Clinical Vignette

A 23-year-old medical student noted swollen lymph nodes in the left posterior triangle of his neck. He was otherwise asymptomatic. The student health service told him that he was overly concerned and there was nothing wrong. Within a period, he became quite fatigued with bouts of fever and sought another opinion from a respected internist. Except for the presence of abnormal left posterior cervical and axillary lymphadenopathy, his clinical examination was normal. Results of a mononucleosis spot test were normal but liver function studies revealed elevated transaminases. Excision of cervical lymph nodes was performed.

During the procedure, the surgeon queried the student about the risks of this minor operation. The student replied that it is important to exercise caution so as not to cut the spinal accessory nerve (CN-XI) because paralysis of the trapezius muscle would result. When he returned to his rotation on the chief of surgery’s service, the student was informed by the intern that the chief, on hearing about his missing student, commented that there was a 50% 5-year mortality rate among his patients undergoing this procedure.

The professor of pathology could not arrive at a diagnosis and sent the node to the Armed Forces Institute of Pathology and to the Mayo Clinic for more definitive opinions. They did not believe it represented a lymphoma; 6 weeks later, the test for infectious mononucleosis was positive. The senior editor of this text notes that it is now 49 years since he had this biopsy.

The lymph node revealed cellular hyperplasia and atypia but general preservation of lymph node architecture. It was felt that the pathology likely represented a reactive process without evidence of a definitive malignancy or lymphoma. A repeat monospot now returned positive and he was instructed to convalesce, with little physical activity, over 2 weeks. A similar case was encountered by the author soon after. However, in this case, upon returning to exercise, sagging of the left shoulder, restricted shoulder movements, and pain (especially when elevating the arm) were noted by the patient. An evaluation revealed atrophy and weakness of the trapezius on the left with downward and outward winging of the scapula upon arm extension. An electromyography (EMG) confirmed an accessory nerve lesion with denervation potentials isolated to the upper trapezius.

Comment: This vignette exemplifies that physicians always need to give careful consideration to every patient complaint, especially those in the medical profession. The patient was labeled with “medical studentitis,” and a peer created further emotional turmoil for him by suggesting he might die within 5 years. Fortunately, a benign mechanism was established.

Occasionally, patients undergoing similar procedures experience iatrogenic laceration to the spinal accessory nerve. Such leads to significant shoulder pain and atrophy of the unilateral trapezius muscle and residual scapular winging. The more proximally innervated sternocleidomastoid muscle (SCM) is spared. Cervical lymph node biopsies may be the most common cause of CN-XI palsy.

Cranial nerve CN-XI, or the spinal accessory nerve (SAN), serves primarily a motor function for the neck and shoulder. It has an intriguing functional array with one of the two major muscles it innervates, the SCM, inserting on the ipsilateral occiput. When one side contracts, it turns the head in the opposite direction; for example, a right SCM contraction turns the head to the left and vice versa. Both SCM muscles contracting simultaneously results in neck flexion.

The seemingly paradoxical function of the SCM is also of interest and used in rare circumstance of a hysterical pseudo-hemiparesis or functional somatization with secondary gain. Patients feigning a right hemiparesis will give way when asked to turn their head against resistance to the right, not realizing that it is the left SCM that turns the head contralaterally. Thus when asked to turn their head to the asymptomatic left, they use the right SCM without difficulty.

Anatomy

The SAN is primarily a motor nerve innervating the SCM and trapezius muscles in the neck and back (Fig. 10-1). In contrast to the other cranial nerves, its lower motor neuron cell bodies are located primarily within the spinal cord. The accessory nucleus is a cell column within the lateral anterior gray column of the upper five or six cervical spinal cord segments. Proximally it lies nearly in line with the nucleus ambiguus and caudally within the dorsolateral ventral horn. Originating from the accessory nucleus, the rootlets emerge from the cord and unite to form the trunk of CN-XI. This extends rostrally through the foramen magnum into the posterior cranial fossa. Intracranially, it accompanies the caudal fibers of the vagus nerve (CN-X) exiting the skull through the jugular foramen. The SAN then descends in close proximity to the internal carotid artery and internal jugular vein (Fig. 10-2).

Figure 10-1 Accessory Nerve (XI): Schema.

Figure 10-2 Cervical Plexu in Situ.

Once the spinal accessory nerve is extracranial, it is joined by fibers derived from the third and fourth upper cervical ventral rami. Some of these cervical fibers may innervate the caudal trapezius, whereas the proximal trapezius and the entire SCM muscle are primarily innervated by CN-XI. The spinal accessory nerve then emerges from the midpoint of the posterior border of the SCM, to cross the posterior triangle of the neck superficial to the levator scapulae. It is here that this cranial nerve is in close proximity to the superficial cervical lymph nodes. Further caudally, approximately 5 cm above the clavicle, it passes into the anterior border of the trapezius muscle, which it also innervates.

There is a minor afferent component to the SAN that carries primary proprioceptive function for the two muscles it innervates. Also, a minor cranial root contribution to the spinal accessory consists of a few fibers originating in the caudal portion of the nucleus ambiguus. These fibers traverse with the intracranial spinal accessory nerve and exit through the jugular foramen.

The supranuclear innervation of the CN-XI nuclei is still a matter of debate. Although the trapezius muscle is innervated from the opposite hemisphere, there is some question as to whether the supranuclear innervation of the SCM is also contralateral. One standard neuroanatomy text, Brodal 1998, states that with clinical corticobulbar lesions there is paresis of the contralateral SCM as well as the trapezius. Others note, based on intracarotid Amytal injections, that the SCM is innervated predominantly from the ipsilateral hemisphere. Suffice it to say that the most proximal and midline musculature can be activated bilaterally. Therefore, one needs to be circumspect when attempting to lateralize the source of unilateral SCM weakness.

Clinical Presentation and Diagnostic Approach

SAN lesions located intracranially or proximally to the innervation of the SCM cause weakness of both the SCM and the trapezius. Damage to this nerve within the posterior triangle of the neck spares the SCM and results in weakness of the trapezius only. If the SCM is weak, the patient experiences weakness when turning the head to the opposite side.

Involvement of the trapezius manifests as drooping of the shoulder and mild scapular winging away from the chest wall with slight lateral displacement. Weakness in shoulder elevation and arm abduction above horizontal is typical. Winging is apparent with arms hanging along the trunk, and becomes accentuated when patients abduct the arms. In contrast, scapular winging from serratus anterior weakness due to long thoracic nerve palsy is most prominent on forward elevation of the arms (Fig. 10-3).

Figure 10-3 Clinical Findings with Cranial Nerve XI Damage.

Most individuals with CN-XI palsies present with shoulder or neck pain or both. The painful paresis can be sudden, because of direct injury during procedures as seen in the above vignette or with trauma or delayed, such as with entrapment of the nerve within scar tissue or structural lesions such as tumors. As in all patients with neck and shoulder pain, careful exam and history are necessary to exclude lesions at the level of the cervical nerve roots or brachial plexus.

Electromyography is important for confirming that the lesion is confined to the distribution of CN-XI. In addition, a gadolinium-enhanced magnetic resonance imaging (MRI) is appropriate if any question exists of a more widespread lesion other than a simple CN-XI neuropathy.

Differential Diagnosis

The most common site of isolated CN-XI neuropathy is within the neck. The close association of CN-XI with superficial cervical lymph nodes renders it vulnerable to iatrogenic damage during lymph node biopsy or a radical neck surgical dissection. The spinal accessory nerve can also be directly compressed by swollen lymph nodes or other solid tumors. Rarely, CN-XI neuropathy occurs after blunt or penetrating neck trauma, or due to radiation injury with treatment of adjacent tumors. Although it is not part of the brachial plexus, CN-XI can be involved in patients with brachial plexitis (neuralgic amyotrophy). Damage also rarely occurs after carotid endarterectomy or jugular vein cannulation because of the nerve’s proximity to large neck vessels.

Intraspinal and intracranial portions of CN-XI may be affected by intrinsic spinal cord lesions, posterior fossa meningiomas, or metastases. Benign tumors such as an en plaque meningioma at the base of the brain or metastatic tumors at the jugular foramen or foramen magnum may impinge on the SAN; however, these various lesions usually affect concomitantly the glossopharyngeal, vagal, and sometimes even the hypoglossal nerve exiting through the adjacent hypoglossal foramen. Very rarely, varied pathologic lesions of the SAN occur just after it leaves the skull and courses through the space behind the parotid gland and pharynx. Cranial nerves IX, X, XI, XII, and adjacent sympathetic chain fibers, causing Horner syndrome, are potentially involved in variable combinations with primary or metastatic tumors.

Various disorders at the anatomic level of the anterior horn cell are within the differential of CN-XI neuropathy, including motor neuron disease, syringomyelia, and poliomyelitis. In these cases, one finds prominent atrophy and fasciculations affecting both the SCM and trapezius muscles.

Prognosis

For patients with benign traumatic lesions, the likelihood of reinnervation is good unless the proximal and distal SAN segments are widely separated. Sometimes surgical exploration is helpful. The time frame for reinnervation is similar to that for any peripheral nerve: 1 mm per day or 3 cm per month.

Anatomy

CN-XII carries motor fibers that supply all intrinsic and most extrinsic tongue muscles, that is, the hyoglossus, styloglossus, genioglossus, and geniohyoid (Fig. 10-4). Its fibers originate from the hypoglossal nucleus beneath the floor of the fourth ventricle (Fig. 10-5). In its intramedullary course, CN-XII axons pass ventrally and lateral to the medial lemniscus emerging from the medulla in the ventrolateral sulcus between the olive and the pyramid. The rootlets unite to form CN-XII, which exits the skull through the hypoglossal foramen adjacent to the foramen magnum within the posterior cranial fossa (Fig. 10-6).

Figure 10-4 Hypoglossal Nerve (XII): Schema.

Figure 10-5 Hypoglossal Nerve Intramedullary Course.

Figure 10-6 Base of Skull.

After exiting the skull, CN-XII runs medial to CN-IX, -X, and -XI. It continues between the internal carotid artery and internal jugular vein, and deep into the posterior belly of the digastric muscle. It then loops anteriorly, coursing on the lateral surface of the hyoglossus muscle, and later, it divides to supply the intrinsic and extrinsic muscles of the ipsilateral tongue (see Fig. 10-4).

The anterior primary ramus of the spinal nerve C1 sends fibers to accompany CN-XII for a short distance; these fibers later connect with the fibers of C2 and C3 anterior primary rami, forming a loop called the ansa cervicalis. This innervates the infrahyoid muscles, that is, sternohyoid, omohyoid, sternothyroid, thyrohyoid, and geniohyoid. These small muscles aid in head flexion.

Clinical Vignette

This 64-year-old lady presented with a 2-month history of unrelenting, increasingly disconcerting left occipital headache. This occasionally radiated with brief jabs toward her left ear. Whenever she bent her head forward the pain became unbearable. Although she was initially diagnosed with occipital neuralgia, two local nerve blocks were ineffective. She admitted that her tongue also felt “leathery” and “numb.” One year earlier she was treated for adenocarcinoma of the breast with a partial mastectomy and axillary node dissection. Sampled lymph nodes were negative for cancer.

Neurologic exam demonstrated atrophy and fasciculations of the left half of the tongue. This was best observed with the tongue at rest inside the mouth. Upon protrusion, the tongue deviated to the left. The head pain was aggravated by neck flexion and suboccipital palpation.

Contrast-enhanced computed tomography (CT) of the skull base revealed an infiltrating lesion eroding the left occipital condyle. Further imaging showed multiple metastases in the ribs and thoracic vertebrae, as well as liver and lungs. The lesions were assumed to represent metastatic carcinoma. Radiation therapy led to resolution of her headache; however, her hypoglossal neuropathy persisted. Subsequently, she was placed on systemic chemotherapy for disseminated cancer.

A unilateral hypoglossal neuropathy must always lead to consideration of the presence of a neoplasm, particularly in a patient with history of cancer. In this case, the nerve was damaged by a destructive metastasis as it exited the skull through the hypoglossal foramen at the occipital condyle. Bony metastases at this location, also called occipital condyle syndrome, are typically accompanied by occipital pain and neck stiffness. Breast, lung, and prostate cancer account for most of these metastatic lesions.

Patients with a unilateral hypoglossal neuropathy rarely present with complaints related to tongue function. They may comment that their tongue feels “numb” or “clumsy” but not necessarily weak, yet when asked they are unaware of any intraoral sensory loss per se. This vignette illustrates the value of a careful clinical evaluation and its unique potential to lead to the diagnosis of a unilateral hypoglossal palsy, in this instance a most sinister etiology for this woman’s headache.

Clinical Presentation

Clinical evaluation of the hypoglossal nerve requires careful observation of the tongue at rest and during activation by attempting to protrude it directly forward.

Straight protrusion of the tongue is accomplished by balanced action of both genioglossus muscles. Therefore, bilateral CN-XII lesions impair tongue protrusion as well as up, down, and side-to-side movements. This in turn causes dysarthria and swallowing difficulties. A unilateral lower motor neuron hypoglossal nerve lesion causes the tongue to deviate toward the side of the lesion when the patient attempts to protrude the tongue forwards. Typically, these lesions are also associated with atrophy, fasciculations, and increased furrowing of the ipsilateral side of the tongue (Fig. 10-7). Swallowing and/or speech dysfunction may not be present early on. Fine quivering or flickering movements are normally seen in healthy patients asked to hold the tongue protruded for more than a few seconds, and these may occasionally be confused with true fasciculations. The most reliable way to evaluate for fasciculations is to keep the tongue at rest on the floor of the mouth. Sometimes, fasciculations may be enhanced by stroking the lateral aspect of the resting tongue with a standard wooden tongue blade. A unilateral upper motor neuron lesion may on occasion result in deviation of the tongue; however, this is contralateral to the central lesion, and there is never any accompanying atrophy or fasciculations. In certain disorders, particularly amyotrophic lateral sclerosis, both upper and lower motor neuron components may be present, with the combination leading to some initial diagnostic confusion if this area is the first to become clinically affected.

Figure 10-7 Hypoglossal Nerve (XII).

Differential Diagnosis

Anterior horn cell disorders frequently affect the hypoglossal nucleus, particularly with motor neuron disease, spinal muscular atrophy, or poliomyelitis. Other intramedullary processes such as syringobulbia, intramedullary tumors, cavernomas, or multiple sclerosis may also lead to tongue paresis. Because of the close midline proximity of the two hypoglossal nuclei, these structural intramedullary lesions often lead to bilateral tongue paralysis.

When there is a precipitous onset of tongue weakness, this is usually caused by rare atherosclerotic occlusion within a midline penetrating branch of the vertebral basilar system and stroke. This leads to damage of the hypoglossal nucleus and its emerging fibers, the corticospinal tract, and the medial lemniscus. This medial medullary syndrome is clinically characterized by an ipsilateral lower motor tongue weakness accompanied by a contralateral hemiparesis and loss of proprioception and vibration. The more proximally innervated face is spared.

The intracranial course of the 12th cranial nerve can also be damaged by lesions, typically neoplasms, at the basal meninges and skull base. Metastatic bronchial or breast carcinomas, lymphomas, or benign lesions such as meningiomas, chordomas, or cholesteatomas occasionally affect the hypoglossal nerve. The proximity of hypoglossal and jugular foramina explains frequent concomitant involvement of other lower cranial nerves (CN-IX, -X, and -XI) in these cases. Both neoplastic and infectious–inflammatory lesions may lead to a basal meningitis affecting multiple cranial nerves, including the hypoglossal. Rarely other non-neoplastic, primary bony processes, such as platybasia and Paget disease, may be implicated.

The close spatial relation between the hypoglossal nerve and the carotid artery makes this nerve vulnerable to primary carotid pathology within the neck. Very rarely, dissection of the internal carotid artery is accompanied by a CN-XII neuropathy, most likely related to nerve compression by the increased circumference of the dissected vessel. Occasionally, an iatrogenic hypoglossal neuropathy occurs subsequent to a carotid endarterectomy or other types of neck surgery. A nasopharyngeal cancer may damage CN-XII along its intracranial course or within the neck per se; this is usually in conjunction with involvement of other cranial nerves. Glomus jugulare tumor is a rare hypervascular malignancy that arises from the paraganglionic tissue at the jugular foramen and can compress CN-XII either at the base of the brain or conceivably within the neck (Fig. 10-8A–C). Similar to other cranial nerves, the CN-XII may also be affected by radiation therapy and neck trauma. Most uncommonly, the hypoglossal nerve is affected as part of two primary demyelinating peripheral nerve syndromes, namely, hereditary neuropathy with liability to pressure palsies (HNPP) or a variant of chronic inflammatory demyelinating polyneuropathy (CIDP), the Lewis–Sumner syndrome.

Figure 10-8 Glomus Jugulare with Hypoglossal Palsy.

Glossodynia is a controversial syndrome with no specific etiology as yet defined. This is characterized by an uncomfortable burning pain within the tongue unassociated with any tongue weakness or atrophy. The condition occurs more frequently in women. Vitamin B₁, or B₁₂, deficiency, as well as Sjögren syndrome, have been suggested as pathophysiologic mechanisms. Unfortunately, many of these patients with idiopathic tongue pain are subsequently suspected of having a psychogenic basis, but this may simply reflect our lack of full understanding of this often distressing complaint.

Diagnostic Approach

Magnetic resonance imaging of the brain, skull base, and neck are the diagnostic tests of choice. If these imaging studies do not define evidence of a specific mass lesion, a careful search for leptomeningeal enhancement is in order. This is typically seen with metastatic tumors, sarcoidosis, or other rare leptomeningeal infiltrating lesions such as tuberculosis. Contrast-enhanced CT with thin slices through the skull base may also be useful to identify very discrete bony lesions.

Cerebrospinal fluid (CSF) analysis is indicated if an infiltrative process is clinically suspected or suggested from MRI. CSF analysis must include routine studies and cytologic analysis for malignant cells.

Electromyography of the genioglossus as well as anatomically adjacent muscles are indicated when the above studies are unremarkable. Unfortunately, an asymmetrically atrophied tongue is commonly the presenting sign of motor neuron disease.