Cranial Nerve Impairments

Olfactory Nerve (Cranial Nerve I)

Olfactory nerves transmit the sensation of smell to the brain. As the work that led to the 2004 Nobel Prize in Physiology or Medicine has shown, olfaction begins with highly complex, genetically determined specific G protein-coupled olfactory receptors. Odoriferous molecules bind to one or more receptors that lead to their identification. Rats, which live by their sense of smell, have about 1400 olfactory receptor genes. Humans have about 350 olfactory receptor genes, but they comprise almost 1.5% of our total genome.

From the olfactory receptors located deep in the nasal cavity, branches of the pair of olfactory nerves pass upward through the multiple holes in the cribriform plate of the skull to several areas of the brain. Some branches terminate in the entorhinal cortex and other regions on the undersurface of the frontal lobe. Others terminate deep in the hypothalamus and amygdala—cornerstones of the limbic system (see Fig. 16.5 ). The olfactory nerves’ input into the limbic system accounts, at least in part, for the influence of smell on sexual behavior and memory. Also, unlike other sensations—touch, vision, and hearing—whose pathways synapse in the thalamus or geniculate bodies en route to the cerebral cortex, some olfactory pathways project directly to the cortex without an intervening synapse in the diencephalon. Also, technically speaking, the olfactory bulb is structurally an extension of the brain.

To test the olfactory nerve, a neurologist will compress one nostril and ask the patient to identify certain substances by smelling through the other. Neurologists use readily identifiable and aromatic but innocuous substances, such as coffee. They do not use volatile or irritative substances, such as ammonia and alcohol, because they may trigger intranasal trigeminal nerve receptors and bypass a possibly damaged olfactory nerve. Patients are unreliable when estimating their sense of smell. For qualitative and quantitative testing, neurologists utilize commercial, standardized sets of “scratch and sniff” odors, such as the University of Pennsylvania Smell Identification Test.

When disorders impair both olfactory nerves, patients cannot perceive smell, identify the odor, or estimate its strength. Neurologists say that these patients have anosmia . Anosmia carries potentially life-threatening consequences, as when patients cannot smell toxic gas. More commonly, because individuals with anosmia cannot appreciate the aroma of food, their food remains almost tasteless. Thus, people with anosmia, to whom food is bland, tend to have a decreased appetite and lose weight.

Lack of smell sensation in one nostril may result from head trauma or a tumor adjacent to the olfactory nerve, such as an olfactory groove meningioma. In the classic Foster-Kennedy syndrome , a meningioma compresses the olfactory nerve and the nearby optic nerve. Damage to those two nerves causes the combination of unilateral blindness and anosmia. If the tumor grows into the frontal lobe, it can also produce personality changes, dementia, or seizures.

Anosmia commonly afflicts anyone with a respiratory tract infection (as happened with individuals infected with COVID-19), nasal congestion, and those who regularly smoke cigarettes or snort cocaine. With advancing age, otherwise normal individuals begin to lose their sense of smell. More than 50% of individuals older than 65 years and 75% of those older than 80 years have some degree of anosmia. Also, individuals with genetic mutations in their G protein-coupled receptor complex have anosmia for one or more specific odors.

Although mundane problems underlie most cases of bilateral anosmia, more serious issues may be responsible. Radiotherapy and some chemotherapy agents damage the olfactory nerve. Inadvertently inhaling zinc, which had been a constituent of popular “cold remedies,” has caused anosmia. Another situation where inhaled metal causes anosmia has occurred in welders who routinely inhale fumes containing vaporized iron, chromium, aluminum, and other metals. Head trauma, even from minor injuries, can shear the olfactory nerves as they pass through the cribriform plate and cause anosmia (see Traumatic Brain Injury, Chapter 22 ).

Loss of sense of smell is also a manifestation of many neurodegenerative illnesses. For example, almost 90% of patients with Parkinson, dementia with Lewy bodies, Wilson, Creutzfeldt-Jakob, and Alzheimer diseases develop anosmia. In fact, of Parkinson disease patients, more have anosmia than tremor, and anosmia correlates with the most disabling manifestation of the illness—dementia. Similarly, anosmia serves as a risk factor of, and often a precursor to, cognitive impairment in some neurodegenerative diseases. The olfactory bulb manifests the same pathology as the brain in Alzheimer, Parkinson, dementia with Lewy bodies, and Creutzfeldt-Jakob diseases (see Chapter 7, Chapter 18 ). Although cigarette smoking may be the explanation, schizophrenic patients have an increased incidence of anosmia, but not to the degree brought on by neurodegenerative diseases.

In the situation opposite to anosmia, sometimes individuals have a heightened sense of smell, hyperosmia . Migraine patients, before or during an attack, and pregnant women frequently report hypersensitivity to smells or irritation by common, innocuous ones.

Olfactory hallucinations may represent the first phase or aura (Latin, breeze) of seizures that originate in the medial-inferior surface of the temporal lobe, the uncus. These auras usually consist of a series of several-second episodes of ill-defined and unpleasant, but occasionally sweet or otherwise pleasant, smells preceding or superimposed on impaired consciousness and behavioral disturbances (see Chapter 10 ). Also, although most migraine auras consist of visual hallucinations, sometimes olfactory hallucination constitute an aura (see Chapter 9 ).

Anosmia may, of course, be psychogenic. Malingerers may claim inability to “smell” a noxious, volatile substance, such as ammonia, that actually stimulates the trigeminal nerve. Because irritation of the nasal passages is transmitted by the trigeminal nerve, a complete sensory loss would be possible only if an illness obliterated both pairs of trigeminal as well as olfactory nerves. In addition, given a forced-choice test of four smells, the malingering individual chooses a correct response less frequently than by chance, i.e., less than 25%.

On the other hand, olfactory hallucinations, as well as anosmia, can be psychogenic. In contrast to smells induced by seizures, psychogenic “odors” are typically foul-smelling, continuous, and not associated with impaired consciousness. Olfactory hallucinations or delusions may constitute a manifestation of a psychiatric illness.

Optic Nerve (Cranial Nerve II)

The optic nerves have two main functions: vision and adjustment of the size of the pupil in response to the intensity of light. The optic nerve fibers carrying visual information ultimately project to the cerebral cortex, while the others, carrying light intensity information, project to the midbrain.

As for vision, those optic nerve fibers originate in visual receptors in the retina and project posteriorly to the optic chiasm. At the chiasm, nasal fibers of the nerves cross, but temporal fibers continue uncrossed ( Fig. 4.1 ). Temporal fibers of one optic nerve join the nasal fibers of the other to form the optic tracts . The tracts travel to the lateral geniculate nuclei, from which the optic radiations emerge and pass through the temporal and parietal lobes to terminate in the calcarine cortex of the occipital lobe. Thus, each occipital lobe receives visual information from the contralateral visual field. Further projections relay the visual information to other areas of the cerebral cortex for higher level processing, such as tracking moving objects, reading, and interpreting.

Neurologists consider visual field deficits among the most important and reliable clinical findings. Many visual field deficits point to specific disorders, such as optic neuritis, pituitary adenomas, and migraine (see Fig. 12.8 ). In addition, visual field deficits are comorbid with certain neuropsychiatric conditions, such as left homonymous hemianopsia with anosognosia, right homonymous hemianopsia with aphasia or apraxia, and tubular vision with a psychogenic disturbance.

As for their role in regulating pupil size, the optic nerves form the afferent limb of the pupillary light reflex by sending small branches transmitting impulses proportional to light intensity to the midbrain. The efferent limb emerges from the Edinger-Westphal nuclei in the midbrain as parasympathetic fibers that travel in the oculomotor nerves (the third cranial nerves) and innervate the pupils’ constrictor muscles. Overall, the light reflex—optic nerves to midbrain and midbrain to oculomotor nerves—constricts the pupil in response to the intensity of light striking the retina.

Because of the pupillary light reflex, shining light into one eye will normally result in bilateral pupillary constriction. Simply put, when a neurologist shines a bright light into one or both eyes, the light reflex constricts both pupils ( Fig. 4.2 ). In an example of an abnormality detectable by testing the light reflex, if an examiner shines light into the right eye and neither pupil constricts, and then into the left eye and both pupils constrict, the right optic nerve (afferent limb) is impaired. In a different example, if an examiner shines light into the right eye and it produces no constriction of the right pupil but succeeds in provoking left eye pupil constriction, the right oculomotor nerve (efferent limb) is impaired.

In contrasting the optic nerves’ two functions, the visual system relies upon a high-level cortical system, whereas the light reflex remains a basic brainstem function. Thus, devastating occipital cortex injuries—from trauma, anoxia, or degenerative illnesses—produce blindness (cortical blindness) . However, no matter how severe the cerebral cortex damage, the pupils continue to react to light. Absence of the pupillary light reflex is one of the criteria for the diagnosis of brain death, though it can also occur secondary to ocular trauma, certain drug exposures, or other unusual circumstances.

Routine testing of the optic nerve includes examination of (1) visual acuity, (2) visual fields ( Fig. 4.3 ), and (3) the ocular fundi ( Fig. 4.4 ), in addition to testing of the pupillary light reflex. Because the visual system is important, complex, and subject to numerous ocular, neurologic, iatrogenic, and psychogenic disturbances, this book dedicates an entire chapter to visual disturbances particularly relevant to psychiatrists (see Chapter 12 ).

Unique among the cranial nerves, the optic nerves (and a small proximal portion of the acoustic nerves) are actually extensions of the central nervous system (CNS) and therefore are coated by myelin derived from oligodendrocytes (as opposed to peripheral nerves, whose myelin comes from Schwann cells). Thus, illnesses that attack the CNS, particularly childhood-onset metabolic storage diseases and multiple sclerosis (MS)-induced optic neuritis (see Chapter 15 ), characteristically involve the optic nerves. On the other hand, the optic nerves remain relatively spared in diseases that attack the peripheral nervous system (PNS) myelin, such as Guillain-Barré syndrome.

Oculomotor, Trochlear, and Abducens Nerves (Cranial Nerves III, IV, and VI)

The oculomotor, trochlear, and abducens nerves constitute the extraocular muscle system because, acting in unison, they move the eyes together in parallel to provide normal conjugate gaze (Latin, coniugātiō , yoking together). Damage of any of these nerves or muscles they innervate causes dysconjugate gaze, which results in characteristic patterns of diplopia (double vision). In addition, with oculomotor nerve damage, patients also lose pupillary constriction to light, as well as the elevation of their eyelid.

The oculomotor nerves (third cranial nerves) originate in the midbrain ( Fig. 4.5 ) and supply the pupil constrictor, eyelid, and adductor and elevator muscles of each eye (medial rectus, inferior oblique, inferior rectus, and superior rectus). Oculomotor nerve impairment, a common condition, thus leads to a distinctive constellation: a dilated pupil, ptosis, and outward deviation (abduction) of the eye ( Fig. 4.6 ). As just discussed, oculomotor nerve injury also impairs the efferent limb of the light reflex. In addition, it impairs the efferent limb of the accommodation reflex , in which the visual system adjusts the shape of the lens to focus on either near or distant objects. (Impaired focusing ability in older individuals, presbyopia [Greek, presbys , old man; opia , eye] results from the loss of flexibility in the aging lens, not from oculomotor nerve impairment.)

The trochlear nerves (fourth cranial nerves) also originate in the midbrain. They supply only the superior oblique muscle, which is responsible for depression of the eye when it is adducted (turned inward). To compensate for an injured trochlear nerve and avoid diplopia, patients tilt their head away from the affected side. Unless physicians observe a patient with diplopia perform this telltale maneuver, they may overlook a diagnosis of a trochlear nerve palsy or misinterpret it as a head tilt or torticollis ( Chapter 18 ).

Unlike the third and fourth cranial nerves, the abducens nerves (sixth cranial nerves) originate in the pons ( Fig. 4.7 and see Fig. 2.9 ). They perform only a single function and innervate only a single muscle. Each abducens nerve innervates its ipsilateral lateral rectus muscle, which abducts that eye. Abducens nerve impairment, which is relatively common, leads to inward deviation (adduction) of the eye, due to the unopposed medial pull of the medial rectus, but does not cause ptosis or pupil changes ( Fig. 4.8 ).

To review: The lateral rectus muscle is innervated by the sixth cranial (abducens) nerve and the superior oblique by the fourth (trochlear), while all the other extraocular muscles are innervated by the third (oculomotor). A mnemonic device, “LR ₆ SO ₄ ,” captures this relationship.

To produce conjugate horizontal eye movements, the oculomotor nerve on one side works in tandem with the abducens nerve on the other. Neurologists say that their actions are conjugate or yoked together. For example, when an individual looks to the left, the left sixth nerve and right third nerve simultaneously activate the left lateral rectus and right medial rectus muscles to produce conjugate leftward eye movement. Such complementary innervation is essential for conjugate gaze. If both medial rectus muscles were simultaneously active, the eyes would look toward the nose; if both lateral rectus muscles were simultaneously active, the eyes would look toward opposite walls.

Neurologists most often attribute horizontal diplopia to a lesion in the oculomotor nerve on one side or the abducens nerve on the other. For example, if a patient has diplopia when looking to the left, then either the left abducens nerve or the right oculomotor nerve is impaired. Diplopia on right gaze, of course, suggests a paresis of either the right abducens or left oculomotor nerve. As a clue, the presence or absence of other signs of oculomotor nerve palsy (a dilated pupil and ptosis, for example) usually indicates whether that nerve is responsible.

Lesions within the brainstem, along the nerves’ course from the brainstem to the ocular muscles, or at the neuromuscular junction may result in diplopia, but not lesions in the cerebral hemispheres (the cerebrum), and weaken the extraocular muscles. Because cerebral damage does not injure the cranial nerves, patients’ eyes remain conjugate despite cerebral infarctions or tumors. Even patients with advanced Alzheimer disease, ones who have sustained cerebral anoxia, and those lingering in a vegetative state retain conjugate eye movement.

Similarly, in motor neuron diseases, most notably amyotrophic lateral sclerosis (ALS) and poliomyelitis, the oculomotor and abducens nerves retain normal function despite destruction of large numbers of motor neurons. Patients with motor neuron diseases may have full, conjugate eye movements despite being unable to breathe, lift their limbs, or move their head.

Because the anatomy is so compact, brainstem lesions that damage cranial nerves typically produce classic combinations of injuries of the ocular nerves and the adjacent corticospinal (pyramidal) or cerebellar outflow tracts. These lesions cause diplopia accompanied by contralateral hemiparesis or ataxia. The pattern of the diplopia localizes the lesion. The etiology in almost all cases is an occlusion of a small branch of the basilar artery causing a small brainstem infarction (see Chapter 11 ).

The following frequently occurring, classic brainstem strokes, despite the physical deficits, do not include cognitive impairment because the cerebrum is unscathed:

• Patients with a right-sided midbrain infarction have a right oculomotor nerve palsy, which causes right ptosis, a dilated pupil, and diplopia accompanied by left hemiparesis ( Fig. 4.9 ). With a slightly different right-sided midbrain infarction, patients have right oculomotor nerve palsy and tremor of left sided limbs ( Fig. 4.10 ).

  
  

• A right-sided pons lesion typically produces a right abducens nerve paresis and left hemiparesis ( Fig. 4.11 ).

  

• Another brainstem syndrome, which includes ocular motility impairment, results from damage to the medial longitudinal fasciculus (MLF ). This structure is a heavily myelinated midline tract that carries fibers linking the nuclei of the abducens and oculomotor nerves (see Figs. 2.9 , 4.11 , Figure 15.3 , Figure 15.4 ). Its interruption produces the MLF syndrome , also called internuclear ophthalmoplegia (INO ). This classic syndrome consists of nystagmus of the abducting eye contralateral to the damaged MLF, and failure of the adducting eye ipsilateral to the MLF to cross the midline. It most often signifies MS or a small midbrain stroke.

The oculomotor and abducens nerves are particularly vulnerable to injury in their long intracranial paths between their brainstem nuclei and ocular muscles. Lesions along the course of those nerves produce simple, readily identifiable clinical pictures: extraocular muscle impairment without hemiparesis, ataxia, or mental status impairment. Diabetic infarction , the most frequent lesion of the oculomotor nerves, produces a sharp headache and paresis of the affected muscles. Diabetic oculomotor nerve infarctions characteristically spare the pupil. In other words, diabetic infarctions cause ptosis and ocular abduction, but the pupil remains equal in size to its counterpart and normally reactive to light.

Ruptured or expanding aneurysms of the posterior communicating artery may compress the oculomotor nerve just as it exits from the midbrain. In this case, oculomotor nerve palsy—which would be the least of the patient’s problems—would be only one manifestation of a life-threatening subarachnoid hemorrhage. In this case, pupillary enlargement accompanies the ptosis and abduction. In a more benign condition, children occasionally have migraine headaches accompanied by temporary oculomotor nerve paresis (see Chapter 9 ).

Disorders of the neuromuscular junction—where the motor nerve terminal of cranial and peripheral nerves synapses with a muscle—also can mimic oculomotor or abducens nerve paresis. In myasthenia gravis (see Fig. 6.3 ) and botulism, for example, impaired acetylcholine neuromuscular transmission leads to combinations of ocular and other facial muscle paresis. These deficits may puzzle neurologists because the muscle weakness is often subtle and variable in severity and pattern. Occasionally, neurologists overlook mild cases or misdiagnose them as a psychogenic disorder.

A related condition, congenital dysconjugate or “crossed” eyes, strabismus , does not cause double vision because the developing brain learns to suppress one of the images. If uncorrected in childhood, strabismus leads to blindness of the deviated eye, amblyopia .

People can usually feign ocular muscle weakness by staring inward, as if looking at the tip of their nose. Children often do this playfully; however, neurologists readily identify adults with their eyes in this position as displaying voluntary, bizarre activity. Another disturbance, found mostly in health care workers, comes from their surreptitiously instilling eye drops into one or both of the eyes to dilate their pupils so that they mimic ophthalmologic or neurologic disorders.

Some conditions that affect eye movements also impair cognitive function. Wernicke encephalopathy , for example, consists of memory impairment (amnesia) accompanied by nystagmus and oculomotor or abducens nerve abnormalities (see Chapter 7 ). Another example is transtentorial herniation , in which a cerebral mass lesion, such as a subdural hematoma, forces the anterior tip or medial edge of the temporal lobe through the tentorial notch. It compresses the oculomotor nerve and adjacent brainstem to cause coma, decerebrate posturing, and a dilated pupil (see Fig. 19.3 ).

Trigeminal Nerve (Cranial Nerve V)

In contrast to the exclusively sensory function of cranial nerves I, II, and VIII and the exclusively motor functions of cranial nerves III, IV, VI, XI, and XII, the trigeminal nerves have both sensory and motor functions. The trigeminal (Latin, threefold ) nerves convey sensation from the three areas of the face, and they innervate the large, powerful muscles that protrude and close the jaw. Because these muscles’ main function is to chew, neurologists often call them “muscles of mastication.”

The trigeminal motor nucleus is situated in the pons, but the sensory nuclei extend from the midbrain through the medulla. The trigeminal nerves leave the brainstem at the side of the pons, together with the facial and acoustic nerves, after which these three cranial nerves—V, VII, and VIII—emerge through the cerebellopontine angle .

Examination of the trigeminal nerve begins by testing sensation in three sensory divisions ( Fig. 4.12 ). Neurologists touch the side of the patient’s forehead, cheek, and jaw. Areas of reduced sensation, hypalgesia , should conform to anatomic outlines.

Assessing the corneal reflex is worthwhile, especially when examining patients whose sensory loss does not conform to neurologic expectations. The corneal reflex is a superficial reflex that is essentially independent of upper motor neuron (UMN) status. Its testing begins with stimulation of the cornea with a wisp of cotton or a breath of air. The trigeminal nerve’s ophthalmic (V ₁ ) division, which forms the afferent limb of the corneal reflex, connects via synapses in the brainstem to both facial (CN VII) nerves, which constitute the efferent limb of the reflex arc. The facial nerves innervate the bilateral orbicularis oculi muscles. Alternatively, to avoid transmitting infection or causing an abrasion of the cornea, neurologists substitute stroking the nostril with a cotton swab to elicit a sneeze or wince (“the nasal tickle”) for the corneal reflex.

The corneal reflex—whose pathway travels from trigeminal nerves to pons to facial nerves—produces an ipsilateral direct and a contralateral consensual response, analogous to the pupillary light reflex. Stimulating one cornea will normally provoke a bilateral blink. If neurologists apply the cotton tip to the right cornea and neither eye blinks, but applying the cotton tip to the left cornea prompts both eyes to blink, the right trigeminal nerve (afferent limb) is impaired. In a different scenario, if stimulation of the right cornea fails to provide a right eye blink, but it succeeds in provoking a left eye blink, the right facial nerve (efferent limb) is impaired.

To test the trigeminal nerve’s motor component, neurologists assess jaw muscle strength by asking the patient to clench, open, and then protrude the jaw. The jaw jerk reflex consists of a prompt but not overly forceful closing after a tap ( Fig. 4.13 ). Alterations in the response follow the rules of a deep tendon reflex (DTR): a hyperactive response indicates an UMN (corticobulbar tract) lesion, and a hypoactive response indicates a lower motor neuron (LMN), i.e., a cranial nerve lesion. The neurologist should include testing of the jaw jerk reflex in patients with dysarthria, dysphagia, and emotional lability—mostly to assess them for the likelihood of pseudobulbar palsy, in which case, the jaw jerk is hyperactive (see later).

Injury of a trigeminal nerve causes facial hypalgesia, afferent corneal reflex impairment, jaw jerk hypoactivity, and deviation of the jaw toward the side of the lesion. Various conditions—nasopharyngeal tumors, gunshot wounds, and tumors of the cerebellopontine angle, such as acoustic neuromas (see Fig. 20.27 )—may cause trigeminal nerve injury.

In trigeminal neuralgia , an aberrant vessel or other lesion in the cerebellopontine angle, MS plaques in the pons, or other disorder irritates the trigeminal nerve. Patients typically suffer lancinating jabs in the distribution of the third, or less frequently the second, division of the nerve (see Chapter 9 ). Similarly, when herpes zoster infects the trigeminal nerve, it causes a rash in the distribution of one division of the trigeminal nerve, sometimes followed by excruciating pain (postherpetic neuralgia) (see Chapter 14 ).

Finally, psychogenic sensory loss involving the face usually encompasses the entire face or the lateral half of the body, i.e., a hemisensory loss. In most cases, the following three nonanatomic features may be present: (1) the sensory loss will not involve the scalp (although the actual territory of the trigeminal nerve extends to the vertex); (2) the corneal reflex will remain intact; and (3) when only one half of the face is affected, sensation will be lost sharply rather than gradually (i.e., the patient will “split the midline”) (see Fig. 3.5 ).