Neurology_Adams

Neurology_Adams. There are few persons who do not at some time experience periods of severe discouragement and despair. As with nervousness, irritability, and anxiety, depression of mood that is appropriate to a given situation in life (e.g., grief reaction) is seldom the basis of medical concern. People in these situations tend to seek help only when their grief or unhappiness is persistent and beyond control. However, there are numerous instances in which the symptoms of depression assert themselves for reasons that are not apparent. Often the symptoms are interpreted as a medical illness, bringing the patient first to the internist or neurologist. Sometimes another disease is found (such as cancer, chronic hepatitis, or other infection or postinfectious asthenia) in which chronic fatigue is confused with depression; more often the opposite pertains, that is, an endogenous depression is the essential problem even when there has been evidence earlier of a viral or bacterial infection.


Neurology_Adams

Neurology_Adams. From the patient and the family it is learned that the patient has been “feeling unwell,” “low in spirits,” “blue,” “down,” “unhappy,” or “morbid.” There has been a change in his emotional reactions of which the patient may not be fully aware. Activities that were formerly found pleasurable are no longer so. Often, however, change in mood is less conspicuous than reduction in psychic and physical energy, and it is in this type of patient that diagnosis is most difficult. A complaint of fatigue is almost invariable; not uncommonly, it is worse in the morning after a night of restless sleep. The patient complains of a “loss of energy,” “weakness,” “tiredness,” “having no energy,” that his job has become more difficult. His outlook is pessimistic. The patient is irritable and preoccupied with uncontrollable worry over trivialities. With excessive worry, the ability to think with accustomed efficiency is reduced; the patient complains that his mind is not functioning properly, and he is


Neurology_Adams

Neurology_Adams. uncontrollable worry over trivialities. With excessive worry, the ability to think with accustomed efficiency is reduced; the patient complains that his mind is not functioning properly, and he is forgetful and unable to concentrate. If the patient is naturally of suspicious nature, paranoid tendencies may assert themselves.


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Neurology_Adams. Particularly troublesome may be the patient’s tendency to hypochondriasis. Indeed, most cases formerly diagnosed as hypochondriasis are now regarded by some writers as depression with superimposed anxiety. The patient passes from doctor to doctor, seeking relief from symptoms that would not trouble the normal person, and no amount of reassurance relieves his state of mind. The anxiety and depressed mood of these persons may be obscured by their preoccupation with visceral functions.


Neurology_Adams

Neurology_Adams. When the patient is examined, the facial expression is often plaintive, troubled, pained, or anguished. The patient’s attitude and manner betray a prevailing mood of depression, hopelessness, and despondency. In other words, the affect, which is the outward expression of feeling, is consistent with the depressed mood. During the interview, the patient may be tearful and may cry openly. In some, there is a kind of immobility of the face that mimics parkinsonism, though others are restless and agitated (pacing, wringing their hands, etc.). Occasionally the patient will smile, but the smile impresses one as more a social gesture than a genuine expression of feeling.


Neurology_Adams

Neurology_Adams. The stream of speech is slow. Sighing is frequent. There may be long pauses between questions and answers. The latter are brief and may be monosyllabic. There is a paucity of ideas. The impediment extends to all topics of conversation and affects movement of the limbs as well. The most extreme forms of decreased motor activity, rarely seen in the office or clinic, border on muteness and stupor (“anergic depression”). Conversation is replete with pessimistic thoughts, fears, and expressions of unworthiness, inadequacy, inferiority, hopelessness, and sometimes guilt. In severe depressions, bizarre ideas and bodily delusions may be expressed (“blood drying up,” “bowels are blocked with cement,” “I am half dead”). Several theories have emerged concerning the cause of the pathologic depressive state, but none can be confirmed with confidence except for a heritable aspect. These views are elaborated on in Chap. 48.


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Neurology_Adams. It is the authors’ belief that depressive states are among the most commonly overlooked diagnoses in clinical medicine. Part of the trouble is with the word itself, which implies being unhappy about some specific aspect of life, whereas most depressions are endogenous and instead are the agents of negativity and discouragement about almost all life events. Endogenous depression may be suspected in states of chronic ill health without explanation, hypochondriasis, disability that exceeds the manifest signs of a medical disease, asthenia and ongoing fatigue, and chronic pain syndromes. Inasmuch as recovery is the rule, suicide is a tragedy for which the medical profession must sometimes share responsibility. In extreme circumstances, however, the patient is impelled to suicide and efforts on the part of the physician cannot be considered as a failure. Depressive illnesses and theories of their causation and management are considered extensively in Chap. 48.


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Neurology_Adams. Depressive illnesses and theories of their causation and management are considered extensively in Chap. 48. Bagnall AM, Hempel S, Chambers D, et al: The treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis in adults and children. National Health Service Centre for Reviews and Dissemination. CRD Report; 35, 2007. Barratt ES, White R: Impulsiveness and anxiety related to medical students’ performance and attitudes. J Med Educ 44:604, 1969. Beard J: Neurasthenia, or nervous exhaustion. Boston Med Surg J III:217, 1869. Brodal A: Self-observations and neuro-anatomical considerations after a stroke. Brain 96:675, 1973. Chambers D, Bagnall AM, Hempell S, et al: Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med 99:506, 2006. Chaudhuri A, Behan PO: Fatigue in neurological disorders. Lancet 363:978, 2004.


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Neurology_Adams. Chaudhuri A, Behan PO: Fatigue in neurological disorders. Lancet 363:978, 2004. Cope H, David A, Pelosi A, et al: Predictors of chronic “postviral” fatigue. Lancet 344:864, 1994. Dawson DM, Sabin TD: Chronic Fatigue Syndrome. Boston, Little, Brown, 1993. Digon A, Goicoechea A, Moraza MJ: A neurological audit in Vitoria, Spain. J Neurol Neurosurg Psychiatry 55:507, 1992. Editorial: The essence of stress. Lancet 344:1713, 1994. Freud S: On the grounds for detaching a particular syndrome from neurasthenia under the description “anxiety neurosis.” In: Strachey J (ed): The Complete Psychological Works of Sigmund Freud, standard edition. Vol 3. London, Hogarth Press, 1962, p 90. Holmes GP, Kaplan JE, Glantz NM, et al: Chronic fatigue syndrome: a working case definition. Ann Intern Med 108:387, 1988. Kahn E: Psychopathic Personalities. New Haven, CT, Yale University Press, 1931.


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Neurology_Adams. Kahn E: Psychopathic Personalities. New Haven, CT, Yale University Press, 1931. Lader M: The nature of clinical anxiety in modern society. In: Spielberger CD, Sarason IG (eds): Stress and Anxiety. Vol 1. New York, Halsted, 1975, pp 3–26. Lesch KP, Bengel D, Jeils A, et al: Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory system. Science 274:1527, 1996. Lloyd AR, Gandevia SC, Hales JP: Muscle performance: voluntary activation, twitch properties, and perceived effort in normal subjects and patients with chronic fatigue syndrome. Brain 114:85, 1991. McDougall W: Outlines of Abnormal Psychology. New York, Scribners, 1926. Rosen G: Emotions and sensibility in ages of anxiety: a comparative historical review. Am J Psychiatry 124:771, 1967. Rowe PC, Bou-Holaigah I, Kan JS, et al: Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet 345:623, 1995.


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Neurology_Adams. Rowe PC, Bou-Holaigah I, Kan JS, et al: Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet 345:623, 1995. Roy-Byrne P, Craske MG, Stein MB: Panic disorder. Lancet 368:1023, 2006. Samii A, Wassermann EM, Ikoma K, et al: Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue or depression. Neurology 47:1410, 1996. Shorter E: From Paralysis to Fatigue: A History of Psychosomatic Illness in the Modern Era. New York, Free Press, 1992. Snaith RP, Taylor CM: Irritability: Definition, assessment, and associated factors. Br J Psychiatry 147:127, 1985. Southwick SM, Krystal JH, Morgan CA, et al: Abnormal noradrenergic function in post traumatic stress disorder. Arch Gen Psychiatry 50:266, 1993. Stein MB, Sareen J: Generalized anxiety disorder. New Engl J Med 373:2059, 2015. Straus SE: The chronic mononucleosis syndrome. J Infect Dis 157:405, 1988.


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Neurology_Adams. Stein MB, Sareen J: Generalized anxiety disorder. New Engl J Med 373:2059, 2015. Straus SE: The chronic mononucleosis syndrome. J Infect Dis 157:405, 1988. Straus SE, Dale JK, Tobi M, et al: Acyclovir treatment of the chronic fatigue syndrome. N Engl J Med 319:1692, 1988. Swartz MN: The chronic fatigue syndrome—one entity or many? N Engl J Med 319:1726, 1988. Wessely S, Chalder T, Hirsch S, et al: Postinfectious fatigue: Prospective cohort study in primary care. Lancet 345:1333, 1995. Wessely S, Powell R: Fatigue syndromes: a comparison of chronic “postviral” fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry 52:940, 1989. Yehuda R: Post-traumatic stress disorder. N Engl J Med 346:108, 2002. Chapter 23 Fatigue, Asthenia, Anxiety, and Depression The Limbic Lobes and the Neurology of Emotion


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Neurology_Adams. Yehuda R: Post-traumatic stress disorder. N Engl J Med 346:108, 2002. Chapter 23 Fatigue, Asthenia, Anxiety, and Depression The Limbic Lobes and the Neurology of Emotion Emotion may be defined as any feeling state—for example, fear, anger, excitement, love, or hate—associated with certain autonomic, mainly visceral bodily changes. If the emotion is intense, there may ensue a disturbance of intellectual functions, that is, a disorganization of rational thought and a tendency toward a more automatic behavior of unmodulated, stereotyped character.


Neurology_Adams

Neurology_Adams. In its most easily recognized human form, emotion is initiated by a stimulus, real or imagined, the perception of which involves recognition, memory, and specific associations. The emotional state that is engendered is mirrored in a psychic experience, that is, a feeling, which is purely subjective and known to others only through the patient’s verbal expressions or by judging his behavioral reactions. This behavioral aspect, for which we use the term affect, is in part autonomous (hormonal–visceral) and in part somatic and shows itself in the patient’s facial expression, bodily attitude, vocalizations, or directed voluntary activity. In other words, the components of emotion appear to consist of (1) the perception of a stimulus, which may be internal (an idea) or external, (2) the feeling, (3) the autonomic–visceral changes, (4) the outward display (affect), and (5) the impulse to a certain type of activity. In many cases of neurologic disease, it is not possible to separate these


Neurology_Adams

Neurology_Adams. (3) the autonomic–visceral changes, (4) the outward display (affect), and (5) the impulse to a certain type of activity. In many cases of neurologic disease, it is not possible to separate these components from one another.


Neurology_Adams

Neurology_Adams. The occurrence of abnormal emotional reactions in the course of disease is associated with lesions that preferentially involve certain parts of the nervous system. These structures are grouped under the term limbic and are among the most complex and least understood parts of the nervous system. The Latin word limbus means “border” or “margin.” Credit for introducing the term limbic to neurology is usually given to Broca, who used it to describe the ring of gray matter formed primarily by the cingulate and parahippocampal gyri that encircles the corpus callosum and underlying upper brainstem. Actually, Thomas Willis had pictured this region of the brain and referred to it as the limbus in 1664. Broca preferred his term, le grand lobe limbique, to rhinencephalon, which was the term then in vogue and referred more specifically to structures having an olfactory function. Neuroanatomists have extended the boundaries of the limbic lobe to include not only the cingulate and parahippocampal


Neurology_Adams

Neurology_Adams. vogue and referred more specifically to structures having an olfactory function. Neuroanatomists have extended the boundaries of the limbic lobe to include not only the cingulate and parahippocampal gyri but also the underlying hippocampal formation, the subcallosal gyrus, and the paraolfactory area. The terms visceral brain and limbic system, introduced by MacLean, have an even wider designation and more completely describe the structures involved in emotion and its expression; in addition to all parts of the limbic lobe, they include a number of associated subcortical nuclei such as those of the amygdaloid complex, septal region, preoptic area, hypothalamus, anterior thalamus, habenula, and central midbrain tegmentum, including the raphe nuclei and interpeduncular nucleus. The major structures that constitute the limbic system and their relationships are illustrated in Figs. 24-1 and 24-2.


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Neurology_Adams. The cytoarchitectonic arrangements of the limbic cortex clearly distinguish it from the surrounding neocortex. The latter, as stated in Chap. 21, differentiates into a characteristic six-layer structure. In contrast, the inner part of the limbic cortex, including the hippocampus, is referred to as archior allocortex and is composed of irregularly arranged aggregates of nerve cells that tend to be in a trilaminate configuration. The cortex of the cingulate gyrus, which forms the outer ring of the limbic lobe, is transitional between neocortex and allocortex—hence, it is called mesocortex. The entorhinal cortex adjacent to the anterior hippocampus has a similar transitional architecture. Information from a wide array of cortical neurons is funneled into the dentate gyrus and then to the CA (cornu ammonis) pyramidal cells of the hippocampus. Output from the hippocampus is mainly from the pyramidal cells of the CA1 segment and subiculum, whose axons form the fibria and fornix. The


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Neurology_Adams. the CA (cornu ammonis) pyramidal cells of the hippocampus. Output from the hippocampus is mainly from the pyramidal cells of the CA1 segment and subiculum, whose axons form the fibria and fornix. The amygdaloid complex, a subcortical nuclear component of the limbic system, also has a unique composition, consisting of several separable nuclei, each with connections to other limbic structures.


Neurology_Adams

Neurology_Adams. The connections between the orbitofrontal neocortex and limbic lobes, between the individual components of the limbic lobes, and between the limbic lobes and the hypothalamus and midbrain reflect their many functional relationships in regard to emotion. At the core of this system lies the medial forebrain bundle, a complex set of ascending and descending fibers that connect the orbitomesiofrontal cortex, septal nuclei, amygdala, and hippocampus rostrally, and certain nuclei in the midbrain and caudal pons. This system, of which the hypothalamus is the central part, was designated by Nauta as the septohypothalamo–mesencephalic continuum.


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Neurology_Adams. There are many other interrelationships among various parts of the limbic system, only a few of which can be indicated here. The best known of these is Papez circuit. It leads from the hippocampus, via the fornix, to the mammillary body and septal and preoptic regions (Fig. 24-1). The mammillothalamic tract (bundle of Vicq d’Azyr) connects the mammillary nuclei with the anterior nuclei of the thalamus, which, in turn project to the cingulate gyrus and then, via the cingulum back to the hippocampus. The cingulum runs concentric to the curvature of the corpus callosum; it connects various parts of the limbic lobe to one another and projects to the striatum and to certain brainstem nuclei. Also, the cingulum receives fibers from the inferior parietal lobule and temporal lobe, which are multimodal association centers for the integration of visual, auditory, and tactile perceptions. It is connected to the opposite cingulum through the anterior corpus callosum.


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Neurology_Adams. Physiology of the Limbic System The functional properties of the limbic structures first became known during the third and fourth decades of the twentieth century. From ablation and stimulation studies, Cannon, Bard, and others established the fact that the hypothalamus contains the suprasegmental integrations of the sympathetic and parasympathetic autonomic nervous systems. Soon after, anatomists found efferent pathways from the hypothalamus to the neural structures subserving parasympathetic and sympathetic reflexes. One such segmental reflex, involving the sympathetic innervation of the adrenal gland, served as the basis of Cannon’s theory of sympathoadrenal action, which for many years dominated thinking about the neurophysiology of acute emotion.


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Neurology_Adams. Following Cannon, Bard incorrectly localized the central regulatory apparatus for respiration, wakefulness, and sexual activity in the hypothalamus. Only later, the hypothalamus was found to contain neurosecretory cells, which control the secretion of the pituitary hormones; also within it are special sensory receptors for the regulation of hunger, thirst, body temperature, and levels of circulating electrolytes. Gradually the idea emerged of a hypothalamic–pituitary–autonomic system that is essential to both the basic homeostatic and emergency (“fight-or-flight”) reactions of the organism. The functional anatomy of these autonomic and neuroendocrine systems is discussed in Chaps. 26 and 27.


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Neurology_Adams. The impression of the leading psychologists of the nineteenth century that autonomic reactions were the essential motor component of instinctual feeling has been partially partially corroborated. It was proposed that emotional experience was merely the self-awareness of these visceral activities (the James-Lange theory of emotion alluded to in Chap. 23). The limitations of this theory became evident when it was demonstrated by Cannon that the capacity to manifest emotional changes remained after all visceral afferent fibers had been interrupted. Nonetheless, it remains true that perception of visceral activities can greatly alter the emotional state. An example is the perception of a rapid heartbeat, leading to heightened anxiety, which results in further acceleration in the heart rate.


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Neurology_Adams. Although the natural stimuli for emotion involve the same neocortical perceptive–cognitive mechanisms, that underlie nonemotional sensory experiences, there are important differences relating to the prominent visceral effects and particular behavioral reactions evoked by emotion. Bard, in 1928, first produced “sham rage” in cats by removing the cerebral hemispheres and leaving the hypothalamus and brainstem intact. This is a state in which the animal reacts to all stimuli with expressions of intense anger and signs of autonomic overactivity. In subsequent studies, Bard and Mountcastle found that only if the ablations included the amygdala on both sides would sham rage be produced; removal of all the neocortex, but sparing of the limbic structures resulted in the opposite state—placidity. Removal of the amygdaloid nuclei in the macaque, a normally aggressive and recalcitrant animal, greatly reduced the reactions of fear and anger (Klüver-Bucy syndrome, see further on). The precise role


Neurology_Adams

Neurology_Adams. of the amygdaloid nuclei in the macaque, a normally aggressive and recalcitrant animal, greatly reduced the reactions of fear and anger (Klüver-Bucy syndrome, see further on). The precise role of the hypothalamus and amygdala in the production of both directed and undirected anger and displays of rage has turned out to be far more complex. In any case, Papez, on the basis of these and his own anatomic observations, postulated that the limbic parts of the brain elaborate the functions of central emotion and participate as well in emotional expression.


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Neurology_Adams. The cingulate gyrus plays a key role in the behavior of animals and humans. According to Bear, and as conceptualized by Baleydier and Mauguiere, the cingulate gyri serve dual functions in cognition and in emotional reactions. Stimulation produces autonomic effects similar to the vegetative correlates of emotion (increase in heart rate and blood pressure, dilatation of pupils, piloerection, respiratory arrest, breathholding). More complex responses, such as fear, anxiety, or pleasure, have been reported during neurosurgical stimulative and ablative procedures, although these results are inconsistent. Bilateral cingulectomies performed in the past on psychotic and anxious patients result in an overall diminution of emotional reactions (Ballantine et al; Brown). Some investigators believe that the cingulate gyri are also involved in memory processing (functioning presumably in connection with the mediodorsal thalamic nuclei and mediotemporal lobes) and in exploratory behavior and


Neurology_Adams

Neurology_Adams. that the cingulate gyri are also involved in memory processing (functioning presumably in connection with the mediodorsal thalamic nuclei and mediotemporal lobes) and in exploratory behavior and visually focused attention. In humans, this system appears to be more efficient in the nondominant hemisphere.


Neurology_Adams

Neurology_Adams. Another aspect of limbic function has come to light with information about the neurotransmitters that interconnect the structures within the system. The concentration of norepinephrine is highest in the hypothalamus and next highest in the medial parts of the limbic system; at least 70 percent of this monoamine is concentrated in terminals of axons that arise in the medulla and in the locus ceruleus of the rostral pons. Serotonin is a major transmitter for neurons originating in the reticular formation of the midbrain whose axons terminate in the amygdala septal nuclei, and lateral parts of the limbic lobe. The axons of neurons in the ventral tegmental parts of the midbrain, which ascend in the medial forebrain bundle and the nigrostriatal pathway, contain a high content of dopamine. Perhaps this explains the observation that a severe depressive reaction may be produced by electrical stimulation of the substantia nigra with an aberrantly placed electrode for the treatment of Parkinson


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Neurology_Adams. this explains the observation that a severe depressive reaction may be produced by electrical stimulation of the substantia nigra with an aberrantly placed electrode for the treatment of Parkinson disease (see Chap. 38).


Neurology_Adams

Neurology_Adams. Many of the foregoing ideas about the role of the limbic system have come from experimentation in laboratory animals. Only in relatively recent years have neurologists, primed with the knowledge of these studies, begun to relate emotional disturbances in patients with disease of limbic structures. These clinical observations, summarized in the following pages, form an interesting chapter in neurology. Table 24-1 lists the most readily recognized disturbances of emotion. The list is tentative, as our understanding of many of these states, particularly their pathologic basis, is incomplete. Only a small number of these derangements can be used as indicators of lesions and diseases in particular parts of the human brain. Taken in context, however, these disturbances are useful diagnostically. As knowledge of emotional disorders increases, an understanding of the functioning of limbic structures will continue to bring together large segments of psychiatry and neurology.


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Neurology_Adams. Threatened by imaginary figures and voices that seem real and inescapable, the hallucinating, delirious patient trembles, struggles to escape, and displays the full picture of terror. The patient’s affect, emotional reaction, and visceral and somatic motor responses are altogether appropriate to the content of hallucinations. We have seen a patient slash his wrists and another try to drown himself in response to hallucinatory voices that admonished them for their worthlessness and the shame they had brought on their families. Beyond a derangement solely of emotional expression, the abnormality in these circumstances is one of disordered perception and thinking.


Neurology_Adams

Neurology_Adams. There also occurs a state, difficult to classify, of overwhelming emotionality in patients who are in severe, acute pain. The patient’s attention can be captured only briefly, and within moments, there is a return to an extreme state of angst, groaning, and anger. We have encountered this with spinal subdural hemorrhage, subarachnoid hemorrhage, explosive migraine, trauma with multiple fractures, and intense pelvic, renal, or abdominal pain. Disinhibition of Emotional Expression


Neurology_Adams

Neurology_Adams. It is a commonplace clinical experience that cerebral diseases of many types, seemingly without respect to location, weaken the mechanism of control of emotional expression. A patient whose cerebrum has been damaged, for example, by a series of vascular lesions, may involuntarily cry in public upon meeting an old friend or hearing the national anthem, or display uncontrollable laughter in response to a mildly amusing remark. There may also be easy vacillation from one state to another, an emotional lability. In this type of emotional disturbance, the response, while excessive, does not quite reach the degree of forced emotionality described as pseudobulbar (see below); furthermore, it is appropriate to the stimulus and the affect is congruent with the visceral and motor components of the expression. Lesions of the frontal lobes are the most common identifiable cause of this state. However, emotional lability is also a frequent accompaniment of diffuse cerebral conditions, such as


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Neurology_Adams. the expression. Lesions of the frontal lobes are the most common identifiable cause of this state. However, emotional lability is also a frequent accompaniment of diffuse cerebral conditions, such as Alzheimer disease. Also under this heading might be included the shallow facetiousness (witzelsucht), tearfulness and facile mood, and behavioral disinhibition of the patient with frontal lobe disease.


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Neurology_Adams. This form of disordered emotional expression, characterized by outbursts of involuntary, uncontrollable, and stereotyped laughing or crying, has been recognized since the late nineteenth century. Numerous references to these conditions (the Zwangslachen and Zwangsweinen noted by German neurologists and the rire et pleurer spasmodiques described by the French) can be found in the writings of Oppenheim, von Monakow, and Wilson (see Wilson for historical references). The term emotional incontinence applied by psychiatrists may be accurate but is a bit pejorative. Forced laughing or crying always has a pathologic basis in the brain, either diffuse or focal. There have been reports of spasmodic laughter following unilateral striatocapsular infarction (Ceccaldi et al) and occasional cases after unilateral pontine infarction or arteriovenous malformation, but these were not verified. It may occur with degenerative and vascular diseases of the brain (Table 24-2), but often the diffuse nature


Neurology_Adams

Neurology_Adams. unilateral pontine infarction or arteriovenous malformation, but these were not verified. It may occur with degenerative and vascular diseases of the brain (Table 24-2), but often the diffuse nature of the underlying disease precludes useful topographic analysis and clinicoanatomic correlation.


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Neurology_Adams. The best examples of pathologic laughing and crying are provided by multiple lacunar vascular disease and by amyotrophic lateral sclerosis, multiple sclerosis, and progressive supranuclear palsy, in each case the lesions being distributed bilaterally and generally involving the corticobulbar motor system. The condition also occurs with the more widespread lesions of hypoxic–ischemic encephalopathy, Binswanger ischemic encephalopathy, cerebral trauma, infiltrative gliomas of the frontal lobe or pons, and infectious and noninfectious encephalitides. Another important presentation is the Foix-Marie-Chavany syndrome, in which there is a sudden hemiplegia from a stroke that is engrafted upon a preexistent (and often clinically silent) lesion in the opposite hemisphere; this sets the stage for the pathologic displays of emotionality. In this state, there is sometimes a striking incongruity between the loss of voluntary movements of muscles innervated by the motor nuclei of the lower pons


Neurology_Adams

Neurology_Adams. the pathologic displays of emotionality. In this state, there is sometimes a striking incongruity between the loss of voluntary movements of muscles innervated by the motor nuclei of the lower pons and medulla (inability to forcefully close the eyes, elevate and retract the corners of the mouth, open and close the mouth, chew, swallow, phonate, articulate, and move the tongue) and the preservation of reflexive movements of the same muscles in yawning, coughing, throat clearing, and spasmodic laughing or crying. This is the motor syndrome of pseudobulbar palsy for which reason the term pseudobulbar affective state has been applied to the emotional disorder.


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Neurology_Adams. On the slightest provocation and sometimes for no apparent reason, the patient is thrown into a stereotyped spasm of laughter that may last for moments or up to many minutes, to the point of exhaustion. Or, far more often, the opposite happens—the mere mention of the patient’s family or the sight of the doctor provokes an uncontrollable spasm of crying that resembles a caricature of crying itself. The severity of the emotional display and the ease with which it is provoked does not correspond with the severity of the pseudobulbar motor paralysis or with an exaggeration of the facial and masseter (“jaw jerk”) tendon reflexes. In some patients with forced crying and laughing, there is little or no detectable weakness of facial and bulbar muscles; in others, forced laughing and crying are lacking despite a severe upper motor neuron weakness of these muscles. In certain diseases, such as progressive supranuclear palsy and central pontine myelinolysis, of which pseudobulbar palsy is a


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Neurology_Adams. lacking despite a severe upper motor neuron weakness of these muscles. In certain diseases, such as progressive supranuclear palsy and central pontine myelinolysis, of which pseudobulbar palsy is a frequent manifestation, forced laughing and crying are less dramatic or absent. Consequently, the pathologic emotional state cannot be equated with pseudobulbar palsy even though the two frequently occur together.


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Neurology_Adams. Is this state, whether one of involuntary laughing or of crying, activated by an appropriate stimulus? In other words, does the emotional response accurately reflect the patient’s affect or feeling? There are no simple answers to these questions. One problem is to determine what constitutes an appropriate stimulus for the patient in question. Oppenheim and others stated that these patients need not feel sad when crying or mirthful when laughing, and at least in some cases, this is in agreement with our experience. Other patients, however, do report a general congruence of affect and emotional experience (mood), but the amplitude of the response is utterly excessive.


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Neurology_Adams. Noteworthy are the stereotyped nature of the initial motor facial response, and the relatively undifferentiated nature of the emotional reaction. As Poeck emphasized, laughter or crying may merge—reflective of the closeness of these two forms of emotional expression, a phenomenon that is particularly evident in young children. More impressive to us is the fact that in some patients with pseudobulbar palsy, laughing and crying are the only available forms of emotional expression; intermediate phenomena, such as smiling and frowning, are lost. In other patients with pseudobulbar palsy, there are lesser degrees of forced laughing and crying, perhaps bridging the gap between this phenomenon, and the type of emotional lability discussed earlier.


Neurology_Adams

Neurology_Adams. Two major supranuclear pathways control the ponto-medullary mechanisms of the movements required in laughing and crying. One is the familiar corticobulbar pathway that runs from the motor cortex through the posterior limb of the internal capsule and controls volitional movements; the other is a more anterior pathway that descends just rostral to the genu of the internal capsule, and contains facilitatory and inhibitory fibers. Unilateral involvement of the anterior pathway leaves the opposite side of the face under volitional control but paretic during laughing, smiling, and crying (emotional facial paralysis); the opposite is observed with a unilateral lesion of the posterior pathway. Wilson pointed out that both forced laughing and crying involve the same facial, vocal, and respiratory musculature and have similar visceral accompaniments (dilatation of facial vessels, secretion of tears, etc.). Wilson’s argument, based to some extent on clinicopathologic evidence, was that in


Neurology_Adams

Neurology_Adams. musculature and have similar visceral accompaniments (dilatation of facial vessels, secretion of tears, etc.). Wilson’s argument, based to some extent on clinicopathologic evidence, was that in pseudobulbar palsy resulted from interruption of the descending motor pathways that naturally inhibit the expression of the emotions. Of interest is the beneficial effect on distressing pseudobulbar displays of drugs such as imipramine and fluoxetine (Schiffer et al). Dextromethorphan combined with quinidine in the pseudobulbar state, as shown in a study of patients with amyotrophic lateral sclerosis (Brooks et al). In a few personally observed cases, both the emotional lability and pathologic laughter and crying were partially suppressed by these drugs; but in most others, however, there was no effect.


Neurology_Adams

Neurology_Adams. A rare but probably related syndrome is le fou rire prodromique (prodromal laughing madness) of Féré, in which uncontrollable laughter begins abruptly and is followed after several hours by hemiplegia. We have seen two such cases in which basilar artery occlusion evolved after a brief bout of such forced laughter. There are dramatic examples, cited by Martin, where patients laughed themselves to death. Again, the pathologic anatomy is unsettled. Protracted laughing and (less often) crying may occur rarely as a manifestation of epileptic seizures, usually originating in the temporal lobe. Ictal laughter is usually without affect (mirthless laughter); Daly and Mulder referred to these as “gelastic” seizures. The concurrence of gelastic seizures and precocious puberty is characteristic of an underlying hamartoma (or other lesion) of the hypothalamus (see Chaps. 26 and 27). Aggressiveness, Anger, Rage, and Violence


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Neurology_Adams. Aggressiveness is an integral part of social behavior. The emergence of this trait early in life enables the individual to secure a position in the family and later in an ever- widening social circle. Individual differences are noteworthy. Timidity, for example, is a persistent trait recognized in infancy (Kagan). Males tend to be more aggressive than females. The degree to which excessively aggressive behavior is tolerated varies in different cultures. In most civilized societies, tantrums, rage reactions, and outbursts of violence and destructiveness are not condoned and one of the principal objectives of child rearing and education is the suppression and sublimation of such behavior. The rate at which this developmental process proceeds varies from one individual to another. In some males and the cognitively impaired, it is not complete until 25 to 30 years of age; the deviant behavior results in sociopathy (see Chap. 28). Undoubtedly, from our own casual and others’ more


Neurology_Adams

Neurology_Adams. some males and the cognitively impaired, it is not complete until 25 to 30 years of age; the deviant behavior results in sociopathy (see Chap. 28). Undoubtedly, from our own casual and others’ more systematic observations, aggressiveness is an inherited tendency.


Neurology_Adams

Neurology_Adams. Seemingly groundless outbreaks of unbridled and disorganized rage may rarely represent the initial or main manifestation of disease. A patient with these symptoms may, with little provocation, change from a reasonable state to one of the wildest rage, with a blindly furious impulse to violence and destruction. In such states, the patient appears out of contact with reality and is impervious to all argument or pleading. There are examples also of a dissociation of affect and behavior in which the patient may spit, cry out, attack, or bite without seeming to be angry. This is especially true of the developmentally delayed.


Neurology_Adams

Neurology_Adams. All the human and animal data point to an origin of aggressiveness, anger, and rage in the temporal lobes and particularly in the amygdala. In humans, stimulation of the medial amygdaloid nuclei, through depth electrodes, evokes a display of anger, whereas stimulation of the lateral nuclei does not; destruction of the amygdaloid complex bilaterally reportedly reduces aggressiveness (Kiloh; Narabayashi et al). In an unintended experiment in a patient with Parkinson disease, Bejjani and colleagues found that aggressive behavior could be induced by stimulation of the posteromedial hypothalamus. As with the comparable elicitation of depression from an aberrant electrode in the substantia nigra that was reported by the same group, it is not clear whether the effect was because of changes induced in adjacent neuronal pathways or if the physiologic response was the result of excitatory or inhibitory neuronal activity in the hypothalamus.


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Neurology_Adams. Sex hormones influence the activity of these temporal lobe circuits; testosterone promotes aggressiveness and estradiol suppresses it, suggesting an explanation for sex differences in the disposition to anger. Surprisingly, propranolol and lithium have benefited such patients more than haloperidol, other neuroleptics, or sedatives.


Neurology_Adams

Neurology_Adams. Animal studies have corroborated observations in humans. As mentioned in the introductory section, bilateral removal of the amygdaloid nuclei in the macaque greatly reduces the expressions of both fear and anger. Electrical stimulation in or near the amygdala of the unanesthetized cat yields a variety of motor and vegetative responses. One of these has been referred to as the fear or flight response, in which the animal appears frightened, and runs away and hides; another is the anger or defense reaction, characterized by growling, hissing, and piloerection. However, structures other than the amygdaloid nuclei are also involved in these reactions. Lesions in the ventromedial nuclei of the hypothalamus (which receive abundant input from the amygdaloid nuclei) have been shown to cause aggressive behavior, and bilateral ablation of Brodmann area 24 (rostral cingulate gyrus) has produced the opposite state—tameness and reduced aggressiveness—at least in some species.


Neurology_Adams

Neurology_Adams. Rage reactions of the intensity described above may be encountered in the following medical settings: (1) rarely as part of a temporal lobe seizure; (2) as an episodic reaction without recognizable seizures or other neurologic abnormality, as in certain sociopaths; (3) in the course of a recognizable acute neurologic disease; and (4) with the clouding of consciousness that accompanies a metabolic or toxic encephalopathy; (5) as a reaction to designed psychogenic drugs (dragonfly, K4, and others). Rage in Temporal Lobe Seizures (See Also “Focal Seizures” in Chap. 15)


Neurology_Adams

Neurology_Adams. Rage in Temporal Lobe Seizures (See Also “Focal Seizures” in Chap. 15) According to Gastaut and colleagues, a directed attack of uncontrollable rage may occur either as part of a seizure or as an interictal phenomenon. Some patients describe a gradual heightening of excitability for 2 to 3 days, either before or after a seizure, before bursting into a rage. While such attacks have been observed, they are rare. Geschwind emphasized that a profound deepening of all of the patient’s emotional experiences is a frequent occurrence in temporal lobe epilepsy. A lesser degree of aggressive behavior as part of a temporal lobe seizure is not uncommon; it is usually part of the ictal or postictal behavioral automatism and tends to be brief in duration and poorly directed. Usually, the lesion is in the temporal lobe of the dominant hemisphere.


Neurology_Adams

Neurology_Adams. In some instances of this type, the patient has a life-long history of being hot-headed, intolerant of frustration, and impulsive, exhibiting behavior that would be classified as sociopathic (Chap. 47). There are others, however, who, at certain periods of life, usually adolescence or early adulthood, begin to have episodes of wild, aggressive behavior. Alcohol or some other drug may trigger episodes. One suspects epilepsy, but there is no history of a recognizable seizure or interruption of consciousness, typical of focal temporal lobe epilepsy. We have been consulted from time to time on patients who report a proclivity to anger, cursing, and momentary unreasonableness in behavior that is acquired in adulthood. Each of these patients described a first-order relative with the same traits. Most such individuals are remorseful afterward and otherwise function at a high cognitive level. In a very few such cases, in which aggression has resulted in serious injury to others (or homicide),


Neurology_Adams

Neurology_Adams. Most such individuals are remorseful afterward and otherwise function at a high cognitive level. In a very few such cases, in which aggression has resulted in serious injury to others (or homicide), depth electrodes placed in the amygdaloid nuclear complex have recorded what could be construed as seizure discharges. Attacks of excitement and various autonomic accompaniments have been aroused by stimulation of the same region, and the abnormal behavior has in some instances been relieved by ablation of the abnormally discharging structures. Mark and Ervin have documented a number of examples of this “dyscontrol syndrome,” but we are doubtful that they are truly epileptic.


Neurology_Adams

Neurology_Adams. Violent Behavior in Acute or Chronic Neurologic Disease One encounters patients in whom intense excitement, rage, and aggressiveness begin abruptly in association with an acute neurologic disease or in a phase of partial recovery. In most cases, the medial and anterior temporal lobes have been damaged. Serious head injury with protracted coma may be followed by personality changes consisting of aggressive outbursts, suspiciousness, poor judgment, indifference to the feelings of family, and variable degrees of cognitive impairment. Hemorrhagic leukoencephalitis, lobar hemorrhage, infarction, traumatic contusion, and herpes simplex encephalitis affecting the medial and orbital portions of the frontal lobes and anterior portions of the temporal lobes may have the same effect (Fig. 24-3). Fisher noted the occurrence of intense rage reactions as an aftermath of a dominant temporal lobe lesion that had caused a Wernicke type of aphasia. Cases of this type have also been reported with


Neurology_Adams

Neurology_Adams. Fisher noted the occurrence of intense rage reactions as an aftermath of a dominant temporal lobe lesion that had caused a Wernicke type of aphasia. Cases of this type have also been reported with ruptured aneurysm of the circle of Willis and extension of a pituitary adenoma; references to these reports can be found in the articles of Poeck (1969) and of Pillieri.


Neurology_Adams

Neurology_Adams. Also of interest are the effects of slow-growing tumors of the temporal lobe. Malamud described outbursts of rage in association with temporal lobe gliomas. Other of his patients harboring such tumors had no rage reactions but exhibited a clinical picture superficially resembling schizophrenia. It is noteworthy that 8 of the 9 patients with temporal lobe glioma described by Malamud also had seizures. The anteromedial part of the left temporal lobe has been the site of the tumor in the majority of cases. Falconer and Serafetinides have described patients with rage reactions in whom there was a hamartoma or sclerotic focus in this region. A special form of violent outburst can occur during REM sleep. REM sleep behavior disorder, which may be associated with certain degenerative brain diseases, is detailed in Chap. 18, on Sleep.


Neurology_Adams

Neurology_Adams. A special form of violent outburst can occur during REM sleep. REM sleep behavior disorder, which may be associated with certain degenerative brain diseases, is detailed in Chap. 18, on Sleep. Here the patient is not in a clear-headed state and rage or aggression is superimposed on an encephalopathy of toxic or metabolic origin. The most dramatic examples in our experience have been during hypoglycemic reactions. When the patient is left alone, the aggressive behavior is undirected and disorganized, but anyone in the immediate neighborhood may be struck by the agitated individual. Attempts at physical restraint provoke an even more violent reaction.


Neurology_Adams

Neurology_Adams. A similar state may occur with phencyclidine and cocaine intoxication, and with other hallucinogens, accompanied by agitation and, usually, by hallucinosis. Perhaps the most berserk episodes we have encountered have been after ingestion of large amounts of designed street drugs such as the hallucinogen dragonfly and with cannabis derivatives such as K4 (Spice). These furious behaviors may last for hours or days and are resistant to large doses of haloperidol and benzodiazepines. We have found α2-agonists such as dexmedetomidine to be effective. Outbursts of rage and violence with alcohol intoxication are somewhat different in nature: some instances represent a rare paradoxical or idiosyncratic reaction to alcohol (see Chap. 42); more typically alcohol appears to disinhibit an underlying sociopathic behavior pattern.


Neurology_Adams

Neurology_Adams. Animals normally indulge in and display highly energized, exploratory activity of their environment. Some of this activity is motivated by the drive for sexual satisfaction and procurement of food; in humans, it may be a matter of curiosity. These activities are governed by “expectancy circuits,” involving nuclear groups in mesolimbic and mesocortical dopaminergic circuits connected with the diencephalon and mesencephalon via the medial forebrain bundles; lesions that interrupt these connections are said to abolish the expectancy reactions. Positron emission tomography (PET) studies correlate functional difficulty in the initiation of movements with impaired activation of the anterior cingulum, putamen, prefrontal cortex, and supplementary motor area (Playford et al).


Neurology_Adams

Neurology_Adams. A quantitative reduction in all activity is probably the most frequent of all psychobehavioral alterations in patients with cerebral disease, particularly in those with involvement of the anterior parts of the frontal lobes. There are fewer thoughts, fewer words uttered, and fewer movements per unit of time. That this is not a purely motor phenomenon is disclosed in conversation with the patient, who seems to perceive and think more slowly, to make fewer associations with a given idea, to initiate speech less frequently, and to exhibit less inquisitiveness and interest. This reduction in psychomotor activity is recognized as a striking personality change by the family.


Neurology_Adams

Neurology_Adams. Depending on how this state is viewed, it may be interpreted as a heightened threshold to stimulation, inattentiveness or inability to maintain an attentive attitude, impaired thinking, apathy, or lack of impulse (abulia). In a sense, all are correct, for each represents a different aspect of the reduced mental activity. Impairment of learning and memory functions may be added. Typically, the patient is attentive, wide awake, and looks around. If recovery occurs, memory is retained for all that happened. In this respect, abulia differs from stupor and hypersomnolence.


Neurology_Adams

Neurology_Adams. Patients who exhibit abulia are difficult to test because they respond slowly or not at all to every type of test. Yet on rare occasions, when intensely stimulated, they may speak and act normally. It is as though some energizing mechanism (possibly striatocortical), different from the reticular activating system of the upper brainstem, were impaired. Often, patients with severe abulia perform better with automatic or overlearned behaviors, such as talking on the telephone. Quite apart from this abulic syndrome, which has already been discussed in relation to coma and to extensive lesions of the frontal lobes (Chaps. 16 and 21), there are lesser degrees in which a lively, sometimes volatile person has been rendered placid (hypobulic) by a disease of the nervous system.


Neurology_Adams

Neurology_Adams. Clinicoanatomic correlates are inexact, but bilateral lesions deep in the septal region (basal frontal, as sometimes occur with bleeding from an anterior communicating aneurysm) have resulted in the most striking lack of impulse, spontaneity, and conation (drive) (Fig. 24-3). Most often, the frontal lobe damage is bilateral, but sometimes on the left only, as discussed in Chap. 21. Diseases as diverse as hydrocephalus, glioma, strokes, trauma, and encephalitis may be causative. Formerly, changes of this type were observed following bilateral prefrontal leukotomy. Barris and Schuman, and many others have documented states of extreme placidity with lesions of the anterior cingulate gyri. Unlike the case in depression, the mood is neutral; the patient is apathetic rather than depressed.


Neurology_Adams

Neurology_Adams. The subdued emotional behavior described earlier differs from that observed in the Klüver-Bucy syndrome, which results from total bilateral temporal lobectomy in adult rhesus monkeys (see also Chap. 21). While these animals were made rather placid and lacked the ability to recognize objects visually (they could not distinguish edible from inedible objects), they had a striking tendency to examine everything orally, were unusually alert and responsive to visual stimuli (they touched or mouthed every object within their visual fields), became hypersexual, and increased their food intake. This complete constellation of behavioral changes has occurred only infrequently in human beings, for example, after removal of the temporal lobes (Marlowe et al; Terzian and Dalle). Pillieri and Poeck (1969) have collected cases that have come closest to reproducing the syndrome (Fig. 24-3). Many human examples have occurred in conjunction with diffuse diseases (Alzheimer and Pick cerebral atrophies,


Neurology_Adams

Neurology_Adams. have collected cases that have come closest to reproducing the syndrome (Fig. 24-3). Many human examples have occurred in conjunction with diffuse diseases (Alzheimer and Pick cerebral atrophies, meningoencephalitis because of toxoplasmosis, herpes simplex, and AIDS) and hence are of limited value for anatomic analysis. With bitemporal surgical ablations, placidity and enhanced oral behavior were the most frequent consequences; altered sexual behavior and visual agnosia were less frequent. In all patients who showed placidity and an amnesic state, the hippocampi and medial parts of the temporal lobe had been destroyed, but not the amygdaloid nuclei.


Neurology_Adams

Neurology_Adams. Reduced emotionality in humans, albeit one that is very restricted in scope, is associated with acute lesions in the right, or nondominant, parietal lobe. The patient may not only be indifferent to the accompanying paralysis but, as Bear points out, also appear unconcerned about other diseases as well as personal and family problems, be less able to interpret the emotional facial expressions of others, and be inattentive in general. There may be a lack of emotional inflection to speech (aprosodia) and an inability to interpret the emotional state of other individuals, as discussed in Chap. 22. Dimond and coworkers interpret this to mean that the right hemisphere is more involved in affective-emotional experience than the left, which is committed to language. Observations derived from the study of split-brain patients and from selective anesthetization of the cerebral hemispheres by intracarotid injection of amobarbital (Wada test) lend some support to this probably oversimplified


Neurology_Adams

Neurology_Adams. the study of split-brain patients and from selective anesthetization of the cerebral hemispheres by intracarotid injection of amobarbital (Wada test) lend some support to this probably oversimplified view. Rarely, lesions of the left (dominant) hemisphere appear to induce the opposite effect, a frenzied excitement lasting for days or weeks.


Neurology_Adams

Neurology_Adams. The normal pattern of sexual behavior in both males and females may be altered by cerebral disease quite apart from impairment due to physical disability or to diseases that affect segmental reflex mechanisms (see Chap. 26). Hypersexuality in men or women is a rare but well-documented complication of neurologic disease. It has long been believed that lesions of the orbital frontal lobes may remove moral-ethical restraints and lead to indiscriminate sexual behavior, and that superior frontal lesions may be associated with a general loss of initiative that reduces all, including sexual, impulsivity. In rare cases, extreme hypersexuality marks the onset of encephalitis or develops gradually with tumors of the temporal region. Possibly the limbic parts of the brain are disinhibited, the ones from which MacLean and Ploog could evoke penile erection and orgasm by electrical stimulation (medial dorsal thalamus, medial forebrain bundle, and septal preoptic region).


Neurology_Adams

Neurology_Adams. In humans, Heath has observed that stimulation of the ventroseptal area (through depth electrodes) evokes feelings of pleasure and lust. Also, Gorman and Cummings have described two patients who became sexually disinhibited after a shunt catheter had perforated the dorsal septal region. This is in keeping with the experience of Heath and Fitzjarrell, who found that infusion of acetylcholine into the septal region (as an experimental treatment for Parkinson disease) produced euphoria and orgasm, and with Heath’s recordings from the septum of patients during sexual intercourse, showing greatly increased activity with spikes and slow waves. Although it remains unproven, perhaps these are examples of a true overdrive of libido, as contrasted with simple disinhibition of sexual behavior.


Neurology_Adams

Neurology_Adams. In clinical practice, the most common cause of disinhibited sexual behavior, next to the aftermaths of head injury and cerebral hemorrhage, is the use of dopaminergic drugs in Parkinson disease. An intriguing effect of the administration of l-dopa in a few patients has been excessive or perverse sexual behavior, as in the cases described by Quinn and colleagues. Usually there are other manifestations of manic behavior. Primary mania may do the same. Hyposexuality, meaning loss of libido, is a typical accompaniment of depressive illness. However, certain medications, notably antihypertensive, antiepileptic, serotonergic antidepressant, and neuroleptic drugs may be responsible in individual patients. A variety of cerebral diseases may also have this effect, in parallel with a loss of interest and drive in a number of spheres.


Neurology_Adams

Neurology_Adams. Lesions that involve the tuberoinfundibular region of the hypothalamus are known to cause specific disturbances in sexual function. If such lesions are acquired early in life, pubertal changes may be prevented from occurring. Conversely, with hamartomas of the hypothalamus, as in von Recklinghausen neurofibromatosis and tuberous sclerosis, sexual precocity may occur. Autonomic neuropathies and lesions involving the sacral parts of the parasympathetic system, the most common being prostatectomy, may abolish normal sexual performance but do not alter libido or orgasm.


Neurology_Adams

Neurology_Adams. Blumer and Walker have reviewed the literature on the association of epilepsy and abnormal sexual behavior. They note that sexual arousal, as an ictal phenomenon, is apt to occur in relation to temporal lobe seizures, particularly when the discharging focus is in the mediotemporal region. However, these authors also emphasize the high incidence of global hyposexuality in patients with temporal lobe epilepsy. Temporal lobectomy in such patients has sometimes been followed by a period of hypersexuality. Acute Fear, Anxiety, Elation, and Euphoria


Neurology_Adams

Neurology_Adams. Acute Fear, Anxiety, Elation, and Euphoria The phenomena of acute fear and anxiety occurring as a prelude to or part of a seizure is familiar to every neurologist. Williams’s study, already mentioned, is of particular interest; from a series of about 2,000 epileptics, he was able to cull 100 patients in whom an emotional experience was part of the seizure. Of the latter, 61 experienced feelings of fear and anxiety, and 21 experienced depression. Daly has made similar observations. These clinical data call to mind the effects that had been noted by Penfield and Jasper when they stimulated the upper, anterior, and inferior parts of the temporal lobe and cingulate gyrus during surgical procedures; frequently, the patient described feelings of strangeness, uneasiness, and fear. In most instances, consciousness was variably impaired at the same time, and some patients had hallucinatory experiences as well.


Neurology_Adams

Neurology_Adams. In these cortical stimulations, neuronal circuits subserving fear are coextensive with those of anger; both are thought to lie in the medial part of the temporal lobe and amygdala, as discussed earlier. Both in animals and in humans, electrical stimulation in this region can arouse each emotion, but the circuitry subserving fear appears to be located lateral to that of anger and rage. Destruction of the central part of the amygdaloid nuclear complex abolishes fear reactions. These nuclei are connected to the lateral hypothalamus and midbrain tegmentum, regions from which Monroe and Heath, as well as Nashold and associates, have been able to evoke feelings of fear and anxiety by electrical stimulation.


Neurology_Adams

Neurology_Adams. Depression is less frequent as an ictal emotion, although it occurs often enough as an interictal phenomenon (Benson et al). Of interest is the observation that lesions of the dominant hemisphere are more likely than nondominant ones to be attended by an immediate pervasive depression of mood, disproportionate to the degree of severity of physical disability (Robinson et al). It has been challenging, however, to identify the specific neural substrates that are linked with post-stroke depression, and it must also be considered that in many cases depression is a reaction to disability akin to that which follows myocardial infarction. Odd mixtures of depression and anxiety are often associated with temporal lobe tumors and less often with tumors of the hypothalamus and third ventricle (see review by Alpers), and they sometimes occur at the onset of a degenerative disease, such as multiple system atrophy.


Neurology_Adams

Neurology_Adams. Elation and euphoria are less well documented as limbic phenomena, nor has this elevation in mood in some patients with multiple sclerosis ever been adequately explained. Feelings of pleasure and satisfaction as well as “stirring sensations” are unusual, but well-described emotional experiences in patients with temporal lobe seizures. In states of hypomania and mania, every experience may be colored by feelings of delight and pleasure, and a sense of power, and the patient may remember these experiences after he has recovered. Differential Diagnosis of Perturbations in Emotion and Affect


Neurology_Adams

Neurology_Adams. Differential Diagnosis of Perturbations in Emotion and Affect Aside from clinical observation, there are no reliable means of evaluating or quantifying the emotional disorders described earlier. Although neurologic medicine has done little more than describe and classify some of the clinical states dominated by emotional derangements, knowledge of this type is nonetheless of both theoretical and practical importance. In theory, it prepares one for the next step, of passing from a superficial to a deeper order of inquiry, where questions of pathogenesis and etiology can be broached. Practically, it provides certain clues that are useful in differential diagnosis. A number of particular neurologic possibilities must always be considered when one is confronted with one of the following clinical states.


Neurology_Adams

Neurology_Adams. As indicated earlier, one may confidently assume that the syndrome of forced or spasmodic laughing and crying signifies cerebral disease, and, more specifically, bilateral disease of the corticobulbar tracts (Table 24-2). Usually the motor and reflex changes of spastic bulbar (pseudobulbar) palsy (described in the discussion of “Spastic [Pseudobulbar] Dysarthria” in Chap. 22) are associated usually, but not always, with heightened facial and mandibular reflexes (“jaw jerk”), and often corticospinal tract signs in the limbs as well. Extreme emotional lability also indicates bilateral cerebral disease, although only the signs of unilateral disease may be apparent clinically. The most common pathologic bases for these clinical states are lacunar infarction or other cerebrovascular lesions, diffuse hypoxic-hypotensive encephalopathy, amyotrophic lateral sclerosis, and multiple sclerosis, as already indicated; but in a number of less-common processes, such as progressive supranuclear palsy


Neurology_Adams

Neurology_Adams. hypoxic-hypotensive encephalopathy, amyotrophic lateral sclerosis, and multiple sclerosis, as already indicated; but in a number of less-common processes, such as progressive supranuclear palsy and Wilson disease, it may be quite a prominent feature. Abrupt onset, of course, points to vascular disease.


Neurology_Adams

Neurology_Adams. These may be the earliest and most important signs of cerebral disease. Clinically, placidity and apathy must be distinguished from the akinesia or bradykinesia of Parkinson disease and the reduced mental activity of depressive illness. Here, Alzheimer disease, normal-pressure hydrocephalus, and frontal-corpus callosum tumors are the most common pathologic states underlying apathy and placidity, but these disturbances may complicate a variety of other frontal and temporal lesions, such as those occurring with demyelinating disease or as an aftermath of ruptured anterior communicating aneurysm. Outbursts of Rage and Violence


Neurology_Adams

Neurology_Adams. Outbursts of Rage and Violence Most often such an outburst is but another episode in a lifelong sequence of sociopathic behaviors (see Chap. 47). More significance attaches to its abrupt appearance as a sudden departure from an individual’s normal personality. If an outburst of rage accompanies a seizure, the rage should be viewed as the consequence of the disruptive effect of seizure activity on temporal lobe function; however, as indicated earlier, an outburst of uncontrolled rage and violence is only rarely a manifestation of temporal lobe epilepsy. Lesser degrees of poorly directed combative behavior as part of ictal or postictal automatism are more common. Rarely, rage and aggressivity are expressive of an acute neurologic disease that involves the mediotemporal and orbitofrontal regions, such as a glioma. We have several times observed such states in the course of a dementing disease and in a stable individual as a transient expression of an obscure encephalopathy.


Neurology_Adams

Neurology_Adams. Rage reactions with continuous violent activity must be distinguished from mania, in which there is flight of ideation to the point of incoherence, euphoric or irritable mood, and incessant psychomotor activity; from organic drivenness, in which continuous motor activity, accompanied by no clear ideation occurs, usually in a child, as an aftermath of encephalitis; and from extreme instances of akathisia, where incessant restless movements and pacing may occur in conjunction with extrapyramidal symptoms.


Neurology_Adams

Neurology_Adams. Here the central problem must be clarified by determining whether the patient is delirious (clouding of consciousness, psychomotor overactivity, and hallucinations), deluded (schizophrenia), manic (overactive, flight of ideas), or experiencing an isolated panic attack (palpitation, trembling, feeling of suffocation). Rarely does panic prove to be an expression of temporal lobe epilepsy. In an adult without a characterologic trait of anxiety, an acute panic attack may signify the onset of a depressive illness or schizophrenia.


Neurology_Adams

Neurology_Adams. Although these symptoms are usually caused by a psychosis (schizophrenia or bipolar disease), one should consider a tumor, immune or paraneoplastic encephalitis, or other lesion of the temporal lobe, particularly when accompanied by temporal lobe seizures, aphasic symptoms, rotatory vertigo (rare), and quadrantic visual field defects. Such states have also been described in hypothalamic disease, suggested by somnolence, diabetes insipidus, visual field defects, and in hydrocephalus (see Chap. 27). Alpers BJ: Personality and emotional disorders associated with hypothalamic lesions. Res Publ Assoc Nerv Ment Dis 20:725, 1939. Baleydier C, Mauguiere F: The duality of the cingulate gyrus in monkey. Brain 103:525, 1980. Ballantine HT, Cassidy WL, Flanagan NB, et al: Stereotaxic anterior cingulotomy for neuropsychiatric illness and chronic pain. J Neurosurg 26:488, 1967.


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Neurology_Adams. Ballantine HT, Cassidy WL, Flanagan NB, et al: Stereotaxic anterior cingulotomy for neuropsychiatric illness and chronic pain. J Neurosurg 26:488, 1967. Bard P: A diencephalic mechanism for the expression of rage with special reference to the sympathetic nervous system. Am J Physiol 84:490, 1928. Bard P, Mountcastle VB: Some forebrain mechanisms involved in the expression of rage with special reference to suppression of angry behavior. Assoc Res Nerv Ment Dis Proc 27:362, 1947. Barris RW, Schuman HR: Bilateral anterior cingulate gyrus lesions: Syndrome of the anterior cingulate gyri. Neurology 3:44, 1953. Bear DM: Hemispheric specialization and the neurology of emotion. Arch Neurol 40:195, 1983. Bejjani BP, Houeto JL, Hariz M, et al: Aggressive behavior induced by intraoperative stimulation in the triangle of Sano. Neurology 59:1425, 2002. Benson DF, Mendez MF, Engel J, et al: Affective symptomatology in epilepsy. Int J Neurol 19–20:30, 1985–1986.


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Neurology_Adams. Benson DF, Mendez MF, Engel J, et al: Affective symptomatology in epilepsy. Int J Neurol 19–20:30, 1985–1986. Blumer D, Walker AE: The neural basis of sexual behavior. In: Benson F, Blumer D (eds): Psychiatric Aspects of Neurologic Disease. New York, Grune & Stratton, 1975, pp 199–217. Brooks BR, Thisted SH, Appel WG, et al: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: A randomized trial. Neurology 63:1364, 2004. Brown JW: Frontal lobe syndromes. In: Vinken PJ, Bruyn GW, Klawans HL (eds): Handbook of Clinical Neurology. Vol 45. Amsterdam, Elsevier Science, 1984, pp 23–42. Cannon WB: Bodily Changes in Pain, Hunger and Fear, 2nd ed. New York, Appleton, 1929. Ceccaldi M, Poncet M, Milandre L, Rouyer C: Temporary forced laughter after unilateral strokes. Eur Neurol 34:36, 1994. Daly DD: Ictal affect. Am J Psychiatry 115:97, 1958. Daly DD, Mulder DW: Gelastic epilepsy. Neurology 7:189, 1957.


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Neurology_Adams. Daly DD: Ictal affect. Am J Psychiatry 115:97, 1958. Daly DD, Mulder DW: Gelastic epilepsy. Neurology 7:189, 1957. Dimond SJ, Farrington L, Johnson P: Differing emotional responses from right and left hemisphere. Nature 261:690, 1976. Falconer MA, Serafetinides EA: A follow-up study of surgery in temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 26:154, 1963. Féré MC: Le fou rire prodromique. Rev Neurol 11:353, 1903. Fisher CM: Anger associated with dysphasia. Trans Am Neurol Assoc 95:240, 1970. Gastaut H, Morin G, Lefevre N: Etude de comportement des épileptiques psychomoteurs dans l’intervalle de leurs crises. Ann Med Psychol (Paris) 1:1, 1955. Geschwind N: The clinical setting of aggression in temporal lobe epilepsy. In: Field WS, Sweet WH (eds): The Neurobiology of Violence. St. Louis, MO, Warren H Green, 1975. Gorman DG, Cummings JL: Hypersexuality following septal injury. Arch Neurol 49:308, 1992.


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Neurology_Adams. Gorman DG, Cummings JL: Hypersexuality following septal injury. Arch Neurol 49:308, 1992. Heath RG: Pleasure and brain activity in man. J Nerv Ment Dis 154:3, 1972. Heath RG, Fitzjarrell AT: Chemical stimulation to deep forebrain nuclei in parkinsonism and epilepsy. Int J Neurol 18:163, 1984. Kagan J: The Nature of the Child. New York, Basic Books, 1984. Kiloh LG: The treatment of anger and aggression and the modification of sex deviation. In: Smith JS, Kiloh LG (eds): Psychosurgery and Psychiatry. Oxford, UK, Pergamon Press, 1977, pp 37–54. Klüver H, Bucy PC: An analysis of certain effects of bilateral temporal lobectomy in the rhesus monkey with special reference to psychic blindness. J Psychol 5:33, 1938. MacLean PD: Contrasting functions of limbic and neocortical systems of the brain and their relevance to psychophysiological aspects of medicine. Am J Med 25:611, 1958. MacLean PD, Ploog DW: Cerebral representation of penile erection. J Neurophysiol 25:29, 1962.


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Neurology_Adams. MacLean PD, Ploog DW: Cerebral representation of penile erection. J Neurophysiol 25:29, 1962. Malamud N: Psychiatric disorder with intracranial tumors of limbic system. Arch Neurol 17:113, 1967. Mark VH, Ervin FR: Violence and the Brain. New York, Harper & Row, 1970. Marlowe WB, Mancall EL, Thomas JJ: Complete Klüver-Bucy syndrome in man. Cortex 11:53, 1975. Martin JP: Fits of laughter (sham mirth) in organic cerebral disease. Brain 70:453, 1950. Monroe RR, Heath RC: Psychiatric observations on the patient group. In: Heath RC (ed): Studies in Schizophrenia. Cambridge, MA, Harvard University Press, 1983, pp 345–383. Narabayashi H, Nacao Y, Yoshida M, Nagahata M: Stereotaxic amygdalectomy for behavior disorders. Arch Neurol 9:1, 1963. Nashold BS, Wilson WP, Slaughter DE: Sensations evoked by stimulation in the midbrain of man. J Neurosurg 30:14, 1969. Nauta WJH: The central visceromotor system: A general survey. In: Hockman CH (ed): Limbic System Mechanisms and


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Neurology_Adams. Nauta WJH: The central visceromotor system: A general survey. In: Hockman CH (ed): Limbic System Mechanisms and Autonomic Function. Springfield, IL, Charles C Thomas, 1972, pp 21–33. Papez JW: A proposed mechanism of emotion. Arch Neurol Psychiatry 38:725, 1937. Penfield W, Jasper H: Epilepsy and the Functional Anatomy of the Human Brain. Boston, Little, Brown, 1954, pp 413–416. Pillieri G: The Klüver-Bucy syndrome in man. Psychiatr Neurol (Basel) 152:65, 1966. Playford ED, Jenkins LH, Passingham RE, et al: Impaired mesial frontal and putamen activation in Parkinson’s disease: A positron emission tomography study. Ann Neurol 32:151, 1992. Poeck K: Pathological laughter and crying. In: Vinken PJ, Bruyn GW, Klawans HL (eds): Handbook of Clinical Neurology. Vol 45. Amsterdam, North-Holland, 1985, pp 219–225.


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Neurology_Adams. Poeck K: Pathological laughter and crying. In: Vinken PJ, Bruyn GW, Klawans HL (eds): Handbook of Clinical Neurology. Vol 45. Amsterdam, North-Holland, 1985, pp 219–225. Poeck K: Pathophysiology of emotional disorders associated with brain damage. In: Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Vol 3: Disorders of Higher Nervous Activity. Amsterdam, North-Holland, 1969, pp 343–367. Quinn ND, Toone B, Lang AE, et al: Dopa dose-dependent sexual deviation. Br J Psychiatry 142:296, 1983. Robinson RG, Kubos KL, Starr LB, et al: Mood disorders in stroke patients: Importance of location of lesion. Brain 107:81, 1984. Schiffer RB, Herndon RM, Rudick RA: Treatment of pathologic laughing and weeping with amitriptyline. N Engl J Med 312:1480, 1985. Terzian H, Dalle G: Syndrome of Klüver-Bucy reproduced in man by bilateral removal of the temporal lobes. Neurology 5:373, 1955. Williams D: The structure of emotions reflected in epileptic experiences. Brain 79:29, 1956.


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Neurology_Adams. Williams D: The structure of emotions reflected in epileptic experiences. Brain 79:29, 1956. Wilson SAK: Some problems in neurology. II: Pathological laughing and crying. J Neurol Psychopathol 16:299, 1924.


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Neurology_Adams. Wilson SAK: Some problems in neurology. II: Pathological laughing and crying. J Neurol Psychopathol 16:299, 1924. Figure 24-1. Sagittal diagram of the limbic system. A. Surface topography of the limbic system and associated prefrontal cortex. B. Connections of the limbic structures and their relation to the thalamus, hypothalamus, and midbrain tegmentum. The cortical parts of the limbic system, or limbic lobe, are interconnected by a septohypothalamic–mesencephalic bundle ending in the hippocampus, and the fornix, which runs from the hippocampus back to the mammillary bodies, and by tracts from the mammillary bodies to the thalamus and from the thalamus to the cingulate gyrus. The Papez circuit is the internal component of this system. See also Fig. 24-2 and the text. (Reproduced with permission from Kandel ER, Schwartz JH, Jessell TM: Principles of Neural Science, 4th ed. New York, McGraw-Hill, 2000.)


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Neurology_Adams. Figure 24-2. Schematic block diagram of the limbic connections. The internal connections (bold lines) represent the circuit described by Papez. The external connections (thin lines) are more recently described pathways. This figure also shows the connections to the amygdala and prefrontal and association cortices. (Reproduced with permission from Kandel ER, Schwartz JH, Jessell TM: Principles of Neural Science, 4th ed. New York, McGraw-Hill, 2000.) Figure 24-3. A. Localization of lesions that, in humans, can lead to aggressive behavior and placidity. B. Localization of lesions that, in humans, can lead to placidity, release of oral behavior, and hypersexuality. (From Poeck [1969].) Chapter 24 The Limbic Lobes and the Neurology of Emotion Disorders of the Autonomic Nervous System, Respiration, and Swallowing


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Neurology_Adams. Chapter 24 The Limbic Lobes and the Neurology of Emotion Disorders of the Autonomic Nervous System, Respiration, and Swallowing The human internal environment is regulated in large measure by the integrated activity of the autonomic nervous system and endocrine glands. Their visceral and homeostatic functions, essential to life and survival, are involuntary. Why the forces of evolution favored this separation from volition is an interesting question. Claude Bernard expressed this idea in sardonic terms when he wrote, “nature thought it prudent to remove these important phenomena from the caprice of an ignorant will.”


Neurology_Adams

Neurology_Adams. Although only few neurologic diseases exert their effects primarily or exclusively on the autonomic– neuroendocrine axis, there are numerous medical diseases that implicate this system in some way: hypertension, asthma, and certain disorders of cardiac conduction including congestive heart failure, to name some of the important ones. However, many general neurologic diseases involve the autonomic nervous system to a varying extent, giving rise to symptoms such as orthostatic intolerance and syncope, sphincteric dysfunction, pupillary abnormalities, erectile dysfunction, diaphoresis, cardiac dysrhythmias, and disorders of thermoregulation. Finally, in addition to their central role in visceral innervation, autonomic parts of the neuraxis and parts of the endocrine system are engaged in all emotional experience and its display, as discussed in Chap. 24.


Neurology_Adams

Neurology_Adams. Breathing is unusual among nervous system functions. Although continuous throughout life, it is not altogether automatic, being partly under volitional control. Current views of the central and peripheral control of breathing, and the ways in which it is altered by certain diseases are of considerable interest to neurologists, if for no other reason than respiratory failure is common in neurologic conditions such as coma, cervical spinal cord injury, and a large number of acute and chronic neuromuscular diseases. Many of these same comments pertain to the function of swallowing, which is largely automatic and continues at regular intervals even in sleep but is also initiated voluntarily. Furthermore, swallowing fails in ways similar to breathing as a consequence of neurologic diseases.


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Neurology_Adams. The autonomic, endocrine, and respiratory systems, although closely related, give rise to disparate clinical syndromes. This chapter deals more strictly with the autonomic nervous system and the neural mechanisms of respiration and swallowing, and the next chapter, with the hypothalamus and neuroendocrine disorders. The following discussion of anatomy and physiology serves as an introduction to both chapters.


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Neurology_Adams. The most remarkable feature of the autonomic nervous system is that a major part of it is located outside the brain and spinal cord, in proximity to the visceral structures that it innervates. This position alone seems to symbolize its relative independence from the cerebrospinal system. In distinction to the somatic neuromuscular system, where a single motor neuron bridges the gap between the central nervous system (CNS) and the effector organ, in the autonomic nervous system there are always two efferent neurons serving this function, one (preganglionic) arising from its nucleus in the brainstem or spinal cord and the other (postganglionic) arising from specialized nerve cells in peripheral ganglia. Figure 25-1 illustrates this fundamental anatomic feature. Preganglionic neurons are part of CNS, forming a central autonomic network, which consists of reciprocally connected structures located at the cortex, hypothalamus, brainstem, and spine. Postganglionic neurons are divided into


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Neurology_Adams. of CNS, forming a central autonomic network, which consists of reciprocally connected structures located at the cortex, hypothalamus, brainstem, and spine. Postganglionic neurons are divided into sympathetic and parasympathetic.


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Neurology_Adams. The autonomic nervous system, from an anatomic point of view, is divided into two parts: the craniosacral, or parasympathetic, and the thoracolumbar, or sympathetic (Figs. 25-2 and 25-3). Systems differ architecturally in that the ganglion in the sympathetic nervous system is located in a contiguous and interconnected, longitudinal chain (sympathetic chain) paravertebrally, whereas the parasympathetic ganglia are distributed in proximity to the structures they innervate. Moreover, the main neurotransmitter of the postganglionic connection to the end organ is norepinephrine in the case of the sympathetic nerves and acetylcholine for parasympathetic innervation. There are exceptions with regard to the sympathetic innervation of sweat glands (sudomotor), which are cholinergic. The neurotransmitter between the preand postneurons throughout the autonomic nervous system, sympathetic and parasympathetic, is acetylcholine as reiterated further on. These synapses between preand postganglionic


Neurology_Adams

Neurology_Adams. between the preand postneurons throughout the autonomic nervous system, sympathetic and parasympathetic, is acetylcholine as reiterated further on. These synapses between preand postganglionic cholinergic nerves are not blocked by atropine (nicotinic) whereas the postganglionic impulses are blocked by atropine (muscarinic).


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Neurology_Adams. Functionally, the two parts are complementary in maintaining a balance in the tonic activities of many visceral structures and organs. This rigid separation into sympathetic and parasympathetic parts, although useful for purposes of exposition, is physiologically not absolute. From a neurologist’s perspective, the two components are often affected together. Nonetheless, the notion of a balanced sympathetic and parasympathetic autonomic system has stood the test of time and remains a valid concept. The Parasympathetic Nervous System (See Fig. 25-2) There are two divisions of the parasympathetic nervous system: cranial and sacral. The cranial division originates in the visceral nuclei of the midbrain, pons, and medulla. These nuclei include the Edinger-Westphal pupillary nucleus, superior and inferior salivatory nuclei, dorsal motor nucleus of the vagus, and adjacent reticular nuclei.


Neurology_Adams

Neurology_Adams. Axons (preganglionic fibers) of the visceral cranial nuclei course through the oculomotor, facial, glossopharyngeal, and vagus cranial nerves. The preganglionic fibers from the Edinger-Westphal nucleus traverse the oculomotor nerve and synapse in the ciliary ganglion in the orbit; axons of the ciliary ganglion cells innervate the ciliary muscle and pupillary sphincter (see Fig. 13-9).


Neurology_Adams

Neurology_Adams. The preganglionic fibers of the superior salivatory nucleus enter the facial nerve and, at a point near the geniculate ganglion, form the greater superficial petrosal nerve, through which they reach the sphenopalatine ganglion; postganglionic fibers from the cells of this ganglion innervate the lacrimal gland (see also Figs. 25-2 and 44-3). Other fibers originating in the salivatory nuclei are carried in the facial nerve and traverse the tympanic cavity as the chorda tympani to eventually join the submandibular ganglion. Cells of this ganglion innervate the submandibular and sublingual glands. Axons of the inferior salivatory nerve cells enter the glossopharyngeal nerve and reach the otic ganglion through the tympanic plexus and lesser superficial petrosal nerve; cells of the otic ganglion send fibers to the parotid gland.


Neurology_Adams

Neurology_Adams. Preganglionic fibers, derived from the dorsal motor nucleus of the vagus and adjacent visceral nuclei in the lateral reticular formation (mainly the nucleus ambiguus), enter the vagus nerve and terminate in ganglia situated in the walls of many thoracic and abdominal viscera. The ganglionic cells give rise to short postganglionic fibers that activate smooth muscle and glands of the pharynx, esophagus, and gastrointestinal tract (the vagal innervation of the colon is somewhat uncertain but considered to extend up to the descending colon) and of the heart, pancreas, liver, gallbladder, kidneys, and ureter.


Neurology_Adams

Neurology_Adams. The sacral part of the parasympathetic system originates in the lateral horn cells of the second, third, and fourth sacral segments. Axons of these sacral neurons, constituting the preganglionic fibers, traverse the sacral spinal nerve roots of the cauda equina and synapse in ganglia that lie within the walls of the distal colon, bladder, and other pelvic organs. Thus, the sacral autonomic neurons, like the cranial ones, have long preganglionic and short postganglionic fibers, a feature that permits a circumscribed influence upon the target organ.


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Neurology_Adams. In organs containing smooth muscle that is innervated by parasympathetic fibers and therefore not under voluntary control, there is a parallel innervation of adjacent voluntary striated muscle by anterior horn cells. For example, the neurons that activate the external sphincter of the bladder (voluntary muscle) differ from those that supply the smooth muscle of the internal sphincter as discussed further on. In 1900, Onufrowicz (calling himself Onuf) described a discrete group of relatively small cells in the anterior horns of sacral segments 2 to 4. These neurons were originally thought to be autonomic in function, mainly because of their histologic features. There is now evidence that they are somatomotor, innervating the skeletal muscle of the external urethral and anal sphincters (Holstege and Tan). Neurons in sacral cord segments located in a region analogous to the intermediolateral cell column of the sympathetic nervous system (see later), innervate the detrusor and internal


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Neurology_Adams. and Tan). Neurons in sacral cord segments located in a region analogous to the intermediolateral cell column of the sympathetic nervous system (see later), innervate the detrusor and internal sphincter of the bladder wall. In passing, it is worth noting that in motor system disease, in which bladder and bowel functions are usually preserved until late in the disease, the neurons in the Onuf nucleus, in contrast to other somatomotor neurons in the sacral cord, tend not to be involved in the degenerative process (Mannen et al).


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Neurology_Adams. There are elaborate connections between supranuclear centers, mainly in the hypothalamus, to the pupillary sphincters, lacrimal and salivary glands that course the brainstem. With regard to the supranuclear innervation of parasympathetic nuclei in the sacral segments, little is known. There appear to be connections to these neurons from the hypothalamus, locus ceruleus, and pontine micturition centers but their course in the human spinal cord has not been identified with certainty. The Sympathetic Nervous System (See Fig. 25-3)


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Neurology_Adams. The Sympathetic Nervous System (See Fig. 25-3) The preganglionic neurons of the sympathetic division originate in the intermediolateral cell column of the spinal gray matter, from the eighth cervical to the second lumbar segments. Low and Dyck (1977) have estimated that each segment of the cord contains approximately 5,000 lateral horn cells and that there is an attrition of 5 to 7 percent per decade in late adult life. The axons of the nerve fibers originating in the intermediolateral column are of small caliber and are myelinated; when grouped, they form the white communicating rami as shown in Fig. 25-1. These preganglionic fibers synapse with the cell bodies of the postganglionic neurons, which are collected into two large ganglionated chains or cords, one on each side of the vertebral column (paravertebral ganglia), and several single prevertebral ganglia. These constitute the sympathetic ganglia.


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Neurology_Adams. Axons of the sympathetic ganglion cells are also of small caliber but are unmyelinated. Most of the postganglionic fibers pass via gray communicating rami to their adjacent spinal nerves of T5 to L3; they supply blood vessels, sweat glands, and hair follicles, and also form plexuses that supply the heart, bronchi, kidneys, intestines, pancreas, bladder, and sex organs. The postganglionic fibers of the prevertebral ganglia (located in the retroperitoneal posterior abdomen rather than paravertebrally, along the sides of the spinal column) form the hypogastric, splanchnic, and mesenteric plexuses, which innervate the glands, smooth muscle, and blood vessels of the abdominal and pelvic viscera (see Fig. 25-3).


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Neurology_Adams. The sympathetic innervation of the adrenal medulla is unique in that its secretory cells receive preganglionic fibers directly, via the splanchnic nerves. This is an exception to the rule that organs innervated by the autonomic nervous system receive only postganglionic fibers. This special arrangement can be explained by the fact that cells of the adrenal medulla are the morphologic homologues of the postganglionic sympathetic neurons and secrete epinephrine and norepinephrine (the postganglionic transmitters) directly into the bloodstream. In this way, the sympathetic nervous system and the adrenal medulla act in unison to produce diffuse effects, as one would expect from their role in emergency reactions.


Neurology_Adams

Neurology_Adams. There are 3 cervical (superior, middle, and inferior, or stellate), 11 thoracic, and 4 to 6 lumbar sympathetic ganglia. The head receives its sympathetic innervation from the eighth cervical and first two thoracic cord segments, the fibers of which pass through the inferior to the middle and superior cervical ganglia. Postganglionic fibers from cells of the superior cervical ganglion follow the internal and external carotid arteries and innervate the blood vessels and smooth muscle, as well as the sweat, lacrimal, and salivary glands of the head. Included among these postganglionic fibers, issuing mainly from T1, are the pupillodilator fibers and those innervating the Müller muscle of the upper eyelid (it connects the upper tarsus to the undersurface of the levator); there is a separate small inferior tarsus muscle that is also sympathetically innervated. The arm receives its postganglionic innervation from the inferior cervical ganglion and uppermost thoracic ganglia (the two are


Neurology_Adams

Neurology_Adams. small inferior tarsus muscle that is also sympathetically innervated. The arm receives its postganglionic innervation from the inferior cervical ganglion and uppermost thoracic ganglia (the two are fused to form the stellate ganglion). The cardiac plexus and other thoracic sympathetic nerves are derived from the stellate ganglion and the abdominal visceral plexuses, from the fifth to the ninth or tenth thoracic ganglia. The lowermost thoracic ganglia have no abdominal visceral connections; their axons course rostrally and caudally in the sympathetic chain. The upper lumbar ganglia supply the descending colon, pelvic organs, and legs.


Neurology_Adams

Neurology_Adams. The terminals of autonomic nerves and their junctions with smooth muscle and glands have been more difficult to visualize and study than the motor end plates of striated muscle. As the postganglionic axons enter an organ, usually via the vasculature, they ramify into many smaller branches and disperse, without a Schwann cell covering, to innervate the smooth muscle fibers, the glands, and, in largest number, the small arteries, arterioles, and precapillary sphincters (see Burnstock). Some of these terminals penetrate the smooth muscle of the arterioles; others remain in the adventitia. At the ends of the postganglionic fibers and in part along their course there are swellings that lie in close proximity to the sarcolemma or gland cell membrane; often the muscle fiber is grooved to accommodate these swellings. The axonal swellings contain synaptic vesicles, some clear and others with a dense granular core. The clear vesicles contain acetylcholine and those with a dense core contain


Neurology_Adams

Neurology_Adams. these swellings. The axonal swellings contain synaptic vesicles, some clear and others with a dense granular core. The clear vesicles contain acetylcholine and those with a dense core contain catecholamines, particularly norepinephrine (Falck). This is well illustrated in the iris, where nerves to the dilator muscle (sympathetic) contain dense-core vesicles and those to the constrictor (parasympathetic) contain clear vesicles. A single nerve fiber innervates multiple smooth muscle and gland cells.


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Neurology_Adams. Visceral afferents Somewhat arbitrarily, anatomists have declared the autonomic nervous system to be purely efferent motor and secretory in function. However, most autonomic nerves are mixed, also containing afferent fibers that convey sensory impulses from the viscera and blood vessels. The cell bodies of these sensory neurons lie in the posterior root sensory ganglia; some central axons of these ganglionic cells synapse with lateral horn cells of the spinal cord and subserve visceral reflexes; others synapse in the dorsal horn and convey or modulate impulses for conscious sensation. Secondary afferents carry sensory impulses to certain brainstem nuclei, particularly the nucleus tractus solitarius, as described later, and the thalamus via the lateral spinothalamic and polysynaptic pathways. The Central Regulation of Visceral Function


Neurology_Adams

Neurology_Adams. The principal functions of central autonomic network are the modulation of stress responses, baroregulation, thermoregulation and energy balance. Integration of autonomic function takes place at two levels, the brainstem and the cerebrum. In the brainstem, the main visceral afferent nucleus is the nucleus tractus solitarius (NTS). Cardiovascular, respiratory, and gastrointestinal afferents, carried in cranial nerves X and IX via the nodose and petrosal ganglia, terminate on specific subnuclei of the NTS. The caudal subnuclei are the primary receiving site for viscerosensory fibers; other less-well-defined areas receive baroreceptor and chemoreceptor information. The caudal NTS integrates these signals and projects to a number of critical areas in the hypothalamus, amygdala, and insular cortex, involved primarily in cardiovascular control, as well as to the pontine and medullary nuclei controlling respiratory rhythms. The NTS therefore serves a critical integratory function for both


Neurology_Adams

Neurology_Adams. cortex, involved primarily in cardiovascular control, as well as to the pontine and medullary nuclei controlling respiratory rhythms. The NTS therefore serves a critical integratory function for both circulation and respiration, as described further on.


Neurology_Adams

Neurology_Adams. Perhaps the major advance in our understanding of the autonomic nervous system occurred with the elaboration of the autonomic regulating functions of the hypothalamus. Small, insignificant-appearing nuclei in the walls of the third ventricle and in buried parts of the limbic cortex have rich bidirectional connections with autonomic centers in various parts of the nervous system. As indicated in Chap. 24, the hypothalamus serves as the integrating mechanism of the autonomic nervous system and limbic system. The regulatory activity of the hypothalamus is accomplished in two ways, through direct pathways that descend to particular groups of cells in the brainstem and spinal cord, and through the pituitary and thence to other endocrine glands. The supranuclear regulatory apparatus of the hypothalamus includes three main cerebral structures: the frontal lobe cortex, the insular cortex, and the amygdaloid and adjacent nuclei.


Neurology_Adams

Neurology_Adams. The ventromedial prefrontal and cingulate cortices function as the highest levels of autonomic integration. Stimulation of one frontal lobe may evoke changes in temperature and sweating in the contralateral arm and leg; massive lesions here, which usually cause a hemiplegia, may modify the autonomic functions in the direction of either inhibition or facilitation. Lesions involving the posterior part of the superior frontal and anterior part of the cingulate gyri (usually bilateral, occasionally unilateral) result in loss of voluntary control of the bladder and bowel. Most likely a large contingent of these fibers terminates in the hypothalamus, which, in turn, sends fibers to the brainstem and spinal cord. The descending spinal pathways from the hypothalamus are believed to lie ventromedial to the corticospinal fibers.


Neurology_Adams

Neurology_Adams. The insular cortex receives projections from the NTS, the parabrachial nucleus of the pons, and the lateral hypothalamic nuclei. Direct stimulation of the insula produces cardiac arrhythmias and a number of other alterations in visceral function. The cingulate and hippocampal gyri and their associated subcortical structures (substantia innominata and the amygdaloid, septal, piriform, habenular, and midbrain tegmental nuclei) have been identified as important cerebral autonomic regulatory centers. Together they have been called the visceral brain (see Chap. 24). Of particular importance in autonomic regulation is the amygdala, the central nucleus of which is a major site of origin of projections to the hypothalamus and brainstem. The anatomy and the effects of stimulation and ablation of the amygdala have been discussed in Chap. 24, in relation to the neurology of emotion.


Neurology_Adams

Neurology_Adams. In addition to the aforementioned central relationships, it should be noted that important interactions between the autonomic nervous system and the endocrine glands occur at a peripheral level. The best-known example is in the adrenal medulla. A similar relationship pertains to the pineal gland, in which norepinephrine (NE) released from postganglionic fibers that end on pineal cells stimulates several enzymes involved in the biosynthesis of melatonin. Similarly, the juxtaglomerular apparatus of the kidney and the islets of Langerhans of the pancreas may function as neuroendocrine transducers insofar as they convert a neural stimulus (in these cases adrenergic) to an endocrine secretion (renin, glucagon, and insulin, respectively). The numerous autonomic–endocrine interactions are elaborated in the next chapter.