3436 PART 13 Neurologic Disorders

TABLE 440-9 Initial Treatment of Orthostatic Hypotension (OH)

Patient education: mechanisms and stressors of OH

High-salt diet (10–20 g/d)

High-fluid intake (2 L/d)

Elevate head of bed 10 cm (4 in.) to minimize supine hypertension

Maintain postural stimuli

Learn physical counter-maneuvers

Compression garments

Correct anemia

should be similarly approached in a gradual manner. One maneuver

that can reduce OH is leg-crossing with maintained contraction of

leg muscles for 30 seconds; this compresses leg veins and increases

systemic resistance. Compressive garments, such as compression

stockings or abdominal binders, are helpful on occasion but are

uncomfortable for many patients. For transient worsening of OH,

drinking two 250-mL (8-oz) glasses of water within 5 min can raise

standing BP 20–30 mmHg for about 2 h, beginning ~5 min after the

fluid load. The patient can increase intake of salt and fluids (bouillon treatment), increase use of physical counter-maneuvers (elevate

the legs when supine), or temporarily resort to a full-body stocking

(compression pressure 30–40 mmHg).

Anemia can be corrected with erythropoietin, administered

subcutaneously at doses of 25–75 U/kg three times per week. The

hematocrit increases after 2–6 weeks. A weekly maintenance dose is

usually necessary. However, the increased intravascular volume that

accompanies the rise in hematocrit can exacerbate supine hypertension and requires monitoring.

If these measures are not sufficient, additional pharmacologic

treatment may be necessary. Midodrine, a directly acting α1

-agonist

that does not cross the blood-brain barrier, is effective. It has a

duration of action of 2–4 h. The usual dose is 5–10 mg orally tid, but

some patients respond best to a decremental dose (e.g., 15 mg on

awakening, 10 mg at noon, and 5 mg in the afternoon). Midodrine

should not be taken after 6:00 pm. Side effects include pruritus,

uncomfortable piloerection, and supine hypertension, especially at

higher doses. Droxidopa (Northera) for treatment of neurogenic

OH associated with PAF, PD, or MSA is effective in decreasing

symptoms of OH. Pyridostigmine appears to improve OH without

aggravating supine hypertension by enhancing ganglionic transmission (maximal when orthostatic, minimal when supine), but

with only modest clinical effects on BP. Fludrocortisone will reduce

OH but aggravates supine hypertension. At doses between 0.1 mg/d

and 0.3 mg bid orally, it enhances renal sodium conservation and

increases the sensitivity of arterioles to NE. Susceptible patients

may develop fluid overload, congestive heart failure, supine hypertension, or hypokalemia. Potassium supplements are often necessary with chronic administration of fludrocortisone. Sustained

elevations of supine BP >180/110 mmHg should be avoided. Supine

hypertension (>180/110 mmHg) can be self-treated by avoiding

the supine position (e.g., sleeping in a recumbent chair or elevating

the head of the bed) and reducing fludrocortisone. If these simple

measures are not adequate, drugs to be considered include oral

hydralazine (25 mg qhs), oral nifedipine (Procardia; 10 mg qhs), or

a nitroglycerin patch.

A promising drug combination (atomoxetine and yohimbine)

has been studied for use in human subjects with severe OH not

responsive to other agents, as can occur in some patients with

diabetes and severe autonomic neuropathy not responsive to other

medications. The atomoxetine blocks the NE reuptake transporter,

and yohimbine blocks α2

 receptors that mediate the sympathetic

feedback loop for downregulation of BP in response to atomoxetine. The result is a dramatic increase in BP and standing tolerance. Yohimbine is no longer produced commercially and must be

obtained from a compounding pharmacy. This combination is not

FDA approved for this purpose.

Postprandial OH may respond to several measures. Frequent,

small, low-carbohydrate meals may diminish splanchnic shunting

of blood after meals and reduce postprandial OH. Prostaglandin inhibitors (ibuprofen or indomethacin) taken with meals or

midodrine (10 mg with the meal) can be helpful. The somatostatin

analogue octreotide can be useful in the treatment of postprandial

syncope by inhibiting the release of GI peptides that have vasodilator and hypotensive effects. The subcutaneous dose ranges from

25 μg bid to 200 μg tid.

■ FURTHER READING

Campbell WW, Barohn RJ: The Autonomic Nervous System, in

DeJong’s The Neurologic Examination, 8th ed. WW Campbell, RJ

Barohn (eds). Philadelphia, Wolters Kluwer, 2020.

Francescangeli J et al: The serotonin syndrome: From molecular

mechanisms to clinical practice. Int J Mol Sci 20:2288, 2019.

Gibbons CH et al: The recommendations of a consensus panel for the

screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 264:1587, 2017.

Golden EP et al: Seronegative autoimmune autonomic neuropathy:

A distinct clinical entity. Clin Auto Res 28:115; 2018.

Kaufmann H et al: Natural history of pure autonomic failure:

A United States prospective cohort. Ann Neurol 81:287, 2017.

MacDonald S et al: Longitudinal follow-up of biopsy-proven small

fiber neuropathy. Muscle Nerve 60:376, 2019.

Novak P: Autonomic disorders. Am J Med 132:420, 2018.

Woerman AL et al: Kinetics of α-synuclein prions preceding neuropathological inclusions in multiple system atrophy. PLoS Pathol

16:e1008222, 2020.

The cranial nerves consist of 12 paired nerves that mediate variable

combinations of motor, sensory, and autonomic functions. They are

considered as a group because of their close anatomic relationship to

the brainstem (Fig. 441-1) and to one another, and tendency to be

involved together in a variety of disease states. Nine cranial nerves

connect directly with brainstem nuclei; the exceptions are cranial

nerves 1 (olfactory) and 2 (optic) that are more accurately considered

fiber tracts of the brain, and cranial nerve 11 (spinal accessory) whose

motor neurons reside largely in the upper cervical cord. Analogous to

spinal nerves (Chap. 442), motor fibers of the cranial nerves have their

origin in the brainstem or upper cervical cord, while sensory nerves are

pseudounipolar, with ganglia outside the central nervous system and a

synapse with second-order fibers in the brainstem.

Symptoms and signs of cranial nerve pathology are common in

internal medicine. They often develop in the context of a widespread

neurologic disturbance, and in such situations, cranial nerve involvement may represent the initial manifestation of the illness. In other

disorders, involvement is largely restricted to one or several cranial

nerves; these distinctive disorders are reviewed in this chapter. Disorders of olfaction are discussed in Chap. 33, vision and ocular

movement in Chap. 32, hearing in Chap. 34, and vestibular function

in Chap. 22.

441 Trigeminal Neuralgia,

Bell’s Palsy, and Other

Cranial Nerve Disorders

Vanja C. Douglas, Stephen L. Hauser

3437Trigeminal Neuralgia, Bell’s Palsy, and Other Cranial Nerve Disorders CHAPTER 441

very rarely, in the distribution of the ophthalmic division of the fifth

nerve. The pain seldom lasts more than a few seconds or a minute or

two but may be so intense that the patient winces, hence the term tic.

The paroxysms, experienced as single jabs or clusters, tend to recur

frequently, both day and night, for several weeks at a time. They may

occur spontaneously or be brought on with movements of affected

areas by speaking, chewing, or smiling. Another characteristic feature

is the presence of trigger zones, typically on the face, lips, or tongue,

that provoke attacks; patients may report that tactile stimuli—e.g.,

washing the face, brushing the teeth, or exposure to a draft of air—

generate excruciating pain. An essential feature of trigeminal neuralgia is that objective signs of sensory loss cannot be demonstrated on

examination.

Trigeminal neuralgia is relatively common, with an estimated annual

incidence of 4–8 per 100,000 individuals. Middle-aged and elderly persons are affected primarily, and ~60% of cases occur in women. Onset

is typically sudden, and bouts tend to persist for weeks or months

before remitting spontaneously. Remissions may be long-lasting, but in

most patients, the disorder ultimately recurs.

Pathophysiology Symptoms result from ectopic generation of

action potentials in pain-sensitive afferent fibers of the fifth cranial

nerve root just before it enters the lateral surface of the pons. Compression or other pathology in the nerve leads to demyelination of

large myelinated fibers that do not themselves carry pain sensation but

become hyperexcitable and electrically coupled with smaller unmyelinated or poorly myelinated pain fibers in close proximity; this may

explain why tactile stimuli, conveyed via the large myelinated fibers,

can stimulate paroxysms of pain. Compression of the trigeminal nerve

root by a blood vessel, most often the superior cerebellar artery or on

occasion a tortuous vein, is believed to be the source of trigeminal neuralgia in most patients. In cases of vascular compression, age-related

brain sagging and increased vascular thickness and tortuosity may

explain the prevalence of trigeminal neuralgia in later life.

Differential Diagnosis Trigeminal neuralgia must be distinguished from other causes of face and head pain (Chap. 16) and from

pain arising from diseases of the jaw, teeth, or sinuses. Pain from

migraine or cluster headache tends to be deep-seated and steady,

unlike the superficial stabbing quality of trigeminal neuralgia; rarely,

cluster headache is associated with trigeminal neuralgia, a syndrome

known as cluster-tic. Other rare headaches include short-lasting

unilateral headache attacks with conjunctival injection and tearing

(SUNCT; Chap. 430). In temporal arteritis, superficial facial pain is

present but is not typically shocklike, the patient frequently complains

of myalgias and other systemic symptoms, and an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) is usually

present (Chap. 363). When trigeminal neuralgia develops in a young

adult or is bilateral, MS is a key consideration, and in such cases, the

cause is a demyelinating plaque near the root entry zone of the fifth

nerve in the pons; often, evidence of facial sensory loss can be found on

careful examination. Cases that are secondary to mass lesions—such as

aneurysms, neurofibromas, acoustic schwannomas, or meningiomas—

usually produce objective signs of sensory loss in the trigeminal nerve

distribution (trigeminal neuropathy, see below).

Laboratory Evaluation An ESR or CRP is indicated if temporal

arteritis is suspected. In typical cases of trigeminal neuralgia, neuroimaging studies are usually unnecessary but may be valuable in patients

younger than 40 years or when symptoms are bilateral and MS is a

consideration or in assessing overlying vascular lesions in order to plan

for decompression surgery.

TREATMENT

Trigeminal Neuralgia

Drug therapy with carbamazepine is effective in ~50–75% of

patients. Carbamazepine should be started as a single daily dose of

100 mg taken with food and increased gradually (by 100 mg daily

in divided doses every 1–2 days) until substantial (>50%) pain relief

Frontal

lobe

Temporal

lobe

Cranial

nerves

Olfactory

bulb and

peduncle

Pituitary

gland

Mamillary

bodies

Trigeminal

ganglion

Cerebellopontine

angle

Cerebellum

XII

XI

X

IX

VIII

VII

VI

V

IV

III

II

FIGURE 441-1 Ventral view of the brain, illustrating relationships between the

12 pairs of cranial nerves and the brainstem. (Adapted from SG Waxman: Clinical

Neuroanatomy, 29th ed. http://www.accessmedicine.com)

FACIAL PAIN OR NUMBNESS

■ ANATOMIC CONSIDERATIONS

The trigeminal (fifth cranial) nerve supplies sensation to the skin

of the face, anterior half of the head, and the nasal and oral mucosa

(Fig. 441-2). The motor part innervates the muscles involved in

chewing (including masseters and pterygoids) as well as the anterior

belly of the digastric, mylohyoid, tensor veli palatini, and the tensor

tympani (hearing especially for high-pitched tones). It is the largest

of the cranial nerves. It exits in the lateral midpons and traverses the

middle cranial fossa to the semilunar (gasserian, trigeminal) ganglion

in Meckel’s cave, where the nerve splits into three divisions (ophthalmic [V1], maxillary [V2], and mandibular [V3]). V1 and V2 traverse

the cavernous sinus to exit in the superior orbital fissure and foramen

rotundum; V3 exits through the foramen ovale. The trigeminal nerve

is predominantly sensory, and motor innervation is exclusively carried

in V3. The cornea is primarily innervated by V1, although an inferior

crescent may be V2. Upon entering the pons, pain and temperature

fibers descend ipsilaterally to the upper cervical spinal cord as the

spinal tract of V, before synapsing with the spinal nucleus of V; this

accounts for the facial numbness that can occur with spinal cord

lesions above C2. In the brainstem, the spinal tract of V is also located

adjacent to crossed ascending fibers of the spinothalamic tract, producing a “crossed” sensory loss for pain and temperature (ipsilateral face,

contralateral arm/trunk/leg) with lesions of the lateral lower brainstem.

CN V is also ensheathed by oligodendrocyte-derived, rather than

Schwann cell–derived, myelin for up to 7 mm after it leaves the brainstem, unlike just a few millimeters for other cranial and spinal nerves;

this may explain the high frequency of trigeminal neuralgia in multiple

sclerosis (MS) (Chap. 444), a disorder of oligodendrocyte myelin.

■ TRIGEMINAL NEURALGIA (TIC DOULOUREUX)

Clinical Manifestations Trigeminal neuralgia is characterized by

excruciating paroxysms of pain in the lips, gums, cheek, or chin and,

3438 PART 13 Neurologic Disorders

is achieved. Most patients require a maintenance dose of 200  mg

four times daily. Doses >1200 mg daily provide no additional benefit. Dizziness, imbalance, sedation, and rare cases of agranulocytosis

are the most important side effects of carbamazepine. If treatment

is effective, it is usually continued for 1 month and then tapered

as tolerated. Oxcarbazepine (300–1200 mg bid) is an alternative

to carbamazepine that has less bone marrow toxicity and probably is equally efficacious. If these agents are not well tolerated or

are ineffective, phenytoin (300–400 mg daily) is another option.

Lamotrigine (400 mg daily), baclofen (10–20 mg tid), or topiramate

(50 mg bid) may also be tried. Gabapentin, up to 3600 mg daily in

divided doses, may occasionally provide relief.

If drug treatment fails, surgical therapy should be offered. The

most widely used method is currently microvascular decompression to relieve pressure on the trigeminal nerve as it exits the

pons. This procedure requires a suboccipital craniotomy. This

procedure appears to have a >70% efficacy rate and a low rate

of pain recurrence in responders; the response is better for classic ticlike symptoms than for nonlancinating facial pains. Highresolution magnetic resonance angiography is useful preoperatively

to visualize the relationships between the fifth cranial nerve root

and nearby blood vessels.

Gamma knife radiosurgery of the trigeminal nerve root is also

used for treatment and results in complete pain relief, sometimes

delayed in onset, in approximately one-half of patients and a low

risk of persistent facial numbness; the response is sometimes

long-lasting, but recurrent pain develops over 2–3 years in onethird of patients. Compared with surgical decompression, gamma

knife surgery appears to be somewhat less effective but has few

serious complications.

Another procedure, radiofrequency thermal rhizotomy, creates

a heat lesion of the trigeminal ganglion or nerve. Short-term relief

Ophthalmic (V1)

KEY

Maxillary (V2)

Mandibular (V3)

Supraorbital nerve

Anterior ethmoidal nerve

Posterior ethmoidal nerve

Nasociliary nerve

Frontal nerve

Ophthalmic nerve

Semilunar

ganglion

Frontal branch

of frontal nerve

Supratrochlear

nerve

Infratrochlear

nerve

Ciliary ganglion

nerve

Internal nasal

rami

Infraorbital

nerve

External

nasal rami

Nasal and labial

rami of infraorbital

nerve

Anterior superior

alveolar neves

Submaxillary

ganglion

Submaxillary

and sublingual

glands

Mental nerve

Pterygopalatine ganglion

Auriculotemporal nerve

Otic ganglion

Buccinator nerve

Internal pterygoid muscle

Masseter muscle

Mylohyoid nerve

Anterior belly of

digastric muscle

External pterygoid muscle

Chorda tympani nerve

Anterior and posterior deep temporal

nerves (to temporal muscles)

Mandibular nerve

Mesencephalic nucleus of V

Main sensory nucleus of V

Main motor nucleus of V

Nucleus of spinal tract of V

Lacrimal Maxillary

Inferior alveolar nerve

Lingual nerve

C2

C3

C4

FIGURE 441-2 The trigeminal nerve and its branches and sensory distribution on the face. The three major sensory divisions of the trigeminal nerve consist of the

ophthalmic, maxillary, and mandibular nerves. (Reproduced with permission from Waxman SG: Clinical Neuroanatomy, 26th ed. New York, McGraw-Hill, 2009.)

3439Trigeminal Neuralgia, Bell’s Palsy, and Other Cranial Nerve Disorders CHAPTER 441

TABLE 441-1 Trigeminal Nerve Disorders

Nuclear (Brainstem) Lesions

Multiple sclerosis

Stroke

Syringobulbia

Glioma

Lymphoma

Preganglionic Lesions

Acoustic neuroma

Meningioma

Metastasis

Chronic meningitis

Cavernous carotid aneurysm

Semilunar Ganglion Lesions

Trigeminal neuroma

Herpes zoster

Infection (spread from otitis media or mastoiditis)

Cavernous Sinus Lesions (see Table 441-2)

Peripheral Nerve Lesions

Tumor (e.g., nasopharyngeal carcinoma, squamous cell carcinoma, lymphoma)

Trauma

Guillain-Barré syndrome

Sjögren’s syndrome

Collagen-vascular diseases

Sarcoidosis

Leprosy

Drugs (stilbamidine, trichloroethylene)

Idiopathic trigeminal neuropathy

FACIAL WEAKNESS

■ ANATOMIC CONSIDERATIONS

(Fig. 441-3) The seventh cranial nerve supplies all the muscles concerned with facial expression, as well as the stapedius, stylohyoid,

and posterior belly of the digastric. The sensory and parasympathetic

components (the nervus intermedius) convey taste sensation from

the anterior two-thirds of the tongue, cutaneous impulses from the

anterior wall of the external auditory canal, and preganglionic parasympathetic signals to the pterygopalatine and submaxillary ganglia,

stimulating lacrimation, rhinorrhea and salivation. The motor nucleus

of the seventh nerve lies anterior and lateral to the abducens nucleus.

After leaving the pons, the seventh nerve enters the internal auditory

meatus with the acoustic nerve. The nerve continues its course in its

own bony channel, the facial canal, and exits from the skull via the

stylomastoid foramen. It then passes through the parotid gland and

subdivides to supply the facial muscles.

A complete interruption of the facial nerve at the stylomastoid

foramen paralyzes all muscles of facial expression. The corner of the

mouth droops, the creases and skinfolds are effaced, the forehead is

unfurrowed, and the eyelids will not close. Upon attempted closure of

the lids, the eye on the paralyzed side rolls upward (Bell’s phenomenon). The lower lid sags and falls away from the conjunctiva, permitting tears to spill over the cheek. Food collects between the teeth and

lips, and saliva may dribble from the corner of the mouth. The patient

complains of a heaviness or numbness in the face, but sensory loss is

rarely demonstrable and taste is intact.

If the lesion is in the middle-ear portion, taste is lost over the anterior two-thirds of the tongue on the same side. If the nerve to the stapedius is interrupted, there is hyperacusis (sensitivity to loud sounds).

Lesions in the internal auditory meatus may affect the adjacent auditory and vestibular nerves, causing deafness, tinnitus, or dizziness.

Intrapontine lesions that paralyze the face usually affect the abducens

nucleus as well, and often the corticospinal and sensory tracts.

If the peripheral facial paralysis has existed for some time and recovery of motor function is incomplete, a continuous diffuse contraction of

facial muscles may appear. The palpebral fissure becomes narrowed, and

the nasolabial fold deepens. Facial spasms, initiated by movements of the

face, may develop (hemifacial spasm). Anomalous regeneration of seventh

nerve fibers may result in other troublesome phenomena. If fibers originally connected with the orbicularis oculi come to innervate the orbicularis

oris, closure of the lids may cause a retraction of the mouth (synkinesis),

or if parasympathetic fibers originally connected with salivary glands later

innervate the lacrimal gland, anomalous tearing (“crocodile tears”) may

occur with eating. Another facial synkinesia is triggered by jaw opening,

causing closure of the eyelids on the side of the facial palsy (jaw-winking).

■ BELL’S PALSY

The most common form of facial paralysis is Bell’s palsy. The annual

incidence of this idiopathic disorder is ~25 per 100,000 annually, or

about 1 in 60 persons in a lifetime. Risk factors include pregnancy and

diabetes mellitus.

Clinical Manifestations The onset of Bell’s palsy is fairly abrupt,

with maximal weakness being attained by 48 h as a general rule. Pain

behind the ear may precede the paralysis for a day or two. Taste sensation may be lost unilaterally, and hyperacusis may be present. In some

cases, there is mild cerebrospinal fluid lymphocytosis. MRI may reveal

swelling and uniform enhancement of the geniculate ganglion and

facial nerve and, in some cases, entrapment of the swollen nerve in the

temporal bone. Approximately 80% of patients recover within a few

weeks or months. Electromyography may be of some prognostic value;

evidence of denervation after 10 days indicates there has been axonal

degeneration, that there will be a long delay (3 months as a rule) before

regeneration occurs, and that it may be incomplete. The presence of

incomplete paralysis in the first week is the most favorable prognostic

sign. Recurrences are reported in ~7% of cases.

Pathophysiology In acute Bell’s palsy, there is inflammation of

the facial nerve with mononuclear cells, consistent with an infectious

is experienced by >95% of patients; long-term studies indicate that

pain recurs in up to one-third of treated patients. Postoperatively,

partial numbness of the face is common, masseter (jaw) weakness

may occur especially following bilateral procedures, and corneal

denervation with secondary keratitis can follow rhizotomy for firstdivision trigeminal neuralgia. Percutaneous balloon compression of

the trigeminal ganglion is an alternative approach performed under

general anesthesia that results in similar rates of short- and longterm pain relief and is also commonly complicated by ipsilateral

facial numbness.

■ TRIGEMINAL NEUROPATHY

A variety of diseases can affect the trigeminal nerve (Table 441-1).

Most present with sensory loss on the face or with weakness of the jaw

muscles. Deviation of the jaw on opening indicates weakness of the

pterygoids on the side to which the jaw deviates. Some cases are due

to Sjögren’s syndrome or a collagen-vascular disease such as systemic

lupus erythematosus, scleroderma, or mixed connective tissue disease.

Among infectious causes, herpes zoster (acute or postherpetic) and

leprosy should be considered. Tumors of the middle cranial fossa

(meningiomas), of the trigeminal nerve (schwannomas), or of the base

of the skull (metastatic tumors) may cause a combination of motor

and sensory signs. Lesions in the cavernous sinus can affect the

first and second divisions of the trigeminal nerve, and lesions of

the superior orbital fissure can affect the first (ophthalmic) division;

the accompanying corneal anesthesia increases the risk of ulceration

(neurokeratitis).

Isolated sensory loss over the chin (mental neuropathy) can be the

only manifestation of systemic malignancy. Rarely, an idiopathic form

of trigeminal neuropathy is observed. It is characterized by numbness

and paresthesias, sometimes bilaterally, with loss of sensation in the

territory of the trigeminal nerve but without weakness of the jaw.

Gradual recovery is the rule. Tonic spasm of the masticatory muscles,

known as trismus, is symptomatic of tetanus (Chap. 152) or may occur

in patients treated with phenothiazines.

3440 PART 13 Neurologic Disorders

or immune cause. Herpes simplex virus (HSV) type 1 DNA was frequently detected in endoneurial fluid and posterior auricular muscle,

suggesting that a reactivation of this virus in the geniculate ganglion

may be responsible for most cases. Reactivation of varicella-zoster

virus is associated with Bell’s palsy in up to one-third of cases and

may represent the second most frequent cause. A variety of other

viruses have also been implicated less commonly, and Bell’s palsy can

be observed in the setting of human immunodeficiency virus (HIV)

seroconversion.

Differential Diagnosis There are many other causes of acute

facial palsy that must be considered in the differential diagnosis of

Bell’s palsy. Lyme disease can cause unilateral or bilateral facial palsies; in endemic areas, ≥10% of cases of facial palsy are likely due

to infection with Borrelia burgdorferi (Chap. 186). Ramsay Hunt

syndrome, caused by reactivation of herpes zoster in the geniculate

ganglion, consists of a severe facial palsy associated with a vesicular

eruption in the external auditory canal and sometimes in the pharynx

and other parts of the cranial integument; often the eighth cranial

nerve is affected as well. Facial palsy that is often bilateral occurs in

sarcoidosis (Chap. 367) and in Guillain-Barré syndrome (Chap. 447).

Leprosy frequently involves the facial nerve, and facial neuropathy may also occur in diabetes mellitus, connective tissue diseases

including Sjögren’s syndrome, and amyloidosis. The rare MelkerssonRosenthal syndrome consists of recurrent facial paralysis; recurrent—

and eventually permanent—facial (particularly labial) edema; and,

less constantly, plication of the tongue. Its cause is unknown. Acoustic

neuromas frequently involve the facial nerve by local compression.

Infarcts, demyelinating lesions of MS, and tumors are the common

pontine lesions that interrupt the facial nerve fibers; other signs of

brainstem involvement are usually present. Tumors that invade the

temporal bone (carotid body, cholesteatoma, dermoid) may produce

a facial palsy, but the onset is insidious and the course progressive.

Facial palsy after temporal bone fracture can present acutely or after a

delay of several days; blunt head injury without temporal bone fracture

may also trigger facial palsy.

All these forms of nuclear or peripheral facial palsy must be distinguished from the supranuclear type. In the latter, the frontalis

and orbicularis oculi muscles of the forehead are involved less than

those of the lower part of the face, since the upper facial muscles

are innervated by corticobulbar pathways from both motor cortices,

whereas the lower facial muscles are innervated only by the opposite

hemisphere. In supranuclear lesions, there may be a dissociation of

emotional and voluntary facial movements, and often some degree of

paralysis of the arm and leg or an aphasia (in dominant-hemisphere

lesions) is present.

Laboratory Evaluation The diagnosis of Bell’s palsy can usually

be made clinically in patients with (1) a typical presentation, (2) no

risk factors or preexisting symptoms for other causes of facial paralysis,

(3) absence of cutaneous lesions of herpes zoster in the external ear

canal, and (4) a normal neurologic examination with the exception of

the facial nerve. Particular attention to the eighth cranial nerve, which

courses near to the facial nerve in the pontomedullary junction and in

the temporal bone, and to other cranial nerves is essential. In atypical

or uncertain cases, an ESR or CRP, testing for diabetes mellitus, a

Lyme titer, HIV serologies, angiotensin-converting enzyme and chest

imaging studies for possible sarcoidosis, a lumbar puncture for possible

Guillain-Barré syndrome, or MRI scanning may be indicated. MRI

often shows swelling and enhancement of the facial nerve in idiopathic

Bell’s palsy (Fig. 441-4).

TREATMENT

Bell’s Palsy

Symptomatic measures include (1) the use of paper tape to depress

the upper eyelid during sleep and prevent corneal drying, (2) artificial tears; and (3) massage of the weakened muscles. A course of

glucocorticoids, given as prednisone 60–80 mg daily during the first

5 days and then tapered over the next 5 days, modestly shortens the

recovery period and improves the functional outcome. Although

large and well-controlled randomized trials found no added benefit

Lacrimal gland

Sublingual gland

Submandibular gland

Submandibular

ganglion

Nucleus

fasciculus

solitarius

Motor nucleus

VII n.

Motor nucleus

VI n.

Superior

salivatory

nucleus

Fasciculus

solitarius

Geniculate

ganglion

Trigeminal

ganglion

Major superficial

petrosal nerve

Pterygopalatine

ganglion

Lingual

nerve

Chorda

tympani

To nasal and

palatine glands

VII n.

V n.

1

2

3

B

C

A

FIGURE 441-3 The facial nerve. A, B, and C denote lesions of the facial nerve at the stylomastoid foramen, distal and proximal to the geniculate ganglion, respectively. Green

lines indicate the parasympathetic fibers, red line indicates motor fibers, and purple lines indicate visceral afferent fibers (taste). (Reproduced with permission from MB

Carpenter: Core Text of Neuroanatomy, 2nd ed. Williams & Wilkins, 1978.)

3441Trigeminal Neuralgia, Bell’s Palsy, and Other Cranial Nerve Disorders CHAPTER 441

of the antiviral agents valacyclovir (1000 mg daily for 5–7 days) or

acyclovir (400 mg five times daily for 10 days) compared to glucocorticoids alone, either of these agents should be used if vesicular

lesions are observed in the palate or external auditor canal. For

patients with permanent paralysis from Bell’s palsy, a number of

cosmetic surgical procedures have been used to restore a relatively

symmetric appearance to the face.

■ OTHER MOTOR DISORDERS OF THE FACE

Hemifacial spasm consists of painless irregular involuntary contractions on one side of the face. Most cases appear related to vascular

compression of the exiting facial nerve in the pons. Other cases

develop as a sequela to Bell’s palsy or are secondary to compression

and/or demyelination of the nerve by tumor, infection, or MS. Local

injections of botulinum toxin into affected muscles can relieve spasms

for 3–4 months, and the injections can be repeated. Refractory cases

due to vascular compression usually respond to surgical decompression of the facial nerve. Anecdotal reports describe success using

carbamazepine, gabapentin, or baclofen. Blepharospasm is an involuntary recurrent spasm of both eyelids that usually occurs in elderly

persons as an isolated phenomenon or with varying degrees of spasm

of other facial muscles. Severe, persistent cases of blepharospasm can

be treated by local injection of botulinum toxin into the orbicularis

oculi. Clonazepam, baclofen, and trihexyphenidyl have also been used

to treat this disorder. Facial myokymia refers to a fine rippling activity

of the facial muscles; it may be caused by MS or follow Guillain-Barré

syndrome (Chap. 447).

OTHER CRANIAL NERVE DISORDERS

■ GLOSSOPHARYNGEAL NEURALGIA

The ninth cranial (glossopharyngeal) nerve (Fig. 441-5) conveys

somatic sensation from the pharynx, middle ear, tympanic membrane,

eustachian tube, and posterior third of the tongue to the spinal trigeminal nucleus. It also relays taste from the posterior third of the tongue

and information about blood pressure from baroreceptors in the

carotid sinus to the nucleus solitarius, which also serves as the sensory

nucleus for the vagus nerve. Motor function originates in the nucleus

ambiguus and is limited to the stylopharyngeus muscle. Parasympathetic fibers from the medullary inferior salivatory nucleus synapse in

the otic ganglion with postganglionic fibers that innervate the parotid

gland. Glossopharyngeal neuralgia resembles trigeminal neuralgia in

many respects but is much less common. Sometimes it involves portions of the tenth (vagus) nerve. The pain is intense and paroxysmal;

it originates on one side of the throat, approximately in the tonsillar

fossa. In some cases, the pain is localized in the ear or may radiate from

the throat to the ear because of involvement of the tympanic branch

of the glossopharyngeal nerve. Spasms of pain may be initiated by

swallowing or coughing. There is no demonstrable motor or sensory

deficit. Cardiac symptoms—bradycardia or asystole, hypotension, and

fainting—have been reported. Glossopharyngeal neuralgia can result

from vascular compression, MS, or tumors, but many cases are idiopathic. Medical therapy is similar to that for trigeminal neuralgia, and

carbamazepine is generally the first choice. If drug therapy is unsuccessful, surgical procedures—including microvascular decompression

if vascular compression is evident—or rhizotomy of glossopharyngeal

and vagal fibers in the jugular bulb is frequently successful.

■ DYSPHAGIA AND DYSPHONIA

The tenth cranial (vagus) nerve (Fig. 441-6) carries somatic sensation

from the posterior aspect of the external auditory canal, laryngopharynx, superior larynx, and meninges of the posterior fossa to the spinal

trigeminal nucleus, as well as taste from the epiglottis and pharynx

and visceral sensation from chemoreceptors and baroreceptors in the

aortic arch, heart, and gastrointestinal tract to the splenic flexure to the

nucleus solitarius. The motor part originates in the nucleus ambiguous

and innervates most muscles of the oropharynx and soft palate as well

as all laryngeal muscles. Parasympathetic fibers originate in the dorsal

motor nucleus of the vagus nerve and decrease the heart rate through

action at the sino-atrial and atrioventricular nodes; others promote

peristalsis and secretion of the alimentary tract from the esophagus

to the splenic flexure. When the intracranial portion of one vagus

(tenth cranial) nerve is interrupted, the soft palate droops ipsilaterally

and does not rise in phonation. There is loss of the gag reflex on the

affected side, as well as of the “curtain movement” of the lateral wall of

the pharynx, whereby the faucial pillars move medially as the palate

rises in saying “ah.” The voice is hoarse and slightly nasal, and the vocal

cord lies immobile midway between abduction and adduction. Loss of

sensation at the external auditory meatus and the posterior pinna may

also be present.

The vagus nerve may be involved at the meningeal level by neoplastic and infectious processes and within the medulla by tumors, vascular

lesions (e.g., the lateral medullary syndrome), and motor neuron disease. The nerve may be involved by infection with varicella zoster virus.

Injury to the vagus nerve in the carotid sheath can occur with carotid

dissection or following endarterectomy. The pharyngeal branches of

both vagal nerves may be affected in diphtheria; the voice has a nasal

quality, and regurgitation of liquids through the nose occurs during

swallowing. Polymyositis and dermatomyositis, which cause hoarseness and dysphagia by direct involvement of laryngeal and pharyngeal

muscles, may be confused with diseases of the vagus nerves. Dysphagia

is also a symptom in some patients with myotonic dystrophy. Nonneurologic causes of dysphagia are discussed in Chap. 44.

The recurrent laryngeal nerves, especially the left, are most often

damaged as a result of intrathoracic disease. Aneurysm of the aortic

arch, an enlarged left atrium, and tumors of the mediastinum and

FIGURE 441-4 Axial and coronal T1-weighted images after gadolinium with fat suppression demonstrate diffuse smooth linear enhancement of the left facial nerve,

involving the genu, tympanic, and mastoid segments within the temporal bone (arrows), without evidence of mass lesion. Although highly suggestive of Bell’s palsy, similar

findings may be seen with other etiologies such as Lyme disease, sarcoidosis, and perineural malignant spread.

3442 PART 13 Neurologic Disorders

bronchi are much more frequent causes of an isolated vocal cord palsy

than are intracranial disorders. However, a substantial number of cases

of recurrent laryngeal palsy remain idiopathic.

When confronted with a case of laryngeal palsy, the physician must

attempt to determine the site of the lesion. If it is intramedullary,

there are usually other signs, such as ipsilateral cerebellar dysfunction, loss of pain and temperature sensation over the ipsilateral face

and contralateral arm and leg, and an ipsilateral Horner’s syndrome.

If the lesion is extramedullary, the glossopharyngeal and spinal accessory nerves are frequently involved (jugular foramen syndrome). If it

is extracranial in the posterior laterocondylar or retroparotid space,

there may be a combination of ninth, tenth, eleventh, and twelfth cranial nerve palsies and Horner’s syndrome (Table 441-2). If there is no

sensory loss over the palate and pharynx and no palatal weakness or

dysphagia, the lesion is below the origin of the pharyngeal branches,

which leave the vagus nerve high in the cervical region; the usual site

of disease is then the mediastinum.

■ NECK WEAKNESS

The eleventh cranial nerve (spinal accessory) is a pure motor nerve arising from the nucleus ambiguus and the ventral horn of the spinal cord

from C1–C6. The nerve travels superiorly through the foramen magnum and exits through the jugular foramen to innervate the ipsilateral

sternocleidomastoid and trapezius muscles. Isolated involvement of the

accessory (eleventh cranial) nerve can occur anywhere along its route,

resulting in partial or complete paralysis of the sternocleidomastoid

and trapezius muscles. Spinal accessory nerve palsy does not result in

significant neck weakness because several other muscles also turn the

head and flex the neck; therefore, detection of accessory nerve injury

relies on palpating the absence of sternocleidomastoid contraction

Inferior salivatory nucleus

(parasympathetic)

Facial

nerve

Geniculotympanic

nerve

Great petrosal

nerve

Nerve of the

pterygoid canal

Pterygopalatine

ganglion

Otic

ganglion

Parotid

gland

Small petrosal

nerve

Auditory tube

(eustachian)

Deep petrosal nerve

(sympathetic)

Internal carotid artery

Tympanic nerve

(of jacobson) to

tympanic plexus

Styloglossus

muscle

Communication

with facial nerve

Stylopharyngeal

muscle

Sensory branches to

soft palate, fauces,

and tonsils

Tonsils

Taste and sensation to

posterior third of tongue

Ambiguus nucleus

(motor)

Nucleus of solitary

tract (sensory)

Superior or jugular ganglion

Jugular

foramen

VII

FO

FR TP

Petrous

portion of

temporal

bone

Communication

with auricular

branch of X

Petrous ganglion

Nodose ganglion X

Carotid body

Carotid sinus and

nerve plexus

Sinus

nerve

Common carotid artery

Vagal root

(motor and

sensory)

Pharyngeal

plexus

Sympathetic root

(vasomotor)

To muscles and mucous

membrane of the pharynx

and soft palate

Parasympathetic

nerves

Sensory nerves

Motor nerves

Sympathetic

nerves

IX (Sensory)

Superior cervical

sympathetic ganglion

FIGURE 441-5 The ninth cranial (glossopharyngeal) nerve. TP, tympanum plexus; FR, foramen rotundum; FO, foramen ovale. (Reproduced with permission from SG Waxman:

Clinical Neuroanatomy, 29th ed. New York, McGraw Hill, 2020.)

3443Trigeminal Neuralgia, Bell’s Palsy, and Other Cranial Nerve Disorders CHAPTER 441

during head turning. Similarly, shoulder shrug is only slightly impacted

by trapezius weakness, although the affected shoulder is lower at rest,

scapular winging occurs, and the arm cannot abduct beyond 90°.

Isolated spinal accessory nerve palsy is often iatrogenic due to neck

surgery or jugular vein cannulation, or traumatic. An idiopathic form

of accessory neuropathy, akin to Bell’s palsy, has been described, and

it may be recurrent in some cases. Most but not all patients recover.

■ TONGUE PARALYSIS

The twelfth cranial nerve (hypoglossal) supplies the ipsilateral muscles of the tongue. Nerve lesions cause the tongue to deviate toward

the ipsilateral side during protrusion due to ipsilateral genioglossus

weakness, in addition to weakness of tongue movements toward the

affected side to weakness of ipsilateral intrinsic tongue musculature.

Atrophy and fasciculation of the tongue develop weeks to months after

interruption of the nerve. The nucleus of the nerve or its fibers of exit

may be involved by intramedullary lesions such as tumor, poliomyelitis, or most often motor neuron disease. Lesions of the basal meninges

and the occipital bones (platybasia, invagination of occipital condyles,

Paget’s disease) may compress the nerve in its extramedullary course

or as it exits the skull in the hypoglossal canal. Isolated lesions of

unknown cause can occur.

MULTIPLE CRANIAL NERVE PALSIES

Several cranial nerves may be affected by the same disease process. In

this situation, the main clinical problem is to determine whether the

lesion lies within the brainstem or outside it. Lesions that lie on the

surface of the brainstem are characterized by involvement of adjacent

cranial nerves (often occurring in succession) and late and rather slight

involvement of the long sensory and motor pathways and segmental

structures lying within the brainstem. The opposite is true of primary

lesions within the brainstem. The extramedullary lesion is more likely

Meningeal branch to

posterior fossa Auricular branch to

posterior auricle

and part of

external meatus

Muscles to

palate and

pharynx

Sensation to

lower pharynx

Epiglottic and

lingual rami

Inferior pharyngeal

constrictor

Cricothyroid muscle

Right recurrent

laryngeal nerve

Left recurrent

laryngeal nerve

Left vagus nerve

Aortic arch

Diaphragm

Stomach

Spleen

Pancreas

Left kidney

Superior

laryngeal

Sternocleidomastoid muscle nerve

Nucleus of solitary tract

Nucleus of spinal

tract of V

Ambiguus nucleus

Dorsal motor nucleus

of vagus

Spinal roots of

accessory nerve

Trapezius muscle

Arytenoid, thyroarytenoid,

and cricoarytenoid muscles

Esophagus

Glottis

Right subclavian artery

Cardiac nerves

Cardiac plexus

Pulmonary plexus

Esophageal plexus

Liver

Gallbladder

Right kidney

Small intestine

Celiac plexus

C1

C5

N

J

IX

VII

X

XI

Sensory nerves

Parasympathetic nerves

Motor nerves

FIGURE 441-6 The vagus nerve. J, jugular (superior) ganglion; N, nodose (inferior) ganglion. (Reproduced with permission from SG Waxman: Clinical Neuroanatomy,

29th ed. New York, McGraw Hill, 2020.)

3444 PART 13 Neurologic Disorders

to cause bone erosion or enlargement of the foramens of exit of cranial

nerves. The intramedullary lesion involving cranial nerves often produces a crossed sensory or motor paralysis (cranial nerve signs on one

side of the body and tract signs on the opposite side).

Involvement of multiple cranial nerves outside the brainstem

is frequently the result of trauma, localized infections including

varicella-zoster virus, infectious and noninfectious (especially carcinomatous) causes of meningitis (Chaps. 138 and 139), granulomatous

diseases such as granulomatosis with polyangiitis (Chap. 363), Behçet’s

disease, vascular disorders including those associated with diabetes,

enlarging aneurysms, or locally infiltrating tumors. Among the tumors,

nasopharyngeal cancers, lymphomas, neurofibromas, meningiomas,

chordomas, cholesteatomas, carcinomas, and sarcomas have all been

observed to involve a succession of lower cranial nerves. Owing to

their anatomic relationships, the multiple cranial nerve palsies form a

number of distinctive syndromes, listed in Table 441-2. Sarcoidosis is

the cause of some cases of multiple cranial neuropathy; tuberculosis,

the Chiari malformation, platybasia, and basilar invagination of the

skull are additional causes.

Cavernous sinus syndrome (Fig. 441-7) is a distinctive and frequently life-threatening disorder. It often presents as orbital or facial

pain; orbital swelling, chemosis due to occlusion of the ophthalmic

veins; fever; oculomotor neuropathy affecting the third, fourth, and

sixth cranial nerves; and trigeminal neuropathy affecting the ophthalmic (V1) and occasionally the maxillary (V2) divisions of the trigeminal nerve. Cavernous sinus thrombosis, often secondary to infection

from orbital cellulitis (frequently Staphylococcus aureus), a cutaneous

source on the face, or sinusitis (especially with mucormycosis in

diabetic patients), is the most frequent cause; other etiologies include

aneurysm of the carotid artery, a carotid-cavernous fistula (orbital

bruit may be present), meningioma, nasopharyngeal carcinoma, other

tumors, or an idiopathic granulomatous disorder (Tolosa-Hunt syndrome). The two cavernous sinuses directly communicate via intercavernous channels; thus, involvement on one side may extend to become

bilateral. Early diagnosis is essential, especially when due to infection,

and treatment depends on the underlying etiology.

In infectious cases, prompt administration of broad-spectrum

antibiotics, drainage of any abscess cavities, and identification of the

offending organism are essential. Anticoagulant therapy may benefit

cases of primary thrombosis. Repair or occlusion of the carotid artery

may be required for treatment of fistulas or aneurysms. Tolosa-Hunt

syndrome generally responds to glucocorticoids. A dramatic improvement in pain is usually evident within a few days; oral prednisone

(60 mg daily) is usually continued for 2 weeks and then gradually

tapered over a month, or longer if pain recurs. Occasionally an immunosuppressive medication, such as azathioprine or methotrexate, needs

to be added to maintain an initial response to glucocorticoids.

Lesions in the superior orbital fissure and orbital apex cause more

prominent vision loss than those in the cavernous sinus due to compression of the optic nerve; the second branch of the trigeminal nerve

is usually spared. The cause is often an invasive fungal infection,

frequently due to osseous erosion through the wall of the maxillary,

sphenoid, or ethmoid sinuses. Infiltrative processes such as amyloidosis, granulomatosis with polyarteritis, and an idiopathic inflammatory

syndrome similar to Tolosa-Hunt are additional causes, and biopsy is

often necessary for diagnosis.

As noted above, Guillain-Barré syndrome commonly affects the

facial nerves bilaterally. In the Fisher variant of Guillain-Barré syndrome, oculomotor paresis occurs with ataxia and areflexia in the

limbs (Chap. 447). Wernicke’s encephalopathy can cause a severe

ophthalmoplegia combined with other brainstem signs (Chap. 307).

Progressive bulbar palsy is a slowly progressive purely motor disorder

affecting multiple cranial nerve nuclei. Weakness of the face, jaw, pharynx, neck and tongue is usually present accompanied by atrophy and

fasciculations. It is a form of motor neuron disease (Chap. 437). Pure

motor syndromes without atrophy raise the question of myasthenia

gravis (Chap. 448), and with rapidly evolving Guillain Barre syndrome,

diphtheria and poliomyelitis are additional considerations.

Glossopharyngeal neuropathy in conjunction with vagus and accessory nerve palsies may occur with herpes zoster infection or with a

tumor or aneurysm in the posterior fossa or in the jugular foramen,

through which all three nerves exit the skull. Hoarseness due to vocal

cord paralysis, some difficulty in swallowing, deviation of the soft palate to the intact side, anesthesia of the posterior wall of the pharynx,

and weakness of the upper part of the trapezius and sternocleidomastoid muscles make up jugular foramen syndrome.

Paralysis of the vagus and hypoglossal nerves (Tapia syndrome) can

rarely follow endotracheal intubation and has been reported during

the COVID-19 pandemic; symptoms consist of dysphonia and tongue

deviation, and usually resolve within a few months.

An idiopathic form of multiple cranial nerve involvement on one or

both sides of the face is occasionally seen. The syndrome consists of

a subacute onset of boring facial pain, followed by paralysis of motor

cranial nerves. The clinical features overlap those of Tolosa-Hunt

syndrome and appear to be due to idiopathic inflammation of the

dura mater, which may be visualized by MRI. The syndrome is usually

responsive to glucocorticoids.

TABLE 441-2 Cranial Nerve Syndromes

SITE CRANIAL NERVES USUAL CAUSE

Orbital apex II, III, IV, first

division V, VI

Invasive fungal infections,

amyloidosis, granulomatous

disease

Sphenoid fissure

(superior orbital)

III, IV, first division

V, VI

Invasive tumors of sphenoid bone;

aneurysms

Lateral wall of

cavernous sinus

III, IV, first division

V, VI, often with

proptosis

Infection, thrombosis, aneurysm

or fistula of cavernous sinus;

invasive tumors from sinuses and

sella turcica; benign granuloma

responsive to glucocorticoids

Retrosphenoid space II, III, IV, V, VI Large tumors of middle cranial

fossa

Apex of petrous bone V, VI Petrositis; tumors of petrous bone

Internal auditory

meatus

VII, VIII Tumors of petrous bone (dermoids,

etc.); infectious processes; acoustic

neuroma

Pontocerebellar

angle

V, VI, VII, VIII, and

sometimes IX

Acoustic neuroma; meningioma

Jugular foramen IX, X, XI Tumors and aneurysms

Posterior

laterocondylar space

IX, X, XI, XII Tumors of parotid gland and carotid

body and metastatic tumors

Posterior retroparotid

space

IX, X, XI, XII, and

Horner’s syndrome

Tumors of parotid gland, carotid

body, lymph nodes; metastatic

tumor; tuberculous adenitis

Ant. cerebral a.

Int. carotid a.

Ant. clinoid process

Subarachnoid

space

Oculomotor (III) n.

Trochlear (IV) n.

Ophthalmic (VI

) n.

Abducens (VI) n.

Maxillary (V2) n.

Pia

Dura

Arachnoid

Sphenoid

 sinus

Optic

 chiasma

Hypophysis

FIGURE 441-7 Anatomy of the cavernous sinus in coronal section, illustrating the

location of the cranial nerves in relation to the vascular sinus, internal carotid artery

(which loops anteriorly to the section), and surrounding structures.

3445 Diseases of the Spinal Cord CHAPTER 442

■ FURTHER READING

Bendtsen L et al: Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet 19:784, 2020.

Decavel P et al: Tapia syndrome at the time of the COVID-19 pandemic: Lower cranial neuropathy following prolonged intubation.

Neurology 95:312, 2020.

Gagyor I et al: Antiviral treatment of Bell’s palsy (idiopathic facial

paralysis). Cochrane Database Syst Rev 9:CD001869, 2019.

Gutierrez S et al: Lower cranial nerve syndromes: A review. Neurosurg Rev 44:1345, 2020.

Kelly HR, Curtin HD: Imaging of skull base lesions. Handb Clin

Neurol 135:637, 2016.

Madhok VB et al: Corticosteroids for Bell’s palsy (idiopathic facial

paralysis). Cochrane Database Syst Rev 7:CD001942, 2016.

Diseases of the spinal cord are frequently devastating. They produce quadriplegia, paraplegia, and sensory deficits far beyond the

damage they would inflict elsewhere in the nervous system because

the spinal cord contains, in a small cross-sectional area, almost the

entire motor output and sensory input of the trunk and limbs. Many

spinal cord diseases are reversible if recognized and treated at an

early stage (Table 442-1); thus, they are among the most critical

of neurologic emergencies. The efficient use of diagnostic procedures, guided by knowledge of the anatomy and the clinical features

of spinal cord diseases, is required to maximize the likelihood of a

successful outcome.

APPROACH TO THE PATIENT

Spinal Cord Disease

SPINAL CORD ANATOMY RELEVANT TO CLINICAL SIGNS

The spinal cord is a thin, tubular extension of the central nervous

system contained within the bony spinal canal. It originates at the

medulla and continues caudally to the conus medullaris at the

lumbar level; its fibrous extension, the filum terminale, terminates

at the coccyx. The adult spinal cord is ~46 cm (18 in.) long, oval in

shape, and enlarged in the cervical and lumbar regions, where neurons that innervate the upper and lower extremities, respectively,

are located. The white matter tracts containing ascending sensory

and descending motor pathways are located peripherally, whereas

nerve cell bodies are clustered in an inner region of gray matter

shaped like a four-leaf clover that surrounds the central canal (anatomically an extension of the fourth ventricle). The membranes that

cover the spinal cord—the pia, arachnoid, and dura—are continuous with those of the brain, and the cerebrospinal fluid is contained

within the subarachnoid space between the pia and arachnoid.

The spinal cord has 31 segments, each defined by an exiting ventral motor root and entering dorsal sensory root. During

embryologic development, growth of the cord lags behind that of

the vertebral column, and the mature spinal cord ends at approximately the first lumbar vertebral body. The lower spinal nerves

take an increasingly downward course to exit via intervertebral

foramina. The first seven pairs of cervical spinal nerves exit above

the same-numbered vertebral bodies, whereas all the subsequent

nerves exit below the same-numbered vertebral bodies because of

the presence of eight cervical spinal cord segments but only seven

cervical vertebrae. The relationship between spinal cord segments

442 Diseases of the Spinal Cord

Stephen L. Hauser

TABLE 442-1 Treatable Spinal Cord Disorders

Compressive

Epidural, intradural, or intramedullary neoplasm

Epidural abscess

Epidural hemorrhage

Cervical spondylosis

Herniated disk

Posttraumatic compression by fractured or displaced vertebra or hemorrhage

Vascular

Arteriovenous malformation and dural fistula

Antiphospholipid syndrome and other hypercoagulable states

Inflammatory

Multiple sclerosis

Neuromyelitis optica

Sarcoidosis

 Systemic immune-mediated disorders: SLE, Sjögren’s, Behcet’s disease, APL

antibody syndrome, others vasculitis

 Other CNS disorders: anti-MOG, anti-GFAP, paraneoplastic,a

 CLIPPERS,

Erdheim-Chester

Infectious

Viral: VZV, HSV-1 and 2, CMV, HIV, HTLV-1, others

Bacterial and mycobacterial: Borrelia, Listeria, syphilis, others

Mycoplasma pneumoniae

Parasitic: schistosomiasis, toxoplasmosis, cysticercosis

Developmental

Syringomyelia

Meningomyelocele

Tethered cord syndrome

Metabolic

Vitamin B12 deficiency (subacute combined degeneration)

Folate deficiency

Copper deficiency

a

Including anti-amphiphysin, CRMP-5, Hu.

Abbreviations: CLIPPERS, chronic lymphocytic inflammation with pontine

perivascular enhancement responsive to steroids; CMV, cytomegalovirus; CNS,

central nervous system; CRMP5, collapsin response mediator 5-IgG; GFAP,

glial fibrillary acidic protein; HSV, herpes simplex virus; HTLV, human T-cell

lymphotropic virus; MOG, myelin oligodendrocyte glycoprotein; SLE, systemic lupus

erythematosus; VZV, varicella-zoster virus.

TABLE 442-2 Spinal Cord Levels Relative to the Vertebral Bodies

SPINAL CORD LEVEL CORRESPONDING VERTEBRAL BODY

Upper cervical Same as cord level

Lower cervical 1 level higher

Upper thoracic 2 levels higher

Lower thoracic 2–3 levels higher

Lumbar T10–T12

Sacral T12–L1

and the corresponding vertebral bodies is shown in Table 442-2.

These relationships assume particular importance for localization

of lesions that cause spinal cord compression. Sensory loss below

the circumferential level of the umbilicus, for example, corresponds to the T10 cord segment but indicates involvement of the

cord adjacent to the seventh or eighth thoracic vertebral body

(see Figs. 25-2 and 25-3). In addition, at every level, the main

ascending and descending tracts are somatotopically organized

with a laminated distribution that reflects the origin or destination

of nerve fibers.

Determining the Level of the Lesion The presence of a horizontally defined level below which sensory, motor, and autonomic

function is impaired is a hallmark of a lesion of the spinal cord. This

3446 PART 13 Neurologic Disorders

sensory level is sought by asking the patient to identify a pinprick

or cold stimulus applied to the proximal legs and lower trunk and

successively moved up toward the neck on each side. Sensory loss

below this level is the result of damage to the spinothalamic tract on

the opposite side, one to two segments higher in the case of a unilateral spinal cord lesion, and at the level of a bilateral lesion. The discrepancy in the level of a unilateral lesion is the result of the course

of the second-order sensory fibers, which originate in the dorsal

horn, and ascend for one or two levels as they cross anterior to the

central canal to join the opposite spinothalamic tract. Lesions that

transect the descending corticospinal and other motor tracts cause

paraplegia or quadriplegia with heightened deep tendon reflexes,

Babinski signs, and eventual spasticity (upper motor neuron syndrome). Transverse damage to the cord also produces autonomic

disturbances consisting of absent sweating below the implicated

cord level and bladder, bowel, and sexual dysfunction.

The uppermost level of a spinal cord lesion can also be localized

by attention to the segmental signs corresponding to disturbed

motor or sensory innervation by an individual cord segment.

A band of altered sensation (hyperalgesia or hyperpathia) at the

upper end of the sensory disturbance, fasciculations or atrophy

in muscles innervated by one or several segments, or a muted or

absent deep tendon reflex may be noted at this level. These signs

also can occur with focal root or peripheral nerve disorders; thus,

they are most useful when they occur together with signs of longtract damage. With severe and acute transverse lesions, the limbs

initially may be flaccid rather than spastic. This state of “spinal

shock” lasts for several days, rarely for weeks, and may be mistaken

for extensive damage to the anterior horn cells over many segments

of the cord or for an acute polyneuropathy.

The main features of transverse damage at each level of the spinal

cord are summarized below.

Cervical Cord Upper cervical cord lesions produce quadriplegia

and weakness of the diaphragm. The uppermost level of weakness

and reflex loss with lesions at C5–C6 is in the biceps; at C7, in finger

and wrist extensors and triceps; and at C8, finger and wrist flexion.

Horner’s syndrome (miosis, ptosis, and facial hypohidrosis) may

accompany a cervical cord lesion at any level.

Thoracic Cord Lesions here are localized by the sensory level on

the trunk and, if present, by the site of midline back pain. Useful

markers of the sensory level on the trunk are the nipples (T4) and

umbilicus (T10). Leg weakness and disturbances of bladder and

bowel function accompany the paralysis. Lesions at T9–T10 paralyze the lower—but not the upper—abdominal muscles, resulting

in upward movement of the umbilicus when the abdominal wall

contracts (Beevor’s sign).

Lumbar Cord Lesions at the L2–L4 spinal cord levels paralyze

flexion and adduction of the thigh, weaken leg extension at the

knee, and abolish the patellar reflex. Lesions at L5–S1 paralyze only

movements of the foot and ankle, flexion at the knee, and extension

of the thigh, and abolish the ankle jerks (S1).

Sacral Cord/Conus Medullaris The conus medullaris is the

tapered caudal termination of the spinal cord, comprising the sacral

and single coccygeal segments. The distinctive conus syndrome

consists of bilateral saddle anesthesia (S3–S5), prominent bladder

and bowel dysfunction (urinary retention and incontinence with lax

anal tone), and impotence. The bulbocavernosus (S2–S4) and anal

(S4–S5) reflexes are absent (Chap. 422). Muscle strength is largely

preserved. By contrast, lesions of the cauda equina, the nerve roots

derived from the lower cord, are characterized by low back and

radicular pain, asymmetric leg weakness and sensory loss, variable

areflexia in the lower extremities, and relative sparing of bowel and

bladder function. Mass lesions in the lower spinal canal often produce a mixed clinical picture with elements of both cauda equina

and conus medullaris syndromes. Cauda equina syndromes are

also discussed in Chap. 17.

Special Patterns of Spinal Cord Disease The location of the

major ascending and descending pathways of the spinal cord are

shown in Fig. 442-1. Most fiber tracts—including the posterior columns and the spinocerebellar and pyramidal tracts—are situated on

the side of the body they innervate. However, afferent fibers mediating pain and temperature sensation ascend in the spinothalamic

tract contralateral to the side they supply. The anatomic configurations of these tracts produce characteristic syndromes that provide

clues to the underlying disease process.

Brown-Sequard Hemicord Syndrome This consists of ipsilateral weakness (corticospinal tract) and loss of joint position

and vibratory sense (posterior column), with contralateral loss of

pain and temperature sense (spinothalamic tract) one or two levels

below the lesion. Segmental signs, such as radicular pain, muscle

atrophy, or loss of a deep tendon reflex, are unilateral. Partial forms

are more common than the fully developed syndrome.

Central Cord Syndrome This syndrome results from selective

damage to the gray matter nerve cells and crossing spinothalamic

tracts surrounding the central canal. In the cervical cord, the central

cord syndrome produces arm weakness out of proportion to leg

weakness and a “dissociated” sensory loss, meaning loss of pain and

temperature sensations over the shoulders, lower neck, and upper

trunk (cape distribution), in contrast to preservation of light touch,

joint position, and vibration sense in these regions. Spinal trauma,

syringomyelia, and intrinsic cord tumors are the main causes.

Anterior Spinal Artery Syndrome Infarction of the cord is

generally the result of occlusion or diminished flow in this artery.

The result is bilateral tissue destruction at several contiguous levels

that spares the posterior columns. All spinal cord functions—motor,

sensory, and autonomic—are lost below the level of the lesion, with

the striking exception of retained vibration and position sensation.

Foramen Magnum Syndrome Lesions in this area interrupt

decussating pyramidal tract fibers destined for the legs, which cross

caudal to those of the arms, resulting in weakness of the legs (crural

paresis). Compressive lesions near the foramen magnum may

produce weakness of the ipsilateral shoulder and arm followed by

weakness of the ipsilateral leg, then the contralateral leg, and finally

the contralateral arm, an “around-the-clock” pattern that may begin

in any of the four limbs. There is typically suboccipital pain spreading to the neck and shoulders.

Intramedullary and Extramedullary Syndromes It is useful

to differentiate intramedullary processes, arising within the substance of the cord, from extramedullary ones that lie outside the

cord and compress the spinal cord or its vascular supply. The differentiating features are only relative and serve as clinical guides. With

extramedullary lesions, radicular pain is often prominent, and there

is early sacral sensory loss and spastic weakness in the legs with

incontinence due to the superficial location of the corresponding

sensory and motor fibers in the spinothalamic and corticospinal

tracts (Fig. 442-1). Intramedullary lesions tend to produce poorly

localized burning pain rather than radicular pain and to spare sensation in the perineal and sacral areas (“sacral sparing”), reflecting

the laminated configuration of the spinothalamic tract with sacral

fibers outermost; corticospinal tract signs appear later. Regarding

extramedullary lesions, a further distinction is made between extradural and intradural masses, as the former are generally malignant

and the latter benign (neurofibroma being a common cause). Consequently, a long duration of symptoms favors an intradural origin.

ACUTE AND SUBACUTE

SPINAL CORD DISEASES

Symptoms of the cord diseases that evolve over days or weeks are focal

neck or back pain, followed by various combinations of paresthesias,

sensory loss, motor weakness, and sphincter disturbance. There may

be mild sensory symptoms only or a devastating functional transection

of the cord. When paresthesias begin in the feet and then ascend a

3447 Diseases of the Spinal Cord CHAPTER 442

polyneuropathy is often considered, and in such cases the presence of

bladder disturbances and a sharply demarcated spinal cord level provide important clues to the spinal cord origin of the disease.

In severe and abrupt cases, areflexia reflecting spinal shock may be

present, but hyperreflexia supervenes over days or weeks; persistent

areflexic paralysis with a sensory level usually indicates necrosis over

multiple segments of the spinal cord.

APPROACH TO THE PATIENT

Compressive and Noncompressive Myelopathy

DISTINGUISHING COMPRESSIVE FROM

NONCOMPRESSIVE MYELOPATHY

The first priority is to exclude treatable compression of the cord

by a mass lesion. The common causes are tumor, epidural abscess

or hematoma, herniated disk, and spondylitic vertebral pathology.

Epidural compression due to malignancy or abscess often causes

warning signs of neck or back pain, bladder disturbances, and sensory symptoms that precede the development of paralysis. Spinal

subluxation, hemorrhage, and noncompressive etiologies such as

infarction are more likely to produce myelopathy without antecedent symptoms. MRI with gadolinium, centered on the clinically

suspected level, is the initial diagnostic procedure if it is available;

it is often appropriate to image the entire spine (cervical through

sacral regions) to search for additional clinically silent lesions. Once

compressive lesions have been excluded, noncompressive causes of

acute myelopathy that are intrinsic to the cord are considered, primarily vascular, inflammatory, and infectious etiologies.

■ COMPRESSIVE MYELOPATHIES

Neoplastic Spinal Cord Compression In adults, most neoplasms are epidural in origin, resulting from metastases to the adjacent

vertebral column. The propensity of solid tumors to metastasize to

the vertebral column probably reflects the high proportion of bone

marrow located in the axial skeleton. Almost any malignant tumor can

metastasize to the spinal column, with breast, lung, prostate, kidney,

lymphoma, and myeloma being particularly frequent. The thoracic

spinal column is most commonly involved; exceptions are metastases

from prostate and ovarian cancer, which occur disproportionately

in the sacral and lumbar vertebrae, probably from spread through

Batson’s plexus, a network of veins along the anterior epidural space.

Retroperitoneal neoplasms (especially lymphomas or sarcomas) enter

the spinal canal laterally through the intervertebral foramina and produce radicular pain with signs of weakness that corresponds to the level

of involved nerve roots.

Pain is usually the initial symptom of spinal metastasis; it may be

aching and localized or sharp and radiating in quality and typically

worsens with movement, coughing, or sneezing and characteristically

awakens patients at night. A recent onset of persistent back pain,

particularly if in the thoracic spine (which is uncommonly involved

by spondylosis), should prompt consideration of vertebral metastasis.

Rarely, pain is mild or absent. Plain radiographs of the spine and radionuclide bone scans have a limited role in diagnosis because they do

not identify 15–20% of metastatic vertebral lesions and fail to detect

paravertebral masses that reach the epidural space through the intervertebral foramina. MRI provides excellent anatomic resolution of the

extent of spinal tumors (Fig. 442-2) and is able to distinguish between

malignant lesions and other masses—epidural abscess, tuberculoma,

lipoma, or epidural hemorrhage, among others—that present in a similar fashion. Vertebral metastases are usually hypointense relative to a

normal bone marrow signal on T1-weighted MRI; after the administration of gadolinium, contrast enhancement may deceptively “normalize”

the appearance of the tumor by increasing its intensity to that of normal bone marrow. Infections of the spinal column (osteomyelitis and

related disorders) are distinctive in that, unlike tumor, they often cross

the disk space to involve the adjacent vertebral body.

Anterior horn

(motor neurons)

Lateral

corticospinal

(pyramidal) tract

Dorsal root

Dorsal

spinocerebellar

tract

Ventral

spinocerebellar

tract

Lateral

spinothalamic

tract

Ventral

spinothalamic

tract

Pressure, touch

(minor role)

Ventral

(uncrossed)

corticospinal

tract

Tectospinal

tract

S L T C

C T L S

Fasciculus

cuneatus

Rubrospinal

tract

Lateral

reticulospinal

tract

Vestibulospinal

tract

Ventral

root

Axial and

proximal

limb

movements

(Joint Position, Vibration, Pressure)

Posterior Columns

Distal limb

movements

(minor role)

Pain,

temperature Ventral

reticulospinal

tract

Fasciculus

gracilis

S

L T C

Distal limb

movements

L/

S

L/ S

P

E

D

F

FIGURE 442-1 Transverse section through the spinal cord, composite representation, illustrating the principal ascending (left) and descending (right) pathways. The lateral

and ventral spinothalamic tracts ascend contralateral to the side of the body that is innervated. In humans, the lateral corticospinal (pyramidal) tract is thought to lack strict

somatotopic organization in the spinal cord. C, cervical; D, distal; E, extensors; F, flexors; L, lumbar; P, proximal; S, sacral; T, thoracic.

3448 PART 13 Neurologic Disorders

A B

FIGURE 442-2 Epidural spinal cord compression due to breast carcinoma. Sagittal

T1-weighted (A) and T2-weighted (B) magnetic resonance imaging scans through

the cervicothoracic junction reveal an infiltrated and collapsed second thoracic

vertebral body with posterior displacement and compression of the upper thoracic

spinal cord. The low-intensity bone marrow signal in A signifies replacement by

tumor.

If spinal cord compression is suspected, imaging should be obtained

promptly. If there are radicular symptoms but no evidence of myelopathy, it may be safe to defer imaging for 24–48 h. Up to 40% of

patients who present with cord compression at one level are found to

have asymptomatic epidural metastases elsewhere; thus, imaging of the

entire length of the spine is important to define the extent of disease.

TREATMENT

Neoplastic Spinal Cord Compression

Proper management of cord compression is based on multiple

considerations, including radiosensitivity of the primary tumor,

extent of compression, prior therapy to the site, and stability of the

spine. Treatment includes glucocorticoids to reduce cord edema,

surgery and/or local radiotherapy (initiated as early as possible)

to the symptomatic lesion, and specific therapy for the underlying tumor type. Glucocorticoids (typically dexamethasone, 10 mg

intravenously) can be administered before an imaging study if

there is clinical suspicion of cord compression and continued at a

lower dose (4 mg every 6 h orally) until definitive treatment with

radiotherapy and/or surgical decompression is completed. In one

trial, initial management with surgery followed by radiotherapy

was more effective than radiotherapy alone for patients with a single area of spinal cord compression by extradural tumor; however,

patients with recurrent cord compression, brain metastases, radiosensitive tumors, or severe motor symptoms of >48 h in duration

were excluded from this study. Stereotactic body radiotherapy,

which delivers high doses of focused radiation, is preferred for

radioresistant tumor types and for patients requiring re-irradiation.

Biopsy of the epidural mass is unnecessary in patients with

known primary cancer, but it is indicated if a history of underlying cancer is lacking. Surgical treatment, either decompression by

laminectomy or a spinal fixation procedure, is also indicated when

signs of cord compression worsen despite radiotherapy; the maximum-tolerated dose of radiotherapy has been delivered previously

to the site; a vertebral compression fracture or spinal instability

contributes to cord compression; or in cases of high-grade spinal

cord compression from a radioresistant tumor.

A good response to therapy can be expected in individuals who

are ambulatory at presentation. Treatment usually prevents new

weakness, and some recovery of motor function occurs in up to

one-third of patients. Motor deficits (paraplegia or quadriplegia),

once established for >12 h, do not usually improve, and beyond

48 h the prognosis for substantial motor recovery is poor. Although

most patients do not experience recurrences in the months following radiotherapy, with survival beyond 2 years recurrence

becomes increasingly likely and can be managed with additional

radiotherapy.

In contrast to tumors of the epidural space, most intradural mass

lesions are slow-growing and benign. Meningiomas and neurofibromas

account for most of these, with occasional cases caused by chordoma,

lipoma, dermoid, or sarcoma. Meningiomas (Fig. 442-3) are often

located posterior to the thoracic cord or near the foramen magnum,

although they can arise from the meninges anywhere along the spinal

canal. Neurofibromas are benign tumors of the nerve sheath that typically arise from the posterior root; when multiple, neurofibromatosis

is the likely etiology. Symptoms usually begin with radicular sensory

symptoms followed by an asymmetric, progressive spinal cord syndrome. Therapy is surgical resection.

Primary intramedullary tumors of the spinal cord are uncommon.

They present as central cord or hemicord syndromes, often in the

cervical region. There may be poorly localized burning pain in the

extremities and sparing of sacral sensation. In adults, these lesions

are ependymomas, hemangioblastomas, or low-grade astrocytomas

(Fig. 442-4). Complete resection of an intramedullary ependymoma

is often possible with microsurgical techniques. Debulking of an

intramedullary astrocytoma can also be helpful, as these are often

slowly growing lesions; the value of adjunctive radiotherapy and

chemotherapy is uncertain. Secondary (metastatic) intramedullary

tumors also occur, especially in patients with advanced metastatic

disease (Chap. 90), although these are not nearly as frequent as brain

metastases.

Spinal Epidural Abscess Spinal epidural abscess presents with

midline back or neck pain, fever, and progressive limb weakness.

Prompt recognition of this distinctive process may prevent permanent

sequelae. Aching pain is almost always present, either over the spine

or in a radicular pattern. The duration of pain prior to presentation is

generally ≤2 weeks but may on occasion be several months or longer.

FIGURE 442-3 Magnetic resonance imaging of a thoracic meningioma. Coronal

T1-weighted postcontrast image through the thoracic spinal cord demonstrates

intense and uniform enhancement of a well-circumscribed extramedullary mass

(arrows) that displaces the spinal cord to the left.

3449 Diseases of the Spinal Cord CHAPTER 442

Fever is typically but not invariably present, accompanied by elevated

white blood cell count, sedimentation rate, and C-reactive protein. As

the abscess expands, further spinal cord damage results from venous

congestion and thrombosis. Once weakness and other signs of myelopathy appear, progression may be rapid and irreversible. A more

chronic sterile granulomatous form of abscess is also known, usually

after treatment of an acute epidural infection.

Risk factors include an impaired immune status (HIV, diabetes mellitus, renal failure, alcoholism, malignancy), intravenous drug abuse,

and infections of the skin or other tissues. Two-thirds of epidural

infections result from hematogenous spread of bacteria from the skin

(furunculosis), soft tissue (pharyngeal or dental abscesses; sinusitis), or

deep viscera (bacterial endocarditis). The remainder arises from direct

extension of a local infection to the subdural space; examples of local

predisposing conditions are vertebral osteomyelitis, decubitus ulcers,

lumbar puncture, epidural anesthesia, or spinal surgery. Most cases

are due to Staphylococcus aureus; gram-negative bacilli, Streptococcus,

anaerobes, and fungi can also cause epidural abscesses. Methicillinresistant Staphylococcus aureus (MRSA) is an important consideration,

and therapy should be tailored to this possibility. Tuberculosis from an

adjacent vertebral source (Pott’s disease) remains an important cause

in the developing world.

MRI (Fig. 442-5) localizes the abscess and excludes other causes of

myelopathy. Blood cultures are positive in more than half of cases, but

direct aspiration of the abscess at surgery is often required for a microbiologic diagnosis. Lumbar puncture is only required if encephalopathy

or other clinical signs raise the question of associated meningitis, a

feature that is found in <25% of cases. The level of the puncture should

be planned to minimize the risk of meningitis due to passage of the

needle through infected tissue. A high cervical tap is sometimes the

safest approach. Cerebrospinal fluid (CSF) abnormalities in epidural

and subdural abscesses consist of pleocytosis with a preponderance

of polymorphonuclear cells, an elevated protein level, and a reduced

glucose level, but the responsible organism is not cultured unless there

is associated meningitis.

TREATMENT

Spinal Epidural Abscess

Treatment is by decompressive laminectomy with debridement

combined with long-term antibiotic treatment. Surgical evacuation

prevents development of paralysis and may improve or reverse

paralysis in evolution, but it is unlikely to improve deficits of more

than several days in duration. Broad-spectrum antibiotics typically

vancomycin 15–20 mg/kg q12h (staphylococcus including MRSA,

streptococcus), ceftriaxone 2 gm q24h (gram-negative bacilli), and

when indicated metronidazole 30 mg/kg per day divided into q6h

intervals (anaerobes) should be started empirically before surgery

and then modified on the basis of culture results; medication is

generally continued for 6–8 weeks. If surgery is contraindicated or if

there is a fixed paraplegia or quadriplegia that is unlikely to improve

following surgery, long-term administration of systemic and oral

antibiotics can be used; in such cases, the choice of antibiotics

may be guided by results of blood cultures. Surgical management

remains the treatment of choice unless the abscess is limited in size

and causes few or no neurologic signs.

With prompt diagnosis and treatment of spinal epidural abscess,

up to two-thirds of patients experience significant recovery.

Spinal Epidural Hematoma Hemorrhage into the epidural (or

subdural) space causes acute focal or radicular pain followed by variable signs of a spinal cord or conus medullaris disorder. Therapeutic

anticoagulation, trauma, tumor, or blood dyscrasias are predisposing

conditions. Rare cases complicate lumbar puncture or epidural anesthesia. MRI and CT confirm the clinical suspicion and can delineate

the extent of the bleeding. Treatment consists of prompt reversal of any

underlying clotting disorder and surgical decompression. Surgery may

be followed by substantial recovery, especially in patients with some

preservation of motor function preoperatively. Because of the risk of

hemorrhage, lumbar puncture should be avoided whenever possible in

patients with severe thrombocytopenia or other coagulopathies.

Hematomyelia Hemorrhage into the substance of the spinal cord

is a rare result of trauma, intraparenchymal vascular malformation

(see below), vasculitis due to polyarteritis nodosa or systemic lupus

erythematosus (SLE), bleeding disorders, or a spinal cord neoplasm.

Hematomyelia presents as an acute painful transverse myelopathy.

With large lesions, extension into the subarachnoid space results in

subarachnoid hemorrhage (Chap. 302). Diagnosis is by MRI or CT.

Therapy is supportive, and surgical intervention is generally not useful.

An exception is hematomyelia due to an underlying vascular malformation, for which spinal angiography and endovascular occlusion may

be indicated, or surgery to evacuate the clot and remove the underlying

vascular lesion.

FIGURE 442-4 Magnetic resonance imaging of an intramedullary astrocytoma.

Sagittal T1-weighted postcontrast image through the cervical spine demonstrates

expansion of the upper cervical spine by a mass lesion emanating from within the

spinal cord at the cervicomedullary junction. Irregular peripheral enhancement

occurs within the mass (arrows).

A B

FIGURE 442-5 Magnetic resonance (MR) imaging of a spinal epidural abscess

due to tuberculosis. A. Sagittal T2-weighted free spin-echo MR sequence. A

hypointense mass replaces the posterior elements of C3 and extends epidurally to

compress the spinal cord (arrows). B. Sagittal T1-weighted image after contrast

administration reveals a diffuse enhancement of the epidural process (arrows) with

extension into the epidural space.

3450 PART 13 Neurologic Disorders

Acute Spondylytic Myelopathy Of particular concern are

hyperextension injuries in patients with underlying degenerative cervical spine disease (Chap. 17). The provoking stimulus may be obvious

such as a forward fall, or occur after seemingly innocuous low-impact

movements of the neck. A preexisting stenotic spinal canal is often

present and “buckling” of the posterior ligamentum flavum (less commonly acute disc herniation or subluxation) is believed to produce the

cord compression, sometimes with a central cord syndrome (see above)

and involvement of the upper, more than lower, limbs. Deficits can be

transient, resulting in a “concussion” of the spinal cord, or permanent.

The more common syndrome of chronic spondylitic myelopathy is discussed below.

■ NONCOMPRESSIVE MYELOPATHIES

Once a compressive etiology has been excluded as the cause of an acute

myelopathy, the principal challenge is to distinguish vascular/ischemic

from inflammatory/infectious causes. This is often not straightforward,

because clinical presentations can overlap. Moreover, findings that

usually point to an inflammatory etiology—such as focal gadolinium

enhancement on MRI scans or pleocytosis in the CSF—can also occur

with spinal cord ischemia. Ischemia is likely in hyperacute presentations with back or neck pain, and when an anterior pattern of spinal

cord injury is identified on clinical examination or by MRI. By contrast,

inflammation is more likely in cases that develop subacutely, or when

systemic symptoms, CSF oligoclonal bands, or multiple discrete spinal

cord MRI lesions are present. The most frequent inflammatory causes

of acute myelopathy are multiple sclerosis (MS); neuromyelitis optica

(NMO); sarcoidosis; systemic inflammatory diseases such as SLE and

Behcet’s disease; postinfectious or idiopathic transverse myelitis, which

is presumed to be an immune condition related to acute disseminated

encephalomyelitis (Chap. 441); and infectious (primarily viral) causes.

The evaluation generally requires a lumbar puncture and a search

for underlying systemic disease (Table 442-3).

Spinal Cord Infarction The cord is supplied by three arteries that

course vertically over its surface: a single anterior spinal artery and

paired posterior spinal arteries. The anterior spinal artery originates in

paired branches of the vertebral arteries at the craniocervical junction

and is fed by additional radicular vessels that arise at C6, at an upper

thoracic level, and, most consistently, at T11–L2 (artery of Adamkiewicz). At each spinal cord segment, paired penetrating vessels branch

from the anterior spinal artery to supply the anterior two-thirds of the

cord; the posterior spinal arteries, which often become less distinct

below the midthoracic level, supply the posterior columns.

Spinal cord ischemia can occur at any level; however, the presence of

the artery of Adamkiewicz below, and the anterior spinal artery circulation above, creates a region of marginal blood flow in the upper thoracic segments. With hypotension or cross-clamping of the aorta, cord

infarction typically occurs at the level of T3–T4, and also at boundary

zones between the anterior and posterior spinal artery territories. The

latter may result in a rapidly progressive syndrome over hours of weakness and spasticity with little sensory change.

Acute infarction in the territory of the anterior spinal artery produces paraplegia or quadriplegia, dissociated sensory loss affecting

pain and temperature sense but sparing vibration and position sense,

and loss of sphincter control (“anterior cord syndrome”). Onset may be

sudden but more typically is progressive over minutes or a few hours,

unlike stroke in the cerebral hemispheres. Sharp midline or radiating

back pain localized to the area of ischemia is frequent. Areflexia due

to spinal shock is often present initially; with time, hyperreflexia and

spasticity appear. Less common is infarction in the territory of the

posterior spinal arteries, resulting in loss of posterior column function

either on one side or bilaterally.

Causes of spinal cord infarction include aortic atherosclerosis, dissecting aortic aneurysm, vertebral artery occlusion or dissection in the

neck, aortic surgery, or profound hypotension from any cause. A surfer’s myelopathy usually in the thoracic region, has been associated with

prolonged back extension due to lifting the upper body off the board

while waiting for waves; it typically manifests as back pain followed

by an anterior cord syndrome with progressive paralysis and loss of

sphincter control, and is likely vascular in origin. Cardiogenic emboli,

vasculitis (Chap. 363), and collagen vascular disease (particularly SLE

[Chap. 356], Sjögren’s syndrome [Chap. 361], and the antiphospholipid antibody syndrome [Chap. 357]) are other etiologies. Occasional

cases develop from embolism of nucleus pulposus material into spinal

vessels, usually from local spine trauma. In a substantial number of

cases, no cause can be found, and thromboembolism in arterial feeders

is suspected. MRI may fail to demonstrate infarctions of the cord, especially in the first day, but often the imaging becomes abnormal at the

affected level. MRI features suggestive of cord infarction include diffusion weighted restriction; longitudinally extensive anterior T2 signal

brightness on sagittal images (“pencil-like sign”); focal enhancement

in the anterior horns; and paired areas of focal T2 hyperintensity in

the anterior medial cord on axial images (“owl’s eyes”). When present,

infarction of a vertebral body adjacent to the area of cord involvement

is diagnostically helpful.

With cord infarction due to presumed thromboembolism, acute

anticoagulation is not indicated, with the possible exception of the

unusual transient ischemic attack or incomplete infarction with a stuttering or progressive course. The antiphospholipid antibody syndrome

is treated with anticoagulation (Chap. 357). Increasing systemic blood

pressure to a mean arterial pressure of >90 mmHg, or lumbar drainage

of spinal fluid, was reportedly helpful in a few published cases of cord

infarction, but neither of these approaches has been studied systematically. Prognosis following spinal cord infarction is influenced by

the severity of the deficits at presentation; patients with severe motor

weakness and those with persistent areflexia usually do poorly, but in

one recent large series some improvement over time occurred in many

patients, with more than half ultimately regaining some ambulation.

Inflammatory and Immune Myelopathies (Myelitis) This

broad category includes the demyelinating conditions MS, NMO, and

postinfectious myelitis, as well as sarcoidosis, systemic autoimmune

disease, and infections. In approximately one-quarter of cases of myelitis, no underlying cause can be identified. Some will later manifest

TABLE 442-3 Evaluation of Myelopathy

1. MRI of spinal cord with and without contrast (exclude compressive causes).

2. CSF studies: Cell count, protein, glucose, IgG index/synthesis rate,

oligoclonal bands, VDRL; Gram’s stain, acid-fast bacilli, and India ink stains;

PCR for VZV, HSV-2, HSV-1, EBV, CMV, HHV-6, enteroviruses, HIV; antibody

for HTLV-1, Borrelia burgdorferi, Mycoplasma pneumoniae, and Chlamydia

pneumoniae; viral, bacterial, mycobacterial, and fungal cultures.

3. Blood studies for infection: HIV; RPR; IgG and IgM enterovirus antibody; IgM

mumps, measles, rubella, group B arbovirus, Brucella melitensis, Chlamydia

psittaci, Bartonella henselae, schistosomal antibody; cultures for B.

melitensis. Also consider nasal/pharyngeal/anal cultures for enteroviruses;

stool O&P for Schistosoma ova.

4. Vascular causes: MRI, CT myelogram; spinal angiogram.

5. Multiple sclerosis: Brain MRI scan; evoked potentials.

6. Neuromyelitis optica and related disorders: Serum anti-aquaporin-4

antibody, anti-MOG antibody, anti-GFAP antibody.

7. Sarcoidosis: Serum angiotensin-converting enzyme; serum Ca; 24-h urine

Ca; chest x-ray; chest CT; slit-lamp eye examination; total-body gallium scan;

lymph node biopsy.

8. Systemic immune-mediated disorders: ESR; ANA; ENA; dsDNA; rheumatoid

factor; anti-SSA; anti-SSB, complement levels; antiphospholipid and

anticardiolipin antibodies; p-ANCA; antimicrosomal and antithyroglobulin

antibodies; if Sjögren’s syndrome suspected, Schirmer test, salivary gland

scintigraphy, and salivary/lacrimal gland biopsy.

9. Paraneoplastic disorders: Antibody for amphiphysin, CRMP5, Hu, others.

10. Other: vitamin B12, copper, zinc.

Abbreviations: ANA, antinuclear antibodies; CMV, cytomegalovirus; CRMP5,

collapsin response mediator 5-IgG; CSF, cerebrospinal fluid; CT, computed

tomography; EBV, Epstein-Barr virus; ENA, epithelial neutrophil-activating peptide;

ESR, erythrocyte sedimentation rate; GFAP, glial fibrillary acidic protein; HHV, human

herpes virus; HSV, herpes simplex virus; HTLV, human T-cell leukemia/lymphoma

virus; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance

imaging; O&P, ova and parasites; p-ANCA, perinuclear antineutrophilic cytoplasmic

antibodies; PCR, polymerase chain reaction; RPR, rapid plasma reagin (test); VDRL,

Venereal Disease Research Laboratory; VZV, varicella-zoster virus.