696 e1 Sympathetic Parasympathetic Cerebellum HippocampusCerebral hemispheres Peripheral nerves/ganglia Nervous system Basal ganglia Cerebral cortex ANS PNS Spinal cordCNS Pons Thalamus Brain Cerebrum[.]
696.e1 Sympathetic ANS PNS Parasympathetic Peripheral nerves/ganglia Medulla Nervous system CNS Spinal cord Brain Pons Thalamus Brainstem Midbrain Cerebrum Diencephalon Hypothalamus Cerebral hemispheres Hippocampus Cerebellum Basal ganglia Cerebral cortex • eFig 58.2 General subdivisions of the nervous system ANS, Autonomic nervous system; CNS, central nervous system; PNS, peripheral nervous system (Modified from Nolte J The Human Brain An Introduction to Its Functional Anatomy 3rd ed St Louis: Mosby–Year Book; 1993.) CHAPTER 58 Structure, Function, and Development of the Nervous System the trochlear nerve (CN IV), where it transitions into the midbrain The trigeminal nerve (CN V) exits from the lateral aspect of the pons approximately midway between the medulla and midbrain In addition to the cranial nerves, the pons contains several other important structures Its eponymous bulb, called the basis pontis, is formed by bundles of corticopontine fibers that connect the cerebral cortex with ipsilateral pontine nuclei Postsynaptic fibers originating in the pontine nuclei then cross the midline and form the middle cerebellar peduncle, which comprises one of the major input pathways into the cerebellum Cerebellar output to the thalamus and other structures takes place via the superior cerebellar peduncle contained in the rostral pons Additionally, the rostral pons contains the locus ceruleus (from the Latin, blue spot) Locus ceruleus neurons use norepinephrine as a neurotransmitter, innervate wide-ranging areas of the brain, and likely regulate sleep and arousal Injury to pontine structures is of significant relevance in the PICU First, increased intracranial pressure (ICP) from any cause may result in compression of the medially located small abducens nerve (CN VI), leading to paralysis of the lateral rectus eye muscle and associated turning in of the affected eye Abducens nerve palsy due to increased ICP may precede the notorious fixed and dilated pupil phenomenon observed when CN III is compressed during impending uncal herniation (see later discussion) Second, damage to the rostral pons (or lower midbrain) results in decerebrate posturing, characterized by extension of both upper and lower extremities on painful stimulation Importantly, decerebrate posturing corresponds to the motor score of on the Glasgow Coma Scale (GCS) score Finally, infarction of the basis pontis with sparing of the more dorsal pontine structures results in the locked-in syndrome The locked-in state is characterized by complete paralysis of all voluntary muscles except the muscles of ocular movement and by complete cognitive awareness Because the locked-in patient can communicate only via eye gaze, recognition of the locked-in state by the physician requires extreme diligence in patients with brainstem lesions lest the patient be misdiagnosed as comatose, with potentially dire consequences 697 lower extremities in response to painful stimulation Decorticate posturing corresponds to a motor score of on the GCS Second, the “blown” pupil universally recognized as a sign of increased ICP and impending transtentorial brain herniation results from compression of the oculomotor nerve (CN III) as it exits the midbrain Pupillary dilation results from compression and inactivation of the parasympathetic fibers that run on the outer surface of CN III and which are actually responsible for pupillary constriction When these fibers are damaged, unopposed sympathetic stimulation arising from the cervical sympathetic ganglia results in a constitutively dilated pupil that cannot constrict in response to light stimulation or, in other words, is fixed Unilateral fixed and dilated pupil is an emergency that requires immediate medical and/or surgical intervention Reticular Formation The brainstem reticular formation is not a separate anatomic structure but is instead distributed throughout the core of the brainstem from the medulla into the midbrain It plays a fundamental role in arousal and consciousness, control of movement and sensation, and in regulation of visceral functions A subset of the reticular formation neurons sends fibers to the intralaminar thalamic nuclei, which, in turn, project widely throughout the cerebral cortex Damage to these ascending brainstem fibers, collectively called the ascending reticular activating system, results in loss of consciousness and coma, even in the absence of any damage to the cerebral hemispheres Thus, the cerebral cortex requires input from the brainstem to maintain awareness and arousal In addition, the reticular formation contains neuronal circuits responsible for regulation of respiration, cardiovascular responses to blood pressure and oxygen level modulations, and coordination of swallowing and other oromotor functions Finally, complex reflexes, such as walking and maintenance of body orientation with respect to gravity, are coordinated by the brainstem reticular formation and may occur in the absence of input from higher brain regions Immaturity of the brainstem reticular formation, in particular of its serotonergic component, has been implicated in the etiology of SIDS.15 Midbrain Cerebellum The midbrain is the most rostral and smallest of the brainstem structures It is characterized by the presence of the bilateral inferior and superior colliculi on its dorsal surface Additionally, the oculomotor nerve (CN III) emerges from its ventral surface, immediately below the temporal lobe of the cerebral hemisphere The midbrain contains structures important for hearing, sound localization, and generation of saccadic eye movements Furthermore, the substantia nigra in the midbrain contains neurons that use dopamine as their neurotransmitter These dopaminergic neurons project to the basal ganglia, where dopamine release participates in initiation of voluntary movements, to the limbic system in the cerebral cortex, where dopamine plays a role in reward and emotion, and to the frontal and temporal cortices, indicating that dopamine affects thought and memory Destruction of dopaminergic substantia nigra neurons underlies the pathology of idiopathic Parkinson disease in older individuals and of parkinsonian symptoms in drug abusers exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, sometimes a contaminant in heroin preparations Two clinical phenomena of significant importance in pediatric critical care medicine arise from damage to midbrain structures First, global injury to the midbrain results in decorticate posturing, characterized by flexion of upper extremities and extension of The cerebellum overlies the majority of the brainstem and is separated from the cerebral cortex by a sheetlike reflection of the dura mater, called the tentorium cerebelli Hence, the brainstem and cerebellum are referred to as infratentorial structures while the cerebral cortex and the diencephalon are referred to as supratentorial structures The cerebellum consists of a midline vermis and two large cerebellar hemispheres.41 The outer surface of the cerebellum consists of a three-layered cortex, which includes the outer molecular layer, Purkinje cell layer, and granular layer The molecular layer contains mostly axons and dendrites The Purkinje cell layer contains the eponymous large GABA-ergic neurons that constitute the sole cerebellar output Finally, the granular layer contains small granule cells that interact with other granule cells and with Purkinje neurons In addition to the cerebellar cortex, each cerebellar hemisphere also contains a set of deep nuclei From lateral to medial, these are the dentate, interposed, and fastigial nuclei Cerebellar function has traditionally been confined to regulation and coordination of movement of the eyes, head, and body in space However, evidence from neuroanatomic and functional neuroimaging studies has suggested that the cerebellum—in particular, the dentate nucleus—plays a significant role in cognition, memory, and language.43,44 Consequently, lesions in the cerebellum 698 S E C T I O N V I Pediatric Critical Care: Neurologic are characterized by ataxia, ipsilateral dysmetria, and intention tremor, as well as by scanning speech, in which each syllable is produced slowly and separately, and by disorders of memory and executive function.44 In the PICU, cerebellar lesions are seen most frequently in the setting of infratentorial tumors but also occasionally in cerebellar strokes and in viral cerebellitis Diencephalon The diencephalon consists of four major structures: the thalamus, hypothalamus, subthalamus, and epithalamus Of these, only the thalamus and hypothalamus are discussed in detail, as they serve crucial functions relevant to pediatric critical care medicine The thalamus is the major relay station for all sensory information except olfaction as it travels from peripheral sensory organs to the cerebral cortex For example, optic nerve neurons carrying visual information synapse onto neurons in the lateral geniculate nucleus in the thalamus, which process and transmit the signal to the primary visual cortex in the occipital lobe Furthermore, the thalamus participates in coordination of motor activity via multiple neuronal loops that connect the cerebellum with the basal ganglia and cerebral cortex.44 Last, inhibitory thalamic nuclei, such as the reticular nucleus (distinct from the brainstem reticular formation) are thought to participate in gating of attention and consciousness.45 Injury to the thalamus occurs frequently in both term and preterm neonates exposed to hypoxia-ischemia at birth.46 Additionally, thalamic necrosis is observed in infectious encephalitis, particularly that associated with the influenza virus47,48 and Mycoplasma pneumoniae.49 Vascular diseases, such as occlusion of the basilar artery or systemic lupus erythematosus, can result in thalamic injury that can occasionally be reversible.50 Apparent life-threatening events have been rarely associated with thalamic lesions.51 Thalamic damage is associated with a wide range of symptoms, including pure sensory loss due to destruction of sensory relay nuclei, acute abnormalities in mental status, labile emotions, and motor dysfunction The hypothalamus is located inferior to the thalamus and plays a major role in regulation of emotion, homeostasis, circadian rhythms, and ANS function Most important, it controls hormone release in the pituitary gland via two separate pathways Large hypothalamic neurons in the supraoptic and paraventricular nuclei project their axons via the pituitary stalk into the posterior pituitary lobe (neurohypophysis), where they release antidiuretic hormone (ADH) and oxytocin directly into the bloodstream ADH promotes water reabsorption in the kidney, whereas oxytocin participates in parturition and milk secretion Damage to the posterior pituitary produces diabetes insipidus Hypothalamic projections into the anterior pituitary (adenohypophysis) also travel down the pituitary stalk and release a multitude of release-promoting or release-inhibiting factors into the pituitary portal vein.41 These factors then control the release of all anterior pituitary hormones, including adrenocorticotropic hormone, thyroid-stimulating hormone, growth hormone, prolactin, and luteinizing/follicle-stimulating hormone Of these, only prolactin release is constitutively inhibited by the hypothalamus, while the release of all remaining pituitary hormones is under positive control Thus, transection of the pituitary stalk, as can occur during skull base and pituitary surgery,52 results in panhypopituitary syndrome characterized by diabetes insipidus, hypothyroidism, cortisol deficiency, and hyperprolactinemia Damage to hypothalamic nuclei, in addition to disrupting control of the pituitary gland, also results in emotional lability, aggression, and extreme overeating or anorexia leading to rapid weight gain or loss, respectively Thus, overwhelming aggression combined with acute weight changes should raise suspicion for a hypothalamic tumor in a child Basal Ganglia The basal ganglia are a set of deep nuclei that reside below the surface of the cerebral cortex and surround the thalamus They are composed of the caudate, putamen, globus pallidus, substantia nigra, and subthalamic nucleus The caudate receives most of its input from the prefrontal cortex and projects via the globus pallidus and thalamus back to the prefrontal cortex Thus, it is involved with cognitive function and tends to be one of the nuclei that degenerates slowly over time after a hypoxic-ischemic insult to the cortex The putamen receives most of its input from the somatosensory and motor cortices and, like the caudate, projects back to these cortices via the globus pallidus and thalamus The putamen plays a major role in coordination of motor function The globus pallidus serves as an inhibitory modulator in the cortex–basal ganglia–thalamus–cortex loop Hence, deep brain stimulation in the globus pallidus in patients with Parkinson disease results in resolution of motor symptoms attributable to hyperactivity in the loop, such as tremor and rigidity The substantia nigra contains dopaminergic neurons that project to the other nuclei in the basal ganglia and participate in initiation and coordination of voluntary movement The basal ganglia are the site of injury in multiple processes in pediatrics They are often injured by hypoxia and hypoglycemia due to interruption of energy supply Similarly, carbon monoxide poisoning effectively prevents oxygen delivery to the basal ganglia, resulting in characteristic neuroradiologic findings.53 A number of metabolic diseases, including methylmalonic acidemia, Leigh disease, maple syrup urine disease, and glutaric acidemia type II, also result in degeneration in the basal ganglia The basal ganglia accumulate iron and copper and, consequently, can be injured by iron overload or in Wilson disease Finally, a juvenile form of Huntington disease presents with characteristic degeneration in the caudate nucleus.53 Clinical signs of injury to the basal ganglia are often nonspecific: lethargy, irritability, and decreased mental status Movement disorders such as dystonia or chorea can be seen early in the course of injury but are relatively uncommon, being more likely to emerge with chronic deterioration in basal ganglia function Cerebral Hemispheres The cerebral hemispheres are the most rostral part of the CNS, and in humans and some other mammals, they are characterized by extensive folding of the cerebral cortex The folding greatly expands the area of the cerebral cortex that can fit into the cranial vault In humans, the cortical sheet has an area of 2.5 square feet when all the folds are flattened, yet the surface area of the adult skull is closer to 0.5 square feet The folds consist of ridges termed gyri (singular, gyrus) and spaces separating the ridges termed sulci (singular, sulcus) Although the detailed organization of each gyrus and sulcus is quite individualized, the larger organizational features are common to all mammals Each cerebral hemisphere is divided into four lobes: frontal, parietal, temporal, and occipital (eFig 58.3) The frontal lobe extends caudally from the rostral pole of the brain to the central sulcus and inferolaterally to the lateral sulcus The parietal lobe begins at the central sulcus and extends caudally to the parietooccipital sulcus Inferolaterally, the parietal lobe is bounded by the 698.e1 Parietal Frontal Occipital Cerebellum Temporal • eFig 58.3 General subdivisions of the human cerebral cortex Note that the cerebellum is not part of the cortex but is labeled for clarity CHAPTER 58 Structure, Function, and Development of the Nervous System lateral sulcus and imaginary line connecting the extension of the lateral sulcus with the parietooccipital sulcus The temporal lobe is delineated primarily by the lateral sulcus Finally, the occipital lobe resides posteriorly to the parietooccipital sulcus Each of the four lobes performs dedicated functions, some of which are symmetric, occurring in both hemispheres, whereas others are lateralized, specific to either the right or left cerebral hemisphere The frontal lobe is divided into four cortices, reflecting its functional organization The primary motor cortex, located on the precentral gyrus, directly controls volitional movement on the contralateral side via upper motoneurons projecting to the lower motoneurons in the spinal cord Moving rostrally, the premotor cortex is involved in planning, coordination, and initiation of movement The most rostral part of the frontal lobe, the prefrontal cortex, is generally associated with personality and foresight/planning Additionally, one side of the frontal lobe, usually the left, contains the Broca area on its inferolateral surface The Broca area participates in the production of spoken and written language The parietal lobe contains the primary somatosensory cortex, which is located on the postcentral gyrus and receives all tactile and proprioceptive sensory information from the contralateral side of the body The parietal cortex posterior to the primary somatosensory cortex possesses quite lateralized functional areas, with cortex on the left usually involved with language processing and comprehension and that on the right responsible for perception of space and special orientation The occipital lobe is generally devoted to vision in humans, containing the primary visual cortex and several secondary visual areas The temporal lobe, on the other hand, serves more diverse functions It contains the primary auditory cortex, which receives all auditory stimuli from the periphery The temporal lobe also encompasses the hippocampus and the limbic system, thus participating in learning, memory, and emotion Peripheral Nervous System The peripheral nervous system is generally divided into two components: the somatic PNS, which includes the peripheral nerves carrying information to and from muscle and skin, and the visceral (or autonomic) PNS, which regulates homeostatic bodily functions and mainly innervates visceral organs, such as the heart, lungs, and intestines Dysfunction of both the somatic and autonomic systems contributes to the breadth of pathology encountered in pediatric critical care medicine, thus requiring the pediatric intensivist to be familiar with the basic organizational and functional principles of the PNS Somatic Peripheral Nervous System The somatic PNS consists of efferent nerve fibers carrying information to muscle and skin, peripheral sensory receptors, and afferent nerve fibers carrying information from the periphery to the CNS The efferent fibers emerge from neurons located in the spinal gray matter and exit the spinal cord via the ventral root The afferent sensory fibers belong to neurons located in dorsal root ganglia, which send an axonal branch into the spinal cord via the dorsal root The efferent and afferent fibers travel together between the dorsal root ganglia and target organ in the peripheral nerve Diseases of the somatic PNS relevant to pediatric intensive care are generally disorders of myelination, such as Guillain-Barré syndrome, and are discussed in detail in Chapter 68 699 Visceral or Autonomic Peripheral Nervous System The autonomic nervous system regulates bodily functions that not necessarily require conscious control or awareness, such as heart rate, blood pressure, sphincter function, and digestion The ANS is divided into three distinct components: the enteric, parasympathetic, and sympathetic nervous systems The enteric nervous system consists of the myenteric plexus of Auerbach and submucosal plexus of Meissner, both located in the wall of the alimentary canal (see also Chapter 95) The enteric nervous system interacts with the CNS and parasympathetic and sympathetic components of the ANS but can function entirely independently It is responsible for sensation and coordination of peristalsis in the gut Neurons in the enteric nervous system arise from the same progenitors as neurons in the CNS Hence, many neurologic disorders concomitantly affect both the central and enteric nervous systems, including irritable bowel syndrome, anxiety, and depression.54 Sympathetic Nervous System The sympathetic nervous system consists of preganglionic and postganglionic components Preganglionic fibers originate from neurons in the thoracolumbar region of the spinal cord, giving the sympathetic ANS its anatomic name: the thoracolumbar outflow Preganglionic fibers exit the spinal cord via the ventral roots with the thoracic and lumbar nerves After traveling together for a short distance, the preganglionic fibers diverge from the spinal nerves and enter the sympathetic ganglia via the white communicating rami (preganglionic fibers are thinly myelinated; hence, they appear white) The preganglionic fibers carrying output to the head, thorax, and limbs synapse onto neurons in sympathetic ganglia located close to the spinal cord These ganglia form the paravertebral sympathetic chain that extends from the cervix to the coccyx The preganglionic fibers carrying output to the abdominal and pelvic viscera synapse onto cells located in sympathetic ganglia farther away from the spinal cord, called the prevertebral ganglia These include the celiac, superior mesenteric, and inferior mesenteric ganglia Postganglionic neurons from either the paravertebral or prevertebral ganglia send their fibers to the target organs via the gray communicating rami (postganglionic fibers are unmyelinated and, hence, gray) In the sympathetic ANS, preganglionic neurons use acetylcholine as a neurotransmitter, whereas postganglionic neurons use norepinephrine at the target organs The exception is the sweat glands, which receive postganglionic sympathetic fibers using acetylcholine.41 The sympathetic ANS generally functions to prepare the body for states of increased energy expenditure Activation of the sympathetic ANS leads to increased heart rate, decreased peristalsis, redistribution of blood from the gut to the peripheral muscles, and pupillary dilatation (mydriasis) Furthermore, the sympathetic ANS directly innervates the adrenal medulla and, when activated, stimulates the medulla to release norepinephrine and epinephrine into the systemic circulation Systemic catecholamine release produces relatively global and long-lasting effects In critical care, a significant component of vasopressor support relies on mimicking the effect of sympathetic ANS activation with exogenously administered epinephrine and norepinephrine Although autonomous, the sympathetic nervous system is under significant central control Interruption of the descending control pathways, such as occurs with spinal cord trauma above the level of T1, results in sudden loss of sympathetic tone, causing profound bradycardia and hypotension This syndrome, termed neurogenic or spinal shock, emerges early after injury and requires ... and memory Destruction of dopaminergic substantia nigra neurons underlies the pathology of idiopathic Parkinson disease in older individuals and of parkinsonian symptoms in drug abusers exposed... nerves and enter the sympathetic ganglia via the white communicating rami (preganglionic fibers are thinly myelinated; hence, they appear white) The preganglionic fibers carrying output to the head,... of T1, results in sudden loss of sympathetic tone, causing profound bradycardia and hypotension This syndrome, termed neurogenic or spinal shock, emerges early after injury and requires