The central nervous system (CNS) consists of the spinal cord and the brain and is responsible for integrating, processing and coordinating sensory data and motor commands ¹ (see Figure 16.1). The CNS is linked to all parts of the body by the PNS which transmits signals to and from the CNS. The human PNS is composed of 43 pairs of spinal nerves that issue in orderly sequence from the spinal cord, and 12 pairs of cranial nerves that emerge from the base of the brain. All branch and diversify prolifically as they distribute to the tissues and organs of the body. The peripheral nerves carry input to the CNS via their sensory afferent fibres and deliver output from the CNS via the efferent fibres. Specific physiology of the CNS and PNS is discussed in detail later in the chapter. First, however, neuron cell anatomy and physiology is examined.

FIGURE 16.1 The functional divisions of the nervous system.¹

Neurons

Neurons are specialised cells in the nervous system; each is comprised of a dendrite, cell body (soma) and axon.² Each neuron is a cell that uses biochemical reactions to receive, process and transmit information. Most synaptic contacts between neurons are either axodendritic (excitatory) or axosomatic (inhibitory). A neuron’s dendritic tree is connected to many neighbouring neurons and receives positive or negative charges from other neurons. The input is then passed to the soma (cell body). The primary role of the soma and the enclosed nucleus is to perform the continuous maintenance required to keep the neuron functional. Most neurons lack centrioles, important organelles involved in the organisation of the cytoskeleton and the movement of chromosomes during mitosis. As a result, typical CNS neurons cannot divide and cannot be replaced if lost to injury or disease. The fuel source for the neuron is glucose; insulin is not required for cellular uptake in the CNS.

A myelin sheath, consisting of a lipid-protein casing, covers the neuron and provides protection to the axon and speeds the transmission of impulses along nerve cells from node to node.³ (see Figure 16.2b). Myelin is not a continuous layer but has gaps called nodes of Ranvier (see Figure 16.2a).

FIGURE 16.2 (A) Afferent and (B) efferent neurons, showing the soma or cell body, dendrites and axon. Arrows indicate the direction for conduction of action potentials.³

Each synaptic knob contains mitochondria, portions of the endoplasmic reticulum, and thousands of vesicles filled with neurotransmitter molecules. Breakdown products of neurotransmitter released at the synapse are reabsorbed and reassembled at the synaptic knob. The synaptic knob also receives a continuous supply of neurotransmitter synthesised in the cell body, along with enzymes and lysosomes. The movement of materials between the cell body and synaptic knobs is called axoplasmic transport. Some materials travel slowly, at rates of a few millimetres per day. This transport mechanism is known as the ‘slow stream.’ Vesicles containing neurotransmitter move much more rapidly, travelling in the ‘fast stream’ at 5–10 mm per hour which increases synaptic activity. Axoplasmic transport occurs in both directions. The flow of materials from the cell body to the synaptic knob is anterograde flow. At the same time, other substances are being transported towards the cell body in retrograde flow (’retro’ meaning backward). If debris or unusual chemicals appear in the synaptic knob, retrograde flow soon delivers them to the cell body. The arriving materials may then alter the activity of the cell by turning appropriate genes on or off. Retrograde flow is the means of transport for viruses, pathogenic bacteria, heavy metals and toxins to the CNS, with resulting disease such as tetanus, viral encephalitis and lead intoxication. Defective anterograde transport seems to be involved in certain neuropathies, including critical illness neuropathies.⁴

Synapses

The human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Although there are many kinds of synapses within the brain, they can be divided into two general classes: electrical synapses and chemical synapses. Electrical synapses permit direct, passive flow of electrical current from one neuron to another in the form of an action potential; they are described in Table 16.1. The current flows through gap junctions, which are specialised membrane channels that connect the two cells. Chemical synapses, in contrast, enable cell-to-cell communication via the secretion of neurotransmitters; the chemical agents released by the presynaptic neurons produce secondary current flow in postsynaptic neurons by activating specific receptor molecules⁵ (see Figure 16.3).

TABLE 16.1 Generation of action potentials (nervous tissue)

STEP 1: Depolarisation

• A graded depolarisation brings an area of excitable membrane to threshold (−60 mV).

STEP 2: Activation of sodium channels and rapid depolarisation

• The voltage-regulated sodium channels open (sodium channel activation).

• Sodium ions, driven by electrical attraction and the chemical gradient, flood into the cell.

• The transmembrane potential goes from −60 mV, the threshold level, towards +30 mV.

STEP 3: Repolarisation: Inactivation of sodium channels and activation of potassium channels

• The voltage-regulated sodium channels close (sodium channel inactivation occurs) at +30 mV.

• The voltage-regulated potassium channels are now open, and potassium ions diffuse out of the cell.

• Repolarisation begins.

STEP 4: Return to normal permeability

• The voltage-regulated sodium channels regain their normal properties in 0.4–1.0 msec. The membrane is now capable of generating another action potential if a larger than normal stimulus is provided.

• The voltage-regulated potassium channels begin closing at −70 mV. Because they do not all close at the same time, potassium loss continues, and a temporary hyperpolarisation to approximately −90 mV occurs.

• At the end of the relative refractory period, all voltage-regulated channels have closed, and the membrane is back to its resting state.

FIGURE 16.3 Sequence of events involved in transmission at a typical chemical synapse.⁸²

Myelin increases conduction velocity. Demyelination of peripheral nerves, as occurs in the Guillain–Barré syndrome, slows conduction and may result in conduction block, which manifests clinically as weakness. Consequently, chronically demyelinated axons become vulnerable, with axon loss being a major cause of disability. In time, remyelination may occur, requiring the generation of myelin-competent oligodendrocytes but most often does not fully recapitulate developmental myelination.

Neurotransmitters

A neurotransmitter is a chemical messenger used by neurons to communicate in one direction with other neurons. Unidirectional transmission is required for multineuronal pathways, for example to and from the brain. Neurons communicate with each other by recognising specific neuroreceptors.

Chemically, there are four classes of neurotransmitters:

1. acetylcholine (ACh): the dominant neurotransmitter in the peripheral nervous system, released at neuromuscular junctions and synapses of the parasympathetic division

2. biogenic amines: serotonin, histamine, and the catecholamines dopamine and noradrenaline

3. excitatory amino acids: glutamate and aspartate, and the inhibitory amino acids gamma-aminobutyric acid (GABA), glycine and taurine

4. neuropeptides: over 50 of which are known, amino acid neurotransmitters being the most numerous.

In 2009, it was discovered that there is also more than one neurotransmitter per synapse; these are called co-transmitters. For example, neuropeptide Y (NPY) and adenosine triphosphate (ATP) are co-transmitters of noradrenaline, which are released together and mediate their function by activation of α- and β-adrenoceptors, and regulate renovascular resistance.⁶ Similarly, receptors are an important control point for the effectiveness of synapses. Neurotransmitters are the common denominator between the nervous, endocrine and immune systems. Many neurotransmitters are endocrine analogues and acetylcholine, the main parasympathetic neurotransmitter, interacts with immune cells such as macrophages through the anti-inflammatory cholinergic pathway.⁷

Neuroglia

Neuroglia are the non-neuronal cells of the nervous system and are 10–50 times more prevalent than the number of neurons.¹ They are divided into macroglia (astrocytes, oligodendroglia and Schwann cells) and microglia, and are described in Table 16.2. They not only provide physical support but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood–brain and blood–retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons.⁸ The CNS has a greater variety of neuroglia. Unlike neurons, neuroglia continue to multiply throughout life. Because of their capacity to reproduce, most tumours of the nervous system are tumours of neuroglial tissue and not of nervous tissue itself.⁹

TABLE 16.2 Neuroglia, their location and role as supporting nervous tissue

Type	Location	Main Function
Astrocytes	CNS: The largest and most numerous neuroglial cells in the brain and spinal cord.	• Astrocytes are considered as important as the neuron in communication and brain regulation. • They regulate communication, extracellular ionic and chemical environments between neurons. • They respond to injury and have an important role in cerebral oedema.

Ependymal cells CNS: Line the ventricular system of the brain and central cord of the spinal canal.

• Transport of CSF and brain homeostasis.

• Phagocytotic defence against pathogens.

• Store glycogen for brain tissue.

Microglia CNS: Located within the brain parenchyma behind the blood–brain barrier.

• Wander between the peripheral immune system and the CNS as a defence to infection.

• Displace synaptic input in injured neurons.

Oligodendrocytes CNS: Spiral around an axon to form a multilayered lipoprotein coat in both the white and grey matter in the brain and spinal cord.
PNS: Schwann cells are the supporting cells of the PNS.

• Responsible for the formation of myelin sheaths surrounding axons.

• Oligodendrocytes wrap themselves around numerous axons at once.

• Schwann cells wrap themselves around peripheral nerve axon.

• Unlike oligodendrocytes, a single Schwann cell makes up a single segment of an axon’s myelin sheath.

Central Nervous System

The CNS is composed of the brain and spinal cord (see Figure 16.4).⁵ The primary purpose is to acquire, coordinate and disseminate information about the body and its environment. This section describes the anatomy and physiology of the brain and spinal cord.

FIGURE 16.4 The subdivisions and components of the central nervous system.⁸²

Brain

The brain is divided into three regions: forebrain, midbrain and hindbrain, as described in Table 16.3. The forebrain, which consists of two hemispheres and is covered by the cerebral cortex, contains central masses of grey matter, the basal ganglia, the neural tube and the diencephalon with its adult derivatives: the thalamus and hypothalamus.¹ Midbrain structures include two pairs of dorsal enlargements, the superior and inferior colliculi. The medulla, pons and midbrain compose the brainstem.¹ The hindbrain includes the medulla oblongata, the pons and its dorsal outgrowth, the cerebellum.

TABLE 16.3 Organisation of the brain

Division	Description	Functions
Forebrain
Cerebrum	Largest and uppermost portion of the brain. Divided into two hemispheres, each subdivided into the frontal, parietal, temporal and occipital lobes.	Cortex (outer layer) is the site of conscious thought, memory, reasoning and abstract mental functions, all localised within specific lobes.

Diencephalon Between the cerebrum and the brainstem. Contains the thalamus and hypothalamus. Thalamus sorts and redirects sensory input; hypothalamus controls visceral, autonomic, endocrine and emotional function, and the pituitary gland. Contains some of the centres for coordinated parasympathetic and sympathetic stimulation, temperature regulation, appetite regulation, regulation of water balance by antidiuretic hormone (ADH), and regulation of certain rhythmic psychobiological activities (e.g. sleep).

Brain stem Anterior region below the cerebrum: the medulla, pons, and midbrain compose the brainstem. Connects cerebrum and diencephalon with spinal cord. Midbrain Midbrain Below the centre of the cerebrum. Has reflex centres concerned with vision and hearing; connects cerebrum with lower portions of the brain. It contains sensory and motor pathways and serves as the centre for auditory and visual reflexes.

Basal ganglia or corpus striatum The mass of grey matter in the midbrain beneath the cerebral hemispheres. Borders the lateral ventricles and lies in proximity to the internal capsule. An important role in planning and coordinating motor movements and posture. Complex neural connections link the basal ganglia to the cerebral cortex. The major effect of these structures is to inhibit unwanted muscular activity; disorders of the basal ganglia result in exaggerated, uncontrolled movements.

Pons Anterior to the cerebellum. Connects cerebellum with other portions of the brain; contains motor and sensory pathways; helps to regulate respiration; axons from the cerebellum, basal ganglia, thalamus and hypothalamus; portions of the pons also control the heart, respiration and blood pressure. Cranial nerves V–VIII connect the brain in the pons.

Hindbrain Contains a portion of the pons, the medulla oblongata and the cerebellum. Reticular activation system (RAS) The reticular formation networks run through the brainstem core, known as the tegmentum. Activity of the cerebral cortex is dependent on both specific sensory input and non-specific activating impulses from the RAS, and is critical to the existence of the conscious state, states of alertness and arousal.

Medulla oblongata Between the pons and the spinal cord. The medulla oblongata contains motor fibres from the brain to the spinal cord and sensory fibres from the spinal cord to the brain. Most of these fibres cross at this level. Cranial nerves IX–XII connect to the brain in the medulla, which has centres for control of vital functions, such as respiration and the heart rate.

Cerebellum Below the posterior portion of the cerebellum. Divided into two hemispheres. Coordinates voluntary muscles; maintains balance and muscle tone; has both excitatory and inhibitory actions. It also controls fine movement, balance, position sense and integration of sensory input.

Nervous tissue has a high rate of metabolism. Although the brain constitutes only 3% of the body’s weight, it receives approximately 15% of the resting cardiac output and consumes 20% of its oxygen.¹ Despite its substantial energy requirements, the brain can neither store oxygen nor effectively engage in anaerobic metabolism. An interruption in the blood or oxygen supply to the brain rapidly leads to clinically observable signs and symptoms. Without oxygen, brain cells continue to function for approximately 10 seconds. Glucose is virtually the sole energy substrate for the brain, and it is entirely oxidised.¹⁰ The brain can be seen as an almost exclusive glucose-processing machine, producing water (H₂O) and carbon dioxide (CO₂). Glucose also provides the carbon backbone for regeneration of the neuronal pool of glutamate. This process results from close astrocyte–neuron cooperation.¹¹

Cerebral cortex

The forebrain contains the cerebral cortex and the subcortical structures rostral (sideways) to the diencephalon. The cortex, or outermost surface of the cerebrum, makes up about 80% of the human brain. The cerebral cortex varies in thickness from 2 mm to 4 mm, being thinnest in the primary sensory areas and thickest in the motor and association areas. It contains the cell bodies and dendrites of neurons or grey matter which receive, integrate, store and transmit information. Conscious deliberation and voluntary actions also arise from the cerebral cortex. White matter lies beneath the cerebral cortex and is composed of myelinated nerve fibres. The cortex is involved in the processing of both sensory information from the body and the delivery of motor commands. These occur in specific areas of the brain and can be mapped. Topographically, the cerebral cortex is divided into areas of specialised functions, including the primary sensory areas for vision (occipital cortex), hearing (temporal cortex), somatic sensation (postcentral gyrus), and primary motor area (precentral gyrus). As shown in Figure 16.5,¹ these well-defined areas comprise only a small fraction of the surface of the cerebral cortex.

FIGURE 16.5 (A) Major anatomical landmarks on the surface of the left cerebral hemisphere. The lateral sulcus has been pulled apart to expose the insula. (B) The left hemisphere generally contains the general interpretive area and the speech centre. The prefrontal cortex of each hemisphere is involved with conscious intellectual functions. (C) Regions of the cerebral cortex as determined by histological analysis. Several of the 47 regions described by Brodmann are shown for comparison with the results of functional mapping.¹

The majority of the remaining cortical area is known as the association cortex, where the processing of extensive and sophisticated neural information is performed.¹² The association areas are also sites of long-term memory, and they control human functions such as language acquisition, speech, musical ability, mathematical ability, complex motor skills, abstract thought, symbolic thought, and other cognitive functions. Association areas interconnect and integrate information from the primary sensory and motor areas via intra-hemispheric connections. The parietal–temporal–occipital association cortex integrates neural information contributed by visual, auditory, and somatic sensory experiences. The prefrontal association cortex is extremely important as the coordinator of emotionally motivated behaviours, by virtue of its connections with the limbic system. In addition, the prefrontal cortex receives neural input from the other association areas and regulates motivated behaviours by direct input to the premotor area, which serves as the association area of the motor cortex. Sensory and motor functions are controlled by cortical structures in the contralateral hemisphere. Particular cognitive functions or components of these functions may be lateralised to one side of the brain.

The cerebral cortex receives sensory information from many different sensory organs and processes the information. The two hemispheres receive the information from the opposite sides of the body. Sensory information is relayed to the cortex by the thalamus. Parts of the cortex that receive this information are called primary sensory areas and cross at various points in the sensory pathway, because the cerebral cortex operates on a contralateral basis.¹³ The discriminative touch system crosses high, in the medulla. The pain system crosses low, in the spinal cord. The proprioceptive sensory system that guards balance and position goes to the cerebellum, which works ipsilaterally and therefore doesn’t cross. Almost every region of the body is represented by a corresponding region in both the primary motor cortex and the somatic sensory cortex.¹⁴

The homunculus (see Figure 16.6) visualises the connection between different areas of the body and areas in brain hemispheres.¹⁵ The body on the right side is the motor homunculus and on the left the sensory homunculus. Representations of parts of the body that exhibit fine motor control and sensory capabilities occupy a greater amount of space than those that exhibit less precise motor or sensory functions.

FIGURE 16.6 Somatosensory and motor homunculi. Note that the size of each region of the homunculi is related to its importance in sensory or motor function, resulting in a distorted-appearing map.¹⁵

Basal ganglia and cerebellum

The basal ganglia, consisting of the caudate, putamen, globus pallidus, substantia nigra, subthalamic nucleus, and related nuclei in the brainstem, play an important role in movement, as evidenced by the hypokinetic/rigid and hyperkinetic disorders seen with lesions of various components. However, their role in the initiation and control of movement cannot be isolated from the motor activities of the cortex and brainstem centres discussed previously. Procedural memories for motor and other unconscious skills depend on the integrity of the premotor cortex, basal ganglia and cerebellum.¹⁶ The cerebellum plays a more obvious role in coordinating movements by giving feedback to the motor cortex, as well as by providing important influences on eye movements through brainstem connections, and on postural activity through projections down the spinal cord.

Brainstem

The brainstem is composed of the midbrain, the pons and the medulla oblongata.¹ These structures connect the cerebrum and diencephalon with the spinal cord. Brainstem centres are organised into medial, lateral and aminergic systems. Collectively, these integrate vestibular, visual and somatosensory inputs for the control of eye movements and, through projections to the spinal cord, provide for postural adjustments. For example, these centres keep the images on matching regions of the retinas when the head moves by causing conjugate eye movements in the opposite direction to which the head is turned. This is the basis for the ‘doll’s eyes’ test in neurological assessment, in which the head is rapidly turned and the eyes move conjugately in the opposite direction, demonstrating the integrity of much of the brainstem. The sequence of sleep states is governed by a group of brainstem nuclei that project widely throughout the brain and spinal cord.¹⁷

The midbrain, inferior to the centre of the cerebrum, forms the superior part of the brainstem. It contains the reticular formation (which collects input from higher brain centres and passes it on to motor neurons), the substantia nigra (which regulates body movements; damage to the substantia nigra causes Parkinson’s disease) and the ventral tegmental area (which contains dopamine-releasing neurons that are activated by nicotinic acetylcholine receptors).¹⁸ White matter at the anterior of the midbrain conducts impulses between the higher centres of the cerebrum and the lower centres of the pons, medulla, cerebellum and spinal cord. The midbrain contains the autonomic reflex centres for pupillary accommodations to light, which constrict the pupil and accommodate the lens. The fibres travel in cranial nerve III, so damage to that nerve will also produce a dilated pupil. It also contains the ventral tegmental area, packed with dopamine-releasing neurons that synapse deep within the forebrain and seem to be involved in pleasure: amphetamines and cocaine bind to the same receptors that it activates, and this may account at least in part for their addictive qualities.

The medulla oblongata lies between the pons and the spinal cord and looks like a swollen tip to the spinal cord. Running down the ventral aspect of the medulla are the pyramids, which contain corticospinal fibres. The function of the medulla oblongata is to control automatic functions (e.g. breathing and heart rate) and to relay nerve messages from the brain to the spinal cord. Processing of interaural time differences for sound localisation occurs in the olivary nuclei. The neurons controlling breathing have mu (µ) receptors, the receptors to which opiates bind. This accounts for the suppressive effect of opiates on breathing. Impairment of any of the vital functions or reflexes involving these cranial nerves suggests medullary damage.¹⁹

The pons varolii is the part of the brainstem that lies between the medulla oblongata and the mesencephalon. It contains pneumotaxic and apneustic respiratory centres and fibre tracts connecting higher and lower centres, including the cerebellum. The pons seems to serve as a relay station, carrying signals from various parts of the cerebral cortex to the cerebellum. Nerve impulses coming from the eyes, ears and touch receptors are sent on to the cerebellum. The pons also participates in the reflexes that regulate breathing. Table 16.4 contains a description of the cranial nerves including their type of tract, their function and location of origin.

TABLE 16.4 The cranial nerves, their location and functions

Hypothalamus and limbic system

The hypothalamus, the cingulate gyrus of the cortex, the amygdala and hippocampus in the temporal lobes, and the septum and interconnecting nerve fibre tracts among these areas comprise the limbic system. The hypothalamus and limbic systems, which are closely linked to homeostasis, act to regulate endocrine secretion and the autonomic nervous system, and to influence behaviour through emotions and drives.¹ The hypothalamus integrates information from the forebrain, brainstem, spinal cord and various endocrine systems. This area of the brain also contains some of the centres for coordinated parasympathetic and sympathetic stimulation, as well as those for temperature regulation, appetite regulation, regulation of water balance by antidiuretic hormone (ADH), and regulation of certain rhythmic psychobiological activities (e.g. sleep). The release of stored serotonin from axon terminals in the diencephalon, medulla, thalamus, and a small forebrain area (DMTF), results in inactivation of the RAS and activation of the DMTF. DMTF activity results in the four stages of sleep. The hypothalamus contains a plethora of neurotransmitters. These are found in the terminals of axons that originate from neurons outside the hypothalamus, but most are synthesised within the hypothalamus itself. The list of putative neurotransmitters includes the ‘classic’ transmitters ACh, GABA, glutamate, serotonin, dopamine and noradrenaline, as well as literally dozens of peptides that have been identified in recent years.²⁰

Protection and Support of the Brain

The brain occupies the cranial cavity and is covered by membranes, fluid and the bones of the skull. The delicate tissues of the brain are protected from mechanical forces by (a) the bones of the cranium, (b) the cranial meninges, and (c) cerebrospinal fluid. In addition, the neural tissue of the brain is biochemically isolated from the general circulation by the blood–brain barrier.

Cerebral Spinal Fluid

Cerebral spinal fluid (CSF) is an ultrafiltrate of blood plasma composed of 99% water with other constituents, making it close to the composition of the brain extracellular fluid.¹ Approximately 500 mL CSF is secreted each day, but only approximately 150 mL is in the ventricular system at any one time, meaning that the CSF is continuously being absorbed. The CSF produced in the ventricles must flow through the interventricular foramen, the third ventricle, the cerebral aqueduct and the fourth ventricle to exit from the neural tube.²¹ Three openings, or foramina, allow the CSF to pass into the subarachnoid space (see Figure 16.7).¹ Approximately 30% of the CSF passes down into the subarachnoid space that surrounds the spinal cord, mainly on its dorsal surface, and moves back up to the cranial cavity along its ventral surface. Reabsorption of CSF into the vascular system occurs, through a pressure gradient. The normal CSF pressure is approximately 10 mmHg in the lateral recumbent position, although it may be as low as 5 mmHg or as high as 15 mmHg in healthy persons. The microstructure of the arachnoid villi is such that if the CSF pressure falls below approximately 3 mmHg the passageways collapse, and reverse flow is blocked. Arachnoid villi function as one-way valves, permitting CSF outflow into the blood but not allowing blood to pass into the arachnoid spaces. The pressure in the CSF manifests as normal ICP.

FIGURE 16.7 Circulation of the cerebrospinal fluid: (A) sagittal section indicating the sites of formation and routes of circulation of cerebrospinal fluid (arrows); (B) orientation of the arachnoid granulations.¹

Blood–Brain–Cerebral Spinal Fluid Barrier

The CNS is richly supplied with blood vessels that bring oxygen and nutrients to the cells there. However, many substances cannot easily be exchanged between blood and brain because the endothelial cells of the vessels and the astrocytes of the CNS form extremely tight junctions, collectively referred to as the blood–brain barrier (BBB).¹ In particular, small non-charged, lipid-soluble molecules can cross the BBB with ease. Experimental and clinical evidence suggests that the BBB maintains the chemical environment for neuronal function and protects the brain from harmful substances.²² Substances in the blood that gain rapid entry to the brain include glucose, the important source of energy, certain ions that maintain a proper medium for electrical activity, and oxygen for cellular respiration. Small fat-soluble molecules, like ethanol, pass through the BBB. Some water-soluble molecules pass into the brain carried by special proteins in the plasma membrane of the endothelial cells. Excluded molecules include proteins, toxins, most antibiotics, and monoamines (e.g. neurotransmitters). Some of these unwanted molecules are actively transported out of the endothelial cells. When injured (by force or infection or oxidative processes), the permeability of the BBB is disrupted, allowing a proliferation of various chemicals and molecules – even bacteria – into the brain parenchyma, with at times devastating consequences.

Cerebral Circulation

The brain must maintain a constant flow of blood in order for brain activity to occur. The arterial blood flow to the brain consists of approximately 20% of the cardiac output (see Figure 16.8).⁵ Normal cerebral blood flow is 750 mL/min. The brain autoregulates blood flow over a wide range of blood pressure by vasodilation or vasoconstriction of the arteries.¹ In response to decreased arterial flow, the circle of Willis can act as a protective mechanism by shunting blood from one side to the other or from the anterior to posterior portions of the brain. This compensatory mechanism delays neurological deterioration in patients.

FIGURE 16.8 The major arteries of the brain: (A) ventral view: the enlargement of the boxed area showing the circle of Willis; (B) lateral and (C) midsagittal views showing anterior, middle and posterior cerebral arteries; (D) idealised frontal section showing course of middle cerebral artery.⁸²

The cerebral veins drain into large venous sinuses and then into the right and left internal jugular veins (see Figure 16.9).²³ The venous sinuses are found within the folds of the dura mater. The veins and sinuses of the brain do not have valves, so the blood flows freely by gravity.¹ The face and scalp veins can flow into the brain venous sinuses; therefore, infection can easily be spread into the dural venous sinuses and then enter the brain. Patient position can prevent or promote venous drainage from the brain. Head turning and tilting may kink the jugular vein and decrease or stop venous flow from the brain, which will then raise the pressure inside the cranial vault.

FIGURE 16.9 Cerebral venous drainage.²³

Cerebral blood flow (CBF) is the cerebral perfusion pressure (CPP) divided by cerebrovascular resistance (CVR). CVR is the amount of resistance created by the cerebral vessels, and it is controlled by the autoregulatory mechanisms of the brain. Specifically, vasoconstriction (and vasospasm) will increase CVR, and vasodilation will decrease CVR.¹ It is influenced by the inflow pressure (systole), outflow pressure (venous pressure), cross-sectional diameter of cerebral blood vessels, and intracranial pressure (ICP).¹ CVR is similar to systemic vascular resistance; but, due to the lack of valves in the venous system of the brain, cerebral venous pressure also influences the CVR. An important characteristic of the cerebral circulation is its ability to autoregulate, that is, the ability to maintain constant cerebral blood flow despite variations in perfusion pressure (see Table 16.5). This is important in protecting the brain from both ischaemia during hypotension and haemorrhage during hypertension. CBF is affected by extrinsic and intrinsic factors.¹ Extrinsic factors include systemic blood pressure, cardiac output, blood viscosity and vascular tone. The body responds to these demands with changes in blood flow. Aerobic metabolism is critically dependent on oxygen in order to process glucose for normal energy production, and the brain does not store energy. Therefore, without a constant source of oxygen and energy, its supply from CBF can be exhausted within 3 minutes. Intrinsic factors include PaCO₂ (pH), PaO₂ and ICP. The vessels dilate with increases in PaCO₂ (hypercarbia) or low pH (acidosis) and with decreases in PaO₂ (hypoxia). This vasodilation increases CBF. The vessels constrict with decreases in PaCO₂ or high pH and with increases in local PaO₂.¹ This vasoconstriction will decrease the CBF. In addition, intrinsic factors can change the extrinsic factors by altering the metabolic mechanisms. These changes can lead to an alteration in the CBF. For example, there can be a change from aerobic to anaerobic metabolism, which increases the concentrations of other end-products such as lactic acid, pyruvic acid and carbonic acid, which causes a localised acidosis. These end-products result in a high pH which will cause an increase in CBF. Other factors that can affect CBF include pharmacological agents (anaesthetic agents and some antihypertensive agents), rapid-eye-movement sleep, arousal, pain, seizures, elevations in body temperature, and cerebral trauma.

TABLE 16.5 Changes in cerebrovascular and cerebrometabolic parameters when various cerebral variables are reduced with and without intact autoregulation

TABLE 16.6 PTA scale used to determine severity of brain injury

PTA Score	Severity
1–4 hours	Mild brain injury
≤1 day	Moderate brain injury
2–7 days	Severe brain injury
1–4 weeks	Very severe brain injury
1–6 months	Extremely severe brain injury
>6 months	Chronic amnesia state

Spinal Cord

The spinal cord is the link between the peripheral nervous system and the brain. The spinal cord has a small, irregularly shaped internal section of grey matter (unmyelinated tissue) surrounded by a larger area of white matter (myelinated axons). The internal grey matter is arranged so that a column of grey matter extends up and down dorsally, one on each side; another column is found in the ventral region on each side (see Figure 16.10).¹

FIGURE 16.10 The spinal cord and spinal meninges; (A) posterior view of the spinal cord, showing the meningeal layers, superficial landmarks, and distribution of grey matter and white matter; (B) sectional view through the spinal cord and meninges, showing the peripheral distribution of spinal nerves.¹

The spinal cord is an essential component of both the sensory and motor divisions of the nervous system. The first of the primary functions of the spinal cord is to transmit sensory impulses along the ascending tracts to the brain as well as to transmit motor impulses down the descending tracts away from the brain.²⁴ The second primary function of the spinal cord is to house and regulate spinal reflexes. Receipt of sensory impulses may cause a reaction anywhere in the body; alternatively, the signal might be stored in the memory to be used at some stage in the future. Within the motor division of the nervous system the spinal cord helps to control the various bodily activities, including skeletal muscle activity, smooth muscle activity and secretion by both endocrine and exocrine glands.

Sensory neurons from all over the skin, except for the skin of the face and scalp, feed information into the spinal cord through the spinal nerves. The skin surface can be mapped into distinct regions that are supplied by a single spinal nerve ¹⁹ (see Figure 16.11).²⁵ Each of these regions is called a dermatome. Sensation from a given dermatome is carried over its corresponding spinal nerve. This information can be used to identify the spinal nerve or spinal segment that is involved in an injury. In some areas, the dermatomes are not absolutely distinct. Some dermatomes may share a nerve supply with neighbouring regions. For this reason, it is necessary to numb several adjacent dermatomes to achieve successful anaesthesia.

FIGURE 16.11 (A) Anterior and (B) posterior distributions of dermatomes on the surface of the skin.²⁵

The blood supply to the spinal cord arises from branches of the vertebral arteries and spinal radicular arteries.¹⁹ The midthoracic region, at approximately T4–T8, lies between the lumbar and vertebral arterial supplies and is a vulnerable zone of relatively decreased perfusion. This region is most susceptible to infarction during periods of hypotension, thoracic surgery or other conditions, causing decreased aortic pressure and potentially leading to ischaemic spinal injury with devastating consequences.¹⁹

Peripheral Nervous System

The PNS consists of 12 pairs of cranial nerves and 31 pairs of spinal nerves, and includes all neural structures lying outside the spinal cord and brainstem. The cranial nerves have previously been discussed regarding their role in brainstem function. The PNS has both motor and sensory components. The former includes the motor neuron cell body in the anterior horn of the spinal cord and its peripheral axonal process travelling through the ventral root and eventually the peripheral nerve. The motor nerve terminal, together with the muscle endplate and the synapse between the two, comprises the neuromuscular junction. The peripheral sensory axon, beginning at receptors in cutaneous and deep structures, as well as muscle and tendon receptors, travels back through peripheral nerves to its cell body located in the dorsal root ganglion. Its central process, travelling through the dorsal root, enters the spinal cord in the region of the dorsal horn. All commands for movement, whether reflexive or voluntary, are ultimately conveyed to the muscles by the activity of the lower motor neurons.

Motor Control

Movements can be divided into three main classes: voluntary activity, rhythmic motor patterns, and reflex responses. The highest-order activity is voluntary movement, which allows for expression of the will and a purposeful response to the environment (e.g. reading, speaking, performing calculations).¹ Such activity is goal-directed and largely learned, and improves with practice. In rhythmic motor patterns, the initiation and termination may be voluntary, but the rhythmic activity itself does not require conscious participation (e.g. chewing, walking, running). Reflex responses are simple, stereotyped responses that do not involve voluntary control (e.g. deep tendon reflexes or withdrawal of a limb from a hot surface). Motor control is carried out in a hierarchical yet parallel fashion in the cerebral cortex, the brainstem and the spinal cord. Modulating influences are provided by the basal ganglia and cerebellum through the thalamus.¹

Sensory Control

The somatic sensory system has two major components: a subsystem for the detection of mechanical stimuli (e.g. light touch, vibration, pressure, cutaneous tension), and a subsystem for the detection of painful stimuli and temperature.¹ Together, these subsystems give the ability to identify the shapes and textures of objects, to monitor the internal and external forces acting on the body at any moment, and to detect potentially harmful circumstances. Mechanosensory processing of external stimuli is initiated by the activation of a diverse population of cutaneous and subcutaneous mechanoreceptors at the body surface that relays information to the central nervous system for interpretation and ultimately for action. Additional receptors located in muscles, joints and other deep structures monitor mechanical forces generated by the musculoskeletal system, and are called proprioceptors. Mechanosensory information is carried to the brain by several ascending pathways that run in parallel through the spinal cord, brainstem and thalamus to reach the primary somatic sensory cortex in the postcentral gyrus of the parietal lobe.¹ The primary somatic sensory cortex projects in turn to higher-order association cortices in the parietal lobe, and back to the subcortical structures involved in mechanosensory information processing.

Autonomic Nervous System

The autonomic nervous system, with its three major divisions (sympathetic, parasympathetic and enteric), is largely an involuntary system and is part of the efferent division, as we saw in Figure 16.1. It allows the body to adjust to rapidly changing external events (the ‘flight or fight’ response of the sympathetic division), and to regulate internal activities (blood pressure, temperature, airway and breathing, urinary function, digestion by the parasympathetic and enteric divisions).¹ Whereas the major controlling centres for somatic motor activity are the primary and secondary motor cortices in the frontal lobes and a variety of related brainstem nuclei, the major locus of central control in the visceral motor system is the hypothalamus and the complex circuitry that it controls in the brainstem tegmentum and spinal cord.¹ The status of both divisions of the visceral motor system is modulated by descending pathways from these centres to preganglionic neurons in the brainstem and spinal cord, which in turn determine the activity of the primary visceral motor neurons in autonomic ganglia. The postganglionic neurons of the sympathetic system, with few exceptions, act on their effectors by releasing the neurotransmitter adrenaline and the related compound noradrenaline. This system is therefore described as adrenergic, which means ‘activated by adrenaline’.¹ The autonomic regulation of several organ systems of particular importance in clinical practice is illustrated in Figure 16.12.¹⁵

FIGURE 16.12 Sympathetic and parasympathetic divisions of the autonomic nervous system. Sympathetic outputs (left) arise from thoracolumbar spinal cord segments and synapse in paravertebral and prevertebral ganglia. Parasympathetic outputs (right) arise from craniosacral regions and synapse in ganglia in or near effector organs.¹⁵

Neurological Assessment and Monitoring

This section explores the complex issues surrounding cerebral haemodynamics and assessment. The objective of assessment is to determine the extent of neurological injury, recognise fluctuations in condition and imminent deterioration, and assist in maintaining cerebral perfusion as part of multimodal monitoring.

Physical Examination

The neurological physical exam begins at the onset of patient contact, and the priorities are defined by a primary survey and vital signs. The history and contact with family can inform the clinical exam and should include the patient’s normal baseline status, medications and other substance use, and past neurological symptoms such as syncope or seizures.

Specific areas tested during the initial physical exam include level of consciousness, general behaviour, memory, attention and concentration, abstract thought and judgement. Not every aspect of the examination will be relevant in all critical care situations and therefore may not be tested. Nevertheless, the clinician should understand how all components are integrated and how they influence priority decision making for patient care. At change of shift, performing a physical exam with the incoming nurse ensures clear communication of the patient’s previous status. The patient’s ability to perform should be taken into consideration, as it may be necessary to modify assessment techniques. For example, intubated patients who are otherwise awake and aware may gesture or write answers to questions instead of verbalising them. In addition, when patients are the recipients of very frequent neurological assessment over an extended period of time (including arousal and awareness, pupil and motor response) sleep and sensory rest deprivation is common. Sleep deprivation and sensory overload will confound assessment accuracy. Therefore careful consideration needs to be given in regard to the priorities of assessment and rest; a plan needs to implemented to promote rest as neurological injury requires rest and sleep for restoration. See Online resources for links to a full neurological assessment and physical examination protocol.

Conscious State

Arousal and awareness are the fundamental constituents of consciousness and should be evaluated and documented repeatedly for trend analysis. Changes in the conscious state are the first to change in deterioration.

Arousal assessment

The evaluation of arousal focuses on the ability to be able to respond to a variety of stimuli and can be described using the AVPU scale or terms such as disorientated, lethargic, or obtunded. The advanced trauma life support course ²⁶ recommends an initial assessment during initial resuscitation based on the response to stimulation: Awake, Verbal, Pain, Unresponsive (AVPU). Observe the patient’s response (verbal or motor). If there is no response to voice or light touch, painful stimulus is needed to assess neurological status. Central pain should be used first and applied with care. Sternal rub, supraorbital pressure (least used), trapezius pinch (most used) or pinching the fleshy portion of the upper arm near the axilla are methods for introducing central pain. Hand grasp is a reflex and is a poor test for motor strength. If the patient does not respond to verbal stimulus but moves spontaneously in a purposeful manner (picks at linen, pulls at tubes), the patient is localising. Painful stimulus is not required if spontaneous localisation has been observed. Watch for symmetry. Localising is purposeful and intentional movement intended to eliminate a noxious stimulus, whereas withdrawal is a ‘smaller’ movement used to ‘get away from’ noxious stimulus. Abnormal flexion differs from withdrawal in that the flexion is rigid and abnormal looking. Abnormal extension is a rigid movement with extension of the limbs.

Assessment of awareness

If arousable, progress to assessment of awareness using the Glasgow Coma Scale (GCS). Teasdale and Jennett ²⁷ designed the GCS to establish an objective, quantifiable measure to describe the prognosis of a patient with a brain injury and include scoring of separate subscales related to eye opening, verbal response and motor response (Table 16.7). Originally, the GCS was developed as three separate response areas and reported as such. Contemporary use of the GCS automatically adds the three best response scores and easily loses the information given from the separate response areas. Reporting the GCS as three numbers and then the total gives a broader assessment interpretation.

TABLE 16.7 Glasgow Coma Scale
The Glasgow Coma Scale is scored between 3 and 15, 3 being the worst, and 15 the best. It comprises three parameters: best eye response, best verbal response and best motor response. The definition of these parameters is given below.

The Glasgow Coma Scale for adults	Paediatric version of the Glasgow Coma Scale
Best eye response (4) 1. No eye opening 2. Eye opening to pain 3. Eye opening to verbal command 4. Eyes open spontaneously

Best eye response (4)

1. No eye opening

2. Eye opening to pain

3. Eye opening to verbal command

4. Eyes open spontaneously

Best verbal response (5)

1. No verbal response

2. Incomprehensible sounds

3. Inappropriate words

4. Confused

5. Orientated

Best verbal response (5)

1. No vocal response

2. Occasionally whimpers and/or moans

3. Cries inappropriately

4. Less than usual ability and/or spontaneous irritable cry

5. Alert, babbles, coos, words or sentences to usual ability

Best motor response (6)

1. No motor response

2. Extension to pain

3. Flexion to pain

4. Withdrawal from pain

5. Localising pain

6. Obeys commands

Best motor response (6)

1. No motor response to pain

2. Abnormal extension to pain (decerebrate)

3. Abnormal flexion to pain (decorticate)

4. Withdrawal to painful stimuli

5. Localises to painful stimuli or withdraws to touch

6. Obeys commands or performs normal spontaneous movements

The advantage of the GCS is that it allows rapid serial comparisons and categorisation of basic neurological function over time. However, it has several recognised weaknesses, including poor prediction of outcome beyond survival, poor interrater reliability, and inconsistent use in the prehospital and hospital settings. GCS accuracy will be affected if the patient is receiving anaesthetic agents or sedation and noxious stimuli should be avoided. Furthermore, the rare event of a locked-in syndrome where a patient is neurologically aware and awake but not responding is poorly represented by the GCS. Also, interpretation of response in regard to language used or a previous communication disability is important for assessment accuracy. See Online resources for a link to a full GCS procedure.

Eye and pupil assessment

Pupillary responses, including pupil size and reaction to light, are important neurological observations and localise cerebral disease to a specific area of the brain.

The immediate constriction of the pupil when light is shone into the eye is referred to as the direct light reflex. Withdrawal of the light should produce an immediate and brisk dilation of the pupil. Introduction of the light into one eye should cause a similar constriction to occur in the other pupil (consensual light reaction).²⁸

Other points to consider when conducting pupillary observations include the following:²⁹

• pinpoint non-reactive pupils are associated with opiate overdose

• non-reactive pupils may also be caused by local damage

• atropine will cause dilated pupils

• one dilated or fixed pupil may be indicative of an expanding or developing intracranial lesion, compressing the oculomotor nerve on the same side of the brain as the affected pupil

• A sluggish pupil may be difficult to distinguish from a fixed pupil and may be an early focal sign of an expanding intracranial lesion and raised intracranial pressure. A sluggish response to light in a previously reacting pupil must be reported immediately.

Assessment of pupillary function focuses on three areas: (1) estimation of pupil size and shape; (2) evaluation of pupillary reaction to light; and (3) assessment of eye movements. Metabolic disturbances rarely cause pupillary changes, so abnormal pupillary findings are usually due to a nervous system lesion.³⁰ Irregular-sized pupils are normal for some people and eye prostheses are common so it is important to establish and document these findings so a trend can be established to determine normal from altered states.

Eye and eyelid movements

Patients who are comatose will exhibit no eye opening. In patients with bilateral thalamic damage, there may be normal consciousness, but an eye opening apraxia may mimic coma. If the patient’s eyes are closed, the clinician should gently raise and release the eyelids. Brisk opening and closing of the eyes indicates that the pons is grossly intact. If the pons is impaired, one or both eyelids may close slowly or not at all. In the patient with intact frontal lobe and brainstem functioning, the eyes, when opened, should be pointed straight ahead and at equal height. If there is awareness, the patient should look towards stimuli after eye opening. Eye deviation indicates either a unilateral cerebral or brainstem lesion. If the eyes deviate laterally, gently turn the head to see if the eyes will cross the midline to the other side. A pattern of spontaneous, slow and random movements (usually laterally) is termed roving-eye movements. This indicates that the brainstem oculomotor control is intact but awareness is significantly impaired.³¹

Limb movement

Assessment of extremities and body movement (or motor response) provides valuable information about the patient with a decreased level of consciousness.³² The clinician must observe the patient’s spontaneous movements, muscle tone, and response to tactile stimuli. Decorticate (flexor) posturing is seen when there is involvement of a cerebral hemisphere and the brain stem. It is characterised by adduction of the shoulder and arm, elbow flexion, and pronation and flexion of the wrist while the legs extend. In terms of the GCS motor score, the withdrawal flexor scores a higher (4/6) than a spastic flexor movement (3/6). Decerebrate (extensor) posturing is seen with severe metabolic disturbances or upper brainstem lesions. It is characterised by extension and pronation of the arm(s) and extension of the legs. Patients may have an asymmetrical response and may posture spontaneously or to stimuli.

Motor tone is first assessed by flexing the limbs and noting increased or absent tone.³³ If no tone is present, the hand is lifted approximately 30 cm above the bed and carefully dropped while protecting the limb from injury. The test is repeated with all extremities. Typically, the lower the level of consciousness, the closer to flaccid the limb(s) will be. An asymmetrical examination may indicate a lesion in the contralateral hemisphere or brainstem.

The next assessment, peripheral reflex response, is response to tactile stimuli peripherally and usually elicits a reflex response rather than a central or brain response. It is important to apply stimuli in a progressive manner, using the least noxious stimuli necessary to elicit a response. If there is no response to light or firm pressure, the clinician must use noxious stimuli. Each extremity is assessed individually. The typical technique for peripheral noxious stimuli involves pressure on the nail beds for asserting a peripheral stimulus. The triple-flexion response is a withdrawal of the limb in a straight line with flexion of the wrist–elbow–shoulder or the ankle–knee–hip. This response is considered a spinal reflex and is not an indication of brain involvement in the movement. The triple-flexion response is common in patients with severe neurological impairment. It is not uncommon in patients who have become brain dead, and great care must be taken to avoid confusion between brain and spinal-mediated responses. If the patient has any other motor activity to peripheral extremity noxious stimuli, it is an indication of higher brain function.

If a noxious stimuli is applied centrally through a sternal rub, trapezius pinch or supraorbital nerve pressure and the patient moves an extremity, it is an indication of brain involvement in the movement and not a spinal reflex.³⁴ The movement should be noted as normal, decorticate (flexor: either withdrawal or spastic) or decerebrate (extensor) and documented accordingly. It should be noted that careful consideration should be given to the choice of noxious stimuli with trapezius pinch the preferred choice as both sternal rub and supraorbital nerve pressure can be traumatic when applied. In ventilated patients, endotracheal suction can also be a substitute for a central noxious stimulus, but the choice of stimulus needs to be consistent.

Facial symmetry

Facial symmetry is often difficult to appreciate in, for example, severely ill patients due to oedema, endotracheal tube tape and nasogastric tubes. An asymmetric response is indicative of a lesion of CN VII. Complete hemi-facial involvement is typically seen in peripheral dysfunction (Bell’s palsy), whereas superior division (forehead) sparing weakness indicates a pontine/medullary (central) involvement. It is important to refrain from supraorbital pressure until after pupillary responses have been assessed because this noxious stimulation may cause alteration in pupillary reactivity (hence one reason for the lack of preference for its use).

Corneal reflexes

The corneal reflex is assessed by holding the patient’s eye open and lightly stimulating the cornea.³⁵ The stimuli should result in a reflexive blink, best seen in the lower eyelid. The traditional assessment technique involves using a wisp of cotton, lightly brushed along the lower aspect of the cornea. An alternative, and less potentially traumatic, method is to gently instil isotonic eye drops or saline irrigation ampoules onto the cornea. This reflex is dependent upon CN V for its sensation and CN VII for its motor response. Loss of this reflex is indicative of lower brainstem damage, but may be absent due to trauma, surgery, or long-term contact lens usage.

Oropharyngeal reflexes

The oropharyngeal reflexes are controlled by CN IX and CN X.³⁶ The gag reflex is elicited by lightly stimulating the soft palate with a suction catheter or tongue blade. Clinicians should always avoid stimulating a gag reflex by wiggling the endotracheal tube because doing so may result in an inadvertent extubation. A gag reflex is a forceful, symmetrical lowering of the soft palate. The cough reflex is usually assessed only in patients with an endotracheal tube. This reflex is elicited by gently passing a suction catheter through the tube and stimulating a cough. Loss of these reflexes is indicative of lower brainstem damage.³⁷

Post Traumatic Amnesia Scale

Posttraumatic amnesia (PTA) is a disorder after brain injury that is classified as a traumatic delirium and may even be found in patients who rate a GCS of 15.³⁸ The incidence of delirium after a brain injury event is high especially with severe injuries and loss of consciousness. Delirium is discussed in detail in Chapter 7, however, traumatic delirium historically has been referred to in the literature as posttraumatic amnesia. Posttraumatic amnesia is defined as the ‘time elapsed from injury until recovery of full consciousness and the return of ongoing memory’.³⁹^,p.841 It is the initial stage of recovery from brain injury and is characterised by anterograde (formation of new memory) and retrograde (memory before injury) amnesia, disorientation and rapid forgetting. Brief periods of PTA can occur after minor concussion and may be the only clinical sign of any brain injury. This is where PTA is useful for defining severity of injury and alert the clinician in regard to greater surveillance and investigation as described in Table 16.6. Patients often progress directly from coma into delirium without a clearly-defined stupor stage, so using a tool to measure PTA can be useful to gauge the actual condition of the patient in the delirium state. Duration of PTA is extremely variable, ranging from minutes to months. Although the early stages of PTA are easily recognised, identifying the end point is difficult and complex.⁴⁰

The duration of PTA is the best indicator of the extent of cognitive and functional deficits after TBI. In Australia, the most common means of assessing PTA is the Westmead PTA scale.⁴¹ In this scale, four pictures, one with the examiner’s face and name, are to be recalled by the patient on the next day. Those with severe PTA will have difficulty recalling such short-term memory tasks. Often, patients will have a GCS of 15 but have moderate to severe PTA and can be overlooked by inexperienced clinicians who fail to watch for secondary insults. The duration of PTA correlates well with the extent of diffuse axonal injury and with functional outcomes. For example, one study found that 80% of patients with a PTA duration of less than 2 weeks had a good recovery, compared with 46% for those with a PTA duration between 4 and 6 weeks.⁴² A person is said to be absolved of PTA if they can achieve a perfect score for three consecutive days.

Assessment of the Injured Brain

The primary aim of managing patients with acute brain injury in the critical care unit is to maintain cerebral perfusion and oxygenation.⁴³ There is little that can be done to reverse the primary damage caused by an insult. Secondary insults may be subtle and can remain undetected by routine systemic physiological monitoring. Continuous monitoring of the central nervous system in the ICU serves three functions:⁴⁴

1. determine the extent of the primary injury

2. early detection of secondary cerebral insults so that appropriate interventions can be instituted

3. monitoring of therapeutic interventions to provide feedback.

Although serial cranial imaging such as computerised tomography (CT) or functional magnetic resonance imaging (fMRI) provides useful information, these are neither continuous nor can they be undertaken at the bedside. Continuous invasive arterial blood pressure monitoring in addition to pulse oximetry, temperature, end-tidal carbon dioxide and urine output should be included as part of standard general monitoring of brain-injured patients. In addition, techniques specific to the CNS are required. The commonest and most easily performed clinical assessment tool is the GCS. Brain-specific methods of monitoring reflect pressure in the cranial cavity, changes in brain oxygenation and metabolism (brain oxygen saturation), jugular venous oxygen saturation, near-infrared spectroscopy, brain tissue monitoring, cerebral haemodynamics (transcranial Doppler) and electrical activity of the CNS (EEG).

Brain Imaging Techniques

Computed tomography

CT is the primary neuroimaging technique in the initial evaluation of the acute brain injury patient and uses a computer to digitally construct an image based upon the measurement of the absorption of X-rays through the brain. Table 16.8 generally summarises the white to black intensities seen for selected tissues in CT. The advantages of CT are: (1) it is rapidly done, which is especially important in neurological emergencies; (2) it clearly shows acute and sub-acute haemorrhages into the meningeal spaces and brain; and (3) it is less expensive than a MRI.⁴⁵ Disadvantages include: (1) it does not clearly show acute or sub-acute infarcts or ischaemia, or brain oedema, only established injury; (2) it does not clearly differentiate white from grey matter as clearly as an MRI; and (3) it exposes the patient to ionising radiation. Despite these limitations it is still the most prevalent form of neurological imaging.⁴⁶

TABLE 16.8 The brain and related structures in CT

Structure/Fluid/Space	Grey Scale
Bone, acute blood Enhanced tumour Subacute blood Muscle Grey matter White matter Cerebrospinal fluid Air, Fat

Figure 16.13 is a scan from a traumatic brain injury patient and demonstrates a brain perfusion scan radionuclide imaging. In the image the cerebral cortex is dark, indicative of no CBF or perfusion confirming brain death.

FIGURE 16.13 Brain death confirmed with brain perfusion scan radionuclide imaging. The cerebral cortex is dark, indicative of no CBF. Permission received from patient’s next of kin (patient brain dead).

Intracranial Pressure Monitoring

Invasive measures for monitoring intracranial pressure (ICP) are commonly used in patients with a severe head injury or after neurological surgery. Normal ICP varies with age, body position, and clinical condition. The normal ICP is 7–15 mmHg in a supine adult, 3–7 mmHg in children, and 1.5–6 mmHg in term infants. The definition of intracranial hypertension depends on the specific pathology and age, although ICP >15 mmHg is generally considered to be abnormal. Increased ICP causes a critical reduction in CPP and CBF and may lead to secondary ischaemic cerebral injury. A number of studies have shown that high ICP is strongly associated with poor outcome, particularly if the period of intracranial hypertension is prolonged.⁵³ ICP is not a static pressure and varies with arterial pulsation, with breathing and during coughing and straining. Each of the intracranial constituents occupies a certain volume and, being essentially liquid, is incompressible. ICP cannot be reliably estimated from any specific clinical feature or CT finding and must actually be measured. Different methods of monitoring ICP have been described but two methods are commonly used in clinical practice: intraventricular catheters and intraparenchymal fibreoptic microtransducer systems.

The reference point for the transducer is the foramina of Monro (the duct joining the lateral and third ventricle that is in alignment with the middle of the ear), although, in practical terms, the external auditory meatus is often used.

Currently, ventriculostomy is the most accurate (although the intraparenchymal fibreoptic is now similar in accuracy), cost-effective and reliable method of monitoring ICP and is associated with low infection risks if the duration of placement is less than 72 hours.⁵⁴ The ventriculostomy catheter is part of a system that includes an external drainage system and a transducer. The drainage system and transducer are primed on insertion with preservative-free saline. The transducer can easily be calibrated or zeroed against a known pressure. Advantages of using an indwelling ventricular catheter include allowing CSF drainage to effectively decrease ICP and using the catheter as a means to instil medications. Access to CSF drainage allows serial laboratory tests of CSF and determination of volume–pressure relationships. Disadvantages of ventriculostomy include risk of infection, which is higher than that associated with other ICP-monitoring techniques.⁵⁵ In addition, the catheter may become occluded with blood or tissue debris, interfering with CSF drainage or ICP monitoring. Also, if significant cerebral oedema is present, locating the lateral ventricle for insertion of the ventriculostomy catheter may be difficult. Importantly, bleeding or ventricular collapse may occur if CSF is drained too rapidly.⁵⁶ For this last reason, many clinicians set the ventriculostomy drainage system to drain CSF when the ICP is greater than 15–20 mmHg by adjusting the height of the drip chamber. In addition, a limit of ventricular drainage per hour using gravity and three-way taps to 5–10 mL/h has been used to avoid excessively rapid CSF drainage. Using a ventriculostomy may allow lifesaving CSF drainage and control of intracranial hypertension and secondary injury.⁵⁷

Whilst routine ICP monitoring is widely accepted as a mandatory monitoring technique for management of patients with severe head injury and is a guideline suggested by the Brain Trauma Foundation, there is some debate over its efficacy in improving outcome from severe TBI.⁵⁸ A review of neurocritical care and outcome from TBI suggested that ICP/cerebral perfusion pressure (CPP)-guided therapy may benefit patients with severe head injury, including those presenting with raised ICP in the absence of a mass lesion and also patients requiring complex interventions.⁵⁹

Pulse waveforms

Interpretation of waveforms that are generated by the cerebral monitoring devices is important in the clinical assessment of intracranial adaptive capacity (the ability of the brain to compensate for rises in intracranial volume without raising the ICP).⁶⁰ Brain tissue pressure and ICP increase with each cardiac cycle and, thus, the ICP waveform is a modified arterial pressure wave. See Figure 16.14. The cardiac waves reach the cranial circulation via the choroid plexus and resemble the waveforms transmitted by arterial catheters, although the amplitude is lower.

FIGURE 16.14 The intracranial pressure waveforms. ‘A’ depicts the situation of a compliant system, ‘B’ A high pressure wave recorded from a non-compliant system in which P2 exceeds the level of the P1 waveform, due to a marked decrease in cerebral compliance. The lower tracing (C) is an example of an ICP waveform from a patient monitoring system in which can be identified the three distinct components, as indicated in the text.

There are three distinct peaks seen in the ICP waveform:⁶¹

• P1: the percussion wave, which is sharp and reflects the cardiac pulse as the pressure is transmitted from the choroid plexus to the ventricle;

• P2: the tidal wave, which is more variable in nature and reflects cerebral compliance and increases in amplitude as compliance decreases;

• P3: which is due to the closure of the aortic valve and is known as the dicrotic notch. Of recent importance is that the elevation of the P3 may indicate low global cerebral perfusion.⁶²

It is important that the waveform be continuously observed, as changes in mean pressure or in waveform shape usually require immediate attention. In acute states such as head injury and subarachnoid haemorrhage, the value of ICP depends greatly on the link between monitoring and therapy, so close inspection of the trend of the ICP and the details derived from the waveform is extremely important. Simple ongoing visual assessment of the ICP waveform for increased amplitude, elevated P2 and rounding of the waveform provides non-specific information suggestive of decreased intracranial adaptive capacity and altered intracranial dynamics.

Assessment of Cerebral Perfusion

Cerebral perfusion pressure is calculated as the mean arterial pressure minus the intracranial pressure (ICP) and represents the pressure gradient across the vessel that drives cerebral blood flow (CBF):

CPP is a pressure-based indicator of oxygen and metabolite delivery. There is no evidence for the optimum level of CPP, but 70–80 mmHg is probably the critical threshold in adults especially those who are pressure-active (i.e. ICP varies inversely with MAP).⁶³ Higher CPP has been associated with increased lung water and acute respiratory distress syndrome. Furthermore, mortality rises approximately 20% for each 10 mmHg loss of CPP. In those studies where CPP was maintained above 70 mmHg, the reduction in mortality was as much as 35% for those with severe head injury.⁶⁴ The Brain Trauma Foundation recommends a CPP goal of 50–70 mmHg despite the lack of definitive data, such as from randomised controlled trials and intention-to-treat clinical trials.⁶⁵ In the paediatric population a CPP >40 mmHg is the recommended guideline.^66,⁶⁷ Utilising cerebral oxygenation monitoring in combination with pressure has been associated with better outcomes for brain-injured patients, and is part of the multimodal assessment for brain injury.

Assessment of Cerebral Oxygenation

Jugular Venous Oximetry

Jugular venous catheterisation is used for deriving oxygen based variables.⁶⁸ It facilitates the assessment of jugular venous oxygenation (SjvO₂), cerebral oxygen extraction (CEO₂), and arteriovenous difference in oxygen (AVDO₂). All of these variables indicate changes in cerebral metabolism and blood flow, and therefore the catheter generates continuous data that reflect the balance between supply and demand of cerebral oxygen.

The catheter is inserted in the right jugular vein, as it is slightly larger than the left and provides readings that are more representative of overall brain function. The catheter tip is advanced so that the tip sits in the bulb of the internal jugular vein.

The normal requirement for cerebral oxygen delivery is consumption at 35–40% of available oxygen, giving a normal SjvO2 of 60–65%. Changes in SjvO₂ reflect changes in cerebral metabolic rate and cerebral blood flow; however, as it is a global measure it does not detect regional ischaemia. A high SjvO₂ is indicative of increased cerebral blood flow, reduced oxygen consumption, and hyperventilation. Low SjvO₂ levels suggest that cerebral perfusion is reduced, with levels below 40% indicative of global cerebral ischaemia.⁶⁹ However, caution must be used when interpreting values generated using this method, as high values might also imply an increase in arteriovenous shunting secondary to vasoconstriction, maldistribution of blood flow or lack of oxygen consumption as in brain death. Because SjvO2 monitoring is a global measure of cerebral oxygenation,⁷⁰ smaller areas of ischaemia are not detected unless these are of sufficient magnitude to affect global brain saturation. SjvO2 requires special care such as frequent recalibration to ensure accurate measurements, observing for catheter migration that interferes with signal quality, and often, medical intervention is required to reposition the catheter. The position of the patient also affects signal quality, and ideally the patient should be nursed supine with a head elevation of 10–15° and at least a neutral head alignment. It is important that measurement errors be excluded when abnormal readings are noted; algorithms have been developed to assist nurses when caring for patients with jugular bulb oximetry.⁷¹

Partial Brain Tissue Oxygenation Monitoring

Changes in ICP values alone do not accurately depict poor cerebral blood flow or oxygenation deficits to brain tissue. Consequently brain tissue hypoxaemia is often observed during the first 24 hours after injury despite controlled brain pressures. Monitoring partial pressure of oxygen in brain tissue (PbtO₂) can be used to collect more accurate and timely information about cerebral oxygen delivery and demand than ICP allows. A tissue oxygen value of less than 10 mmHg for more than 10 minutes carries a higher risk of death. Normal brain oxygen levels (PbtO₂ between 20 and 25 mmHg) emerge as a critical determinant of outcome, with values below 20 mmHg carrying a higher risk.⁶⁹

Regardless of ICP, brain tissue oxygenation falls with a decrease in cerebral blood flow below an ischaemic threshold of 18 mL/100 g/min. ICP may respond to the changes but often several hours later when the damage can not be reversed. Alterations in cerebral metabolic rate can also change tissue oxygen levels. Reducing the patient’s energy consumption via reduced noise and/or distractions, and increasing their protein caloric intake to complement their increased stress state can improve tissue oxygenation.⁷²

Microdialysis

Cerebral microdialysis (using a catheter ideally placed in the frontal lobe) is a tool for investigating the metabolic status of the injured brain and is part of multimodal monitoring. The microdialysis probe is inserted into the cerebral tissue where substances in the extracellular fluid surround the semipermeable membrane at the tip of the catheter. Following equilibration of the tissue metabolites with the perfusion fluid, the dialysate can be analysed for concentrations of products of energy metabolism (glucose, lactate, pyruvate) as indicators of hypoxia and ischaemia. In addition, interstitial glycerol can be determined, which is a parameter of lipolysis and/or cell membrane damage. In theory, the microdialysis catheter acts like a blood capillary.⁷³ Thereby, it is proposed that microdialysis provides information regarding events that take place in the tissue before any chemical events are reflected by changes in systemic blood levels of indicator substances.⁷⁴ These molecules diffuse across the membrane part of the catheter and equilibrate with the perfusion fluid, which is pumped through the probe at very low rates of flow. Changes in the concentration of a substrate in the surrounding milieu are reflected by subsequent changes in the dialysate.⁷⁵ Rather than inserting an instrument into the tissue, microdialysate is extracted and later analysed in the laboratory or clinically at the patient’s bedside.

Non-Invasive Assessment

Transcranial Doppler

Transcranial Doppler (TCD) ultrasound has proven to be a safe, reliable and relatively inexpensive technology for measuring cerebrovascular blood velocities and evaluating cerebral circulation and haemodynamics. Pulses of ultrasound are directed using a handheld transducer towards the vascular formations in the base of the skull. Velocities from the cerebral arteries, the internal carotids, the basilar and the vertebral arteries can be sampled by altering transducer location, angle and the instrument’s depth setting. The commonest windows in the cranium are located in the orbit (of the eye), and in the temporal and suboccipital regions. TCD measures systolic, diastolic and mean middle cerebral artery (MCA) flow velocities and a derived value, the pulsatility index (PI). Changes in the PI can be used to identify the threshold of autoregulation or cerebral perfusion pressure break point in individual patients. In subarachnoid haemorrhage (SAH) and TBI this may be due to vasospasm, or impaired autoregulation or abnormal intracranial compliance. TCD is a simple, portable and non-invasive tool, well suited to serial monitoring, that can be used at the bedside to detect relative changes in CBF in brain-injured patients.⁷⁶

Continuous Electroencephalography

Electroencephalography (EEG) is the recording of electrical activity by sensors along the scalp produced by the firing of neurons within the brain. Continuous EEG (cEEG) has the advantage of being continuous, noninvasive and carrying the potential to detect alterations in brain physiology at a reversible stage, which may trigger treatment before permanent brain injury occurs. The invention of digital EEG has made cEEG monitoring feasible for ICU patients.⁷⁷ Currently, the main applications of cEEG are diagnosing nonconvulsive status epilepticus, monitoring and guiding the treatment of status epilepticus and detecting delayed cerebral ischaemia from vasospasm in subarachnoid haemorrhage patients. Other applications may include monitoring of reperfusion after tissue plasminogen activator in acute stroke patients and detection of intracranial hypertension. Clinically unrecognised electrographic seizures and periodic epileptiform discharges have been shown to be frequent and associated with poor outcome in patients with severe brain injury from different aetiologies, including TBI, ischaemic and haemorrhagic strokes and CNS infection.⁷⁸ The EEG becomes substantially abnormal (suppressed) when cerebral blood flow declines to 20–30 mL/100 g/min. More subtle abnormalities accompany lesser degrees of hypoperfusion, including initial loss of beta activity, slowing to the theta range, and then to the delta range. Irreversible injury to brain tissue occurs at cerebral flows of about 10–12 mL/100 g/min. Thus, the EEG sensitivity to ischaemia allows its use in situations where cerebral perfusion is at risk.⁷⁹ To facilitate interpretation, digital EEG data can be transformed into power spectra by fast Fourier transformation. Changes over time in these quantitative EEG (qEEG) parameters can trigger remote reading, focused neurological examination, imaging studies and early treatment. Subtle EEG changes may be difficult to interpret in isolation, but may be better understood when interpreted in concert with other components of a multimodality monitoring paradigm, which may include microdialysis, brain tissue oxygen and cerebral perfusion pressure.

Near-Infrared Spectroscopy

Near-infrared spectroscopy (NIRS) is a non-invasive method of monitoring continuous trends of cerebral oxygenated and deoxygenated haemoglobin by utilising an infrared light beam transmitted through the skull. Oxygenated and deoxygenated haemoglobin have different absorption spectra and cerebral oxygenation and haemodynamic status can be determined by their relative absorption of near-infrared light. NIRS allows interrogation of the cerebral cortex using reflectance spectroscopy via optodes, light transmitting and detecting devices, placed on the scalp. Normal saturation is 70%. Because NIRS interrogates arterial, venous, and capillary blood within the field of view, the derived saturation represents a regional tissue oxygenation (rSO₂) measured from these three compartments and can be used to identify tissue hypoxia and ischaemia in the brain cortex.

The clinical and bedside use of NIRS is constrained by potential sources of error, which include contamination of the signal by the extracerebral circulation (such as in the scalp), extraneous light, and the presence of extravascular blood arising from subarachnoid or subdural haemorrhage.⁸⁰ In a recent study in patients with subarachnoid haemorrhage, episodes of angiographic cerebral vasospasm were strongly associated with reduction in trend in the ipsilateral NIRS signal.⁸¹ Furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal demonstrating real-time detection of intracerebral ischaemia.

Summary

This chapter provides an overview of anatomy and physiology in the context of and in application to neurological assessment of the critically ill. Priorities of clinical assessment are described in terms of the critically ill patient. Imaging techniques and assessment incorporate the therapeutics of intracranial pressure, cerebral perfusion pressure and partial brain tissue oxygenation monitoring, cEEG, transcranial Doppler and cerebral perfusion imaging. The research vignette reports how alcohol intoxication impacts upon clinical assessment using the Glasgow Coma Scale score. The clinical case examples neurological assessment priorities in an unstable, traumatic brain injury patient. Clinical, non-invasive and invasive assessment techniques are described within the context of this patient’s care.

Case study

On the 30th August, a 24-year-old male, Daniel, was riding his trail bike on a dirt road. Whilst negotiating a corner he collided at high speed with a truck and was dragged under the truck for approximately 60 metres. He was wearing a helmet. At the scene his GCS was 3 and his pupils, sized 3 mm in diameter, were reacting sequentially to light. Rib and severe bilateral femur fractures were evident to the attending paramedics who applied compression to the profusely-bleeding femur. Daniel’s helmet was removed; his airway was maintained and the cervical spine immobilised, his chest decompressed by needle thorocentesis on the left side. Intravenous access was obtained and normal saline infused. Oxygen was administered and Daniel was transferred to the nearest trauma tertiary centre by helicopter.

Emergency Department

Arrival to the Emergency Department (ED) was 20 minutes later. Daniel bypassed triage and was admitted to the resuscitation area where members of the trauma team conducted primary and secondary surveys. On presentation, Daniel’s vital signs were: heart rate 134 beats/min, respirations 8 breaths/min with paradoxical chest rise and fall, blood pressure 93/65 mmHg, mean arterial pressure (MAP) 74 mmHg, SaO₂ unable to obtain, temperature 34.9°C, with a GCS of 3.

Primary survey

Daniel’s primary survey revealed the following details.

• Airway: Upper airway cleared. Cervical spine: Status unknown, collar in situ.

• Breathing: Hand ventilated on 12 L/min at 14 breaths/min, paradoxical chest rise and fall, generalised poor air entry, decreased bilaterally, no tracheal deviation.

• Circulation: Tachycardic, hypotensive, and hypovolaemic; pulses present on palpation except for the right popliteal and dorsalis pedis; temperature centrally warm, well perfused, skin pink in colour, peripherally cold and pale; capillary refill >4 seconds.

• Disability: He was unresponsive, GCS 3; pupils: left 3 mm and right 5 mm non-reacting. Daniel was intubated using thiopentone, fentanyl and rocuronium and mechanically ventilated in combination with physiological fluid resuscitation.

Secondary survey

The secondary survey revealed the following details.

• Head: scalp clear, nil abrasions. CT revealed widespread petechial haemorrhages consistent with diffuse axonal injury, acute subdural haemorrhage with midline shift of the ventricles, hairline base of skull fracture and cerebral oedema with poor differentiation between grey and white matter.

• Face: No oedema; rhinorrhoea and otorrhoea from both nostrils and ears.

• Neck: Stiff neck collar left in situ; no obvious lacerations observed around neck area; no evidence of tracheal deviation. Cervical spine CT reported no bony injury, spine not cleared; with a stable L4 pedicle fracture.

• Chest: Obvious chest deformity and instability of sternum and ribs; paradoxical chest rise and expansion; decreased air entry bilaterally, no subcutaneous emphysema. Bilateral pulmonary contusions, left haemopneumothorax diagnosed on review of the chest X-ray; a left sided chest drain was inserted.

• Abdomen: Firm, no abnormal distension, some bruising. IDC insertion revealed haematuria.

• Pelvis: Bruising bilaterally with no obvious deformity.

• Back: Marked flank bruising, no lacerations, right perinephric haematoma on CT; rectal tone present. Upper limbs: Obvious deformity of right arm; X-ray revealed right radial and ulna fractures, lacerations and bruising present; pulses present.

• Lower Limbs: Bilateral femur fractures – right one compound; lacerations and extensive bruising; pulses absent right side.

Emergency surgery

Due to his continued bilateral pupil enlargement and non reactivity, Daniel was transferred to the operating theatre within the hour for a craniotomy and insertion of external ventricular drain (EVD) and evacuation of the subdural haematoma. A repeat CT scan revealed reduced cerebral oedema and repositioning of the ventricular midline shift. Widespread petechial hemorrhages remained. In terms of his further injuries, a right femur external fixation, right femoral artery repair, lateral right thigh fasciotomy, and right forearm fracture stabilisation by plaster cast were performed in conjunction with his neurosurgery due to a large amount of blood loss mainly from the right femur. The right perinephric haematoma had stabilised and was managed conservatively. A left subclavian central venous catheter was placed and a radial arterial cannulation for arterial blood pressure monitoring.

Daniel received a massive blood transfusion:

• 34 units packed red blood cells

• 17 units fresh frozen plasma

• 10 units cryoprecipitate

• 5 units platelets

• 7 L voluven (hydroxyethyl starch/normal saline)

• 4.5 L Hartmans solution

• 2.5 L normal saline

Following surgery, he was admitted to the Intensive Care Unit (ICU) for further management

ICU management

Day 1

On arrival to the ICU, Daniel’s condition was critical but stable: heart rate = 132 beats/min; intubated and ventilated at 14 breaths/min, Vt 500 mL, FiO₂ = 0.7, Positive End Expiratory Pressure (PEEP) = 10 cmH₂O; blood pressure 160/65 mmHg (MAP 93) with noradrenaline support for a CPP of 65; SaO₂ 97%; temperature 35.5°C; his pupils returning to a stabilised 3/3 mm (R/L), sluggish sequential reaction; he was heavily sedated, not paralysed initially, and unresponsive with a Glasgow Coma Scale score (GCS) of 3T (eye opening 1, verbal 1 [T = intubated], motor 1). The initial opening intracranial pressure of 28 mmHg was indicative of the cerebral oedema from the diffuse injury. The EVD was positioned at 15 cm above the tragus and remained opened during episodes of increased ICP exceeding 20 mmHg and drained 26 mL of blood-tinged cerebral spinal fluid in the first 24 hours. He required paralysing and increased sedation to control his ICP and CPP. Pain stimulation for neurological assessment under these conditions was only assessed during endotracheal suction. Noradrenaline infusion fluctuated throughout the day and Daniel required hypotonic saline boluses for intracranial hypertension. Normal saline was infused to maintain euovolemia.

Days 2–7

Daniel’s clinical parameters and assessment are shown in Table 16.10. His condition remained variable and on days 3 and 4 his ICP and CPP were unstable with increasing need for sedation and paralysis. His pupils enlarged to size 5 and became unreactive. He was stabilised with boluses of hypertonic saline and increased drainage from the EVD which totalled 35 mL for the day. A repeat CT determined a diffuse injury with global cerebral oedema. The ventricles were effaced but not compressed. After stabilising on day 4, Daniel’s sedation was turned off the morning of day 5 for neurological assessment. His GCS was 5 (E2 V1(T)M3) with normal flexion to pain and remained unchanged until day 7. His GCS may have increased but it was difficult to assess his verbal response whilst intubated. The EVD was removed on day 6 and he remained sedated and ventilated to support his chest injuries. Daniel continued to slowly recover.

TABLE 16.10 Overview of Daniel’s clinical parameters and assessment, Days 1–7