Clinical Approach to Brainstem Lesions

Maria Rosa Querol-Pascual

The brainstem consists of the midbrain, pons, and medulla. The cerebellum is attached to the dorsal surface of the pons and upper medulla. The brainstem contains 9 of the 12 cranial nerves and is crossed by ascending, descending, and cerebellar pathways and their nuclei as well as the reticular formation. Numerous and rare crossed brainstem syndromes have been described in recent years, many of them without clinical signicance. The aim of this article is to provide a brief clinical description of some conditions affecting the brainstem. Semin Ultrasound CT MRI 31:220-229 2010 Elsevier Inc. All rights reserved.

he brainstem is situated in the posterior cranial fossa and is divided into 3 transverse regions. The most caudal is the medulla, the middle or central part is the pons, and nally the most rostral portion is the midbrain or mesencephalon. The brainstem is also organized longitudinally into 3 further regions: the roof or tectum, posteriorly, the basis or basilar portion, anteriorly, and the tegmentum in the center. Nine of the 12 cranial nerves are situated in the brainstem, which is covered by the cerebellum and connected to it by the cerebellar peduncles. The fourth ventricular cavity is located between the tegmentum and the roof.1-5 The brainstem has 3 roles. The rst is to provide transit and procession nuclei for ascending and descending pathways that convey messages to and from the cerebrum, cerebellum, and spinal cord. The second is to play a part in integrative functions, such as level of consciousness, the sleep-wake cycle, muscle tone, posture, and respiratory and cardiovascular control. The third relates to actions of the cranial nerves, which are composed of sensory bers terminating in the brainstem nuclei and motor bers originating in the brainstem nuclei.1,6,7 Therefore, a small and single lesion could produce severe and mixed decits.2 Lesions of the brainstem may manifest as cerebellar, somatosensory, and motor symptoms as well as cranial nerve dysfunction. The level of the lesion can usually be determined by the injured cranial nerve. The affected cranial nerve or fascicles localize the lesion to the medulla, pons, or midbrain. Thus, if the glossopharyngeal, vagus, accessory, and hypoglossal nerves (IX, X, XI, XII) are involved, the lesion lies within the medulla; by contrast, if the cranial nerves affected

Neurology Department, Complejo Hospitalario Universitario de Badajoz, Badajoz, Spain. Address reprint requests to: Maria Rosa Querol-Pascual, Hospital Infanta Cristina, Avda, De Elvas s/n, Badajoz, Spain. E-mail: rquerolp@ hotmail.com

are V, VI, VII, or VIIIl, the lesion is within the pons; and nally, if the lesion is located in the midbrain, the cranial nerves affected are III and IV.5,8 Most of these syndromes comprise ipsilateral cranial nerve lesions and contralateral signs of long tract involvement, such as hemiparesis or hemisensory or bilateral decit. Other symptoms that indicate brainstem disease include vertigo, unsteadiness of gait or ataxia, dysarthria-clumsy Hand disease, blepharospasm, hiccup, palatal myoclonus, respiratory dysfunction, a special type of hallucinosis (peduncular hallucinosis), and conjugate eye deviation towards hemiparesis (Table 1).8 Brainstem ischemia is the most frequent cause of acute brainstem lesions, and most syndromes have been described as a sequel of brainstem infarcts.9-10 Ischemic vertebrobasilar strokes account for 23% of all rst episodes of ischemic brain strokes, and 48% of these affect the brainstem.11 Most ischemic brainstem strokes involve the pons (27%), followed by the medulla (14%), and the midbrain (7%).12-15 The most common mechanism of brainstem stroke includes embolism and lipo hyalinosis.12 An arterial dissection causes 20% to 30% of medullary strokes and approximately 5% of mesencephalic strokes but is rather rare in pontine strokes.14,16,17 Examples of nonvascular disorders that commonly affect the brainstem include demyelinating disease (multiple sclerosis or acute disseminated encephalomyelitis), degenerative disease, trauma, intraaxial neoplasms (such as brainstem gliomas/ependymomas), brainstem encephalitis (Bickerstaffs encephalitis), central pontine myelinolysis, ArnoldChiari malformations, and syringobulbia, which are multifocal and unsuitable for topographic studies.18 Before describing the more common brainstem syndromes, some anatomical features will be reviewed2,5:

Descending motor tracts decussate in lower medulla; Ascending somatosensory tracts decussate in the middle medulla.

220

0887-2171/10/$-see front matter 2010 Elsevier Inc. All rights reserved. doi:10.1053/j.sult.2010.03.004

Clinical approach to brainstem lesions

Spinocerebellar pathways ipsilateral ataxia of the arm and leg. Spinothalamic pathways contralateral alteration of pain and temperature (arm, leg and rarely trunk) Sensory nucleus of the Vth ipsilateral alteration of pain and temperature on the face. Sympathetic pathway; ipsilateral Horners syndrome Cranial nerves; V, VII, IX, and XI

221 Spinothalamic tracts (information on temperature and pain) occupy a more lateral position in medulla and pons than the medial lemniscus (information on stereognosis and position). Most ascending spinocerebellar tracts are ipsilateral; and Effects of the cranial nerves and their nuclei are ipsilateral except for IVth cranial nerve.

Lateral Structures and Decits

We shall now discuss briey some clinical and neuroradiological characteristics of the most common syndromes associated with lesions of certain parts of the brainstem.

Brainstem Syndromes
Mesencephalic Syndromes
The mesencephalon is the most rostral portion of the brainstem. It is located between the forebrain and the hindbrain. The mesencephalon has 2 main divisions: the tectum and the tegmentum. The tectum (roof) is the dorsal surface of the midbrain, which is composed of 4 rounded eminences known as the corpora quadrigemina (quadrigeminal plate): the posterior pair called the inferior colliculi, which have an auditory function, and the anterior pair, called the superior colliculi, which have a visual function. The ventrolateral portion of the tegmentum is formed by the cerebral peduncles. The tegmentum contains 3 colorful structures: the periaqueductal gray matter, the substantia nigra, and the red nucleus. There are 2 ocular nuclei and nerves associated with the mesencephalon; the third and fourth cranial nerves (Fig. 1).5,19 Ventral Mesencephalon Lesions A unilateral lesion located in the ventral portion of the mesencephalon could involve the cerebral peduncles (corticospinal and corticobulbar tracts). Damage of the anteromedial structures causes dysarthria or dysphagia and contralateral facial and upper-extremity weakness without accompanying sensory disturbances. Fibers in the corticospinal tract are somatotopically arranged, with the bers destined to the arm medially placed and those to the leg laterally located, with the trunk bers in between.20 We can observe signs of thirdnerve and Edinger-Westphal nuclei involvement manifest as a deviation of the ipsilateral eye downwards and laterally with pupillary dilatation and ptosis of the lid.2,12 Conversely, more lateral mesencephalic lesions cause contralateral hemiparesis that predominantly affects the lower extremities, loss of the contralateral vibration and joint position sense (medial leminisci), and loss of pain and temperature sensors in the trunk and extremities (ascending spinothalamic tracts). Choreoathetosis, contralateral ataxia, and internuclear ophthalmoplegia are produced by involvement of the red nuclei, superior cerebellar peduncles, and medial longitudinal fasciculus, respectively. Lateral mesencephalic lesions can affect descending sympathetic tracts, producing Horners syndrome. If the medial geniculate bodies are involved, auditory dysfunction could occur as well.21

Table 1 Cranial Nerve Names and Main Functions, Medial and Lateral Structures, and Their Decits

I, olfactory nerve II, optic nerve III, oculomotor IV, trochear nerve V, trigeminal nerve VI, abducens nerve VII, facial nerve VIII, vestibulocochlear nerve

IX, glossopharyngeal nerve X, vagus nerve XI, spinal accessory nerve XII, hypoglossal nerve Medulla

Cranial Nerve

Olfaction Vision Eye movements, pupil constriction Eye movements Facial sensation, muscles of mastication Eye movements muscles, facial expression, taste, lacrimation, salivation Hearing, equilibrium Pharyngeal muscles, salivation Parasympathetics org; laryngeal/pharyngeal muscles Head turning Tongue movement Midbrain Pons
Adapted from Burger et al.12

Brainstem

Main Function

Motor pathway Contraleral weakness (arm and leg) Medial lemniscus contralateral loss of vibration and proprioception (arm and leg) Medial longitudinal fasciculus ipsilateral internuclear ophtalmoplegia Motor nucleus and nerve ipsilateral loss of the cranial nerve; IIIrd, IVth, VIth, XIIth

Medial Structures and Decits

222

M.R. Querol-Pascual

Figure 1 Cranial nerve nuclei. (A) View of the cranial nerve nuclei that settle at the brainstem. It represents the location and the direction of their axons. (B) dorsal view of the brainstem and cranial nerve nuclei location. Corpora quadrigeminal (asterisks); lateral and medial geniculate bodies (arrows). The nuclei of cranial nerves III to XII lie in the brainstem, just in front of the oor of the fourth ventricle and the Sylvian aqueduct. Four are located in the medulla oblongata (IXth, Xth, XIth, XIIth); 4 in the pons (Vth, VIth, VIIth, and VIIIth) and 4 above the pons (3rd, 4th are in the midbrain). The 1st (olfactory) and the 2nd (optic) are above the brainstem. The 4 motor nuclei that are in the midline of the brainstem are those that divides equally into 12, that is, 3, 4, 6, and 12. They emerge through the anterior midline surface, except the IVth, which exits from the dorsal part of the midbrain after its decussation in the superior medullary velum. Although the Vth, VIIth, and IXth cranial nerve nuclei have motor function, they also have sensory components and do not divide evenly into 12. Thus, they are not pure motor nuclei and, on this basis, they are not located medially. The VIIIth cranial nerve nucleus (entirely sensory) and XIth (pure motor, which does not divide equally into 12), are located laterally.42 Salivatory and lacrimal nuclei. (Courtesy of M. ngeles Fernndez-Gil.) (Color version of gure is available online.)

There are 3 classic eponyms describing these syndromes10,12,20,22,23: 1. Webers syndrome involves the third nerve and cerebral peduncle, causing ipsilateral third nerve palsy with contralateral hemiparesis (Fig. 2). 2. Benedikts syndrome involves the red nucleus, causing ipsilateral third nerve palsy and contralateral chorea, tremor or athetosis (Fig. 3). 3. Claudes syndrome involves the superior cerebellar peduncle, causing third-nerve palsy and contralateral ataxia. Dorsal Mesencephalic Lesions Dorsal mesencephalic lesions produce mainly neuro-ophthalmologic abnormalities and are most often seen with hydrocephalus or tumors of the pineal region.6,20 These lesions cause dysfunction of the IVth cranial nerve (trochlear), which produces diplopia, slight elevation of the eye, vertical gaze

abnormalities from periaqueductal gray matter, and tinnitus or auditory alterations from inferior colliculi.24 Bilateral mesencephalic lesions damaging the reticular formation can result in consciousness disturbances.2,12,14 There are 2 syndromes associated with mesencephalic lesions: 1. Parinauds syndrome, characterized by loss of upward gaze, large and irregular pupils, eyelid retraction, convergence nystagmus and loss of accommodation. 2. Top of the basilar syndrome, characterized by pupillary and visual disorders, vertical gaze palsy, delirium and hallucinosis, sensory decits, and motor decits. This syndrome can result from giant basilar artery tip aneurysms, vasculitis, or as a complication of cerebral angiography.20,25 Table 212 summarizes the mesencephalic syndromes.

Clinical approach to brainstem lesions

223

Figure 2 An 85-year-old patient exhibiting sudden right 3d cranial nerve palsy and light loss of strength in left extremities (Webers syndrome). (A, B) Axial uid-attenuated inversion recovery (FLAIR) and (C) coronal spin echo (SE) T2-weighted images show a hyperintense area with imprecise margins affecting the right thalamus just next to the wall of the 3rd ventricle (arrowheads) and the paramedian and anterior right region of mesencephalon (arrows) consistent with ischemic insult. (D, E) Axial isotropic diffusion-weighted magnetic resonance images and (E, F) Apparent diffusion coefcient maps show the typical imaging features of acute ischemic infarcts: hyperintensity on isotropic images and hypointensity on Apparent diffusion coefcient maps (arrows).

Pontine Syndromes
The pons extends from the pontomedullary junction caudally to the pontomesencephalic junction rostrally. The dorsal part of the pons is referred to as the tegmentum, and the ventral portion is referred to as the basis pontis. The fourth ventricle separates the pontine tegmentum from the cerebellum. The pontine tegmentum contains important nuclei and pathways (pontine reticular formation). The basis pontis contains the corticospinal and corticobulbar tracts, cranial nerve nuclei, and transverse cerebellar bers.6,19,20 In the pons there are important structures involved in several functions. Cranial nerve nuclei are associated with ocular movements, facial expression, mastication, salivation, equilibrium, and audition.5 Fiber tracts, such as the paramedian pontine reticular formation, the medial longitudinal fasciculus, the medial lemniscus, the ventral spinocerebellar, spinothalamic, lateral tectospinal, rubrospinal, and corticopontocerebellar tracts, auditory connections and the middle cerebellar peduncle. The main arteries that provide the blood supply to the pons are branches of vertebral artery and basilar artery.6,12,19

This vascular distribution is classied in 5 main clinic-topographic patterns: anteromedial, anterolateral, tegmental, unilateral, and multiple pontine infarcts.12,13 Anteromedial/Anterolateral Syndromes Lesions at this level can produce some of following symptoms, depending on the tract that is damaged. The tracts and possible damage are listed to follow: 1. Corticobulbare tracts: involved in movement of the eyes, face, pharynx, and tongue and produce dysarthria, dysphagia, or facial palsy. 2. Cortipontocerebellar tracts: ataxia or pathologic laughter associated with paresis constitutes the ataxic-hemiparesis syndrome; ataxia or pathologic laughter in conjunction with dysarthria constitutes the dysarthria clumsy-Hand disease.12,26 3. Corticospinal tracts: pure hemiplegia or hemiparesis involving the face, the arm, and the leg are the most common presentations of anteromedial syndromes.12 In addition, pure sensory syndromes or associated mo-

224

M.R. Querol-Pascual

Figure 3 A 75-year-old man with unilateral left IIIrd cranial nerve palsy and contralateral ataxia (Benedikts syndrome). (A, B) Axial SE T2-weighted images show a high-intensity lesion that affects the midbrain in its medial and anterior region (anteromedial or paramedian syndrome) consistent with ischemic infarct. The lesion involves the left 3rd cranial nerve nucleus and tract as it travels near the red nucleus (black arrow). The lesion of the red nucleus interrupts bers from the opposite cerebellar hemisphere, which reach the red nucleus via the superior cerebellar peduncles that decussate in the anterior midbrain (white arrow). (C) coronal FLAIR image shows the left midbrain ischemic lesion (arrowhead), as well as the signal changes in juxta-ventricular white matter related to small vessel angiopathy typical in the elderly patient (arrows).

4.

5. 6.

7.

tor lesions are further manifestations of anteromedial pontine syndrome.12,27 Medial lemnisci: these are responsible for vibration, proprioception, and deep sensation from the contralateral extremities. Nuclei or bers of cranial nerve VII: responsible for ipsilateral facial palsy. Fascicles of cranial nerve VI: responsible for ipsilateral sixth nerve palsy producing diplopia, which is accentuated when the patient looks toward the lesion. Medial longitudinal fasciculus: responsible for internuclear ophthalmoplegia, which produces disconjugate lateral gaze.

contain bers to the lower extremities. The most severe weakness and loss of position sense in the lower extremities could be produced by the involvement of the anterolateral region.12 Three syndromes are associated with these zones:

Raymonds syndrome, which is ipsilateral paresis of the VI nerve and contralateral hemiparesis; Millar-Gublers syndrome, which is an ipsilateral palsy of both the VI and VII cranial nerves and contralateral hemiparesis; and Cheiro-oral syndrome, which is sensory loss in the perioral region and contralateral hand.

The medial zones of the corticospinal tract and the medial leminsci transmit bers to the upper extremities and the more lateral bers affect the lower extremities. In addition, the lateral zones of the medial lemnisci predominantly

Lateral Syndromes Lateral syndrome lesions can produce the following problems:

Contralateral ataxia, by damage to the inferior and middle cerebellar peduncles and pontocerebellar bers;

Clinical approach to brainstem lesions

Table 2 Midbrain Syndromes Midbrain Syndromes Anteromedial Structures Affected Corticospinal tract Corticobulbar tract Red nucleus Decussation of superior cerebellar peduncle Cranial nerve 3 fascicle Corticospinal Medial spinothalamic tract Portions of superior cerebellar peduncle Descending sympathetic bers Lateral spinothalamic tract Superior/inferior colliculi Posterior commissure Cranial nerve 3 nucleus Cranial nerve 4 nucleus Signs and Symptoms

225

Anterolateral

Lateral Dorsal

Bilateral

Midbrain Thalamus Medial temporal lobes Occipital lobes

Contralateral Hemiparesia/hemiplegia Dysartria Choreoathetosis/tremor Ataxia Ipsilateral IIIrd nerve palsy Contralateral Hemiparesia/hemiplegia sensory loss (pain and temperature) in extremities Ataxia Horners syndrome contralateral Sensory loss (pain and temperature) in extremities Vertical gaze palsies Loss of pupillary light reex/loss of accommodation Ipsilateral IIIrd nerve palsy Contralateral Superior oblique weakness Vertical gaze palsies and cranial nerve 3 palsy Sensory nding and inattention Memory disturbances and aphasias Visual decits

Adapted from Burger et al.12

Loss of pain and temperature sensation in the contralateral extremities and trunk caused by damage from the lateral spin thalamic tract excluding the face. Tinnitus and disturbances in hearing from lesions affecting the lateral leminsci. Ipsilateral paresis of the face from the facial nuclei and fascicles involvement. Ipsilateral motor decits of muscles of mastication and loss of ipsilateral corneal reex from lesions of the trigeminal complex. VIth cranial nerve palsy.

Tegmental Lesions at the tegmental level are very unusual and consist of disturbances of consciousness, severe ataxia, skewed deviation of the eyes, VIth cranial nerve palsy, one and a half syndrome, and vertigo.13,17,28,29 Bilateral Lesion The most characteristic clinical symptomatology is the pseudobulbar syndrome and the locked-in syndrome.13 The structures involved on both sides are the motor tracts (corticospinal, corticobulbar, corticopontine), the fascicles of the abducens nerves, paramedian pontine reticular formation (horizontal gaze center), and reticular formation.12,13 Because of this damage, the patient is unable to move (quadriplegia), to speak (aphonia), and experiences bilateral palsy of the facial nerve and horizontal gaze paresis. Consciousness may be affected initially, although it is recovered later. If the spinothalamic tract is affected, there is loss of pain and temperature in the trunk and extremities but not in the face. The patient can communicate through vertical movements of the eyes and blinking of the eyelids. This bilateral lesion in the basal portion of the lower pons is known as locked-in syndrome.2 Table 312 summarizes the pons syndromes.

Dorsolateral Syndromes The characteristic clinical picture associated to these lesions often comprises the following:

Reduced auditory acuity and sound localization from lesions of the lateral lemniscus or cochlear nucleus. Ataxia from lesions involving the superior cerebellar peduncles. Parkinsonian symptoms from the loci cerulei. Ipsilateral jaw jerks from the mesencephalic nuclei of the Vth cranial nerve.

There 3 syndromes associated with dorsolateral lesions:

Marie-Foix syndrome, or ataxia, contralateral hemiparesis, and contralateral hypoesthesia to pain and temperature. Foville syndrome, or ipsilateral horizontal gaze paresis, ipsilateral facial palsy, and contralateral hemiparesis. Raymond-Cestan-Chenais syndrome, which includes ataxia, contralateral loss of facial and body sensation, and contralateral hemiparesis.

Medullary Syndromes
Medial Medullary Syndrome Djerines syndrome, a rare clinical entity, usually is produced by distal occlusion of the vertebral artery or the upper portion of the anterior spinal artery.30,31 Lesions of the pyramidal tract in the medial medulla result in contralateral arm and leg paresis, and sometimes (50% of cases) the contralat-

226
Table 3 Pontine Syndromes Pontine Syndromes Anteromedial Structures Affected Corticospinal tract Corticopontine tract Corticobulbar tract Cranial facial nerve fascicle Cranial abducens nerve fascicle Parmedian pontine reticular formation Medial longitudinal fasciculus

M.R. Querol-Pascual

Signs and Symptoms Contralateral hemiparesis/hemiplegia ataxia or pathologic laughter dysarthria, dysphagia Ipsilateral facial weakness lateral rectus palsy horizontal gaze palsy Others symptoms internuclear ophthalmoplegia Contralateral hemiparesis/hemiplegia ataxia contralateral numbness Contralateral hemiparesis leg > arm contralateral numbness Ipsilateral facial numbness facial weakness hearing loss ataxia aphonia/dysphagia quadriplegia bilateral horizontal gaze paresis bilateral facial weakness transient disturbances of consciousness

Anterolateral

Corticospinal tract Spinothalamic tract

Lateral/dorsolateral

Lateral corticospinal tract Spinothalamic tract Spinal nucleus/tract of cranial nerve 5 Cranial nerve 7 fasciculus/nucleus Cranial nerve 8 Cerebellum

Bilateral

Corticobulbar tract Corticospinal tract Paramedian pontine reticular formation Cranial facial nerve fascicle/nucleus Reticular formation

Adapted from Burger et al.12

eral face can be affected. Often the hypoglossal nerve is damaged, producing ipsilateral tongue weakness. This weakness may a persons position sense of position, stereognosis, and vibratory perception in contralateral extremities, although pain and temperature may be preserved. Occasionally, nystagmus or skew deviation of the eyes is produced by injury of medial longitudinal fasciculus.2,12,30-32

Lateral Medullary Syndrome

The lateral syndrome is the most common in the medulla oblongata (Fig. 4). This is known as Wallenbergs syndrome, a relatively common brainstem infarct, and according to the ndings of Marx10 is the only crossed syndrome with clinical importance. Vertebral artery thrombosis is the most common cause (67%) and isolated involvement of the PICA is less common (10%).8,32,33 Spontaneous dissection of the vertebral artery is a common cause.34 The most characteristic symptoms of the lateral medullary syndrome are2,8,12,20,35,36:

Hypalgesia and thermoanesthesia in ipsilateral face caused by involvement of the spinothalamic tract and nucleus of cranial nerve V. Involvement of the sympathetic pathways, which produces Horners syndrome (ptosis, myosis, and anhydrosis). Headache, especially a unilateral headache localized to the upper posterior cervical region, is common with the lateral medullary syndrome.20 Damage to the nucleus ambiguous and bers of the vagus nerve cause paralysis of the ipsilateral palate, pharynx, and larynx, producing dysphagia, dysarthria, diminished gag reex, and hoarseness. In some case palatal myoclonus is produced by dysfunction of the inferior olive. Finally, there may be horizontal or vertical nystagmus (vestibular nuclei) and skew deviation of the eyes with diplopia (medial longitudinal fasciculus).37

Ipsilateral ataxia produced by involvement of the inferior cerebellar peduncle, restiform body, or dorsal spinocerebellar tract. Vertigo caused by involvement of the vestibular nuclei.

Other Hemimedullary Syndromes A very uncommon combination of the 2 major syndromes occurs as bilateral medial medullary, hemimedullary, and bilateral medullary syndrome: Bilateral medial medullary syndrome. Flaccid quadriplegia sparing the face, bilateral loss of deep sensation, hypoglossal nerve palsy and respiratory failure38,39

Clinical approach to brainstem lesions

227

Figure 4 A 58-year-old patient with vertigo and difculty in walking. The patient demonstrated left Horners syndrome (descending autonomic bers), right loss of pain and temperature sensation, ataxia, left IXth and Xth cranial nerve nuclei impairment, left facial dysesthesias, vertigo, and hiccups (Wallembergs syndrome). (A, B) Axial SE T2-weighted and (C) coronal FLAIR images reveal a diagonal band-shape of high intensity of signal involving the posterolateral left side of the medulla oblongata (arrows) consistent with ischemic lesion. Note the imprecise borders and the correspondence with the posterolateral vascular territory.

Hemimedullary lesions. These may result in contralateral hemiparesis, contralateral hemisensory loss, ipsilateral Horners syndrome, ipsilateral ataxia, ipsilateral facial sensory loss, ipsilateral tongue paresis, dysarthria, nausea, and vomiting.12,40 There are 3 eponyms associated with medulla lesions. Of these, Reinhold syndrome is a hemimedullary syndrome. The other 2 syndromes, Babinski-Nageotte and Cestan-Chenais syndromes, are intermediolateral syndromes of the medulla with all (Babinski-Nageotte) or nearly all (Cestan-Chenais) features of the lateral Wallenberg syndrome and the hemiparesis of the medial medullary syndrome.41 Table 412 summarizes the medullary syndromes.

The principles of the rule of 4 are: 1. There are 4 structures in the midline beginning with (M); X the motor pathway: contralateral weakness, X the medial leminscus (ie, contralateral loss of vibration and propioception in the arm and leg), X the medial longitudinal fasciculus (ie, ipsilateral internuclear opthalmoplegia), X the motor nuclear nerve (ie, ipsilateral loss of affected cranial nerve). 2. There are 4 structures laterally beginning with (S); X the spinocebellar pathway, X the spinothalamic pathway (contralateral alteration of pain and temperature in the arm, leg, and rarely trunk), X The sensory nucleus of the Vth (ie, ipsilateral alteration of pain and temperature on the face),

Summary
The rule of 4 suggested by Gates42 is a simple method developed to diagnose and localize where damage has occurred in the brainstem (Table 4).

228
Table 4 Medullary Syndromes Medullary Syndromes Medial medullary Structures Affected Corticospinal tract Medial lemniscus Cranial nerve XII Nucleus/fascicle

M.R. Querol-Pascual

Signs and Symptoms Contralateral Arm and leg hemiparesis Sensory loss (vibratory and positional) Extremities Ipsilateral Tongue paresis Contralateral Arm/trunk/leg numbness Ipsilateral Absent corneal reex/ facial numbness Ataxia Horner syndrome Other symptoms Dysphagia, dysarthria, hoarse voice Vertigo, nausea, and vomiting Contralateral Arm and leg hemiparesis Sensory loss (vibratory and positional) extremities Arm/trunk/leg numbness Ipsilateral Absent corneal reex/facial numbness Ataxia Horners syndrome Tongue paresis Other symptoms Dysphagia, dysarthria, hoarse voice Vertigo, nausea, and vomiting

Lateral medullary

Lateral spinothalamic tract Spinal trigeminal nucleus/tract Inferior cerebellar peduncle Sympathetic bers Nucleus ambiguous Vestibular nuclei

Hemimedullary syndrome

Both structures (medial and lateral)

Adapted from Burger et al.12

the sympathetic pathway (ie, Horners ipsilateral syndrome). 3. There are 4 nerves in the medulla, 4 in the pons, and 4 above the pons (2 in midbrain). 4. The 4 motor nuclei that are in the midline are those that divide equally into 12 except 1 and 2, that is, 3, 4, 6, and 12. The others, 5, 7, 9, and 11, are in the lateral brainstem.
X

Uncited References
This section consists of references that are included in the reference list but are not cited in the article text. Please either cite each of these references in the text or, alternatively, delete it from the reference list. If you do not provide further instruction for this reference, we will retain it in its current form and publish it as an un-cited reference with your article.24

References
1. Noback ChR, Strominger NL, Demarest R, et al: Brainstem: Medulla, Pons, and Midbrain, in: Noback ChR, Strominger NL, Demarest R, et al (eds): The Human Nervous System: Structure and Function (ed 6). Totowa, NJ: Humana Press, 2005, pp 222-242 2. Mendoza JE, Foundas AL (eds): Clinical Neuroanatomy: A Neurobehavioral Approach. New York, Springer, 2008, pp 98-104 3. Smith LH, DeMyer WE: Anatomy of the brainstem. Semin Pediatr Neurol 10:235-240, 2003

4. Brazis PW, Masdeu JC, Biller J: Localization in Clinical Neurology; Brainstem (ed 5). Philadelphia, Lippincott Williams & Wilkins, 2007, pp 888-920 5. Young PA, Young PH: Anatomia, topografa y niveles funcionales del tronco cerebral, in: Young PA, Young PH (eds): Neuroanatoma Clinico Functional. Barcelona, Masson, 2001, pp 25-37 6. Waxman, SG. Clinical Neuroanatomy, in: Foltin J, Lebowitz H, Panton N (eds): Lange Medical Books/McGraw-Hill Companies. The Brainstem and Cerebellum (ed 25). Connecticut, 2003, pp 81-102 7. Nolte J: Organization of the brainstem, in Nolte J (ed): The Human Brain: An Introduction to Its Functional Anatomy (ed 6). Philadelphia, Mosby-Elsevier, 2009, pp 266-294 8. Blumenfeld H: Surface anatomy of the cranial nerves, in: Blumenfeld H (ed): Neuroanatomy through Clinical Cases. Suderland, MA, Sinauer Associates, 2002, pp 459-529 9. Sinha KK: Brain stem infarction: Clinical clues to localize them. J Indian Acad Clin Med 1:213-221, 2000 10. Marx JM, Thmke F: Classical crossed brain stem syndromes: Myth or reality? J Neurol 256:898-903, 2009 11. Bogouslavsky J, Van Melle G, Regli F: The Laussanne Stroke Registry: Analysis of 1,000 consecutive patients with rst stroke. Stroke 19: 1083-1092, 1988 12. Burger KM, Tuhrim S, Naidich T: Brainstem vascular stroke anatomy. Neuroimaging Clin N Am 15:297-324, 2005 13. Kumral E, Bayulkem G, Evyapan D: Clinical spectrum of pontine infarction. Clinical-MR correlations. J Neurol 249:1659-1670, 2002 14. Kumral E, Bayulkem G, Akyol A, et al: Mesencephalic and associated posterior circulations infarcts. Stroke 33:2224-2231, 2002 15. Martin PJ, Chang HM, Wityk R, et al: Midbrain infarction: Association and aetiologies in the New England Medical Center Posterior

Clinical approach to brainstem lesions

Circulation Registry. J Neurol Neurosurg Psychiatry 64:392-395, 1988 Kameda W, Kawanami T, Kurita K, et al: Lateral and medial medullary infarction: A comparative analysis of 214 patients. Stroke 35:694-699, 2004 Bassetti C, Bogousslavsky J, Barth A, et al: Isolate infarcts of the pons. Neurology 46:165-175, 1996 Carroll CG, Campbell WW: Multiple cranial neuropathies. Semin Neurol 29:53-65, 2009 Carpenter MB (ed): Neuroanatoma: Fundamentos. Editorial Mdica Panamericana. Buenos Aires, Williams & Wilkins, 1994 Brazis PW, Masdeu JC, Biller J: The Brainstem, in: Brazis PW, Masdeu JC, Biller J (eds): Localization in Clinical Neurology (ed 5). Philadelphia, Lippincott Williams & Wilkins, 2007, pp 827-870 Hausler R, Levine RA: Auditory dysfunction in stroke. Acta Otoralungol 120:689-703, 2000 Silverman IE, Liu GT, Volpe NJ, et al: The crossed paralyses: The original brain-stem syndromes of Millard-Gubler, Foville, Weber and Raymon-Cestan. Arch Neurol 52:635-638, 1995 Seo SW, Heo JH, Lee KY, et al: Localization of Claudes syndrome. Neurology 57:2304-2307, 2001 Musiek MF, Charette L, Morse D, et al: Central deafness associated with a midbrain lesion. J Am Acad Audiol 15:133-151, 2004; quiz, 172-173 Mehler MF: The rostral basilar artery syndrome: Diagnosis, etiology, prognosis. Neurology 39:9-16, 1989 Parvizi J, Anderson SW, Martin CO, et al: Pathological laughter and crying: A link to the cerebellum. Brain 124:1708-1719, 2001 Schmahmann JD, Ko R, MacMore J: The human basis pontis: Motor syndromes and topographic organization. Brain, June 127:1269-1269 Fisher CM: Lacunar infarct in the tegmentum if the lower lateral pons. Arch Neurol 46:566-567, 1989 Bronstein AM, Rudge P, Gresty MA, et al: Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging ndings.

229
II. Gaze palsy and internuclear palsy. J Neurol Neurosurg Psychiatry 3:2000-2007, 1990 Bassetti C, Brogousslavsky J, Mattle H, et al: Medial medullary stroke: Report of seven patients and review of the literature. Neurology 48: 882-890, 1997 Pergami P, Poloni TE, Imbesi F, et al: Dejerines syndrome or Spilllers syndrome? Neurol Sci 4:333-336, 2001 Kim JS, Kim HG, Chung SC: Medial medullar syndrome. Stroke 26: 1548-1552, 1995 Kim JS: Pure lateral medullary infarction: Clinical-radiological correlation of 103 acute, consecutive patients. Brain 126:1864-1872, 2003 Kameda W, Kawanami T, Kurita K, et al: Lateral and medial medullary infarction: A comparative analysis of 214 patients. Stroke 35:694-699, 2004 Sacco RL, Freddo L, Bello JA, et al: Wallenbergs lateral medullary syndrome. Clinical-magnetic resonance imaging correlations. Arch Neurol 50:609-614, 1993 Nowak DA, Helge RT: The clinical variability of Wallenbergs syndrome: The anatomical correlate of ipsilateral axial lateropulsion. J Neurol 256:507-511, 2006 Brazis PW: Ocular motor abnormalities in Wallenbergs lateral medullary syndrome. Mayo Clin Pro 67:365-368, 1992 Fukuda M, Aiba T, Takahashi S: Bilateral medial medullary infarction due to bilateral vertebral artery dissection. Clin Neurol Neurosurg 106: 132-135, 2004 Zickler P, Seitz RJ, Hartung HP, et al: Bilateral medullary pyramid infartion. Neurology 64:1801-1801, 2005 Mossoto-Agatiello L, Knaihynicki C: The hemimedullary syndrome; case report and review of the literature. J Neurol 237:208-212, 1990 Krasnianski M, Neudecker S, Schluter A, et al: Babinski-Nageottes syndrome and hemimedullary (Reinholds) syndrome are clinically and morphologically distinct conditions. J Neurol 250:938-942, 2003 Gates P: The rule of 4 the brainstem; a simplied method for understanding brainstem anatomy and brainstem vascular syndromes for the non-neurologist. Intern Med J 35:263-266, 2005

16.

30.

17. 18. 19. 20.

31. 32. 33. 34.

35.

21. 22.

36.

23. 24. 25. 26. 27. 28. 29.

37. 38.

39. 40. 41.

42.