PATHOPHYSIOLOGY

There are four different types of cerebral oedema — left untreated, all can be devastating.

Vasogenic oedema is clinically the most important type and is caused by the increased permeability of the capillary endothelium (the lining cells of the blood vessels) of the brain after injury to the vascular structure. The blood–brain barrier is disrupted and plasma proteins leak into the extracellular spaces, drawing water to them and increasing the water content of the brain parenchyma (neuronal, glial and endothelial cells). Vasogenic oedema starts in the area of injury and spreads, with fluid accumulating in the white matter of the ipsilateral side (on the same side) because the parallel myelinated fibres separate more easily. Oedema promotes more oedema because of ischaemia from the increasing pressure. Vasogenic oedema can arise due to tumours, haemorrhage, infections and brain trauma.

Clinical manifestations of vasogenic oedema include focal neurological deficits (such as cranial nerve disturbances or hemiparesis (one-sided weakness), which provide clues as to the location of damage in the brain), disturbances of consciousness and severe increases in ICP. Vasogenic oedema resolves by slow diffusion.

In cytotoxic oedema, toxic factors directly affect the cellular elements of the brain parenchyma, causing failure of the active transport systems. The cells lose their potassium and gain larger amounts of sodium. Water follows sodium and moves by osmosis into the cells, so that the cells swell. Cytotoxic oedema occurs principally in the grey matter and may increase vasogenic oedema. Cytotoxic oedema can significantly alter global neurological function and result in coma.

Ischaemic oedema follows cerebral infarction (death of neurons, often following a stroke). The ischaemia has components of both vasogenic and cytotoxic oedema. The initial oedema is confined to the intracellular compartment, but over several days, brain cells begin to undergo necrosis and die, releasing lysosomes (see Chapter 3). In this autodigestive process, the blood–brain barrier’s permeability increases, thereby contributing to the oedema.

Interstitial oedema is seen most often with non-communicating hydrocephalus (see next section). The oedema is caused by movement of CSF from the ventricles into the extracellular spaces of the brain tissues. The brain fluid volume increases predominantly around the ventricles, with increased hydrostatic pressure within the white matter. The size of the white matter reduces because of the rapid disappearance of myelin lipids.

CLINICAL MANIFESTATIONS

The signs and symptoms of cerebral oedema can vary. If cerebral oedema is compensated by a decrease in CSF and blood flow, then neurological function may not be impaired. However, when cerebral oedema is significant or ongoing, increase in ICP may occur. The clinical manifestations of raised ICP include — but are not limited to — headache, nausea and vomiting, and a decrease in consciousness. If left untreated, these clinical manifestations will progress and a decrease in global cerebral function will result. Patients with severe cerebral oedema may present with coma and changes in pupillary light reactions.

EVALUATION AND TREATMENT

The treatment of cerebral oedema is dependent on the type of oedema and the extent of the increased ICP. For instance, if a brain tumour is causing localised oedema, patients will often be treated with corticosteroids, such as dexamethasone. Moreover, the tumour can be surgically removed. In the acute phase of cerebral oedema, osmotic diuretics (mannitol) can reduce the water volume and lower the effects of oedema.

There are other options for clinicians to manage cerebral oedema if there is an accompanying raised ICP. They include hyperventilation to lower (‘blow off’) carbon dioxide, which will cause cerebral vasoconstriction; or alternatively, a catheter can be inserted into the lateral ventricles and excess CSF can be drained to lower the ICP (see Figure 8-10). These two methods employ other mechanisms to reduce the pressure and do not actively treat the cause of the cerebral oedema. It should be noted that changing the CSF or blood flow involves using the principles of the Monro-Kellie hypothesis — that is, when one volume increases, the other volumes must decrease by a similar amount to maintain homeostasis between the brain tissue, blood and CSF.

FIGURE 8-10 Ventricular drain.

The catheter is inserted into the lateral ventricles and excess CSF is drained when the ICP increases. This temporarily lowers the ICP, but ultimately does not treat the primary cause.

PATHOPHYSIOLOGY

The obstruction of CSF flow associated with hydrocephalus produces dilation of the ventricles proximal to the obstruction. This is evident on computed tomography (CT) and magnetic resonance imaging (MRI) scans (see Figure 8-11). Obstructed CSF is under pressure, causing atrophy of the cerebral cortex and degeneration of the white matter tracts. There is selective preservation of grey matter. When excess CSF fills a defect caused by atrophy, a degenerative disorder or a surgical excision, this fluid is not under pressure; therefore, atrophy and degenerative changes are not induced.

FIGURE 8-11 Hydrocephalus.

MRI scans of patients with hydrocephalus. A Lateral view showing dilated ventricles (*). B Coronal view also indicating increase in CSF in ventricles (*), which is indicative of hydrocephalus.

Source: Imaging consult. Elsevier. 2009.

CLINICAL MANIFESTATIONS

Acute hydrocephalus presents with signs of rapidly developing increased ICP. The person quickly deteriorates into a deep coma if not treated promptly. Normal-pressure hydrocephalus (dilation of the ventricles without the increased pressure) develops slowly, with the individual or family having a decline in memory and cognitive function. An unsteady, broad-based gait (walking style) with a history of falling is common. Additional clinical manifestations are apathy, inattentiveness and indifference to self, family and the environment. Urinary incontinence is often present.

EVALUATION AND TREATMENT

The diagnosis is based on physical examination and CT and MRI scans. Hydrocephalus can be treated by surgery to resect cysts, neoplasms or haematomas. A ventricular bypass into the normal intracranial channel or into an extracranial compartment using a shunting procedure is one of the most common neurosurgical procedures for the treatment of hydrocephalus. In normal-pressure hydrocephalus, reduction in CSF through a diuresis regimen is often used.

PATHOPHYSIOLOGY

Processes above the tentorial plate (supratentorial) produce changes in arousal by either diffuse or localised dysfunction. Disease processes may produce diffuse dysfunction (e.g. encephalitis — inflammation of the brain) and may affect the cerebral cortex or the underlying sub-cortical white matter. Localised dysfunction generally is caused by masses that directly impinge on deep structures of the diencephalon or that secondarily compress these structures in the process of herniation. Such localised destructive processes directly impair function of the thalamus or hypothalamus.

Disorders outside the brain but within the cranial vault can produce diffuse dysfunction. Examples include neoplasms, closed-head trauma with subsequent subdural bleeding and accumulation of pus in the subdural space. Disorders within the brain substance — bleeding, infarcts and emboli, and tumours — function primarily as masses.

With processes below the tentorial plate (infratentorial), arousal declines by direct destruction of the reticular activating system and its pathways or of the entire brainstem either by direct invasion or by indirect impairment of its blood supply. In addition, decreased awareness may result from compression of the reticular activating system by a disease process. This compression may result from direct pressure or compression as structures either expand or herniate. Causes include accumulations of blood or pus, neoplasms and demyelinating disorders.

CLINICAL MANIFESTATIONS AND EVALUATION

The cause of an altered level of arousal may be functional or organic. Functional conditions arise when no discrete anatomical location can be found for the alteration — for instance, headaches and insomnia. In contrast, organic conditions come about when there are structural alterations that can be located — for instance, brain tumours, bleeding or contusions. Both conditions may contribute to an altered level of arousal.

Further distinctions can be made between metabolic factors and structural factors (see Table 8-2). Metabolic factors include changes in biochemistry that affect brain function. An example is when acute liver failure occurs — the patient is unable to metabolise ammonia, which in elevated concentrations is neurotoxic and can lead to coma. Structural factors are similar to organic factors — they are areas where cellular damage has occurred and this alters central nervous system (CNS) homeostasis.

Table 8-2 CLINICAL MANIFESTATIONS OF METABOLIC AND STRUCTURAL CAUSES OF COMA

Patterns of clinical manifestations help in determining the extent of brain dysfunction and serve as indices for identifying increasing or decreasing central nervous system function. The types of manifestations suggest the cause of the altered arousal state (see Table 8-3). Five categories of neurological function are critical to the evaluation process:

Table 8-3 DIFFERENTIAL CHARACTERISTICS OF STATES CAUSING COMA

Level of consciousness

The level of consciousness is the most critical clinical index of nervous system function, with alterations indicating either improvement or deterioration of the individual’s condition. The most common way of assessing an individual’s level of consciousness is to use an objective assessment tool such as the Glasgow coma scale (GCS; see Table 8-4). The scale assesses an individual’s ability to open their eyes and their verbal and motor responses. Collectively, these provide information about the individual’s level of consciousness. A person who is alert and oriented to self, others, place and time is considered to be functioning at the highest level of consciousness, which implies full use of all the person’s cognitive capacities. From this normal alert state, levels of consciousness diminish in stages, each of which is clinically defined (see Table 8-5). In addition, decreases in the level of consciousness can alter many physiological processes. Some of the major processes are shown in Figure 8-13 and discussed below.

Table 8-4 GLASGOW COMA SCALE

Table 8-5 LEVELS OF ALTERED CONSCIOUSNESS

FIGURE 8-13 The effect of a decrease in consciousness on physiological processes.

Breathing pattern

Characteristic breathing patterns help evaluate the neuroanatomical level of brain dysfunction and coma (see Figure 8-14). Rate, rhythm and pattern should be evaluated. Breathing patterns can be categorised as hemispheric or brainstem breathing patterns (see Table 8-6).

FIGURE 8-14 Abnormal breathing patterns with the corresponding level of anatomical insult.

Source: Urden LD, David JK, Lough ME. Thelan’s critical care nursing: diagnosis and management. 5th edn. St Louis: Mosby; 2006.

Table 8-6 ABNORMAL BREATHING PATTERNS

With normal breathing, a neural centre in the forebrain (cerebrum) produces a rhythmic pattern. When consciousness decreases, lower brainstem centres regulate the breathing pattern, responding only to changes in PaCO₂ levels. The result is the irregular breathing associated with post-hyperventilation apnoea.

Cheyne-Stokes breathing results from an increased ventilatory response to carbon dioxide stimulation, causing hypercapnia and diminished ventilatory stimulus. Changes in PaCO₂ produce irregular breathing, contributing to ‘overbreathing’ with carbon dioxide stimulation. The PaCO₂ level then decreases to below normal and breathing stops until the carbon dioxide reaccumulates to bring the PaCO₂ level back to normal. With opiate or sedative drug overdose, the respiratory centre in the brainstem is depressed so the rate of breathing gradually decreases until respiratory failure occurs. Central neurogenic breathing is also a ventilatory response to carbon dioxide and is characterised by deep and rapid breathing. It is an abnormal breathing pattern and often an indicator of poor prognosis. Ataxic breathing occurs when the injury has extended to or is associated with the medulla. It is characterised by a lack of breathing coordination and breathing appears to be irregular, hence the name. It is associated with an increase in mortality. In summary, the more inferior (towards the feet) the level of insult in the brainstem, the poorer the prognosis.

Pupillary changes

Anatomically, brainstem areas that control arousal are adjacent to areas that control the pupils. In this way, clinicians examine pupillary changes to determine the extent of injury because the pupillary changes indicate the presence and level of brainstem dysfunction (see Figure 8-15). For example, severe ischaemia and hypoxia usually produce dilated, fixed pupils.

FIGURE 8-15 Pupillary changes due to injury at different levels of the brain.

The pupillary changes correspond to the level of consciousness.

The third cranial nerve (oculomotor) controls pupillary constriction, and compression of the nerve causes contralateral dilation of the pupil. This occurs because the oculomotor nerve is compressed when there is an increase in intracranial pressure, which may be a precursor to uncal herniation (refers to the movement of the uncus (medial part of the temporal lobe) down, which increases pressure on the midbrain of the brainstem). Therefore, pupillary changes are crucial to a neurological assessment of a patient who is experiencing a decreased level of consciousness.

Some drugs affect pupils and must be considered in evaluating individuals in comatose states. For instance, large concentrations of atropine (used as an anticholinergic agent) cause full dilation and fixing of the pupils. Opiates, such as morphine, cause pinpoint pupils. Severe barbiturate intoxication may produce fixed pupils.

Oculomotor responses

Resting, spontaneous and reflexive eye movements change at various levels of brain dysfunction. For instance, individuals with metabolically induced coma generally retain ocular reflexes even when other signs of brainstem damage are present. Therefore, evaluation of the movement of the eyes is also essential for thorough assessment of the level of consciousness.

Motor responses

Motor responses help evaluate the level of brain dysfunction and determine the most severely damaged side of the brain. The pattern of response noted may be: (1) purposeful; (2) inappropriate, generalised motor movement; or (3) not present at all. Motor signs indicating loss of cortical inhibition that are commonly associated with decreased consciousness include reflex grasping, reflex sucking and rigidity. Abnormal flexor (decorticate) and extensor (decerebrate) responses in the upper and lower extremities are defined in Table 8-7 and illustrated in Figure 8-16.

Table 8-7 ABNORMAL MOTOR RESPONSES WITH DECREASED RESPONSIVENESS

FIGURE 8-16 Decorticate and decerebrate responses to painful stimuli.

A Decorticate response. Flexion of arms, wrists and fingers with adduction in upper extremities; extension, internal rotation and plantar flexion in lower extremities. B Decerebrate response. All four extremities in rigid extension, with hyperpronation of forearms and plantar extension of feet. C Decorticate response on right side of body and decerebrate response on left side of body.

Source: Rudy EB (ed.). Advanced neurological and neurosurgical nursing. St Louis: Mosby; 1984.

Vomiting

Yawning, vomiting and hiccups are complex reflex-like motor responses that are integrated by neural mechanisms in the lower brainstem. These responses may be produced by compression or diseases involving tissues of the medulla oblongata (e.g. infection, neoplasm, infarct) but also occur relative to other more benign stimuli to the vagal nerve.

Most CNS disorders produce nausea and vomiting. Vomiting without nausea indicates direct involvement of the central neural mechanism. Vomiting often accompanies CNS injuries that: (1) involve the vestibular nuclei (involved in balance and spatial orientation) or its immediate projections, particularly when double vision (diplopia) is also present; (2) impinge directly on the floor of the fourth ventricle; or (3) produce brainstem compression secondary to increased intracranial pressure.

Post-coma unresponsiveness

Essentially, when brain damage is severe, individuals will experience a decreasing level of consciousness often leading to coma and death (see Table 8-5). However, individuals who survive and remain in a prolonged deep coma are in a post-coma unresponsiveness state.⁷ Previously, this was termed persistent vegetative state, but this description has been changed in Australia because it implies that the state is permanent and the word ‘vegetative’ was considered too negative.⁸ In contrast, post-coma unresponsiveness better describes the level of consciousness of the individual following coma. It has been defined as:

complete lack of responses that suggest a cognitive component

preservation of sleep–wake cycles and cardiorespiratory function

partial or complete preservation of hypothalamic and brainstem autonomic functions.⁸

The post-coma unresponsive individual has emerged from coma — that is, sleep–wake cycles are observable over time — but only brainstem reflexes are present. There is a complete unawareness of self or the surrounding environment and cerebral function is lost. The individual’s vital autonomic functions, such as blood pressure and breathing, are maintained without support. There is bowel and bladder incontinence. The individual does not speak any comprehensible words or follow commands. Recovery is unlikely if the state persists for 12 months.

In some individuals, a gradual return to some level of responsiveness occurs. These individuals are considered to be in a minimally responsive state. In this state, individuals may have cognitively mediated behaviour that initiates a minimal level of purposeful response. For instance, these individuals may be able to respond to simple commands with, say, finger movement, as opposed to reflex responses.^8,9 It should be noted that the chances of these individuals returning to full neurological function are remote.

Finally, some individuals exhibit a coma-like appearance but do not have any alteration of level of arousal or cognition. These individuals have locked-in syndrome. This is quite distinct from post-coma unresponsiveness and the minimally responsive state, because there is only specific damage to the brainstem without damage to the cerebrum.^7,8 Therefore, the efferent pathways are disrupted and the individual has a limited capacity to communicate with the environment. The individual cannot communicate through speech or body movement but is fully conscious, with intact cognitive function. The person retains eye movement and blinking as a means of communication.

Brain death

Brain death occurs when the brain is damaged so completely that it can never recover and cannot maintain the body’s internal homeostasis. On postmortem examination, the brain is autolysing (self-digesting) or already autolysed, because the brain tissue has died.

Brain death has occurred when there is no evidence of function above the foramen magnum¹⁰ — that is, in the cerebral hemispheres or brainstem — for an extended period. The abnormality of brain function must result from structural or known metabolic disease and must not be caused by a depressant drug, alcohol poisoning or hypothermia. For brain death to occur there must be severe brain injury with sustained increased ICP above systemic blood pressure, such that intracranial blood flow ceases.¹¹

In Australia and New Zealand brain death guidelines have been determined. They state that:

The following pre-conditions must be present before clinical determination of brain death:

normothermia (core temperature > 35°C)

normal blood pressure (systolic blood pressure > 90 mmHg and mean arterial pressure > 60 mmHg)

the individual must not be affected by sedative drugs

there must be no severe electrolyte, metabolic or endocrine disturbance

neuromuscular function must be intact (that is, the individual must not be paralysed)

brainstem reflexes must be able to be examined

apnoea testing must be able to be performed (apnoea refers to the state of not breathing).¹¹

The clinical testing of brain death requires two medical practitioners with specific experience and qualifications to perform two separate clinical examinations of the brain death test. The clinical test examines three main categories: coma, absence of brainstem reflexes and absence of breathing. The test and responses for brain death determination are included in Table 8-8. It should be noted that if any test results are not conclusive, the patient cannot be confirmed as brain dead. Furthermore, if brain death cannot be determined conclusively from clinical testing, demonstration of an absence of intracranial blood flow can be used via imaging techniques (see Figure 8-17).¹¹ The Australian and New Zealand Intensive Care Society (ANZICS) recommends that in children brain death studies have the same criteria as for adults, but with a longer observation period.

Table 8-8 BRAIN DEATH CLINICAL TESTS

Source: Australian and New Zealand Intensive Care Society. The ANZICS statement on death and organ donation. 3rd edn. Melbourne: ANZICS; 2008.

FIGURE 8-17 Brain death study.

A CT scan of a 73-year-old man showing compression of the brainstem (arrow). Note the lack of gyri and sulci as the brain has swollen following global neuronal death.

Source: Imaging consult. Elsevier. 2009.

PATHOPHYSIOLOGY

Any disorder that alters the neuronal environment may cause seizure activity, so, theoretically, anyone may experience a seizure. The seizure threshold of some persons, however, apparently is genetically lower.

Diseases or other processes that involve the nervous system can produce a seizure disorder. The onset may indicate the presence of an ongoing primary neurological disease. Aetiological factors in seizures generally include (1) cerebral lesions, (2) biochemical disorders, (3) cerebral trauma and (4) epilepsy, which can result from the following conditions:

metabolic defects

congenital malformation

genetic predisposition

perinatal injury

postnatal trauma

myoclonic syndromes

infection

brain tumour

vascular disease

fever

drug or alcohol abuse.

Causes of recurrent seizures are age-related (see Table 8-9).

Table 8-9 CAUSES OF SEIZURES IN DIFFERENT AGE GROUPS

Note: febrile refers to fever; idiopathic means the cause is unknown.

Source: Lownstein DH. Seizures and epilepsy. In: Kasper DL et al (eds). Harrison’s principles of internal medicine. 16th edn. Vol 2. New York: McGraw-Hill; 2005.

Seizures may be precipitated by a range of events. For instance, all of the following can result in seizure activity: hypoglycaemia; fatigue or lack of sleep; emotional or physical stress; febrile illness; large amounts of water ingestion; constipation; use of stimulant drugs; withdrawal from depressant drugs (including alcohol); hyperventilation; and some environmental stimuli, such as blinking lights, a poorly adjusted television screen, loud noises, certain music, certain odours or merely being startled.

Epilepsy is now thought to be the result of complex genetic mutations with environmental effects that cause abnormalities in brain synapses or connections, or an imbalance in chemicals that the brain uses to send signals or abnormal nerve connections made while attempting to repair itself after injury.¹⁵ A group of neurons may exhibit a paroxysmal (short, frequent attacks) depolarisation shift and function as an epileptogenic focus. These neurons are hypersensitive and are more easily activated by conditions that change their depolarisation threshold. Examples include hyperthermia, hypoxia, hypoglycaemia, hyponatraemia, repeated sensory stimulation and certain sleep phases.

Epileptogenic neurons fire more and more frequently. When the intensity reaches a threshold point, cortical excitation spreads. Excitation of the sub-cortical, thalamic and brainstem areas corresponds to the tonic phase (muscle contraction with increased muscle tone) and is associated with loss of consciousness. The clonic phase (alternating contraction and relaxation of muscles) begins when inhibitory neurons in the cortex, anterior thalamus and basal nuclei react to the cortical excitation. The seizure discharge is interrupted, producing intermittent muscle contractions that gradually decrease and finally cease. The epileptogenic neurons are exhausted.

During seizure activity, oxygen is consumed at a high rate — about 60% over normal. Although cerebral blood flow also increases, oxygen is rapidly depleted, along with glucose, and lactate accumulates in brain tissue. Continued, severe seizure activity holds the potential for progressive brain injury and irreversible damage.

Types of seizure disorders

The International League Against Epilepsy (www.ilae-epilepsy.org) has attempted to modify the International Classification of Epileptic Seizures without consensus. Seizures are classified in different ways: by clinical manifestations, site of origin, EEG findings or response to therapy. In addition, a number of terms are used to describe seizure activity and these are defined in Table 8-10. There are more than 40 different types of seizures; however, the most common classification is to divide them into generalised and partial seizures, which are then further subdivided again. A simplified version of the International Classification of Epileptic Seizures is presented in Figure 8-18 and discussed below.

Table 8-10 TERMINOLOGY APPLIED TO SEIZURES

FIGURE 8-18 Classification of epileptic seizures.

See the text for an explanation of the different types of seizures.

Source: Modified from the International Classification of Epileptic Seizures.

The primary difference between generalised and partial seizures is where the epileptic activity occurs:

Partial, or focal, seizures usually involve only a portion of the brain. These are the most common type of seizure; approximately 60% of people who have seizures have partial seizures — mostly teenagers and the older population. The seizures are often subtle and the person may seem not to be aware of their environment, without any other clinical manifestation.

In contrast, generalised seizures, as the name implies, involve widespread epileptic activity in both hemispheres of the brain. They usually result in unconsciousness. It should be noted that partial seizures can progress to generalised seizures in some cases.

Partial seizures can be subdivided as follows:

Simple partial seizures. Simple partial seizures involve a short-lived seizure with no loss of consciousness or awareness. They usually involve only one area of the brain; the area of neuronal epileptic activity will dictate the type of symptoms the person will experience. For instance, if the seizure focus is in the sensory area of the brain, the person may experience numbness or pins and needles in a body area. In addition, some people may have an aura immediately before the seizure. This is a distinct warning sign that a seizure is imminent and it can be visual, motor or sensory — for instance, the person may have a strange taste in their mouth. Auras have not been fully explained, but it is likely that the anatomical location of seizure origin in the brain is related to the type of seizure.

Complex partial seizures. In contrast to simple partial seizures, with complex partial seizures consciousness and arousal are lowered, which can make the person appear confused. The most common location of the epileptic focus is either the temporal or the frontal lobe of the brain. The other defining characteristic feature is that the person experiencing the seizure may respond to vocalisations but demonstrate repetitive, odd actions, such as fidgeting, saying unusual sounds or walking around. The time frame for the seizure is 3 minutes or less.

Generalised seizures can be subdivided as follows:

Absence seizures. Absence seizures, previously referred to as petit mal seizures, are brief episodes (less than 10 seconds) where the person may stare without facial expression and be unresponsive. These seizures commence in childhood and it may appear that the child is daydreaming.

Myoclonic seizures. Myoclonic refers to the muscle jerks that are brief and usually involve one or a group of muscles. In this case the person does not lose consciousness but may fall or drop an item if they were holding it in their hands.

Tonic-clonic seizures. Tonic-clonic seizures, previously referred to as grand mal seizures, are the type of seizure that the general population associates with epilepsy. The person experiencing the seizure loses consciousness, then their body stiffens from a generalised muscle contraction (tonic phase), which is rapidly followed by a strong rhythmical movement of the limbs that appears jerking-like (clonic phase). One distinguishing characteristic is the often loud, sudden cry that people vocalise before commencement of the tonic phase. This occurs when a volume of air is forced past the vocal cords immediately before the tonic contraction. The seizure lasts for about 2–3 minutes and is accompanied by a confused, tired phase after the convulsions have ceased. This is referred to as the post-ictal phase.

Tonic seizures. As the name implies, the person experiences an increase in muscle tone and the body will stiffen. These seizures can cause considerable injury if the person falls after the onset of the seizure.

Atonic seizures. The ‘a’ before tonic refers to without. Therefore, during these seizures the person loses muscle tone, often causing them to fall to the ground if they were standing. There is usually no loss of consciousness and recovery is rapid.

Any seizure that does not follow the pattern of either a partial or a generalised seizure type is referred to as an unclassified seizure, also known as an atypical seizure. Most unclassified seizures occur in early childhood and are not associated with a loss of consciousness.

EVALUATION AND TREATMENT

The health history, physical examination and laboratory tests of blood and urine can identify systemic diseases known to promote seizures. Radiographic studies (CT and MRI scans) and cerebrospinal fluid examination (lumbar puncture to sample the CSF) help identify neurological diseases associated with seizures. Therefore, most tests are to exclude cranial pathology that may explain the seizure activity. When these tests have ruled out any extraneous cause of the epilepsy, an EEG is used to assess the type of seizure and determine its focus.

Treatment involves correcting or controlling the cause and, if none is identified, administering anti-seizure medications to suppress seizure activity. Counselling also may be of value. Prevention of epilepsy is the direction that research has taken.¹⁶

Acute confusional states

The term confusion is used by health professionals to describe a patient’s mental status. It means that the person does not have the ability to be clear in their thoughts and is related to cognitive dysfunction. Therefore, it can be applied to many clinical situations.

Acute confusional states result from cerebral dysfunction secondary to a range of different states (see Table 8-11) — for instance, drug intoxication, metabolic disorder, anaesthetics or nervous system disease. Withdrawal from alcohol, barbiturate or other sedative drug ingestion is a common cause. Acute confusional states may begin either suddenly or gradually, depending on the amount of exposure to the toxin. These states often occur with febrile illnesses, systemic diseases (e.g. heart failure), head injury, anaesthesia or certain focal cerebral lesions. Delirium is one of the most common acute confusional states and is often under-diagnosed.

Table 8-11 COMMON CAUSES OF THE ACUTE CONFUSIONAL STATE

Source: Jacobson JL, Jacobson AM. Psychiatric secrets. 2nd edn. Hanley & Belfus; 2001.

PATHOPHYSIOLOGY

Acute confusional states arise from disruption of a widely distributed neural network involving the reticular activating system of the upper brainstem and its projections into the thalamus, basal nuclei and specific association areas of the cortex and limbic areas. In most cases, both cerebral hemispheres are affected.

Trauma to the brain or conditions that increase ICP can lower consciousness and cause deficits in cognition. Most metabolic disturbances that produce an acute confusional state interfere with neuronal metabolism or synaptic transmission. This may be due to a lowering of oxygen and glucose delivery, thereby suppressing global neuronal function. Many drugs and toxins also interfere with neurotransmission function at the synapse.

CLINICAL MANIFESTATIONS

The predominant feature of an acute confusional state is impaired or lost concentration. The person is highly distractible and unable to concentrate on incoming sensory information or on any one particular mental or motor task.

The onset of an acute confusion state is usually abrupt. The first clinical manifestations are difficulty in concentration, restlessness, irritability, insomnia and poor appetite. Later there are misperceptions, illusions and hallucinations. Obsessions, compulsive behaviour and rituals may be evident.

In other acute confusional states, the individual exhibits decreases in mental function, specifically alertness, attention span, accurate perception, interpretation of the environment and reaction to the environment. Forgetfulness is prominent and the individual is frequently sleepy.

Delirium, a major type of acute confusion state, typically develops over 2–3 days and is seen initially with slurred speech, altered level of consciousness, hallucinations and restlessness. Some persons experience seizures. Unpleasant, even terrifying, dreams may occur.

Delirium has been estimated to affect up to 20% of the hospitalised elderly population.^20,21 In a fully developed delirium state, the individual is completely inattentive and perceptions are grossly altered, with extensive misperception and misinterpretation. Hallucinations may be present. The person appears distressed and often perplexed; conversation is incoherent. Tremor and high levels of restless movement are common. Violent behaviour may be present, but not always. The individual usually cannot sleep, is flushed and has dilated pupils, a rapid pulse (tachycardia), core body temperature elevation and profuse sweating (diaphoresis). Delirium typically abates suddenly or gradually in 2–3 days, although occasionally delirium states persist for weeks.

EVALUATION AND TREATMENT

The initial goals in evaluating an acute confusional state are to:

A complete history and physical examination, as well as laboratory tests (electrocardiogram and blood, urine, CSF and radiological studies) are needed. These are performed to exclude causes, such as those listed in Table 8-11. Once the cause is established, treatment is directed at controlling the primary disorder, with supportive measures used as appropriate (see Figure 8-19).

FIGURE 8-19 Delirium management flowchart.

The management of delirium is aimed at reducing the symptoms and treating the underlying causes.

Source: Walsh D et al. Palliative medicine. Philadelphia: Saunders; 2009.

The determination between delirium and dementia needs to be addressed. The primary differences are that delirium is a reversible condition, associated with acute confusion that normally has an underlying cause — when this is rectified, the delirium abates. In contrast, dementia is a progressive and irreversible condition that is associated with pathological changes in the central nervous system.

Dementia

Dementia is a progressive failure of many cerebral functions not caused by impaired level of consciousness.²² The result may be a decrease in orienting, memory, language and executive attentional networks. Because of declining intellectual ability, the individual exhibits alterations in behaviour. Dementia is a major neurodegenerative condition that slowly affects the ability of the person to function normally and is one of the most prevalent disabling conditions in older Australians.

Currently, almost 30 million people worldwide live with dementia — more than the combined populations of Australia and New Zealand. In 2008, it was estimated that approximately 240,000 people in Australia had dementia.²³ However, because this is a condition associated with ageing, it is predicted that by 2050 almost one million Australians will have dementia.²⁴ The most prevalent dementia is Alzheimer’s disease, which is discussed in detail in Chapter 9.

PATHOPHYSIOLOGY

There are more than 100 different conditions that can cause dementia.²⁵ Mechanisms leading to dementia include degeneration, compression, atherosclerosis and trauma. Genetic predisposition is associated with the degenerative diseases, including Alzheimer’s disease and Huntington’s disease. Central nervous system infections, including the human immunodeficiency virus (HIV) and slow-growing viruses associated with Creutzfeldt-Jakob disease, are associated with dementia in addition to changes in motor function. Progressive dementias produce nerve cell degeneration, brain atrophy and hypoperfusion of particular areas of the brain, such as the parietal and temporal lobes (see Figure 8-20).

FIGURE 8-20 Metabolic deficits in Alzheimer’s disease.

The positron emission tomography (PET) scan shows parietotemporal hypoperfusion or hypoactivity indicated by the arrows. The darker regions are areas of low metabolic activity.

Source: Bradley WG. Neurology in clinical practice. 5th edn. Philadelphia: Butterworth-Heinemann; 2008. Courtesy of Dr C Meltzer.

CLINICAL MANIFESTATIONS

There are many clinical manifestations of dementia, but the onset is always gradual. One of the first signs is short-term memory loss, with mood swings and a decline in the individual’s ability to perform all their activities of daily living. As the condition progresses, the individual may experience the following three conditions:

Agnosia: a defect of pattern recognition — a failure to recognise the form and nature of objects. Agnosia can be tactile, visual or auditory, but generally only one sense is affected.

Apraxia: an impaired capacity to perform motor activities that were previously achievable.

Dysphasia: an impairment of comprehension or production of language. Comprehension or use of symbols, in either written or verbal language, is disturbed or lost. The condition in dementia patients leads to aphasia, which is total loss of the comprehension or production of language. Expressive dysphasia involves primarily expression deficits — that is, the individual may be able to speak, yet the sentences are not clear and may not make sense. Receptive dysphasia occurs when the individual can speak, yet does not understand what is being spoken to them.

As the dementia worsens, the individual’s personality may change and mood swings become common. The person with dementia does not recognise their family members and their manner may be flat or aggressive. Towards the late stage of dementia, the individual loses memory capacity, cannot perform activities of daily living like feeding and requires full care. The condition progresses to coma and ultimately death, most commonly due to chest infections.

EVALUATION AND TREATMENT

Establishing the cause for dementia may be complicated, but individuals with clinical manifestations of dementia should be evaluated with laboratory and neuropsychological testing to identify underlying conditions that may be treatable. Unfortunately, no specific cure exists for most progressive dementias. Therapy is directed at maintaining and maximising the use of the remaining capacities, restoring functions if possible and accommodating for lost abilities. Helping the family to understand the process and to learn ways to assist the individual is essential.

Depression

Depression is a mood disorder that can involve affective, cognitive and physiological manifestations. In older individuals, depression is often under-diagnosed and can be misinterpreted as dementia, due to the lack of initiative, insomnia, increased confusion and general apathy. Furthermore, it has been estimated that depression or depressive symptoms are present in approximately 40% of patients with dementia. Depression is discussed in more detail in Chapter 39.

PAEDIATRICS

Autism spectrum disorders

The autism spectrum disorders are a group of conditions that have the common neurological deficits of communication, social interaction and stereotyped behaviour. The disorder of autism is the most common; however, the spectrum is included to demonstrate that no two children display a classic presentation. For instance, the spectrum includes children with Asperger’s syndrome and pervasive developmental disorder.

There is an increasing incidence of children with autism spectrum disorders in countries such as Australia and New Zealand.^{26–28 4 6} In Australia, the diagnosis rates for autism spectrum disorders have risen significantly, reflecting the changes in the rest of the world over the last 10–15 years.²⁸ This has been attributed to a combination of changing diagnostic criteria and an increased awareness among health professionals. In Australia, it is estimated that some 11,700 children under the age of 16 years are on the autism spectrum, with up to 125,000 people having some form of autism spectrum disorder. This means that approximately 1 in 160 children has an autism spectrum disorder.^28,29 More male children are diagnosed with autism than females, with an average male/female ratio of 3.8:1.^{27–29 4 6}

PATHOPHYSIOLOGY

The exact cause of autism spectrum disorders is unknown. These complex neurodevelopmental disorders have a biological basis. There is a likely genetic component, although this has not been fully identified.³⁰ The predominance in males compared to females is highly suggestive of a genetic link. The two main theories regarding autism spectrum disorder genes are those genes (1) involved in brain development and (2) responsible for neurotransmitter function.

Increasingly, there is evidence that particular regions of the brain are the cause of autism spectrum disorders. Neuroanatomical imaging indicates that there may be abnormalities in several areas of the brain, including the amygdala, hippocampus, septum, mamillary bodies and cerebellum.²⁶ The brains of people with an autism spectrum disorder have been shown to be slightly larger and heavier than people without the disorder.³¹ In addition, some of the brain regions have neurons that seem to be developmentally immature. There appears to be widespread brain dysfunction at both the cortical and the sub-cortical levels.

It has been suggested that environmental factors play a role in the development of autism spectrum disorders. Problems during the perinatal period, such as maternal illness, are likely to be involved. Low birth weight, prematurity and events during delivery have not consistently been shown to lead to an increased incidence of autism spectrum disorders. It was suggested in the 1990s that childhood immunisations might affect the rates of autism spectrum disorders, but this has conclusively been shown to be false, despite parental concerns.²⁶

CLINICAL MANIFESTATIONS

Children with an autistic spectrum disorder have a triad of impairments (see Figure 8-21). This includes, but is not limited to:

1. impairment in social interactions or relationships, such as lack of facial expression, eye contact or spontaneous actions in behaviour

2. communication problems, either as delayed or lack of spoken language, inability to sustain conversations or stereotyped and repetitive language

3. restricted, repetitive and stereotypic behaviour, such as specific routines, repetitive movements (rocking) or persistent preoccupation with inanimate objects and general lack of imagination.³¹

FIGURE 8-21 Autism spectrum disorders or: triad of cognitive impairments.

The social, behavioural and cognitive deficits are often present in early childhood (under the age of 3 years); however, they may be subtle and parents may not recognise these manifestations. The first contact with health professionals is often due to speech delays, which are more noticeable.

The main deficits that are noticeable over time include:

lack of eye contact

flat facial expressions

no vocalisations in response to parents

lack of recognition of parents’ voices

delayed speech, including babbling

lack of nonverbal communication, such as finger pointing

no interaction with others, instead living in their own world

repetitive behaviours, such as lining up objects, rather than constructive play.^26,30

EVALUATION AND TREATMENT

Evaluation is difficult because of the need for a comprehensive, multidisciplinary assessment, which is often not available to parents. In many cases, the child may be demonstrating signs of autism, yet parents do not perceive differences, often meaning that diagnosis is delayed. Despite the likelihood that the disorders are biologically based, diagnosis is derived from developmental testing and behavioural observation. There are no specific treatments, but early intervention with behavioural modification programs have been shown to significantly improve cognitive, behavioural and intellectual development in children with autism spectrum disorders.

Hypotonia

In hypotonia (decreased muscle tone), passive movement of a muscle occurs with little or no resistance. Hypotonia or flaccidity (a state in which the muscle may be moved rapidly without resistance) occurs when the nerve impulses needed for muscle tone are lost, such as in spinal cord injury or stroke.

Individuals with hypotonia tire easily or are weak. They may have difficulty rising from a sitting position, sitting down without using arm support, and walking up and down stairs, as well as an inability to stand on their toes. Because of their weakness, accidents during walking and self-care activities are common. The joints become hyperflexible, so persons with hypotonia may be able to assume positions that require extreme joint mobility.

The muscle mass atrophies because of decreased neural input entering the motor unit and muscles appear flabby and flat. Muscle cells are gradually replaced by connective tissue and fat.

Hypertonia

In hypertonia (increased muscle tone), passive movement of a muscle occurs with resistance.

Spasticity results from hyperexcitability of the stretch reflexes and is associated with damage to the motor, premotor and supplementary motor areas, as well as lateral corticospinal tract damage (review using Figure 6-19). Increased deep tendon reflexes (hyperreflexia) and the spread of reflexes accompany it.

Rigidity produced by tonic reflex activity mediated by motor neurons may be continuous or intermittent. The involved muscles are firm and tense; the increase in muscle movement is even and uniform throughout the range of passive movement.

The muscles may atrophy because of decreased use. However, hypertrophy occasionally occurs as a result of the overstimulation of muscle fibres. Overstimulation occurs when the motor unit reflex arc remains intact and functioning but is not inhibited by higher centres. This causes continual muscle contraction, resulting in enlargement of the muscle mass and firm muscles.