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WINDOWSTOTHEBRAIN   |    
The Brainstem: Anatomy, Assessment, and Clinical Syndromes
Robin A. Hurley, M.D.; Laura A. Flashman, Ph.D.; Tiffany W. Chow, M.D.; Katherine H. Taber, Ph.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2010;22:iv-7.
View Author and Article Information

Drs Taber and Hurley are affiliated with the Veterans Affairs Mid Atlantic Mental Illness Research, Education, and Clinical Center, and the Research and Education Service Line at the W. G. Hefner Veterans Affairs Medical Center in Salisbury, N.C. Dr. Hurley is affiliated with the Departments of Psychiatry and Radiology at Wake Forest University School of Medicine in Winston-Salem, N.C., and the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine in Houston. Dr. Flashman is affiliated with Dartmouth Medical School in Lebanon, N.H. Dr. Chow is affiliated with the Rotman Research Institute, University of Toronto in Toronto, Ontario, Canada. Dr. Taber is affiliated with the Division of Biomedical Sciences at the Virginia College of Osteopathic Medicine in Blacksburg, Va., and the Department of Physical Medicine and Rehabilitation at Baylor College of Medicine in Houston. Address correspondence to Dr. Robin Hurley, Hefner VA Medical Center, 1601 Brenner Ave., Salisbury, NC 28144; Robin.Hurley@va.gov (e-mail).

Copyright © 2010 American Psychiatric Publishing, Inc.

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Overview of Anatomy

The focus in neuropsychiatry is usually on the cortical areas that subserve behavior, cognition, and mood. It is essential to also understand the roles of the brainstem for these functions. Of particular importance, the brainstem is the source for the monoamine (norepinephrine [Figure 1, purple], dopamine [Figure 1, green], and serotonin [Figure 1, yellow]) neurotransmitters that project widely to modulate these circuits. The major subdivisions of the brainstem (from rostral to caudal) are the midbrain, pons, and medulla (Figure 1, left panel). The brainstem serves as a conduit for many ascending and descending pathways (Table 1), contains most cranial nerve nuclei (Figure 1, white, and Table 1), and is important for many key integrative functions. It contains the lower motor neurons for the muscles of the head and does the initial processing of general afferent information concerning the head. The reticular formation forms the central core of the brainstem (Figure 1, area approximated with dashed red lines).1,2 It participates in a wide range of functions including control of movement, modulation of pain, autonomic reflexes, arousal, and consciousness. The vascular supply to the brainstem is primarily from the posterior cerebral artery and the vertebral-basilar system (Figure 1, right panel).3 In general, the small arteries that penetrate and supply the brainstem arise directly from larger arteries.3 These regions are at high risk for ischemia because there is little or no interconnecting surface network to provide collateral circulation.

The most rostral part of the brainstem is the midbrain. It is characterized by four bumps, the paired superior and inferior colliculi on its dorsal (posterior) surface, and by the large cerebral peduncles (containing the descending corticospinal and corticopontine tracts) on its ventral (anterior) surface. The nuclei for cranial nerves III, IV, and part of V (sensory) are found in the midbrain. The ascending superior cerebellar peduncles cross (decussate) in the caudal midbrain. Fibers enter the red nucleus and also continue on to the thalamus. Other key midbrain structures include the substantia nigra and ventral tegmental area (both dopamine-containing [green]), the pedunculopontine nucleus (acetylcholine-containing [orange]) and the first of the raphe nuclei (serotonin-containing [yellow]).

Caudal to the midbrain is the pons. The nuclei for cranial nerves VI, VII, VIII, and part of V (motor) are found in the pons. Here the corticopontine fibers (blue) terminate in the pontine nuclei (gray). These nuclei give rise to the pontocerebellar fibers that cross the midline to form the middle cerebellar peduncle (blue). This area is particularly vulnerable to injury in malnourished individuals, especially if there has been a rapid correction of electrotype abnormalities.8 The classic symmetric areas of myelin disruption that characterize central pontine myelinolysis are thought to result from osmotically active factors expelled by the cells within gray matter that are toxic to myelin. White matter adjacent to edematous gray matter (like the crossing pontocerebellar fibers intermingled with the pontine nuclei) is therefore the most exposed. The ascending and descending fiber tracts are compact white matter bundles and much less affected. Lesions are also found in other gray matter regions containing heavily myelinated fibers, such as thalamus, basal ganglia, and cerebellum.

Caudal to the pons is the medulla, containing the nuclei for cranial nerves IX, X, XI, XII and a portion of V. Ascending spinocerebellar tracts form the inferior cerebellar peduncle at this level. The ascending sensory tracts from the body (posterior columns) terminate in the posterior column nuclei (gracilis, cuneatus) in the lower medulla. These nuclei are the origin of the spinothalamic tracts that cross (sensory decussation) in the lower medulla and ascend to form the medial lemniscus (pink).

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Neuropsychological Deficits

The common perception has long been that brainstem injury results primarily in motor and cranial nerve deficits. More recent work has focused on the transient and permanent cognitive deficits that can occur in conjunction with brainstem lesions. Individuals have been described as being unable to return to their baseline levels of functioning in daily life activities, even after physical and neurological deficits have resolved.9 Although the literature is somewhat limited, there have been several case reports and case series examining cognitive functioning in small cohorts of individuals with brainstem insults.913 The most frequently reported deficits following isolated brainstem lesions are impaired attention and executive functioning. These have been observed across a variety of tests, including letter fluency and category fluency, the Trail Making test, letter cancellation tests, various sorting tests (Weigl sorting test, Modified Card Sorting Test), the Test of Every Day Attention (visual elevator subtest), and the Stroop Color and Word Test. Impaired naming ability also occurs relatively frequently in individuals with brainstem injury. Memory impairment has been reported much less commonly, and sensory-perceptual deficits are not typically reported. Interestingly, one study noted declines in general intellectual ability in approximately 50% of children following resection of low-grade brainstem tumors.14

Injury to the ventral pons can result in locked-in syndrome, characterized by paralysis of all four limbs and mutism (paralytic).15 Using testing based on eye-coded (yes/no) responding, several studies have examined cognitive abilities in individuals with this condition. A self-report survey study of patients (N=44) with chronic locked-in syndrome indicated that six patients (14%) reported impaired attention and 19% reported memory difficulties.16 A recent study utilized neuropsychological testing in patients (N=9) with chronic locked-in syndrome due to isolated brainstem injury.17 While cognitive functioning was generally preserved in the group, individual-specific deficits included mental calculation and problem solving, auditory and visual recognition, and receptive language. In contrast, a case report of two patients with chronic locked-in syndrome found no cognitive deficits on neuropsychological assessment.18 Similarly, a case series (N=10) reported that locked-in patients can recover intact cognitive levels in cases of pure brainstem lesions.19 Although the authors of that study concluded that injuries to additional areas of the brain were most likely responsible for reported deficits in this population, other studies (as noted above) have reported deficits in patients with isolated brainstem insults.

In summary, the literature indicates a variety of circumscribed cognitive deficits may occur after brainstem insults, and these do not always completely resolve. The profile of deficits seen in well-studied individuals implicates disruption of the frontal-subcortical system, with specific impact on regions involved in attentional and executive functioning. The brain areas that are primarily associated with the performance of executive functions are the prefrontal and the anterior cingulate cortices.20,21 These areas are reciprocally interconnected with the brainstem.22,23 The findings of pervasive attentional and executive impairment, with naming and receptive language deficits often present, serve to remind us that specific cognitive abilities can be disrupted by injury to areas remote from the cortical circuitry that is primarily associated with these domains. The implications of these cognitive deficits are important. Several studies examining functional outcome in rehabilitation following stroke have shown that cognition, particularly attention and executive abilities such as abstract thinking, judgment, problem solving, short-term verbal attention and memory, and comprehension can play an important role in determining length of hospital stay and in predicting functional status at time of discharge.2428 Higher-order cognitive skills such as awareness, accurate understanding of one’s impairments, and the capacity to learn and generalize functional skills also impact successful rehabilitation. Unfortunately, individuals who demonstrate significant physical improvement may not make concomitant gains in cognition and therefore may leave rehabilitation with less functional independence and a greater need for follow-up services.

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Clinical Brainstem Syndromes

The clinician needs to be familiar with how neuroanatomical functional units cluster in the brainstem. These can be summarized as cranial nerve nuclei; pigmented nuclei (red nucleus, substantia nigra ["black nucleus"], and locus ceruleus ["blue spot"]); and tracts (e.g., corticospinal, corticopontine, spinothalamic, spinocerebellar) that pass through. When any two of these three categories show impairment simultaneously, particularly when there are alternating signs, the lesion is likely to be within the brainstem. Thus, if the patient has cranial nerve deficits (Table 1) accompanied by parkinsonism or cranial nerve deficits and a crossed corticospinal neurological sign, the first place to localize the lesion would be the brainstem. Lesion location can be approximated (Table 2) by combining cranial nerve-related symptoms (which provide rostral-caudal localization) and long tract-related symptoms (which provide medial-lateral localization).29 There are multiple named brainstem syndromes, most known by eponym (Table 3).3,30 It has been noted that many of these are seldom encountered in clinical practice. The combination of symptoms is the critical factor. Thus, the Weber, Claude, Benedict, Nothnagel, and Parinaud syndromes, all resulting from midbrain lesions, have oculomotor nerve palsy (CN III) in common. This generally causes diplopia on lateral gaze, but there could also be disconjugate vertical gaze. Use of the Maddox Rod and a penlight can help the clinician disentangle the direction in which the eyes are disconjugate.31 The Millard-Gubler syndrome localizes to the pons with its facial palsy (CN VII) and sometimes lateral rectus palsy (CN VI, another way to achieve diplopia). Avellis, Jackson, and Wallenberg syndromes arise from medullary lesions that cause oropharyngeal deficits (CN IX-XII).32,33

The differential diagnosis for brainstem syndromes can be fairly easy to remember. These are typically focal lesions due to stroke, neoplasm, or multiple sclerosis. Less common etiologies for brainstem syndromes would include infectious diseases (especially some meningitides that center on the base of the brain like tuberculosis), vascular malformation, traumatic brain injury, hyponatremia causing a central pontine myelinolysis, and the neurodegenerative movement disorders progressive supranuclear palsy (PSP) and multisystem atrophy. Although not commonly considered a brainstem syndrome, Parkinson’s disease almost always extends beyond the cardinal signs of parkinsonism (resting tremor, postural instability, akinesia, gait changes) associated with degeneration of the substantia nigra.34,35 Depression is highly prevalent among patients with Parkinson’s disease, at times manifesting as a prodrome and certainly complicating disease management.36,37 Antidepressant effects of -dopa and lack of correlation of severities of depressive symptoms with motor disability imply that depression in the Parkinson’s disease context results from the dopaminergic deficit. Autonomic system impairments also impact heavily on Parkinson’s disease quality of life, possibly related to vagal neuropathy (lower pons).38 Parkinson’s disease occurs in one of every 272 people in the population, whereas multiple sclerosis occurs in one of every 700.

While most clinicians are familiar with the cardinal signs of parkinsonism as described above, PSP is less frequently seen, with a prevalence of 1 to 6.5 per 100,000.39 Most patients with PSP have an onset in the 7th decade of life. Reported male to female ratios range from 1:1 to 4:6.40 Twenty percent of patients with PSP present with the behavioral criteria for frontotemporal dementia: insidious onset with gradual progression, early decline in social interpersonal conduct, early impairment in regulation of personal conduct, early emotional blunting, and early loss of insight.41 The other 80% present with the motoric signs of PSP, most frequently referred to as absence of vertical gaze. Clinicians may or may not find it helpful to consider PSP as manifesting with a "leonine facies." Some prefer to describe it as a surprised look, but this may be seen as an angry stare by others. This feature is not included in the diagnostic criteria for PSP. Instead, multiple unexplained falls and impairment of vertical gaze are required for probable PSP.42 When examining for vertical oculomotor movements, the important features of the vertical gaze are the latency and speed of the saccadic movement.43 Abnormality can also be detected if the patient needs to make corrections when they move the gaze from one target to a second target in a vertical direction. Patients with PSP may demonstrate increased latency of saccades, slower speed, or "past pointing." In contrast, the patient who has normal changes to extraocular movements due to aging will have some decreased range of motion on vertical gaze, but the saccades should be intact. In addition, there is some abnormality of horizontal gaze in PSP, in that the square wave jerk can reflect decreased fixation. This is thought to be due to dysfunction of burst cells in the brainstem reticular formation.43 Patients with PSP may show the atrophy of the midbrain in what is called a "hummingbird" or "penguin" sign.44 A recent study by Borroni et al.45 reports a correlation between an isoform of cerebral spinal fluid tau levels and not only the diagnosis of PSP but also the degree of atrophy in the brainstem.

Cranial nerve deficits can be easy to recognize on elemental neurological examination, but lesions to substantia nigra, locus ceruleus or dorsal raphe may be more insidious in their manifestations. As mentioned above, parkinsonism would be a clue that the substantia nigra has been affected. There is also evidence to support attention deficit/hyperactivity disorder arising from a lesion in the substantia nigra (as well as from norepinephrine disturbance, see below).46 Deficits in serotonin production by the dorsal raphe have been associated with depression, suicidality, psychosis, and frontotemporal dementia.4749 Both serotonin and acetylcholine are important to the function of the reticular activating system. Therefore one might anticipate that sleep disturbances and delirium could be related to a brainstem lesion involving the dorsal raphe.50 A lesion in the locus ceruleus will reduce the production of norepinephrine. This is associated with depressive symptoms, attention deficit/hyperactivity disorder, posttraumatic stress disorder, and hypotension.5154 Apathy has been related to all three of these neurotransmitters. Apathy has been reported after pallido-nigral lesions55 and in a patient population with neuro-Behçet disease, affecting the brainstem and cranial nerves.56

In conclusion, a working knowledge of the brainstem anatomy and physiology is essential for the assessment of patients with symptoms of cranial nerve deficits, motor, sensory, or cognitive/behavioral changes. Summary charts, color-coded maps, and tables are available for clinicians who may not regularly assess patients with brainstem injury. The inclusion of the brainstem in discussions of the cognitive/emotion/behavior circuits is necessary for a thorough review of brain function.

TABLE 1. Cranial Nerve Nuclei and Long Tracts
TABLE 2. Key Structures and Symptoms for Brainstem Lesion Localization
 
 The internal anatomy of the brainstem is presented in a simplified, color-coded format.
The approximate locations and extents of nuclei that are important sources for a particular neurotransmitter are color-coded onto a sagittal magnetic resonance image.
The approximate locations and extent of major tracts and nuclei are color-coded onto simplified axial illustrations of brainstem sections (left panel). The most common pattern of arterial territories is also presented (right panel). All illustrations are oriented in the radiographic perspective.
.
DeArmond SJ, Fusco MM, Dewey MM: Structure of the Human Brain: A Photographic Atlas. New York, Oxford University, 1989
 
.
Nolte J: The Human Brain. St Louis, Mosby, 2002
 
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Hayman LA, Taber KH, Dubey N, et al: A functional atlas of brain vascular territories, in Imaging of the Nervous System. Edited by Latchaw RE, Kucharczyk J, Moseley ME. Philadelphia, Elsevier Mosby, 2005, pp 179—197
 
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Pahapill PA, Lozano AM: The pedunculopontine nucleus and Parkinson’s disease. Brain 2000; 123:1767—1783
 
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Hathout GM, Bhidayasiri R: Midbrain ataxia: an introduction to the mesencephalic locomotor region and the pendunculopontine nucleus. AJR Am J Roentgenol 2005; 184:953—956
 
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Sasaki M, Shibata E, Tohyama K, et al: Monoamine neurons in the human brain stem: anatomy, magnetic resonance imaging findings, and clinical implications. Neuroreport 2008; 19:1649—1654
 
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Keren NI, Lozar CT, Harris KC, et al: In vivo mapping of the human locus coeruleus. Neuroimage 2009; 47:1261—1267
 
.
Kumar S, Fowler M, Gonzalez-Toldeo E, et al: Central pontine myelinolysis: an update. Neurol Res 2006; 28:360—366
 
.
van Zandvoort M, de Haan E, van Gijn J, et al: Cognitive functioning in patients with a small infarct in the brainstem. J Int Neuropsychol Soc 2003; 9:490—494
 
.
Crosson B, Trautt GM: Cortical functioning during recovery from brainstem infarction: a case report. Int J Clin Neuropsychol 1981; 2:3—7
 
.
Evyapan D, Kumral E: Pontine anosognosia for hemiplegia. Neurology 1999; 53:647—649
 
.
Garrard P, Bradshaw D, Jäger HR, et al: Cognitive dysfunction after isolated brain stem insult: an underdiagnosed cause of long-term morbidity. J Neurol Neurosurg Psychiatry 2002; 73:191—194
 
.
Hoffmann M, Schmitt F: Cognitive impairment in isolated subtentorial stroke. Acta Neurol Scand 2004; 109:14—24
 
.
Ris MD, Beebe DW, Armstrong FD, et al: Cognitive and adaptive outcome in extracerebellar low-grade tumors in children: a report from the Children’s Oncology Group. J Clin Oncol 2008; 26:4765—4770
 
.
Leon-Carrion J, van Eeckhout P, Dominguez-Morales MR: Review of subject: the locked-in syndrome: a syndrome looking for a therapy. Brain Inj 2002; 16:555—569
 
.
Leon-Carrion J, van Eeckhout P, Dominguez-Morales MR, et al: The locked-in syndrome: a syndrome looking for a therapy. Brain Inj 2002; 16:571—582
 
.
Rousseaux M, Castelnot E, Rigaux P, et al: Evidence of persisting cognitive impairment in a case series of patients with locked-in syndrome. J Neurol Neurosurg Psychiatry 2009; 80:166—170
 
.
Allain P, Joseph PA, Isambert JL, et al: Cognitive functions in chronic locked-in syndrome: a report of two cases. Cortex 1998; 34:629—634
 
.
Schnakers C, Majerus S, Goldman S, et al: Cognitive function in locked-in syndrome. J Neurol 2008; 255:323—330
 
.
Casey BJ, Trainor R, Giedd J, et al: The role of the anterior cingulate in automatic and controlled processes: a developmental neuroanatomical study. Dev Psychobiol 1997; 30:61—69
 
.
Aron AR, Durston S, Eagle DM, et al: Converging evidence for a fronto-basal-ganglia network for inhibitory control of action and cognition. J Neurosci 2007; 27:11860—11864
 
.
Allman JM, Hakeem A, Erwin JM, et al: The anterior cingulate cortex: the evolution of an interface between emotion and cognition. Ann N Y Acad Sci 2001; 935:107—117
 
.
Haber SN, Knutson B: The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 2010; 35:4—26
 
.
Anderson TP, Bourestom N, Greenberg FR, et al: Predictive factors in stroke rehabilitation. Arch Phys Med Rehabil 1974; 55:545—553
 
.
Jongbloed L: Prediction of function after stroke: a critical review. Stroke 1986; 17:765—776
 
.
Mysiw WJ, Beegan JG, Gatens PF: Prospective cognitive assessment of stroke patients before inpatient rehabilitation: the relationship of the Neurobehavioral Cognitive Examination to functional improvement. Am J Phys Med Rehabil 1989; 68:168—717
 
.
Hier DB, Edelstein G: Deriving clinical prediction rules from stroke outcome research. Stroke 1991; 22:1431—1436
 
.
Galski T, Bruno RL, Zorowitz R, et al: Predicting length of stay, functional outcome, and aftercare in the rehabilitation of stroke patients: the dominant role of higher-order cognition. Stroke 1993; 24:1794—1800
 
.
Gates P: The rule of 4 of the brainstem: a simplified method for understanding brainstem anatomy and brainstem vascular syndromes for the non-neurologist. Int Med J 2005; 35:263—266
 
.
Marx JJ, Thomke F: Classical crossed brainstem syndromes: myth or reality? J Neurol 2009; 256:898—903
 
.
Garber N: Evaluating diplopia with the Maddox Rod, Risley’s prism, and red glass. J Ophthalmic Nurs Technol 1995; 14:224—228
 
.
Adams RD, Victor M: Diseases of the cranial nerves, in Principles of Neurology, 4th ed. Edited by Adams RD, Victor M. New York, McGraw-Hill Information Services Company, Health Professions Division, 1989, p 1080
 
.
Wall M: Brainstem syndromes, in Neurology in Clinical Practice: Principles of Diagnosis and Management. Edited by Bradley WG, Daroff RB, Fenichel GM, et al. Boston, Butterworth-Heinemann, 1991, pp 354—361
 
.
Poewe W: Non-motor symptoms of Parkinson’s disease. Eur Neurol 2008; 15:14—20
 
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Grinberg LT, Rueb U, Alho AT, et al: Brainstem pathology and non-motor symptoms of PD. J Neurol Sci 2009 Sep 14. [Epub ahead of print]
 
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Chow TW, Cummings JL: Treatment of depression in the patient with Parkinson’s disease. Clin Geriatrics 1998; 4:34—46
 
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Probst A, Bloch A, Tolnay M: New insights into the pathology of Parkinson’s disease: does the peripheral autonomic system become central? Eur Neurol 2008; 15:1—4
 
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Nath U, Ben-Shlomo Y, Thomson RG, et al: The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001; 124:1438—1449
 
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Kaat LD, Boon AJ, Kamphorst W, et al: Frontal presentation in progressive supranuclear palsy. Neurology 2007; 69:723—729
 
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Neary D, Snowden JS, Gustafson L, et al: Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51:1546—1554
 
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Litvan I, Agid Y, Calne D, et al: Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olsezewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47:1—9
 
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Leigh RJ, Riley DE: Eye movements in parkinsonism: it’s saccadic speed that counts. Neurology 2000; 54:1018—1019
 
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Graber JJ, Staudinger R: Teaching neuroimages: "penguin" or "hummingbird" sign and midbrain atrophy in progressive supranuclear palsy. Neurology 2009; 72:e81
 
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Borroni B, Malinverno M, Gardoni F, et al: Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology 2008; 71:1796—1803
 
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Oades RD: Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD). Prog Brain Res 2008; 172:543—565
 
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Brown GL, Linnoila MI: CSF serotonin metabolite (5-HIAA) studies in depression, impulsivity, and violence. J Clin Psychiatry 1990; 51:31—41
 
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Burke WJ, Dewan V, Wengel SP, et al: The use of selective serotonin reuptake inhibitors for depression and psychosis complicating dementia. Int J Geriatr Psychiatry 1997; 12:519—525
 
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Sjogren M, Minthon L, Passant U, et al: Decreased monoamine metabolites in frontotemporal dementia and Alzheimer’s disease. Neurobiol Aging 1998; 19:379—384
 
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Mirsky AF, Duncan CC: Pathophysiology of mental illness: a view from the fourth ventricle. Int J Psychophysiol 2005; 58:162—178
 
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Southwick SM, Paige S, Morgan CA, et al: Neurotransmitter alterations in PTSD: catecholamines and serotonin. Semin Clin Neuropsychiatry 1999; 4:242—248
 
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Freeman R: Treatment of orthostatic hypotension. Semin Neurol 2003; 23:435—442
 
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Kim CH, Waldman ID, Blakely RD, et al: Functional gene variation in the human norepinephrine transporter: association with attention deficit hyperactivity disorder. Ann N Y Acad Sci 2008; 1129:256—260
 
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Nutt DJ: Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry 2008; 69:4—7
 
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Adam J, Baulac M, Hauw J-J, et al: Behavioral symptoms after pallido-nigral lesions: a clinico-pathological case. Neurocase 2008; 14:125—130
 
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Oktem-Tanör O, Baykan-Kurt,B, Gurvit IH, et al: Neuropsychological follow-up of 12 patients with neuro-Behcet disease. J Neurol 1999; 246:113—119
 

 The internal anatomy of the brainstem is presented in a simplified, color-coded format. The approximate locations and extents of nuclei that are important sources for a particular neurotransmitter are color-coded onto a sagittal magnetic resonance image. The approximate locations and extent of major tracts and nuclei are color-coded onto simplified axial illustrations of brainstem sections (left panel). The most common pattern of arterial territories is also presented (right panel). All illustrations are oriented in the radiographic perspective.
TABLE 1. Cranial Nerve Nuclei and Long Tracts
TABLE 2. Key Structures and Symptoms for Brainstem Lesion Localization
TABLE 3. Brainstem Syndromes
+

References

.
DeArmond SJ, Fusco MM, Dewey MM: Structure of the Human Brain: A Photographic Atlas. New York, Oxford University, 1989
 
.
Nolte J: The Human Brain. St Louis, Mosby, 2002
 
.
Hayman LA, Taber KH, Dubey N, et al: A functional atlas of brain vascular territories, in Imaging of the Nervous System. Edited by Latchaw RE, Kucharczyk J, Moseley ME. Philadelphia, Elsevier Mosby, 2005, pp 179—197
 
.
Pahapill PA, Lozano AM: The pedunculopontine nucleus and Parkinson’s disease. Brain 2000; 123:1767—1783
 
.
Hathout GM, Bhidayasiri R: Midbrain ataxia: an introduction to the mesencephalic locomotor region and the pendunculopontine nucleus. AJR Am J Roentgenol 2005; 184:953—956
 
.
Sasaki M, Shibata E, Tohyama K, et al: Monoamine neurons in the human brain stem: anatomy, magnetic resonance imaging findings, and clinical implications. Neuroreport 2008; 19:1649—1654
 
.
Keren NI, Lozar CT, Harris KC, et al: In vivo mapping of the human locus coeruleus. Neuroimage 2009; 47:1261—1267
 
.
Kumar S, Fowler M, Gonzalez-Toldeo E, et al: Central pontine myelinolysis: an update. Neurol Res 2006; 28:360—366
 
.
van Zandvoort M, de Haan E, van Gijn J, et al: Cognitive functioning in patients with a small infarct in the brainstem. J Int Neuropsychol Soc 2003; 9:490—494
 
.
Crosson B, Trautt GM: Cortical functioning during recovery from brainstem infarction: a case report. Int J Clin Neuropsychol 1981; 2:3—7
 
.
Evyapan D, Kumral E: Pontine anosognosia for hemiplegia. Neurology 1999; 53:647—649
 
.
Garrard P, Bradshaw D, Jäger HR, et al: Cognitive dysfunction after isolated brain stem insult: an underdiagnosed cause of long-term morbidity. J Neurol Neurosurg Psychiatry 2002; 73:191—194
 
.
Hoffmann M, Schmitt F: Cognitive impairment in isolated subtentorial stroke. Acta Neurol Scand 2004; 109:14—24
 
.
Ris MD, Beebe DW, Armstrong FD, et al: Cognitive and adaptive outcome in extracerebellar low-grade tumors in children: a report from the Children’s Oncology Group. J Clin Oncol 2008; 26:4765—4770
 
.
Leon-Carrion J, van Eeckhout P, Dominguez-Morales MR: Review of subject: the locked-in syndrome: a syndrome looking for a therapy. Brain Inj 2002; 16:555—569
 
.
Leon-Carrion J, van Eeckhout P, Dominguez-Morales MR, et al: The locked-in syndrome: a syndrome looking for a therapy. Brain Inj 2002; 16:571—582
 
.
Rousseaux M, Castelnot E, Rigaux P, et al: Evidence of persisting cognitive impairment in a case series of patients with locked-in syndrome. J Neurol Neurosurg Psychiatry 2009; 80:166—170
 
.
Allain P, Joseph PA, Isambert JL, et al: Cognitive functions in chronic locked-in syndrome: a report of two cases. Cortex 1998; 34:629—634
 
.
Schnakers C, Majerus S, Goldman S, et al: Cognitive function in locked-in syndrome. J Neurol 2008; 255:323—330
 
.
Casey BJ, Trainor R, Giedd J, et al: The role of the anterior cingulate in automatic and controlled processes: a developmental neuroanatomical study. Dev Psychobiol 1997; 30:61—69
 
.
Aron AR, Durston S, Eagle DM, et al: Converging evidence for a fronto-basal-ganglia network for inhibitory control of action and cognition. J Neurosci 2007; 27:11860—11864
 
.
Allman JM, Hakeem A, Erwin JM, et al: The anterior cingulate cortex: the evolution of an interface between emotion and cognition. Ann N Y Acad Sci 2001; 935:107—117
 
.
Haber SN, Knutson B: The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 2010; 35:4—26
 
.
Anderson TP, Bourestom N, Greenberg FR, et al: Predictive factors in stroke rehabilitation. Arch Phys Med Rehabil 1974; 55:545—553
 
.
Jongbloed L: Prediction of function after stroke: a critical review. Stroke 1986; 17:765—776
 
.
Mysiw WJ, Beegan JG, Gatens PF: Prospective cognitive assessment of stroke patients before inpatient rehabilitation: the relationship of the Neurobehavioral Cognitive Examination to functional improvement. Am J Phys Med Rehabil 1989; 68:168—717
 
.
Hier DB, Edelstein G: Deriving clinical prediction rules from stroke outcome research. Stroke 1991; 22:1431—1436
 
.
Galski T, Bruno RL, Zorowitz R, et al: Predicting length of stay, functional outcome, and aftercare in the rehabilitation of stroke patients: the dominant role of higher-order cognition. Stroke 1993; 24:1794—1800
 
.
Gates P: The rule of 4 of the brainstem: a simplified method for understanding brainstem anatomy and brainstem vascular syndromes for the non-neurologist. Int Med J 2005; 35:263—266
 
.
Marx JJ, Thomke F: Classical crossed brainstem syndromes: myth or reality? J Neurol 2009; 256:898—903
 
.
Garber N: Evaluating diplopia with the Maddox Rod, Risley’s prism, and red glass. J Ophthalmic Nurs Technol 1995; 14:224—228
 
.
Adams RD, Victor M: Diseases of the cranial nerves, in Principles of Neurology, 4th ed. Edited by Adams RD, Victor M. New York, McGraw-Hill Information Services Company, Health Professions Division, 1989, p 1080
 
.
Wall M: Brainstem syndromes, in Neurology in Clinical Practice: Principles of Diagnosis and Management. Edited by Bradley WG, Daroff RB, Fenichel GM, et al. Boston, Butterworth-Heinemann, 1991, pp 354—361
 
.
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