The dorsal, more primitive portion of the pons is known as the pontine tegmentum. It contains, among others, the following structures of interest to the clinician (Fig. 3.1):
The reticular formation
The pontine reticular formation is located dorsally in the pon- tine tegmentum, and is composed of multiple medial and lateral nuclei, the most important of which are the medially located nucleus reticularis pontis caudalis and nucleus reticu- laris pontis oralis. These are a continuation of medullary retic- ular nuclei, and give rise to the ascending reticular activating system, which plays a major role in consciousness. Therefore, lesions that destroy more than a quarter of the tegmentum may lead to an unconscious state.
The sensory lemniscal system
These structures conduct sensory information to the thala- mus. They consists of the following components:
(1) Most medially are the medial lemnisci, which have become ovoid, flattened and oriented in a mediolateral direction. This is in distinction to their location in the medulla, where they are located anteriorly in a midline location, and are elongated in an anterior–posterior orientation. The medial lemnisci are axons from the gracilis and cuneatus nuclei, and convey proprioception, vibration and deep pressure sensations from the body. Facts to remember are:
– These tracts have already decussated in the medulla. Therefore, lesions of the right medial lemniscus at the level of the pons, for example, will lead to loss of vibra- tion sensation and proprioception in the left body.
– Within the medial lemniscus, fibers from the nucleus cuneatus (upper body) are located medially, while those from the nucleus gracilis (lower body) are located laterally. (2) Lateral to the medial lemnisci are the trigeminal tracts,
which convey all facial sensory modalities; i.e., pain, tem- perature, touch, and proprioception. Please note the following:
– The trigeminal nerve has multiple nuclei (which will be discussed). However, the ascending trigeminothalamic tract has already decussated, and therefore carries sen- sory information from the contralateral face.
(3) Lateral to the trigeminal tracts are the spinothalamic tracts, which convey pain and temperature information from the contralateral body, having decussated in the spinal cord within one or two levels of their entry into the cord.
The trapezoid body
The ascending sensory lemniscal system described above is partially embedded in the transversely oriented fibers of the trapezoid body. This arises from the cochlear nuclei, crosses the midline, and forms the lateral lemniscus in the postero- lateral pons, as part of the auditory pathway. Please note that, although the nuclei for cranial nerve eight are primarily located below the ponto-medullary junction, lesions affecting the auditory and vestibular systems are commonly seen in pontine conditions. Therefore, cranial nerve eight has been placed in this chapter and will be discussed below.
a
b
Fig. 3.1. Anatomic sections through the pons, showing (a) the locations of the major tracts and (b) nuclei within the basis pontis and pontine tegmentum.
The medial longitudinal fasciculus (MLF)
This small but distinctive tract runs from the medulla through the midbrain, maintaining a posterior and midline location, just anterior to the floor of the fourth ventricle and the aque- duct of Sylvius on each side of the midline. It receives input from the vestibular nuclei and connects them to the extraocu- lar muscles to aid in the control of conjugate eye movements. It also connects the sixth nerve nucleus on one side of the brainstem with the contralateral third nerve nucleus, specifi- cally that part which innervates the medial rectus.
The locus ceruleus
These nuclei are the major noradrenergic source to the cortex. They are located posteriorly in the pontine tegmentum, at the anterolateral margins of the fourth ventricle. Ascending fibers innervate wide areas of the brain, passing with the medial fore- brain bundle to the hypothalamus, limbic system, anterior thala- mus and the cortex. As we learn more, this structure will probably play a significant role in neurobehavioral medicine. For instance, the locus ceruleus is thought to play important roles in REM sleep, as well as arousal and attention. Neuronal loss in the locus ceruleus is seen in Parkinson’s, Alzheimer’s and
Down syndromes. Also, one model of hyperactivity attention- deficit disorder (HADD) suggests that a loss of regulation and high tonic activity of the locus ceruleus may cause HADD. In addition, there may be a link between the locus ceruleus and anxiety, as animal experiments in monkeys have shown that its stimulation produces severe anxiety. Its relationship to depres- sion is more complex. Some models of depression posit degen- eration of the locus ceruleus neurons. However, monoamine oxidase inhibitors, effective in treating depression, inhibit the locus ceruleus. This effectiveness may be mediated by ameliorat- ing the anxiety component that often accompanies depression.
Cranial nerve nuclei
The nuclei of the fifth, sixth, and seventh cranial nerves are located in the pontine tegmentum. These cranial nerves course through the belly of the pons to exit the brainstem. The eighth cranial nerve nuclei are predominantly located just below the pontomedullary junction but will be discussed as part of the pons due to the location of their fiber tracts in the pontine tegmentum and the exit of the eighth nerves from the brainstem at the level of the cerebellopontine angle cisterns.
With this brief anatomic prelude, let us take some cases!
Case 3.1
53-year-old man presents with 1-month history of progressive left facial numbness and now with difficulty chewing.
What cranial nerve may be affected?
The history of facial numbness makes us think of the trigem- inal, or fifth, cranial nerve, which subtends sensation to the face. However, the difficulty chewing is confusing, because the seventh cranial nerve innervates the muscles of the face, right? Unfortunately, not completely right. Remember, although most facial motor functions are subtended by the seventh cranial nerve, the muscles of mastication (chewing) are innervated by the motor component of the trigeminal nerve. Therefore, every- thing localizes to the fifth nerve.
Lesions affecting the function of the fifth cranial nerve, how- ever, may occur at many levels in the neuroaxis. Lesions may be
supranuclear, including in the sensory cortex, corona radiata along the course of the sensory pathways, or in the facial sensory region of the thalamus (the VPM nucleus of the thalamus). Lesions may be nuclear, such as in the pons or in the medulla involving the fifth nerve nuclei, or preganglionic, ganglionic, or in the trigeminal nerve branches.
The history of gradual disease progression makes us lean away from a vascular insult and toward an inflammatory or neoplastic process.
Physical examination reveals loss to pinprick and temperature sensation across the left face, from the forehead to the mandible. The temporalis muscle is atrophic, the bulk of the masseter is diminished, and with jaw opening, the jaw tilts to the left. Both the corneal and jaw jerk reflexes are markedly diminished.
How does this affect your thinking?
The examination suggests involvement of the entire fifth nerve (all three sensory divisions and the motor division). The absence of a jaw jerk reflex and a corneal reflex suggests that the lesion is not supranuclear (in such cases, the reflexes would be brisk). Remember also that, with weakness of the masseter and ptery- goid muscles, the jaw will tilt ipsilaterally to the weak side with mouth opening.
An MRI image is shown (Fig. 3.2).
What are your findings? What is your differential?
On the MRI, we see that the cisternal segment (in the prepon- tine cistern, after the fifth nerve exits the belly of the pons) of the left fifth nerve is swollen and diffusely enhancing (Fig. 3.2, arrow). The enhancement does not extend into the pons. However, there is some abnormal tissue in the left Meckel’s cave and some mass effect in the left cavernous sinus, which bulges outward. The image suggests that the pathology involves the fifth nerve itself, and is not secondary to a mass, such as a meningioma, impinging the nerve. Also, while slightly swollen, the nerve is not mass-like, such as to suggest a fifth nerve schwannoma. Differential diagnostic possibilities for an enhan- cing fifth nerve would include carcinomatous meningitis,
lymphoma, viral neuritis, or other infectious processes such as tuberculosis or Lyme disease, as well as non-infectious granuloma- tous diseases such as sarcoidosis. However, the mass effect in the cavernous sinus essentially excludes viral neuritis and Lyme disease.
Diagnosis
Carcinomatous meningitis, secondary to perineural spread of a head and neck adenoid cystic carcinoma.
Please discuss the functional anatomy of the5th cranial nerve. The fifth nerve is usually identified as the main sensory input of the face to the central nervous system. Aside from this main sensory function, it also has a smaller motor root, which supplies the muscles of mastication (masseter, temporalis, medial and lateral pterygoids) as well as the tensor tympani, tensor palatini, myelohyoid and anterior belly of the digastric. The motor fibers arise from the motor nucleus of the fifth nerve, at the midpontine level in the pontine tegmentum (Fig. 3.3).
The motor nucleus receives bilateral symmetric input from the motor cortex. Therefore, cortical or corticobulbar tract lesions do not paralyze the muscles of mastication. Lesions of the root or nerve, however, cause a lower motor neuron type paralysis of these muscles, with denervation atrophy. The motor fibers run with the third sensory division, or V3, of the trigeminal nerve.
The sensory portion of the fifth nerve is divided into three divi- sions: V1 (ophthalmic), V2 (maxillary), V3 (mandibular), each with its own course through the head and neck (Fig. 3.3). These divisions run separately in the cavernous sinus, but collect into a main nerve trunk in the prepontine cistern. The cell bodies of most of these fibers are located in the trigeminal (Gasserian) ganglion, located in Meckels’s cave, just posterior to the cavernous sinus. The nerve fibers synapse in three nuclei of the trigeminal nerve in the brain- stem: the main sensory nucleus, located in the pontine tegmen- tum, the spinal trigeminal nucleus running from the lower pons through the posterolateral medulla and down into the upper cervi- cal cord, and a small mesencephalic nucleus in the midbrain (Fig. 3.3and 3.4).
The sensory fibers of the fifth nerve, once they enter the brain- stem, generally distribute themselves as follows: proprioceptive fibers from the mouth go to the mesencephalic nucleus and then to the thalamus. Actually, their neurons are located in the mesen- cephalic nucleus itself rather than in a peripheral ganglion, a fairly unique arrangement. Fibers subtending touch in each of the three divisions bifurcate, with some synapsing on the main sensory nucleus, and others traveling down the descending spinal trigem- inal tract. From there, they enter the adjacent spinal trigeminal nucleus, towards its rostral and mid portions. Fibers subtending pain and temperature enter the pons, and travel downward in the spinal trigeminal tract, synapsing on the lower-most portion of the spinal trigeminal nucleus, the so-called caudal nucleus, which extends from the obex of the fourth ventricle in the medulla to the upper cervical spine.
Now, all of this sensory information has to make its way to the thalamus, and so we have to follow the output of these nuclei (Fig. 3.4). This is complex, but can be generalized as follows: most of the output of the spinal trigeminal nucleus crosses the mid- line, and ascends to the thalamus via the contralateral brainstem in the ventral trigeminothalamic tract, or trigeminal tract for short, which runs between the medial lemniscus and the spi- nothalamic tract, as described above. This ends in the ventral posteromedial (VPM) nucleus of the thalamus. Most of the output of the main sensory nucleus also crosses the midline, and joins the ventral trigeminothalamic tract. Some of the output, how- ever, travels in an ancillary tract called the dorsal trigeminal tract, ascending ipsilaterally in an uncrossed fashion. Finally,
some fibers also cross the midline and ascend in the contralateral dorsal trigeminal tract.
Some important clinical points can be extracted from this jumble of information, as follows.
Trigeminal nerve findings, such as facial sensory loss, can be caused by cortical, thalamic, capsular, brainstem, prepontine cistern, cavernous sinus, or more peripheral lesions. Some gen- eral clinical guidelines may be offered.
(1) Lesions of the 5th nerve distal to the Gasserian ganglion will typically involve preferentially one of the branches of the 5th nerve, such that the sensory loss, which should affect all sensory modalities, will preferentially involve the ophthal- mic, maxillary, or mandibular (V1, V2, or V3) distributions. (2) Lesions at the level of the Gasserian ganglion or the fifth nerve
itself should involve the entirety of the face, and involve all modalities.
(3) Brainstem lesions may lead to ipsilateral facial sensory loss, from involvement of the 5th nerve as it travels through the belly of the pons, the 5th nerve main sensory nucleus in the pons, or the spinal trigeminal tract and nucleus in the lower pons and medulla. However, facial sensory findings may also occur contralateral to the lesion by involving the ascending ventral trigeminothalamic tract as part of the lemniscal sen- sory system. Recall that the output of the spinal trigeminal nucleus, as well as most of the output of the main sensory nucleus of the 5th nerve crosses the midline, and projects to the contralateral thalamus via the ventral trigeminothalamic tract and trigeminal lemniscus. A case of a midbrain lesion causing contralateral facial sensory symptoms is shown in Fig. 3.5. In the experience of the author, however, ipsilateral facial sensory findings are more common than contralateral facial sensory findings.
(4) Because of the somatotopic organization of the sensory fibers, such that pain and temperature fibers tend largely to project on the inferior aspect of the spinal trigeminal nucleus (caudal portion or caudal nucleus of the spinal trigeminal nucleus), it is possible to treat tic douloureux, a disabling syndrome of facial pain, by a spinal trigeminal tractotomy, where only
Fig. 3.3. Anatomy of the trigeminal nerve. The sensory portion of the trigeminal nerve is composed of three divisions: V1, V2 and V3, which exit the skull through the superior orbital fissure, foramen rotundum and foramen ovale, respectively. These divisions send fibers to the three sensory brainstem nuclei of the fifth nerve: the main sensory nucleus, the mesencephalic nucleus and the spinal trigeminal nucleus. The motor component of the 5th nerve arises from the motor nucleus, and travels along with V3.
Fig. 3.4. Output pathways of the trigeminal nuclei. Inputs to the chief sensory nucleus and the spinal trigeminal nucleus come in through the fifth nerve via the trigeminal ganglion. Most of the output (about 90 percent) from the chief sensory nucleus and the spinal trigeminal nucleus decussates to reach the contralateral thalamus via the ventral trigeminothalamic tract. There is also a small ipsilateral output component (about 10 percent). See text for further details.
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Fig. 3.5. (a) Diffusion-weighted MRI scan shows a small midbrain infarct posterior to the substantia nigra in the region of the left trigeminal lemniscus (arrow). This patient’s only symptom was right facial numbness. (b) Schematic diagram of the midbrain shows that the infarct involves the region of the left trigeminal lemniscus (and ventral trigeminothalamic tract), which is carrying information from the right-sided 5th nerve nuclei up to the left thalamus. This case illustrates that brainstem lesions may cause contralateral facial sensory findings, although ipsilateral sensory deficits are more common.
the inferior portion of the tract, at the cervicomedullary junc- tion, is sectioned. This should leave other sensory modalities intact.
(5) It is noted that fibers for proprioception project predominantly to the mescencephalic nucleus of the 5th cranial nerve. Also, fibers for light touch divide and project both to the main sensory nucleus as well as the spinal trigeminal tract and nucleus. Since touch sensation is processed both through the main sensory nucleus in the pons and the spinal trigeminal nucleus and tract lower in the brainstem, it is difficult for single lesions of the brainstem to ablate touch sensation. Therefore, brainstem infarcts often show a dissociation of sensory modality defects, with pain and temperature sensation usually significantly more affected than other modalities. This is in distinction to more peripheral lesions, such as those of the 5th nerve itself, which should affect all sensory modalities equally. This may help in localizing the site of the lesion.
(6) It is noted that sensory fibers from the perioral region tend to project further rostral in the brainstem along the spinal trigem- inal nucleus than fibers mediating sensation from the skin away from the perioral area, with a somatotopic mapping of these fibers gradually lower in the brainstem as one goes away from the region of the mouth. This may be to allow a smooth transi- tion between cervical dermatomes and cranial nerve derma- tomes to the skin most adjacent to the neck, such as the periauricular areas, and region of the angle of the mandible, with progression more rostrally in the brainstem as fibers pro- gress toward the midline and perioral region. The clinical corre- late of this arrangement is a so-called ‘‘onion-skin’’ sensory deficit, where lesions in the lower brainstem and upper cervical spine will spare the perioral area, where sensation remains intact. This ‘‘onion-skin’’ pattern of sensory loss is thus helpful in localizing a ‘‘5th nerve’’ lesion to the lower brainstem.
(7) The 5th nerve participates in multiple important reflexes. Only two of these are mentioned:
The corneal reflex
This represents a reflex arc between the sensory fibers of the ophthalmic division of the 5th nerve as the afferent limb, and the orbicularis oculis muscles, supplied by the seventh nerve. The 5th nerve fibers will connect to both seventh nerve nuclei. Hence, touching the cornea with sterile gauze will initiate an immediate blink reflex in both eyes. The presence of the corneal reflex verifies the integrity of the afferent 5th nerve, and the efferent seventh nerve.
The jaw jerk reflex
This reflex consists of tap on the closed but relaxed jaw at the chin, eliciting a contraction of the temporalis muscles and a ‘‘jaw jerk.’’ The afferent limb of this reflex is the proprioceptive fiber set synapsing on the mescencephalic nucleus of the 5th cranial nerve, while the efferent limb of the reflex is the motor fiber set of the 5th cranial nerve. An intact jaw jerk would confirm the integrity of the afferent and efferent loops. If other cranial nerve five lesion symptoms are seen, an intact jaw jerk reflex would place the lesion either lower in the brainstem, or along the output sensory limb of the 5th nerve nuclei, such as the trigeminothala- mic tract, thalamus, internal capsule, or sensory cortex, proximal (more central) to the reflex arc.
To round out the imaging issues of the fifth nerve, a few more sets of images are briefly presented.Fig. 3.6presents a patient with right facial numbness who had a fifth nerve schwannoma.
Now that you are comfortable locating the fifth nerve,Fig. 3.7 presents a 62-year-old hypertensive patient with left-sided trigem-