Dementia

 Dementia is caused by progressive, irreversible degener-ation of the cerebral cortex and results in mental deterio-ration, usually over several years. There is gradual impairment of memory (especially short term), intellect and reasoning but consciousness is not affected. Emo-tional lability and personality change may also occur. 
Alzheimer's disease 
This condition is the commonest form of dementia in developed countries. The aetiology is unknown although genetic factors may be involved. Females are affected twice as often as males and it usually affects those over 60 years, the incidence increasing with age. There is pro-gressive atrophy of the cerebral cortex accompanied by deteriorating mental functioning. Death usually occurs between 2 and 8 years after onset. 
Huntington's disease
 This usually manifests itself between the ages of 30 and 50 years. It is inherited as an autosomal dominant disor-der  associated with deficient production of the neurotransmitter gamma aminobutyric acid (GABA). By the time of onset, the individual may have passed the genetic abnormality on to their children. Extrapyramidal changes cause chorea, rapid uncoordinated jerking movements of the limbs and involuntary twitching of the facial muscles. As the disease progresses, cortical atrophy causes personality changes and dementia. 
Secondary dementias 
Dementia may occur in association with other diseases:
 • cerebrovascular disease, e.g. multi-infarct dementia
 • infections, e.g. neurosyphilis, human immunodeficiency virus (HIV), Creutzfeldt-Jakob disease
 • cerebral trauma
 • alcoholism and some drugs
 • vitamin B deficiencies
 • metabolic disorders, e.g. hypothyroidism, uraemia, liver failure. 

Parkinson's disease 07.18 In this disease there is gradual degeneration of dopa.. mine releasing neurones in the extrapyramidal system, This leads to lack of control and coordination of muscle movement resulting in: 
• slowness of movement (bradykinesia) and difficulty initiating movements 
• fixed muscle tone causing expressionless facial features, rigidity of voluntary muscles causing the slow and characteristic stiff shuffling gait and stooping posture 
• muscle tremor of extremities that usually begins in one hand, e.g. 'pill rolling' movement of the fingers. Onset is usually between 45 and ki years. The cause is usu-ally unknown but some cases are associated with repeated trauma as in, e.g., 'punch drunk' boxers; tumours causing midbrain compression; drugs, e.g. phenothiazines; heavy: metal poisoning. There is progressive physical disability but the intellect is not impaired . 

Stroke (cerebrovascular disease)

Stroke (cerebrovascular disease)
 this condition is a common cause of death and disability, especially in older people. Predisposing factors elude: hypertension atheroma cigarette smoking diabetes mellitus. 
It occurs when blood flow to the brain is suddenly interrupted, causing hypoxia. The effects include paralysis of a limb or one side of the body and disturbances of speech and vision. The nature and extent of damage depend on the size and location of the affected blood vessels. The main causes are cerebral infarction (approx. 85%) and spontaneous intracranial haemorrhage (15%). 
Cerebral infarction 
 This is caused by atheroma complicated by thrombosis  or blockage of an artery by an embolus from e.g infective endocarditis. The cerebral hemispheres are usually affected. When complete recovery occurs within 24 hours, the event is called a transient ischaemic attack (TIA). Recurrence or completed stroke associated with permanent damage may follow. 
spontaneous intracranial haemorrhages 
the haemorrhage may be into the subarachnoid space or intracerebral . It is commonly associated with an aeurysm or hypertension. In each case the escaped blood may cause arterial spasm, leading to ischaemia, infarction, fibrosis (gliosis) and hypoxic brain damage. 

A severe haemorrhage may be instantly fatal while repeated small haemorrhages have a cumulative effect in extending brain damage (multi-infarct dementia). 
Intracerebral haemorrhage 
Prolonged hypertension leads to the formation of multi-ple microaneurysms in the walls of very small arteries in the brain. Rupture of one or more of these, due to continuing rise in blood pressure, is usually the cause of intracerebral haemorrhage. The most common sites are branches of the middle cerebral artery in the region of the internal capsule and the basal ganglia. Severe haemorrhage. This causes compression and destruction of tissue, a sudden increase in ICP and dis-tortion and herniation of the brain. Death follows when the vital centres in the medulla oblongata are dam-aged by haemorrhage or if there is coning due to increased ICP. 
Less severe haemorrhage. This causes paralysis and loss of sensation of varying severity, affecting the side of the body opposite the haemorrhage. If the bleeding stops and does not recur a fluid-filled cyst develops, i.e. the haematoma is walled off by gliosis, the blood clot is gradually absorbed and the cavity filled with tissue exudate. When the ICP returns to normal some function may be restored, e.g. speech and movement of limbs. 
Subarachnoid haemorrhage This is usually due to rupture of a berry aneurysm on one of the major cerebral arteries, or bleeding from a congenitally malformed blood vessel . The blood may remain localised but usually spreads in the subarachnoid space round the brain and spinal cord, causing a general increase in ICI' without distortion of the brain . The irritant effect of the blood may cause arterial spasm, leading to ischaemia, infarc-tion, gliosis and the effects of localised brain damage. It occurs most commonly in middle life, but occasionally in young people owing to rupture of a malformed blood vessel. This condition is often fatal or results in perma-nent disability. 

Complications of head injury

Accelerationdeceleration
 injuries Because the brain floats relatively freely in 'a cushion' of CSF, sudden acceleration or deceleration has an inertia effect, i.e. there is delay between the movement of the head and the corresponding movement of the brain. During this period the brain may be compressed and damaged at the site of impact. In 'contre coup' injuries, brain damage is more severe on the side opposite to the site of impact. Other injuries include: 
• nerve cell damage, usually to the frontal and parietal lobes, due to movement of the brain over the rough surface of bones of the base of the skull
• nerve fibre damage due to stretching, especially following rotational movement 
• haemorrhage due to rupture of blood vessels in the subarachnoid space on the side opposite the impact or more diffuse small haemorrhages, following rotational movement.
Complications of head injury 
If the individual survives the immediate effects, compli-cations may develop hours or days later. Sometimes they are the first indication of serious damage caused by a seemingly trivial injury. Their effects may be to increase ICP, damage brain tissue or provide a route of entry for microbes.

Traumatic intracranial haemorrhage 

Haemorrhage may occur causing secondary brain dam-age at the site of injury, on the opposite side of the brain or diffusely throughout the brain. If bleeding continues, the expanding haematoma increases the ICP, compres-sing the brain. 107.16 Extradural haemorrhage. This may follow a direct blow that may or may not cause a fracture. The individual may recover quickly and indications of increased ICP appear only several hours later as the haematoma grows and the outer layer of dura mater (periosteum) is stripped off the bone. The haematoma grows rapidly when arterial blood vessels are damaged. In children there is rarely a fracture because the skull bones are still soft and the joints have not fused. The haematoma usu-ally remains localised. 
Acute subdural haemorrhage.
 This is due to haemor-rhage from small veins in the dun mater or from larger veins between the layers of dura mater before they enter the venous sinuses. The blood may spread in the sub-dural space over one or both hemispheres . There may be concurrent subarachnoid haemorrhage, especially when there are extensive brain contusions and lacerations. Chronic subdural haemorrhage. This may occur weeks or months after minor injuries and sometimes there is no history of injury. It occurs most commonly in people in whom there is some cerebral atrophy, e.g. older people and in alcoholism. Evidence of increased ICP may bedelayed when brain volume is reduced. The haematoma formed gradually increases in size owing to repeated small haemorrhages and causes mild chronic inflamma. tion and accumulation of inflammatory exudate. In time it is isolated by a wall of fibrous tissue.
Intracerebral haemorrhage and cerebral oedema 

These occur following contusions, lacerations and shearing injuries associated with acceleration and deceleration, especially rotational movements. Cerebral oedema is a common complication' of contusions of the brain, leading to increased ICP hypoxia and further brain damage.
Post-traumatic epilepsy
This is usually characterised by seizures (fits) and may. develop in the first week or several months after injury Early development is most common after severe injuries although in children the injury itself may have appeared trivial. After depressed fractures or large haematomas epilepsy tends to develop later. 
Persistent vegetative state In this condition there is severe brain damage that results in unconsciousness but the vital centres that control homeostasis remain intact, e.g. breathing, blood pressure.
Cerebral hypoxia 
Hypoxia may be due to: 
• disturbances in the autoregulation of blood supply to the brain 
• conditions affecting cerebral blood vessels. When the mean blood pressure falls below about 60 mmHg, the autoregulating mechanisms that control the blood flow to the brain by adjusting the diameter the arterioles fail. The consequent rapid decrease in the cerebral blood supply leads to hypoxia and lack of glutcose. If severe hypoxia is sustained for more than a few minutes there is irreversible brain damage. The neurones are affected first, then the neuroglial cells and later the 

meninges and blood vessels. Conditions in which autoregulation breaks down include: cardiorespiratory arrest 
•. sudden severe hypotension carbon monoxide poisoning hypercapnia (excess blood carbon dioxide) drug overdosage with, e.g., opioid analgesics, hypnotics. Conditions affecting cerebral blood vessels that may ead to hypoxia include: occlusion of a cerebral artery by, e.g., a rapidly expanding intracranial lesion, atheroma, thrombosis or embolism (Ch. 5) 
• arterial stenosis that occurs in arteritis, e.g. polyarteritis — nodosa, syphilis, diabetes mellitus, degenerative . changes in older people. If the individual survives the initial episode of ischaemia, then infarction, necrosis and loss of function of the affected area of brain may occur. 

Vascular damage

Vascular damage
There may be stretching or compression of blood vessels, causing: haemorrhage when stretched blood vessels rupture ischaemia and infarction due to compression of blood vessels papilloedema (oedema round the optic disc) due to compression of the retinal vein in the optic nerve sheath where it crosses the subarachnoid space.
Neural damage The vital centres in the medulla oblongata may be damaged when the increased ICP causes ' coning' . Stretching may damage cranial nerves, especially the oculomotor (III) and the abducent (VI), causing disturbances of eye movement and accommodation.
Bone changes Prolonged increase of ICP causes bony changes, e.g erosion, especially of the sphenoid 
• stretching and thinning before ossification is complete.
Cerebral oedema There is movement of fluid from its normal compartment when oedema develops Cerebral oedema occurs when there is excess fluid in brain cells and/or in the interstitial spaces, causing increased intracranial pressure. It is associated with:
 • traumatic injury
 • haemorrhage
 • infections, abscesses
 • hypoxia, local ischaemia or infarcts
 • tumours inflammation of the brain or meninges
 • hypoglycaemia
Hydrocephalus 111 this condition the volume of CSF is abnormally high and is usually accompanied by increased ICP.
An obstruction to CSF flow  is the most common cause. It is described as communicating when there is free flow of CSF from the ventricular system to the subarachnoid space and non-communicating when there is not, i.e. there is obstruction in the system of ven-tricles, foramina or ducts. Enlargement of the head occurs in children when ossi-fication of the cranial bones is incomplete but, in spite of this, the ventricles dilate and cause stretching and thin-ning of the brain. After ossification is complete, hydro-cephalus leads to a marked increase in ICP and destruction of nervous tissue.
Primary hydrocephalus In this condition there is accumulation of CSF accompa-nied by dilation of the ventricles. It is usually caused by obstruction to the flow of CSF but is occasionally due to malabsorption of CSF by the arachnoid vi ii. It may be communicating or non-communicating. Without treatment, permanent brain damage occurs. Congenital primary hydrocephalus is due to malformation of the ventricles, foramina or ducts, usually at a narrow point. Acquired primary hydrocephalus is caused by lesions that obstruct the circulation of the CSF, usually expand-ing lesions, e.g. tumours, haematomas or adhesions between arachnoid and pia maters, following meningitis.
Secondary hydrocephalus Compensatory increases in the amount of CSF and ven-tricle capacity occur when there is atrophy of brain tis-sue, e.g. in dementia and following cerebral infarcts. There may not be a rise in ICP.
Head injuries Damage to the brain may be serious even when there is no outward sign of injury. At the site of injury there may be: 
• a scalp wound, with haemorrhage between scalp and skull bones 
• damage to the underlying meninges and/or brain with local haemorrhage inside the skull • a depressed skull fracture, causing local damage to the underlying meninges and brain tissue 
• temporal bone fracture, creating an opening between the middle ear and the meninges 
• fracture involving the air sinuses of the sphenoid, ethmoid or frontal bones, making an opening between the nose and the meninges.
Acceleration-deceleration injuries Because the brain floats relatively freely in 'a cushion' of CSF, sudden acceleration or deceleration has an inertia

Disorders of the brain

Learning outcomes
After studying this section you should be able to:
■ list three causes of raised intracranial pressure (ICP)
■ relate the effects of raised ICP to the functions of the brain and changes in vital signs 
■ outline how the brain is damaged during different types of head injury
■ describe four complications of head injury 
■ explain the effects of cerebral hypoxia and stroke 
■ outline the causes and effects of dementia
■ relate the pathology of Parkinson's disease to its effects on body function.
Increased intracranial pressure This is a serious complication of many conditions that affect the brain. The cranium forms a rigid cavity enclosing: the brain, the cerebral blood vessels and cerebrospinal fluid (CSF). An increase in volume of any one of these will lead to raised intracranial pressure (ICP). Sometimes its effects are more serious than the condi-tion causing it, e.g. by disrupting the blood supply or distorting the shape of the brain, especially if the ICP rises rapidly. A slow rise in ICP allows time for compen-satory adjustment to be made, i.e. a slight reduction in the volume of circulating blood and of CSF. The slower the rise in ICP, the more effective is the compensation. 

Rising ICP is accompanied by bradycardia and hyper tension. As it reaches its limit a further small increase in pressure is followed by a sudden and usually serious' reduction in the cerebral blood flow as autoregulatiou fails. The result is hypoxia and a rise in carbon dioxide4 levels, causing arteriolar dilation, which humeri increases ICP. This leads to progressive loss of function.; ing neurones, which exacerbates bradycardia and hyper-tension. Further cerebral hypoxia causes vasomotor: paralysis and death. The causes of increased ICP are described on the fol-lowing pages and include:
• cerebral oedema 
• hydrocephalus, the accumulation of excess CSF 
• expanding lesions inside the 'skull, also known as space-occupying lesions - haemorrhage, haematoma (traumatic or spontaneous) - tumours (primary or secondary). Expanding lesions may occur in the brain or in the: meninges and they can damage the brain in various ways
Effects of increased ICP Displacement of the brain Lesions causing displacement are usually one sided but` may affect both sides. Such lesions may cause: 
• herniation (displacement of part of the brain from its usual compartment) of the cerebral hemisphere between the corpus callosurn and the free border of the falx cerebri on the same side 
• herniation of the midbrain between the pons and the free border of the tentorium cerebelli on the same side 
• compression of the subarachnoid space and flattening-of the cerebral convolutions 

distortion of the shape of the ventricles and their ducts herniation of the cerebellum through the foramen magnum protrusion of the medulla oblongata through the foramen magnum ( coning'). 
Obstruction of the flow of cerebrospinal fluid e ventricles or their ducts may be pushed out of position or a duct obstructed. The effects depend on the position of the lesion, e.g. compression of the aqueduct of the midbrain causes dilation of the lateral ventricles and the third ventricle, further increasing the ICP. 

Systemic or general circulation

The blood pumped out from the left ventricle is carried by the branches of the aorta around the body and returns to the right atrium of the heart by the superior and inferior venae curiae.  shows the general positions of the aorta and the main arteries of the limbs. provides an overview of the venae cavae and the veins of the limbs. The circulation of blood to the different parts of the body will be described in the order in which their arteries branch off the aorta.
Aorta The aorta  begins at the upper part of the left ventricle and, after passing upwards for a short way, it arches backwards and to the left. It then descends behind the heart through the thoracic cavity a little to the left of the thoracic vertebrae. At the level of the 12th thoracic vertebra it passes behind the diaphragm then downwards in the abdominal cavity to the level of the 4th lumbar vertebra, where it divides into the right and left common iliac arteries. Throughout its length the aorta gives off numerous branches. Some of the branches are paired, i.e. there is a 
right and left branch of the same name, for instance; the right and left renal arteries supplying the kidneys; and some are single or unpaired, e.g. the coeliac artery. The aorta will be described here according to location: 
• thoracic aorta (see below) 1 
• abdominal aorta . 1 Thoracic aorta This part of the aorta lies above the diaphragm and is] described in three parts: 
• ascending aorta
• arch of the aorta 
• descending aorta in the thorax. Ascending aorta This is the short section of the aorta that rises from; the heart. It is about 5 cm long and lies behind the
sternum. The right and left coronary arteries are its only branches; and they arise from the aorta just above the level of the aortic valve These important arteries supply the myocardium.