prognosis of ocular dystrophy is unknown, and the condition is rare and not well studied.

Oculopharyngeal Dystrophy

Like ocular dystrophy, this disorder is autosomal dominant in its inheritance pattern. It is found most commonly in Quebec, Canada, and the American southwest. It is similar to ocular dystrophy, but the earliest manifestations typically occur in patients between the

ages of 30 to 50 years. Like ocular dystrophy, the earliest clinical signs are ptosis and external ophthalmoplegia. Facial and limb weakness often follow. Dysphagia can be so debilitating that nasogastric feeding is necessary. Like ocular dystrophy, this is a rare and understudied condition.

Myotonic Disorders

Myotonia represents a group of disorders that are characterized by muscle stiffness. This condition is caused by an inherited abnormality of the muscle fiber membrane, or sarcolemma. The muscle stiffness results from the inability of the muscle to relax immediately after contraction.

Myotonic Dystrophy

This autosomal dominant disorder typically manifests in the young adult. The defective gene is located in chromosome 19q13.2-12q13.3. Expression of this gene causes a defect in the protein myotonin-protein-kinase. The ocular signs of myotonic dystrophy include ptosis and cataract formation. The facial and limb muscles begin to weaken, and premature frontal balding, cardiac abnormalities, and cognitive changes in intelligence often occur. The treatment of myotonic dystrophy makes use of quinine sulfate, 300 to 400 mg, three times daily. Other medications that are useful in myotonia include procainamide and phenytoin. No treatment exists for the muscular weakness associated with myotonia.

Dermatomyositis

This inflammatory myopathy exhibits destruction of the muscle fibers. In addition, inflammatory infiltration of the muscles occurs. Dermatomyositis represents a microangiopathy of the skin and muscles with widespread destruction of capillaries caused by an immune response that leads to muscle ischemia. As such, it is understandable that dermatomyositis is associated with such autoimmune disorders as Sjögren’s syndrome, lupus erythematosus, and rheumatoid arthritis.

The myopathy is characterized by an erythematous rash that covers the eyelids known as the heliotrope rash. In patients of any age, the limbs proximal to the body become weak and begin to waste. The muscles become painful, and respiration becomes difficult. Laboratory testing reveals an elevated serum creatine kinase, and electromyography reveals fairly characteristic patterns. Muscle biopsy is essential for the diagnosis. Dermatomyositis is treated with prednisone during a 2- to 3-year tapering period. Immunoglobulins may be administered intravenously instead of steroid treatment, and methotrexate also has been shown to be an effective alternative to prednisone. Alternative and newer immunosuppressants such as mycophenolate mofetil are now under study. Physical therapy is a valuable adjunct to pharmaceutical intervention.

MOVEMENT DISORDERS Tremor

Tremor is characterized by rhythmic movements of a limb. Tremors may be caused by anxiety, physical activity, drugs, inherited disorders, cerebellar disease, and parkinsonism. Intention tremor is an uncontrollable rhythmic movement elicited during physical activity.

Chorea

Unlike the rhythmic, predictable movements of tremor, chorea is characterized by the spastic, irregular, and episodic jerking of disparate muscle groups. Extreme facial grimacing and tongue rolling are often present. A lurching type of gait with swaying to one side or the other may be present. Speech volume becomes just as unpredictable and varied. Interestingly, chorea does not occur during sleep. Chorea appears because of loss of cells in parts of the brain; in particular, the caudate nucleus and putamen. Chorea is characteristic of Wilson’s disease and cerebral palsy, and may result from drugs, lupus, AIDS, stroke, thyrotoxicosis, and subdural hematoma.

Tics

These involuntary movements are characterized by quick and recurrent movements. These movements are made worse by stress and anxiety, but can be suppressed for short periods of time. Tics disappear during sleep.

Parkinsonism

This very common disorder affects approximately 2 of every 1000 people in the United States. The major risk factor for parkinsonism is advancing age. Tremor, rigidity, and abnormal gait characterize the classic parkinsonism patient. Hypokinesia, or the slowing of movements, also causes an immobility of the facial muscles, causing the classic “Parkinson stare.” Patients may complain of blepharospasm, or an involuntary closure of the eyelids. In addition, a fluttering of the eyelids, or blepharoclonus, may occur. Blepharoclonus should be readily differentiated from myokymia, an involuntary and benign fluttering of an eyelid that is unrelated to parkinsonism.

This condition is most commonly idiopathic and known as Parkinson’s disease, but may also be caused by encephalitis, drugs, and toxicity.

In parkinsonism, a loss of cells and an essential protein (alpha-synuclein) occurs in the brainstem. In addition, it appears that an imbalance exists between two antagonistic neurotransmitters, acetylcholine (ACh) and dopamine, in the corpus striatum. This derangement of the normal balance of neurotransmitters would explain the abnormal motor movements characteristic of parkinsonism.

Although no treatment is necessary in early parkinsonism, in the later stages of the disease severe debilitation may be avoided by restoring the normal ACh-dopamine balance. To this end, muscarinic anticholinergic drugs such as trihexyphenidyl and benztropine suppress the effects of ACh and are useful in minimizing rigidity and tremor.

Levodopa enhances dopaminergic transmission, reduces tremor and rigidity, but also causes hypokinesia. Sinemet is a commonly prescribed parkinsonism treatment that combines levodopa with carbidopa. Levodopa administration is contraindicated in patients with narrow-angle glaucoma.

The dopamine agonists bromocriptine, pergolide, pramipexole, and ropinirole stimulate dopamine D2 receptors.

If patients are unresponsive to medical treatment, then surgically induced lesions to the internal segment of the globus pallidus will reduce tremor and rigidity. An alternative to surgery is high-frequency deep brain stimulation, which has been found to reduce all clinical manifestations of the disease.

Progressive Supranuclear Palsy

This progressive disorder represents degeneration of the cortical gray matter. Histologically, degeneration of the neurons occurs, with the presence of neuronal “tangles” in the midbrain and areas of the cerebellum. Biochemically, dopamine levels decrease.

The earliest symptoms include gait abnormalities, drop falls, and supranuclear ophthalmoplegia. The ophthalmic manifestations include vertical and, later, horizontal gaze palsy. The facial muscles become weak, and swallowing becomes difficult. Dementia is characterized by memory issues, personality changes, and slowed cognitive functions.

No treatment exists for progressive supranuclear palsy, and therapeutic measures are aimed at temporary improvement of speech, gait, and rigidity.

Wilson’s Disease

This condition is inherited as an autosomal recessive disease of copper metabolism. The condition is caused by a number of genetic mutations that cause derangement of the copper-transport protein ceruloplasmin. Without proper binding and transportation a significant amount of copper enters the general circulation and deposits in the eye, brain, liver, and kidney. As copper accumulates in the mitochondria of these target organ cells, free radical formation and oxidation lead to tissue damage.

Wilson’s disease begins in the young with an average onset by age 11 years. The most common finding in Wilson’s disease is the Kayser-Fleischer ring of the cornea. These appear as brown, circular deposits in Descemet’s membrane, where they represent abnormal deposits of copper in the cornea.

As the disease progresses, anemia, chronic liver cirrhosis, enlargement of the spleen, and thrombocytopenia may occur. Renal tubular damage may result in elevated amino acids in the urine.

As the cerebellum becomes involved, tremor, facial tics, rigidity, and difficulty swallowing may result. Eventually, dementia may be manifested by mental slowness, memory issues, and personality changes.

Treatment of Wilson’s disease is directed at removal of the copper from the organs. To this end, penicillamine may be effective, because it is a copper-chelating agent.

INCREASED INTRACRANIAL PRESSURE

The brain has a limited ability to compensate for an increase in intracranial volume due to its position inside the rigid skull. In addition, 90% of the cranial cistern is brain, and only 10% is fluid. Therefore, any process that compresses, shifts, or distorts brain tissue causes an almost immediate rise in intracranial pressure (ICP).

As ICP rises, arterial blood flow is compromised, which leads to ischemia and edema of brain tissue. If the etiology is asymmetric, such as a unilateral tumor, then brain tissue may shift across a fixed intracranial structure leading to herniation.

Significant signs and symptoms are related to an increase in ICP. It is essential to recognize these, because elevated ICP can be a life-threatening medical emergency.

The earliest clinical symptom of an increase in ICP is lethargy and fatigue. This vague symptomology rarely provokes alarm, except when it is combined with complaints of an inability to stay awake. These are all early signs that the patient is slipping into coma. Any patient who complains of a decreasing level of consciousness and decreased response to stimuli should have an immediate neurologic evaluation. Often a member of the patient’s family provides the key details describing this descent into coma. Immediate neurologic signs to evaluate include pupils, eye movements, limb mobility, and breathing.

As pressure builds up in the brain, the papillary reactions may change. As cranial nerve (CN) III becomes involved the pupils become irregular and respond poorly to light stimulation. If the medial longitudinal fasciculus (MLF) is affected then eye movements become abnormal. Finally, as pressure continues to elevate, limb paralysis ensues.

As the patient slips into coma, respiration patterns change. The rate and depth of respiration increase, and in some cases there is constant hyperventilation. In other situations intermittent apnea is present.

Causes of ICP include brain tumor, brain abscess, encephalitis, AV malformations, MS, and pseudotumor cerebri.

Pseudotumor Cerebri

Pseudotumor cerebri (PTC) is characterized by an increase in intracranial pressure. This condition most often affects young, overweight women. Many of the patients report a recent, relatively fast and undesired weight gain of as much as 40 pounds within 6 months of presentation.

Patient symptoms include dull, severe, and progressive headaches, and possible diplopia. The diplopia is horizontal and results from a lateral rectus muscle weakness. Other related symptoms include tinnitus and transient visual obscurations.

Ophthalmoscopy will reveal papilledema with nasal blurring of the optic disc. Visual fields taken immediately and quickly will reveal bilateral enlargement of the blind spots associated with concentrically contracted peripheral fields.

The signs of PTC are ominous and reminiscent of the expected clinical picture manifested by intracranial

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space-occupying lesions. No true malignancy is associated with PTC, however, hence the name pseudotumor cerebri.

The underlying cause is unknown, although drugs such as antibiotics, oral contraceptives, steroids, NSAIDs, hormones, and anesthetics may induce the syndrome. PTC is often related to pregnancy and menstrual disturbances.

The condition is often referred to as benign idiopathic intracranial hypertension, but the condition may be far from benign. An MRI is mandatory to exclude the diagnosis of brain tumor.

The treatment of PTC involves weight loss, low-salt diet, the use of diuretics and headache management. During treatment the patient should be routinely monitored with visual fields. As papilledema resolves, the size of the blind spot of the visual field will reduce in size back to normal. If the patient is unresponsive to medical therapy, a CSF shunt procedure is mandatory.

Treatment of Increased ICP

The treatment of increased ICP does not depend on etiology, and extensive testing that may delay initiation of therapy does not improve the outcome. Treatment modalities for increased ICP are described in the text that follows.

Vascular Therapy of Increased ICP

A decrease in ICP can be achieved by reducing the total cerebral blood volume. To achieve this goal, hyperventilation, or the voluntary increase in respiratory rate, is used to induce vasoconstriction. Hyperventilation decreases CO2 pressure, thus inducing vasoconstriction. Vasoconstriction in turn reduces cerebral blood volume, and a reduction in ICP follows. Reduction of ICP occurs within 30 minutes of hyperventilation, but the technique is effective only for short-term therapy.

Osmotic Therapy of Increased ICP

Osmotic agents induce water to move from the cells and interstitium to the plasma, thus reducing the water volume of the brain. The overall affect of this osmotic gradient is to reduce brain volume and ICP. In addition, by diluting the plasma the blood viscosity reduces thus preserving cerebral perfusion. Osmotics also have the added benefit of reducing cerebral spinal fluid (CSF) production and thus further reducing ICP. Mannitol solution is administered, and its desired effect usually achieved within 20 minutes. One administration lasts about 6 hours. Doses are given every 4 hours, although the effectiveness of mannitol reduces with time. In addition to osmotic agents, diuretics may be administered to enhance the ICP decrease.

Metabolic Therapy of Increased ICP

Cell injury and death result in increased oxygen delivery to the brain, resulting in undesirable free radical production. By reducing the metabolic need of the brain cells, blood flow to the brain is reduced, which in turn reduces oxygen delivery to the tissues. Barbiturate anesthesia reduces brain metabolic demand and therefore ICP, but it can have serious cardiac side effects.

Surgical Intervention of Increased ICP

Hemicraniectomy is a surgical technique useful in cases of increased ICP secondary to lobular tumor. This approach allows expansion of the involved lobe and a reduction in ICP in cases in which medical approaches have failed to reduce the ICP.

BRAIN TUMOR

Tumors of the brain may be malignant or benign (Table 17-2). Benign tumors may cause severe and life-threatening effects because of compression, hormonal production, or hemorrhagic effects.

Glioma

The most common malignant brain tumor in the U.S. population is the glioma. Low-grade glioma, such as the astrocytoma, is usually found in patients aged 5 to 30 years. The recommended treatment is observation, and the survival rate is usually 5 to 10 years.

Grade III anaplastic gliomas occur at ages 30 to 50 years, and with radiation and chemotherapy survival is usually 3 to 4 years.

Grade IV glioblastomas usually occur in patients older than 50 years, and with radiation and chemotherapy survival is at best 1 year.

It is impossible to remove all of the glioma surgically because of its infiltrative nature. In addition, total removal may cause severe neurologic deficits that are not compatible with life. Therefore, some neurosurgeons perform subtotal removal, which preserves maximal neurologic integrity while reducing symptoms related to compression.

Meningioma

These benign tumors arise from the arachnoid meningeal cells. They most often occur with increasing age and in women more than men. Meningiomas are very common, composing one seventh of all intracranial tumors. They are located in the meningeal covering the hemispheres, along the sphenoid bone along the base of the skull and the faux cerebri between the two hemispheres.

TABLE 17-2 COMMON TUMORS OF THE CENTRAL NERVOUS SYSTEM AND THEIR PROBABLE CELLS

OF ORIGIN

Meningiomas grow slowly and attain large sizes before symptoms are noticed. Early symptoms depend on location. Occipital meningiomas may produce bilateral, congruous visual field defects. One case study by this author revealed a left superior congruous scotoma resulting from a right, inferior occipital meningioma. The patient detected his bilateral positive scotomas when, on striking a golf ball, he noted that the ball disappeared as it rose up and to his left. The patient, being an artist by avocation, drew his own visual fields that exactly matched his later results with Goldmann bowl perimetry testing. In addition, the patient noted that on looking down at his golf ball, he noted color vision distortion, with the left part of the ball fringed in red and the right part of the ball fringed with green. The patient had surgical resection of the meningioma in 1984 at the age of 72 years, with complete resolution of his visual field and color defects. (He continues to thrive as of this writing at the age of 94, although he no longer plays golf!)

Meningiomas in other locations may produce seizures, abnormal gait, headache, and cranial nerve palsies.

Asymptomatic meningiomas are evaluated every 6 months. If symptoms occur, or if the tumor grows, surgical resection is indicated. Most meningiomas are removed easily if located along the meninges of the

hemispheres, but removal at the base of the brain near blood vessels and nerves is problematic.

Acoustic Neuroma

This benign tumor typically causes increasing hearing loss and mild tinnitus that gradually worsens. Patients often complain that they notice the hearing loss by not being able to use the telephone with one ear. Acoustic neuroma, also known as vestibular schwannoma, arise from vestibular nerve Schwann cells.

These tumors account for almost one tenth of all intracranial tumors. They usually occur in patients older than 20 years and are most common in 40 to 60 year olds.

Early symptoms include unilateral hearing loss and tinnitus, but as the tumor grows, difficulty with walking and ataxia occur.

On examination, a nystagmus often manifests on lateral gaze. As the brainstem becomes compromised, CN-V involvement produces hemifacial sensory loss and reduced corneal sensitivity. CN-VII involvement produces hemifacial muscle weakness.

MRI evaluation allows visualization of the tumor and the adjacent structures involved.

Surgery is performed to resect the tumor with the goal of preserving CN-VII and CN-VIII. Often hearing loss is inevitable in large tumors, because the cochlear nerve cannot be distinguished from the lesion. Because of the risks of permanent hearing loss and hemifacial sensory and motor defects, small asymptomatic acoustic neuromas, particularly in the elderly patient, may be watched with an MRI series every 6 months.

Pituitary Adenoma

This tumor composes approximately one tenth of all intracranial tumors. Most pituitary adenomas arise from the anterior portion of the pituitary gland.

These tumors can secrete hormones and the associated signs and symptoms depend on the actively secreting tumor cell type. Acromegaly occurs if the tumor secretes growth hormone. If the tumor secretes adrenocorticotropic hormone, then Cushing’s disease occurs. Secreting tumors will therefore make their presence known more from their hormonal influences then from their compressional effects.

Nonsecreting pituitary adenomas produce neurologic defects because of mass effect symptoms. Although pituitary adenomas are considered benign, they may exert compressional effects on the visual pathway, cavernous sinus, and temporal lobe tip.

The hallmark visual field defect associated with a pituitary microadenoma is a bitemporal visual field defect. This defect is produced as the adenoma grows superiorly out of the sella turcica and impacts on the

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overlying optic chiasm. This author has documented a bitemporal hemianopsia, denser above, in a 32-year-old who complained of erectile dysfunction for a 6-month period. Neuroimaging confirmed the presence of a pituitary cyst impacting on the optic chiasm. After cyst removal through the transsphenoidal route, complete resolution of the visual field defect, and the erectile dysfunction was experienced.

In some cases hemorrhage into an undetected pituitary adenoma can occur. This causes visual loss, severe headache, and a change in mental function, and is known as pituitary apoplexy.

Pituitary tumors often respond to the medical treatments described in the text that follows.

Prolactin-Secreting Pituitary Tumor

Prolactin is a hormone that in women promotes hirsutism, galactorrhea, infertility, and amenorrhea. In men a loss of pubic hair and impotence occur. Prolactin production is suppressed by the use of bromocriptine, a dopamine agonist that also decreases tumor volume. If the tumor is unresponsive, then surgery is necessary.

Growth Hormone-Secreting Pituitary Tumor

Growth hormone promotes coarse features, acromegaly, cardiac and pulmonary disease, and spinal deformity. In addition, the hormone induces diabetes mellitus in certain individuals. Octreotide, a somatostatin analog, controls pituitary tumors that secrete growth hormone. If the tumor is unresponsive, then surgery is necessary.

Small Pituitary Tumor

If no symptomology is associated with a small, nonsecreting pituitary tumor, then no treatment is necessary, and the tumor is evaluated periodically by MRI.

Macroadenoma

Large, compressive pituitary tumors require surgical excision. The typical approach is transsphenoidal, during which the sella turcica is approached through the sphenoid sinus and nasal cavity. The tumor is dissected from the pituitary gland.

Craniopharyngioma

These tumors account for 2% of all intracranial tumors. They arise from the Rathke’s pouch in the region of the third ventricle or hypothalamus. Their location is variable, but often they compress downward onto the optic chiasm and pituitary gland. In this case, the tumor typically produces bitemporal hemianopsia denser below. On CT scan these tumors have characteristic cystic changes and calcification. Treatment is surgical resection, which is difficult because of their location.

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Often there is subtotal removal of the tumor, and recurrence is common.

CRANIAL NERVE CLINICOPATHOLOGIC CORRELATES

Cranial Nerve I: The Olfactory Nerve

The olfactory nerve controls the sense of smell. The inability to smell is called anosmia. Almost half of all smell disturbances are the result of sinus disease and upper respiratory infection, and one fifth of olfactory disturbances are the result of head trauma that causes damage to the cranial nerve or injury to the frontobasal cerebral cortex. Olfactory groove meningioma represents a slow-growing tumor that causes anosmia. These neoplasias have a significant morbidity, and thus early recognition of the tumor is essential.

Cranial Nerve II: The Optic Nerve

Visual field testing is mandatory in cases of optic nerve involvement. The pattern of visual field deficit may aid anatomical localization of the visual pathway lesion.

Anterior Optic Nerve

A stroke of the optic nerve at the level of the disc is known as anterior ischemic optic neuropathy (AION). The onset of the condition is heralded by a sudden, dramatic, painless loss of vision in one eye. A relative afferent papillary defect will occur on the involved side. Ophthalmoscopy will reveal a swollen, hemorrhagic, and edematous disc (disc edema). Visual field testing, even by facial confrontation, will typically reveal an altitudinal defect. Because this usually occurs on awakening, it is thought that an anatomically congested disc, combined with low blood pressure during sleep, combine to cause artery occlusion and infarct of the optic nerve. The involved eye cannot be treated, but aspirin, 81 mg/day orally, is recommended as antiplatelet therapy to reduce the chance of bilateral eye involvement.

Inflammation of the mediumto large-sized arteries of the body causes giant cell arteritis. At first there is typically a prodrome of fever, malaise, weight loss, and headaches, which may last for weeks. Patients begin to notice pain on chewing or when combing their hair because of a tender superficial temporal artery. Usually the patient seeks medical care when vision, either in one or both eyes, is lost. The condition occurs in the elderly population, usually older than 65 years. An immediate ESR should be ordered with use of the Westergren technique. Elevated sedimentation rates reach 60 to 120 mm/hr. A temporal artery biopsy will reveal giant cell granulomas. Treatment is instituted immediately with high-dose prednisone and

maintained for 3 to 6 months. As the ESR drops, the systemic steroid is tapered.

Retrobulbar Optic Nerve

Optic neuritis is one of the first presenting signs of multiple sclerosis and is characterized by unilateral periocular pain that is made worse by eye movements. The term “optic neuritis” is a misnomer, however, because the condition, originally thought to be inflammatory in nature, is actually caused by demyelination. Nonetheless, the historical name persists throughout the medical literature.

Visual loss in optic neuritis is sudden, with visual field and color vision defects. The optic nerve appears normal, and so optic neuritis is often referred to as “retrobulbar optic neuritis,” a condition in which “the examiner sees nothing and the patient sees nothing.”

Visual recovery to a near-normal state occurs in most cases within 2 to 3 months. Eventually, pallor of the temporal optic nerve head may occur.

Treatment of optic neuritis involves the use of intravenous methylprednisolone for 3 days followed by oral prednisone in an attempt to speed visual recovery and reduce recurrent MS episodes. Oral prednisone should never be used alone in cases of optic neuritis because a greater risk of recurrence of the MS exists when compared with no treatment at all.

Cranial Nerve III: The Oculomotor Nerve

Third cranial nerve disorders are best categorized based on the anatomical location of the lesion. The nerve begins its extensive course at the Edinger-Westphal nucleus, passes through the red nucleus, enters the interpeduncular cistern, then pierces the dura en route to the cavernous sinus. From here it enters the superior orbital fissure and passes through to the orbit.

Cranial Nerve III: Palsy

Oculomotor palsy is characterized by an abducted and depressed eye with ptosis. When the lid is lifted, the involved pupil will be seen to be dilated.

CN-III: Nerve Disorders With Aneurysm

Of all patients with intracranial aneurysms, 90% are seen with CN-III palsy. The most common cause of CN-III palsy with acute headache is an aneurysm of the posterior communicating artery. In these cases pupil dilation will be present on the affected side. One third of all CN-III palsies arise from these aneurysms.

CN-III: Palsy Without Aneurysm

More than two thirds of all CN-III palsies are not the result of an aneurysm. These will present without pupillary involvement. In these cases the underlying

disorder is a systemic disease such as diabetes or systemic hypertension. The outcome is usually favorable once treatment of the underlying disorder commences, and the palsy resolves in 3 to 6 months. It is important to note that a CN-III palsy with pupil sparing does not exclude an aneurysm, but simply implies a greater chance of a benign etiology. All CN-III palsy patients are considered at risk for aneurysm and deserve a neurologic evaluation to consider the use of MRI or MRA.

Traumatic CN-III: Palsy

Traction injury to the third nerve may occur at the level of the dural entrance near the petrous bone. This injury is typical of head trauma in a car accident. Pupillary involvement mandates neuroimaging to exclude serious underlying head trauma. Recovery of traumatic CN-III palsy is characterized by aberrant regeneration, wherein axonal regrowth is misdirected and axons innervate disparate muscle groups.

Cavernous Sinus CN-III: Palsy

Cavernous sinus syndrome (CSS) is caused by slowly growing tumors within the cavernous sinus. Early symptomology includes diplopia with hemicranial facial pain along the route of the ophthalmic branch of CN-V (V2).

Orbital CN-III: Palsy

In orbital apex syndrome, a tumor or inflammatory process of the orbit causes a painful ophthalmoplegia with pupil sparing. Orbital imaging is necessary for pinpointing the etiology.

Cranial Nerve IV: The Trochlear Nerve

The patient with trochlear palsy has a hypertropia develop on the involved side. This patient has difficulty with depression of the eye because of superior oblique muscle palsy. Neuroimaging is not required in all cases of CN-IV palsy. If no other cranial nerve is involved, and the diagnosis is obvious (i.e., diabetes or trauma) then the isolated CN-IV palsy may be watched for 4 months. Typically, spontaneous improvement occurs. If other cranial nerves are involved, neuroimaging is mandatory.

Traumatic CN-IV: Nerve Palsy

Traumatic CN-IV nerve palsy is common in head trauma. These may occur in combination with a contralateral Horner’s syndrome. Often, CN-IV and CN-V palsies occur simultaneously, most likely because of their positions along the lateral wall of the cavernous sinus.

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Cranial Nerve V: The Trigeminal Nerve

Trigeminal Neuralgia

Brief episodes of pain within the distribution of the trigeminal nerve can be excruciating and debilitating. Also known as tic douloureux, the condition is diagnosed on the basis of history of hemifacial pains along the distribution of the trigeminal nerve. Trigeminal pain is caused by myelin loss in the posterior root of the fifth nerve. Treatment involves the use of carbamazepine which increases the threshold of neural stimulation. Other medications include phenytoin, gabapentin, and baclofen (Lioresal). If medical intervention fails, surgical decompression may be effective.

Cranial Nerve VI: The Abducens Nerve

CN-VI palsy produces an adducted eye with esotropia. Movement of the eye beyond the midline is reduced or lost altogether.

Vascular Occlusive CN-VI Palsy

Anterior inferior cerebellar artery occlusion causes extensive damage, producing nystagmus, vertigo, gaze palsy, facial paralysis, deafness, and ataxia.

Foville’s Syndrome

Foville’s syndrome is characterized by CN-VI nuclear palsy, facial analgesia, Horner’s syndrome, and deafness.

Paramedian Basilar Artery Branch Occlusion

Infarction of the pons produces an ipsilateral gaze palsy, hemifacial paralysis, and nystagmus with limb ataxia.

Raymond’s Syndrome

Raymond’s syndrome is similar to other CN-VI palsies and is characterized by abduction deficit and crossed hemiplegia. If ipsilateral facial palsy is present, the condition is referred to as Millard-Gubler syndrome.

Cranial Nerve VII: The Facial Nerve

CN-VII lesions produce some of the most common cranial mononeuropathies. CN-VII has a long course, multiple functions, and four components. All lesions of the seventh cranial nerve produce some degree of facial paralysis.

Cerebral Infarct

Upper motor neuron dysfunction is characterized by facial palsy with sparing of the orbicularis oculi and frontalis muscles.

Intermedullary Pontine Lesion

Because of CN-VII and CN-VI involvement, hemifacial paralysis of the muscles of facial expression will be present, combined with an abduction deficit.

Facial Palsy

Benign idiopathic facial palsy causes loss of motor function to half of the face involving the muscles of facial expression to a variable degree. Lacrimal gland dysfunction is typical in these cases, and patients will often be seen with unilateral dry eye. A unilateral weakness will evolve during a few days. The cause of facial nerve palsy is unknown, but the condition is characterized by edema and ischemia of CN-VII within the bony canal. The condition is diagnosed on the basis of facial asymmetry with eversion of the lower lid on the involved side resulting in epiphora. Lagophthalmos is often present and responsible for an inferior corneal exposure keratitis.

When the patient attempts to close his or her eye, the involved globe is seen to pitch upwards and under the upper lid. This is known as the Bell phenomenon. Other clinical phenomenon include the inability to puff out the cheek on the involved side, the easy parting of the lids on attempted squinting, and the loss of the ability to voluntarily smile on the involved side.

The prognosis of Bell’s palsy is very good, with recovery occurring in 2 weeks to 6 months. In 15% of cases, residual facial weakness or synkinesis is present. Synkinesis is the result of aberrant regeneration.

Cranial Nerve VIII: The Vestibular Nerve

CN-VIII is actually composed of two nerves: the vestibular nerve that controls equilibrium and balance, and the auditory nerve that is responsible for hearing.

Dizziness

In the United States, 8 million patients are seen each year for the complaint of dizziness. This vague complaint is responsible for more doctor visits in the patient population during a 75-year period than for any other complaint. Dizziness is best described as a feeling of light-headedness, a loss of equilibrium, vertigo, a sense of near-fainting, and a cause of unsteadiness.

Vertigo

Vertigo is the illusion of motion when the patient is completely still. The patient will report that they feel as if they are being spun around, and he or she may experience concurrent nausea, vomiting, and nystagmus. One form of vertigo, oscillopsia, is the inability to maintain stable vision during head movements, resulting in unstable visual perception. The patient literally perceives the entire visual world moving whenever head movements are initiated.

Sensorineural Hearing Loss

Sensorineural hearing loss (SNHL) occurs as the result of auditory nerve dysfunction. Hearing loss may be the result of acoustic tumors or serous otitis media. SNHL can be caused by toxic drug exposure, noise exposure, tumors, vascular disorders, and autoimmune disease.

Tinnitus

Tinnitus is an internally produced sound heard only by the patient. This noise may range from a soft ringing noise to a loud and constant roar. It is associated with exposure to loud noise, drugs, acoustic tumor, and Meniere’s disease. Tinnitus may be caused by aspirin and the aminoglycosides.

CN-VIII: Central Nervous System Disorders

Inferior cerebellum infarction will cause diplopia, dysphagia, weakness, and postural instability. If the result of a hemorrhage, brain swelling and death may result. Cerebellar lesions from multiple sclerosis will cause acute vertigo and gait dysfunction similar to cerebellar infarction, but in this case the similar clinical picture does not have as ominous an etiology. Peripheral nervous system disorders likewise can cause vertigo and weakness but will not cause gait dysfunction. Neuroimaging is mandatory to distinguish between these three processes.

Peripheral Nervous System Disorders

Vertigo is caused by an acute peripheral vestibular dysfunction whereby a unilateral reduction in vestibular input compared with the contralateral and normal labyrinth input is interpreted as spinning. With unilateral vestibular loss comes the clinical sign of nystagmus. Labyrinthitis is characterized by hearing loss and tinnitus that lasts for days to weeks, and is most likely of viral etiology. Vertigo that lasts for hours and is associated with hearing loss and tinnitus is a typical sign of Meniere’s disease.

Cranial Nerve IX: The Glossopharyngeal Nerve

CN-IX supplies the primary afferent pathway, and CN-X supplies the secondary afferent pathway for swallowing. Both nerves terminate in the swallowing center located in the medulla. Difficulty swallowing, or dysphagia, can occur from a host of causes.

Cranial Nerve X: The Vagus Nerve

Voice disorders can occur from tumors of the thyroid, lung, or neck. In addition, stroke, infectious diseases, and diabetes can affect voice quality, control, and pitch. Lesions of CN-X, such as are caused by highlevel stroke, cause voice disorders.

Cranial Nerve XI: The Spinal Accessory Nerve

This is the major nerve input to the sternocleidomastoid muscle (SCM) and the trapezius muscle. Lesions of CN-XI cause weakness in the neck and upper back, manifested as a drooping of the shoulder. CN-XI damage occurs most frequently from surgery, carotid endarterectomy, and spinal cord lesions.

Cranial Nerve XII: The Hypoglossal Nerve

This nerve controls the final common pathway for language production and food intake. Lesions of CN-XII produce tongue deviation toward the side of the lesion. Acute carotid artery dissection causes Horner’s syndrome and associated CN-XII neuropathy. Swallowing and speech are not affected unless bilateral CN-XII involvement occurs.

NEUROEYE DISEASE The Pupil

Elegantly simple yet sensitive, the pupil examination offers a significant way to probe the neurologic pathways of the eye. Although the pupil examination requires an understanding of the neurologic anatomy of the pupil system (Box 17-1) the examiner is faced with practical questions such as “How can I differentiate a benign pupil problem from a serious one?” or “How can the pupil examination help me diagnose serious ocular or systemic disease?” This process begins by an examination of the pupil.

Examination of the Pupil

Pupil Observation

Examination of the pupil should be performed by gross observation under the magnification of a slitlamp. The examiner should look for a round pupil that is displaced slightly nasally. Any distortion of pupil shape or misposition must be explained.

Observation of the pupil is best performed in normal, then dim, illumination. It is important to prevent the patient from feeling anxiety or fear, because this may psychologically alter pupil size.

Unequal pupil size is known as anisocoria. If anisocoria is present, then the pupil sizes should be measured. The easiest way to do this is to compare the pupil being examined to a scale on which is printed a gradient of increasing sizes of circles (Figure 17-5). This is known as the Haab scale, and it is held just temporal to the eye.

Pupil size should be measured no matter how subtle the anisocoria. These measurements should be made first in dim illumination and then in bright illumination. Looking at these measurements, the ex-

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aminer should determine whether the anisocoria is greater in bright illumination or in dim light. If the anisocoria is greater in bright illumination, then the dilated pupil is usually the involved eye. If the anisocoria is greatest in dim illumination, then the eye with the constricted pupil is usually the involved eye (Figure 17-6).

When measuring pupil size, the examiner should be sure to have the patient fixate at a distant point slightly above the horizon to avoid the miosis caused by the near reflex.

The Light Reflex

The Direct Response. When a light brighter than the ambient illumination is directed into the eye, the iris will constrict, causing the pupil to reduce in size. This process is known as the pupillary light reflex.

To test the direct light reflex it is appropriate to use two hand-held illuminators such as a penlight and ophthalmoscope. The examiner should dimly illuminate both eyes by holding a light below the patient’s face. The light should be just bright enough to allow the viewer to differentiate the pupil from the iris. A binocular indirect ophthalmoscope with a variable light setting can be used for this purpose. The illuminator held at such an oblique angle to the eyes will allow for only a small amount of light to enter the pupils.

The examiner should elicit the direct reflex by swinging a second bright light source upwards to shine directly into the pupil. This is a superior method to switching the bright light source on and off, because this can annoy the patient.

It is normal to note a constant amount of pupillary unrest, known as pupillary oscillations, under conditions of normal and constant illumination. These periodic fluctuations in pupil size are the result of a process whereby the iris continually adjusts the amount of light entering the eye to produce the appropriate value of retinal illumination.

When light is directed into the eye, the pupil at first constricts vigorously and then oscillates until it stabilizes to a size larger than its initial constriction. This movement is known as the tonic pupillary reflex. The absence of this response should be noted.

The Consensual Response. The examiner should next shine a light into the same eye but observe the dimly lit, unstimulated eye. It will also constrict. This movement is known as the consensual pupillary light reflex. A loss of the consensual light reflex (Figure 17-7) means that the pupil in the unstimulated eye does not constrict.

Swinging Flashlight Test

In this test, the examiner shines a light into one pupil but off the visual axis. Both pupils will constrict because of the direct and consensual light reflex. When