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1.0 Anatomy The nervous system is organized into two parts: the central nervous system, which consists of the brain and the spinal cord, and the peripheral nervous system, which connects the central nervous system to the rest of the body. In the central nervous system, the brain and spinal cord are the main centers where correlation and integration of nervous information occur. Both the brain and spinal cord are covered with a system of membranes, called meninges, and are suspended in the cerebrospinal fluid; they are further protected by the bones of the skull and the vertebral column.The central nervous system is composed of large numbers of excitable nerve cells and their processes, called neurons, which are supported by specialized tissue called neuroglia. The long processes of a nerve cell are called axons or nerve fibers. The interior of the central nervous system is organized into gray and white matter. Gray matter consists of nerve cells embedded in neuroglia; it has a gray color. White matter consists of nerve fibers embedded in neuroglia; it has a white color due to the presence of lipid material in the myelin sheaths of many of the nerve fibers. The billions of neurons in the brain are connected to neurons throughout the body by trillions of synapses. (Richard, 2003). 1

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The nervous system is organized into two parts: the central nervous system, which consists of the brain and the spinal cord, and the peripheral nervous system, which connects the central nervous system to the rest of the body. In the central nervous system, the brain and spinal cord are the main centers where correlation and integration of nervous information occur. Both the brain and spinal cord are covered with a system of membranes, called meninges, and are suspended in the cerebrospinal fluid; they are further protected by the bones of the skull and the vertebral column.The central nervous system is composed of large numbers of excitable nerve cells and their processes, called neurons, which are supported by specialized tissue called neuroglia. The long processes of a nerve cell are called axons or nerve fibers. The interior of the central nervous system is organized into gray and white matter. Gray matter consists of nerve cells embedded in neuroglia; it has a gray color. White matter consists of nerve fibers embedded in neuroglia; it has a white color due to the presence of lipid material in the myelin sheaths of many of the nerve fibers

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1.0 Anatomy

The nervous system is organized into two parts: the central nervous system, which

consists of the brain and the spinal cord, and the peripheral nervous system, which connects

the central nervous system to the rest of the body. In the central nervous system, the brain and

spinal cord are the main centers where correlation and integration of nervous information

occur. Both the brain and spinal cord are covered with a system of membranes, called

meninges, and are suspended in the cerebrospinal fluid; they are further protected by the

bones of the skull and the vertebral column.The central nervous system is composed of large

numbers of excitable nerve cells and their processes, called neurons, which are supported by

specialized tissue called neuroglia. The long processes of a nerve cell are called axons or

nerve fibers. The interior of the central nervous system is organized into gray and white

matter. Gray matter consists of nerve cells embedded in neuroglia; it has a gray color. White

matter consists of nerve fibers embedded in neuroglia; it has a white color due to the presence

of lipid material in the myelin sheaths of many of the nerve fibers. The billions of neurons in

the brain are connected to neurons throughout the body by trillions of synapses. (Richard,

2003).

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2. BACTERIAL MENINGITIS

2.1 Epidemiology

The central nervous system (CNS) consists of the brain and spinal cord, and is the

control center for mental and physical activities of the body. Communication in the CNS is

carried out by chemical messengers known as neurotransmitters that pass messages between

nerve cells (neurons). Bacterial meningitis is a common disease worldwide that happens in

CNS. In the United States, approximately 80% of bacterial meningitis cases are caused by the

bacteria Streptococcus pneumonia and Neisseria meningitides, with Neisseria predominating

in adults less than 45 years of age.The incidence of meningococcal meningitis, caused by

Neisseria meningitides varies by age group, with rates in neonates and infants as high as 400

out of every 100,000 per year and rates in adult in the range of 1 to 2 out of every 100,000

per year.The disease appears to occur in males more than females and is most common in the

late winter and early spring.Over the past two decades, vaccinations have greatly changed the

epidemiology of the disease. The incidence ofpneumococcal meningitis caused by

Streptococcus pneumoniae are beginning to decreaseas a result of the routine vaccination of

children with heptavalent-pneumococcal conjugate vaccine over the past 8 years.Similarly,

the introduction of the Haemophilus influenza type b (Hib) vaccine has resulted in drastic

decreases in cases of Hib meningitis and has nearly eradicated disease caused by this

pathogen from most of the developed world (Schuchat A,dkk,1995).

Pic. 1: Meninges

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2.2 Pathophysiology

The fact that the three most common pathogens are all encapsulated organisms is not

coincidental, and they share features which enable them to invade the host through the upper

airway, survive dissemination through the bloodstream, and gain access to the subarachnoid

space. The infectious organism first colonizes the nasopharynx, where specialized proteins

lead to paralysis of cilia. The host is unable to eradicate the organism and it is able to invade

through the mucosa and into the bloodstream. Once bloodborne,the capsule enables the

organism to avoid detection and destruction by the complement system. Organisms are then

able to cross the blood-brain barrier and proliferate in the CNS. Once in the CNS,

inflammation results and is responsible for most of the hallmark symptoms of CNS infection,

including fever, meningismus, and altered mental status. Inflammation also increases the

permeability of the blood-brain barrier, causing vasogenic edema. Cerebral edema in the non

expandable cranial vault increases intracranial pressure and results in secondary injury from

diminished cerebral perfusion and ischemia. Other routes of pathogen entry occur, including

direct inoculation of the CNS, such as in trauma or surgery, or through direct infection and

seeding through parameningeal structures (Tyler KL,1993).

Upper airwayà bloodstreamà subarachnoid spaceà subcapsular constituents

trigger inflammationà fever, meningimus, change in MSà brain/meningeal

edemaà decreased CSF drainageà hydrocephalusà increased ICPà ICP>CPP

2.3 Clinical Features

Signs and symptoms

The clinical presentation of patients with meningitis include

rapid onset of fever

headache

photophobia

nuchal rigidity

lethargy

malaise

altered mentation

seizure

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vomiting

Older patients with S. pneumoniae meningitis are more likely to have the classic triad.

Other studies have shown the classic triad to be less common, with estimates ranging from

21% to 51%.All cases studied had at least one of the three signs; the absence of the all

components of the classic triad excludes the diagnosis in immune competent individuals.

Immuno compromised individuals are more of a diagnostic challenge, as they may mount

none of the classic responses to infection. Meningitis should be in the differential diagnosis

of any immune compromised patient with an infectious disease with altered mental status. A

careful neurologic examination is important to evaluate for focal deficits and increased

intracranial pressure (ICP). Abnormalities in the neurologic examination may necessitate

neuro imaging studies. Nuchal rigidity is a common finding (Aronin SI,dkk,1998).

Physical examination should include assessment for meningeal irritation with:

Brudzinski’s sign (passive flexion of the neck resulting in flexion of the hips and

knees)

Kernig’s sign (straightening of the knee with a flexed hip resulting in back and neck

pain)

Skin :

Purpura

Petechiae/splinter hem, pustular lesionsàmicroemboli

Fundi

Neuro Exam (Rowland LP,1995)

Pic. 2:Symptoms

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2.4 Diagnosis

There are many ways to diagnose the meningitis infections. Such as :

Parenchymal:

CT is the imaging of choice

Brain abscess, encephalitis, toxoplasmosis

Meningeal :

Lumbar puncture

Neoplasm, CNS vasculitis, SAH

If the diagnosis of meningitis cannot be ruled out based on history and physical,

lumbar puncture (LP) is the procedure of choice for further evaluation. In cases of fulminant

and clinically obvious meningitis, cerebrospinal fluid (CSF) analysis can serve to speciate

causative organisms and guide future antibiotic choice. In most patients with bacterial

meningitis, LP can be safely performed without antecedent neuro imaging. In cases where

meningitis and increased ICP are suspected, it is reasonable to begin empiric antibiotics and

admit the patient for further treatment and work-up, with LP performed at a later time if

necessary. Recommendations regarding neuroimaging before LP are a moving target and

likely will become increasingly controversial in the future: Four tubes of CSF, each

containing about 1 mL to 2 mL of fluid, should be obtained. Typically, tubes one and four are

sent for cell count and differential, tube two for protein and glucose, and tube three for Gram

stain and culture (Greenlee J,1990)

2.5 Treatment

Two major goals of treating bacterial meningitis. The first is the rapid administration

of a bactericidal antibiotic with good CNS penetration to treat the neurologic infection, as

well as with good tissue penetration to treat possible extra-CNS sources. The second, in select

cases, is the use of anti-inflammatory agents to suppress the sequelae of bacterial lysis.

Empiric antibiotic choice is based on broad-spectrum coverage of common pathogens. The

choice of antibiotics has to be made in consideration of the prevailing pathogens in the

locality. Recommendations often include:

Ceftriaxone

Cefotaxime

Vancomycin

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If Listeria is suspected, especially in the very young or old, or those who are

immunosupressed, high-dose ampicillin is added. If a penicillin and cephalosporin allergy is

present, meropenem or chloramphenicol as well as vancomycin are recommended. Delay in

administration of antibiotics has been associated with worsening clinical outcomes. In one

study, a 3-hour delay from time of presentation to the hospital to antibiotic administration

was independently associated with an increase in 3-month case fatality.It is also important to

note that a diagnotic test, whether neuroimaging or CSF testing, must not delay empiric

antibiotic therapy (Gilbert DN,dkk,2003).

Consideration for lumbar puncture without neuroimaging:

Age less than 60

Immunocompetent

No history of CNS disease

No recent seizure (less than 1 week)

Normal sensorium and cognition

No papilledema

No focal neurologic defecits

First priority:

Antibiotics

Second priority in some cases

Anti-inflammatories

Third priority

Counter the adverse effects of increased ICP & vasculopathy (McCullers

JA,dkk,2006).

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Pic.3: Lumbar Puncture

2.6 Complications

Complications from bacterial meningitis are severe, but with more aggressive

antibiotic

and critical-care regimens, outcomes are improved.

Seizures

Hyponatremia

SIADH

CVA

Coagulopathies

Cognitive deficits, epilepsy, hydrocephalus, hearing loss affect 25% of survivors

Delayed complications include seizures, paralysis, intellectual deficits, deafness,

blindness, bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome), and death.

Overall, 20% to 30% of the survivors of pneumococcal meningitis have some residual

neurologic deficit.The use of antibiotics has decreased the mortality of meningococcal

meningitis to less than 20%. The overall mortality rate in community-acquired gram-negative

meningitis has been less than 20% since the introduction of the third-generation

cephalosporins. (Durand ML ,dkk,1993).

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3. ALZHEIMER’S DISEASE

3.1 BACKGROUND

Alzheimer's disease was first discovered in 1907 by an expert in psychiatry and

neuropathology named Alois Alzheimer. He observed a 51-year-old woman, who had

intellectual impairment and memory and did not know back to their homes, while the woman

was not impaired limb, co-ordination and reflexes. At autopsy the brain appears to have

diffuse atrophy and symmetry, and it seems the cortical brain microscopic experiencing

neuritis plaques and neurofibrillary degeneration. (Bird, 2005).

Epidemiologically with the increasing life expectancy in many populations, the

number of elderly people will increase. On the other hand will cause serious problems in the

field of socio-economic and health, so that many would consult with a neurologist because

the old man who had been healthy, would begin to lose their ability effectively as workers or

as family members. This suggests the emergence of degenerative brain diseases, tumors,

multiple strokes, subdural hematoma or depressive illness, which is a major cause of

dementia. (Bird, 2005).

The term dementia is used to describe a clinical syndrome with symptoms of memory

decline and loss of other intellectual functions. Definition of dementia according Neuro

behavior Unit at Boston Veterans Administration Medical Center (BVAMC) is a function

abnormalities and acquired intellect is settled, with an interruption of at least three of the five

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components of noble function is impaired language, memory, visuospasial, emotion and

cognition. (Bird,2005).

The first cause of dementia is Alzheimer's disease (50-60%) and the second by

cerebrovascular (20%). Is estimated that people with dementia, especially Alzheimer's

sufferers in recent decades increased the number of cases that will likely become an epidemic

like in America with the incidence of dementia and Alzheimer populasi/100.000/year 187

123/100.000/year as well as the fourth or fifth leading cause of death. (Bird,2005).

3.2. DEFINITON

Alzheimer disease is the biggest cause of dementia in which demensia is intellectual

function and memory impairment caused by acquired brain disease, disorders that are not

associated with dementia. Patients with this level must have a memory disorder other than

mental ability like abstract thinking, judgment, personality, language, praxis, and

visuospasial. (Cummings,2004).

3.3 EPIDERMOLOGY

The pooled data of population-based studies in Europe suggests that the age-

standardized prevalence in people 65+ years old is 6.4 % for dementia and 4.4 % for AD.3 In

the US, the study of a national representative sample of people aged >70 years yielded a

prevalence for AD of 9.7 %. 4 Worldwide, the global prevalence of dementia was estimated

to be 3.9 % in people aged 60+ years, with the regional prevalence being 1.6 % in Africa, 4.0

% in China and Western Pacific regions, 4.6 % in Latin America, 5.4 % in Western Europe,

and 6.4 % in North America.5 More than 25 million people in the world are currently

affected by dementia, most suffering from AD, with around 5 million new cases occurring

every year. The number of people with dementia is anticipated to double every 20 years.

Despite different inclusion criteria, several meta-analyses and nationwide surveys have

yielded roughly similar age-specific prevalence of AD across regions (Figure). The age-

specific prevalence of AD almost doubles every 5 years after aged 65. Among developed

nations, approximately 1 in 10 older people (65+ years) is affected by some degree of

dementia, whereas more than one third of very old people (85+ years) may have dementia-

related symptoms and signs.10,11 There is a similar pattern of dementia subtypes across the

world, with AD and vascular dementia, the two most common forms of dementia, accounting

for 50 % to 70 % and 15 % to 25 %, respectively, of all dementia cases. (Cummings,2004).

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Figure 1.

Age-specific prevalence of Alzheimer's disease (per 100 population) across continents and

countries. *, prevalence of all types of dementia

Epidemiologic research of dementia and AD in low- and middle-income countries has

drawn much attention in recent years. A systematic review estimated that the overall

prevalence of AD in developing countries was 3.4 % (95 % CI,1.6 % - 5.0 %).The 10/66

Dementia Research Group found that the prevalence of dementia (DSM-IV criteria) in people

aged 65+ years in seven developing nations varied widely from less than 0.5 % to more than

6 %, which is substantially lower than in developed countries. Indeed, the prevalence rates

of dementia in India and rural Latin America were approximately a quarter of the rates in

European countries. (Cummings,2004).

However, the prevalence of AD in persons 65+ years in urban areas of China was

3.5 %, and even higher (4.8 %) after post-hoc correction for negative screening

errors,which is generally comparable with those from Western nations. Similar prevalence

rates of dementia were also reported from the urban populations of Latin American nations

such as Havana in Cuba (6.4 %) and São Paulo in Brazil (5.1 %). (Cummings,2004).

Alzheimer's disease is a neuro degenerative disease that epidemiologists divided into

2 groups: the group that suffered at the age of 58 years is less known as early onset whereas

those who suffered at the age of 58 years referred to as late onset. Alzheimer's disease can

occur at any age, 96% of cases found after 40 years of age or older. Schoenburg and

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Coleangus (1987) reported incidence by age: 4.4 / 1000.000 at the age of 30-50 years, 95.8 /

100 000 at age> 80 years. The prevalence of the disease is about 300 per 100,000 population

in the age group 60-69 years, 3200 in the age group 70-79 years, and 10 800 at age 80.

Estimated in 2000 there were 2 million people with Alzheimer's disease. While in Indonesia

estimated the number of old age range, 18.5 million people with the incidence and prevalence

of Alzheimer's disease is not known with certainty. (Cummings,2004).

Based on gender, the prevalence of three times more women than men. This may be a

reflection of women's life expectancy longer than men. Of the few studies there was no

difference of gender. (Cummings,2004).

3.4. ETIOLOGY

The exact cause is unknown. Some alternatives that have been hypothesized causes

are metal intoxication, impaired immune function, viral infections, air pollution / industrial,

trauma, neurotransmitters, deficits formation of filament cells, presdiposisi heriditer. Basic

abnormalities of Alzheimer's disease pathology consisting of neuronal degeneration, the

death of specific regions of brain tissue resulting in impaired cognitive function with

progressive memory loss. (Cummings,2004).

Deficiency of growth factors or amino acids may play a role in the selective death of

neurons. The possibility of these cells degenerate as a result of an increase in intracellular

calcium, failure of energy metabolism, the formation of free radicals or the presence of

abnormal protein production are non-specific. (Cummings,2004).

Alzheimer's disease is a genetic disease, but several studies have shown that the role

of genetic factors, but some studies have shown that the role of non-genetic factors

(environmental) are involved, where environmental factors only as the originator of genetic

factors. (Cummings,2004).

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3.5. PATHOLOGY AND PATHOPHYSIOLOGY

The brain of a patient with AD often shows marked atrophy, with widened sulci and

shrinkage of the gyri (Fig. 1). In the great majority of cases, every part of the cerebral cortex

is involved; however, the occipital pole is often relatively spared. The cortical ribbon may be

thinned and ventricular dilatation apparent, especially in the temporal horn, due to atrophy of

the amygdala and hippocampus. (Rochmach,2006).

Figure 1.

Microscopically, there is significant loss of neurons, in addition to shrinkage of large

cortical neurons. Many investigators believe that loss of synapses, in association with

shrinkage of the dendritic arbor of large neurons, is the critical pathological substrate. The

neuropathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles (Fig. 2),

although these lesions are not unique to AD and can be found in other neurodegenerative

disorders and in clinically normal individuals as well. Classic neuritic plaques are spherical

structures consisting of a central core of fibrous protein known as amyloid that is surrounded

by degenerating or dystrophic nerve endings (neurites). Two other types of amyloid-related

plaques are recognized in the brains of AD patients: diffuse plaques, which contain poorly

defined amyloid but no well-circumscribed amyloid core, and "burnt-out" plaques, which

consist of an isolated dense amyloid core. The amyloid protein contains a 40 to 42 amino acid

peptide called β-amyloid (Aβ) that is derived from proteolytic processing of a larger amyloid

precursor protein molecule. It is believed that abnormal processing of the amyloid precursor

protein molecule results in fragments, the most toxic of which is the Aβ142 peptide.[4]�

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Because Aβ142 readily forms insoluble clumps in the brain, it has been postulated to initiate�

a cascade of events leading to neuronal dysfunction and death. Although increasing evidence

supports the hypothesis that the accumulation of Aβ is critical to the pathogenesis of

AD,some investigators believe that Aβ is not exclusively responsible for the neuronal

alterations that underlie its symptoms. (Rochmach,2006).

Figure 2.

Neurofibrillary tangles are the other characteristic histopathologic change seen in AD.

Neurofibrillary tangles are found inside neurons and are composed of paired helical filaments

of hyperphosphorylated micro-tubule-associated tau protein. The intracellular deposition may

cause disruption of normal cytoskeletal architecture with subsequent neuronal cell death.

Neuritic plaques and neurofibrillary tangles are not distributed evenly across the brain in AD

but are concentrated in vulnerable neural systems. (Rochmach,2006).

Other pathological alterations commonly seen in the brains of AD patients include

neuropil threads, granulovacuolar degeneration, and amyloid angiopathy. Amyloid

angiopathy is a distinct vascular lesion found in many AD brains, consisting of amyloid

deposition in the walls of small-to medium-sized cortical and leptomeningeal arteries. As a

result of the deposits, the involved vessels may become compromised with resultant

hemorrhage. (Rochmach,2006).

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Pathological criteria for the diagnosis of AD at autopsy require the demonstration of a

sufficient number of neuritic plaques and neurofibrillary tangles on micro-scopic

examination. Because of the presence of amyloid in neuritic plaques and to a variable degree

in cerebral blood vessels in the AD brain, the roles of this protein and its precursor peptide,

amyloid precursor protein, have been widely investigated,although the exact nature of their

roles in the pathogenesis of AD remains unclear. Increasingly, the importance of differential

neuronal vulnerability and the relationship of this to the morphological and biochemical

characteristics of AD are being recognized. The most consistent neurochemical change

associated with AD has been the well-documented decline in cholinergic activity that has

inspired many attempts to treat AD with cholinergic drugs. However, additional deficiencies

in glutamate, norepinephrine, serotonin, somatostatin, and corticotrophin-releasing factors

have also been described. (Rochmach,2006).

3.6. SYMPTOMS

Alzheimer’s disease does more than rob people of their memories; people with

Alzheimer’s actually experience two different kinds of symptoms. The first, which are

referred to as cognitive symptoms, disrupt memory, language and thinking. The second,

known as behavioral and psychiatric symptoms, can cause personality changes and

agitation. (Cummings,2004).

Many people with Alzheimer’s and their families find behavioral symptoms to be the

most challenging and distressing effects of the disease. These symptoms are often a

determining factor in a family’s decision to place a loved one in residential care. They also

often have an enormous impact on the care and quality of life for people living in long-term

care facilities. That’s why recognizing the symptoms, understanding the cause and knowing

treatment options are so important. (Cummings,2004).

What are behavioral and psychiatric symptoms of Alzheimer’s disease?

The term “behavioral and psychiatric symptoms” refers to a large group of symptoms

that occur in many — but not all — individuals with Alzheimer’s. In early stages of the

disease, people may experience irritability, anxiety or depression. In later stages, other

symptoms may occur, including:

• Sleep disturbances

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• Physical or verbal outbursts

• Emotional distress

• Restlessness, pacing, shredding paper or tissues and yelling

• Delusions (firmly held belief in things that are not real)

• Hallucinations (seeing, hearing or feeling things that are not there)

(Cummings,2004).

Causes of behavioral and psychiatric symptoms

The chief cause of behavioral and psychiatric symptoms is the progressive

deterioration of brain cells. However, medication, environmental influences and some

medical conditions can also cause symptoms or make them worse. (Cummings,2004).

For example, behavioral symptoms can sometimes be traced to an underlying medical

condition. Anyone experiencing behavioral symptoms should receive a thorough medical

evaluation, especially when symptoms appear suddenly. Examples of treatable conditions that

can trigger behavioral symptoms include infections of the ear, sinuses, urinary or respiratory

tracts; constipation; and uncorrected problems with hearing or vision. (Cummings,2004).

Side effects of prescription medication are another common contributing factor to

behavioral symptoms. Side effects are especially likely to occur when individuals are taking

multiple medications for several health conditions, as that creates the potential for drug

interactions. (Cummings,2004).

The following situations and environmental conditions can also trigger behavioral

symptoms:

• Moving to a new residence or nursing home

• Changes in the environment or caregiver arrangements

• Misperceived threats. (Cummings,2004).

Normally, these symptoms are very mild, and presence of the disease may not be

apparent to the person experiencing the symptoms, loved ones or even health professionals.

The three stages listed below represent the general progression of the disease. Although these

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symptoms will likely vary in severity and chronology, overlap and fluctuate, the overall

progress of the disease is fairly predictable. On average, people live for 8 to 10 years after

diagnosis, but this terminal disease can last for as long as 20 years. (Cummings,2004).

Alzheimer’s generally leads to impairment of cognitive and memory function,

communication problems, personality changes, erratic behavior, dependence and loss of

control over bodily functions. Alzheimer’s disease doesn’t affect every person the same way,

but symptoms normally progress in these stages. (Cummings,2004).

Stage 1 (Mild): This stage can last from 2 to 4 years. Early in the illness, those with

Alzheimer’s tend to be less energetic and spontaneous. They exhibit minor memory loss and

mood swings, and are slow to learn and react. They may become withdrawn, avoid people

and new places and prefer the familiar. Individuals become confused, have difficulty

organizing and planning, get lost easily and exercise poor judgment. They may have

difficulty performing routine tasks, and have trouble communicating and understanding

written material. If the person is employed, memory loss may begin to affect job

performance. They can become angry and frustrated. (Cummings,2004).

Some specific examples of behaviors that people exhibit in this mild stage include:

i. Getting lost

ii. Difficulty managing money and paying bills

iii. Repetitive questions and conversations

iv. Taking longer than usual to finish routine daily tasks

v. Poor judgment

vi. Losing things or misplacing them in odd places

vii. Noticeable changes in personality or mood (Cummings,2004).

Stage 2 (Moderate): This is generally the longest stage and can last 2 to 10 years. In

this stage, the person with Alzheimer’s is clearly becoming disabled. Individuals can still

perform simple tasks independently, but may need assistance with more complicated

activities. They forget recent events and their personal history, and become more disoriented

and disconnected from reality. Memories of the distant past may be confused with the

present, and affect the person’s ability to comprehend the current situation, date and time.

They may have trouble recognizing familiar people. Speech problems arise and

understanding, reading and writing are more difficult, and the individual may invent words.

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They may no longer be safe alone and can wander. As Alzheimer’s patients become aware of

this loss of control, they may become depressed, irritable and restless or apathetic and

withdrawn. They may experience sleep disturbances and have more trouble eating, grooming

and dressing. (Cummings,2004).

Stage 3 (Severe): This stage may last 1 to 3 years. During this final stage, people may

lose the ability to feed themselves, speak, recognize people and control bodily functions, such

as swallowing or bowel and bladder control. Their memory worsens and may become almost

non-existent. They will sleep often and grunting or moaning can be common. Constant care is

typically necessary. In a weakened physical state, patients may become vulnerable to other

illnesses, skin infections, and respiratory problems, particularly when they are unable to

move around. (Cummings,2004).

3.7. MANAGEMENT

The main purpose of management in a patient with dementia is by treating the causes

of dementia that can be corrected and provide a cozy situation and support for patients. If the

patient more depresi than dementia, then the depression should be dealt with adequately. Anti

depretion yang have minimal adverse effects on cognitive function, such as selective inhibitor

of serotonin receptors (SSRI), is more advisable in patients with dementia depression.

(Christiane, 2011).

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Immobilization, poor food intake, pain, constipation, infection, drug are several

factors that can trigger behavioral disturbances, and if it does not need to be addressed

administering drugs antiphycho. .In managing patients with dementia, should also be noted

the efforts to maintain the condition or physical health of patients. Along with demensia, so

many complications that would arise such as pneumonia and upper respiratory tract

infection, septicemia, decubitus ulcers, fractures, and other problems. These conditions are

sometimes a cause of death for patients with dementia. In the early stages of disease, have to

maintain the patient's health status, such as exercise, controlling hypertension and various

other diseases, attention to oral and dental hygiene, and seeking eye glasses and hearing aids

when there is interference with vision or hearing. It is very important to meet the basic needs

of patients such as nutrition, hydration, mobilization, and skin care. (Christiane, 2011).

3.8 DIAGNOSIS

There are several criteria for the clinical diagnosis of Alzheimer's disease are:

1. Criteria for diagnosis of suspected Alzheimer's disease consists of:

• Dementia established by clinical examination and mini mental status examination or

some similar examination and confirmed by test neuropsikologik

• Obtained impaired cognitive function deficits> 2

• No disturbance of consciousness

• Onset between the ages of 40-90 years, or are> 65 years

• There is no systemic disorders or other brain diseases (Christiane, 2011).

2. Diagnosis of suspected Alzheimer's disease is supported by:

• Progressive worsening of cognition-specific functions such as language, motor

skills, and perception

• ADL impaired and changes in behavior patterns

• A history of the family, especially if confirmed by neuropathology

• In the EEG provides a picture of normal or non-specific changes such as increased

slow wave activity

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• In the examination of cerebral CT scan obtained atropu (Christiane, 2011).

3. Another picture of the suspect diagnosis of Alzheimer's disease after other causes of

dementia excluded consist of:

• Symptoms associated with depression, insomnia, inkontinentia, delusions,

hallucinations, emotional, sexual disorders, weight loss

• other neurological disorders in some patients, especially at an advanced stage of

disease and including motor signs such as increased muscle tone, myoclonus or

impaired walking

• There is a resurrection at an advanced stage (Christiane, 2011).

4. Picture of the suspect diagnosis of Alzheimer's disease is not clearly made up of:

• sudden onset

• Found focal neurologic symptoms such as hemiparese, hipestesia, visual field

deficits, and impaired coordination

• There is a resurrection or a disruption running at the time of onset

(Christiane, 2011).

5. Possible clinical diagnosis of Alzheimer's disease are:

• syndrome of dementia, there are no symptoms other neurologic, psychiatric

symptoms or systemic disorders that cause dementia

• The existence of secondary systemic disorders or abnormalities of the brain that

causes dementia, severe cognitive deficits gradually progressive no other cause

identified (Christiane, 2011).

6. Criteria for definite diagnosis of Alzheimer's disease is a combination of clinical criteria for

suspect and obtained an overview of Alzheimer's disease histopathology of biopsy or autopsy

(Christiane, 2011).

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3.9. TREATMENT

Treatment of Alzheimer's disease is still very limited because of the cause and

pathophysiologic remains unclear. Symptomatic and supportive treatment only seemed to

give satisfaction to the patient and family. (Bird,2005).

Stimulant medication, vitamins B, C, and E does not have a beneficial effect.

1. Cholinesterase inhibitors

Recent years, many researchers used inhibitors for symptomatic treatment of

Alzheimer's disease, where patients with Alzheimer's found decreased levels of

acetylcholine. To prevent the decrease in acetylcholine levels of anti-cholinesterase that

can be used as centrally acting like fisostigmin, THA (tetrahydroaminoacridine). This

drug is said to improve memory danapraksia during the last administration. Some

researchers say that the anti-cholinergic drugs will aggravate intellectual performance in

normal individuals and patients with Alzheimer's. (Bird,2005).

2. Thiamin

Research has shown that in patients with Alzheimer's found decrease in thiamin

pyrophosphatase ketoglutarate dependent enzymes, namely 2 (75%) and transketolase

(45%), this is due to neuronal damage in the nucleus basalis. Provision of thiamin

hydrochlorida a dose of 3 g / day orally for 3 months, showed significant improvement of

cognitive function compared to placebo during the same period. (Bird,2005).

3. Nootropik

Nootropik a psychotropic drug, has been proven to improve cognitive function and

learning processes in experimental animals. But the provision of 4000 mg in patients with

Alzheimer's disease showed no significant clinical improvement. (Bird,2005).

4. Clonidine

Disturbance of intellectual function in patients with Alzheimer's can be caused by

damage to cortical noradrenergic. Giving Clonidine (catapres) which is a noradrenergic

alpha 2 receptor agonist with a maximum dose of 1.2 mg orally for 4 weeks, showed a

less than satisfactory to improve cognitive function. (Bird,2005).

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5. Haloperiodol

In patients with Alzheimer's disease, often occurs disorder psychosis (delusions,

hallucinations) and behavior. Haloperiod oral administration of 1-5 mg / day for 4 weeks

will improve symptoms. When Alzheimer's patients suffer from depression should be

given anti depresant tricyclic (amitryptiline 25-100 mg / day). (Bird,2005).

6. Acetyl L-Carnitine (ALC)

Is a subtrate endogenously synthesized in miktokomdria with the help of ALC

transferase study shows that ALC can increase the activity of acetyl cholinesterase,

choline acetyltransferase. At the dose 1-2 g / day / orally for 1 year in treatment, it was

concluded that can improve or inhibit the progression of cognitive malfunction.

(Bird,2005).

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4.0 HUNTINGTON’S DISEASE

4.1.Background

Huntington disease(HD) is an inherited autosomal- dominant disease characterized

clinically by progressive movement disorders and dementia and histologically by

degeneration of striatal neurons. The movement disorder chorea consist of jerky,

hyperkinetic, sometimes dystonic movements affecting all parts of the body. Patients may

later develop parkinsonism with bradykinesia and rigidity. The disease is relentlessly

progressive, with an average course about 15 years to death. ( Richardson E,2001).

Although the onset of symptoms and the rate of progression may vary, the prognosis

is one of the relentless deterioration. The major pathological features of HD are the primary

loss of cells in the caudate nucleus and putamen(striatum), but other regions of the basal

ganglia, hypothalamus, and the brain stem are also involved. There is a decrease not only in

neuronal levels, but as well in the level of neurotransmitters and associated enzymes, together

with abnormalities in some receptor sites. ( Richardson E,2001).

4.2 Epidemiology

The prevalence of Huntington's disease in European populations is estimated at 4 to 8

per 100,000. In the US it is estimated at about 7 per 100,000. The duration of disease is

approximately 20 years from time of diagnosis to time of death. As such, the incidence can be

estimated at 3.5 cases per million per year or 1000 new cases in the US per year. Data from

the English and Welsh Huntington’s Disease Association suggest that the prevalence may be

higher than previously estimated. The disease affects men and women equally; typical onset

is 35 to 45 years of age with a range of 2 to 80 years of age. It is 10 times more common in

North Americans of European descent than in those of pure African or Asian descent or in

Native Americans. Mixed populations have an intermediate incidence. Similar trends are seen

globally, with a significantly lower incidence in Asia and Africa. In isolated areas, such as

Tasmania or Lake Maracaibo in Venezuela, a founder's effect can be seen, where an affected

early settler can significantly increase the prevalence of Huntington's disease in a

concentrated population.(Harper PS,2002)

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4.3 Etiology

HD is inherited as an autosomal dominant condition. In March 1993, scientists

realized that HD is caused by a mutation in a gene located on chromosome 4. This gene has a

unique genetic sequence for CAG (cytosine-adenine-guanine) and codes for the amino acid

glutamine, a building block for the huntingtin protein. Normal individuals have this sequence

duplicated from 11 to 40 times in their genetic coding without having symptoms of HD.

However, individuals with the disease have from 40 up to 100 repeated CAG segments.

Juvenile Huntington's Disease occurs with 60 or more repeats, linking the longer chains of

CAG sequences to earlier and more aggressive onset of the disease. (Walker, 2009).

4.4 Pathophysiology

Huntington Disease is inherited as an autosomal dominant trait with high penetrance.

The genetic defect is located on the short arm of chromosome 4. There is an abnormally long

polyglutamine tract in the huntingtin protein that is toxic to neurons caused by a cytosine-

adenine-guanine(CAG) trinucleotide repeat expansion(40-70 repeats instead of 9-34). Age of

onset of symptoms is related to the length of the repeat sequences and mechanisms of

toxicity. Increased length leads to progressively earlier presentations.(Guetta E, 2008).

The principal pathologic feature of HD is severe degeneration of the basal ganglia,

particularly the caudate and putamen nuclei, and the frontal cerebral cortex. Tangles of

protein collect in brain cells and chains of glutamine on the abnormal molecules stick

together. Early in the disease, selective loss of the striatal GABA/enkephalin pathway to the

lateral aspect of the pallidum occurs. The basal ganglia normally contain a preponderance of

GABAergic(GABA-secreting) neurons, including the pathway between the basal ganglia and

substantia nigra(pallidonigral pathway). Basal ganglia and nigral depletion of GABA,

aninhibitory neurotransmitter, is the principal biochemical alteration in HD. Degeneration of

the GABAergic pallidonigral pathway causes GABA depletion in the substantia nigra with

decreased inhibitory GABA activity on dopaminergic neurons in the substantia nigra and a

relative excess of dopaminergic activity in the basal ganglia feedback circuit within the

cerebral cortex. A relative excess of dopaminergic activity in this circuit, as in HD, is

manifested by hypotonia and hyperkinesias(involuntary, fragmentary movements such as

chorea). Loss of excitatory glutamate may liberate the pathway from the thalamus to the

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premotor cortex, impairing modulation of movement later in the course of the disease. Within

the neurons, producing the fuel for the brain activity is difficult, with a resultant buildup of

lactic acid. (Jarrar RG,2003).

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4.5 Symptoms

Huntington's disease usually causes movement, cognitive and psychiatric disorders

with a wide spectrum of signs and symptoms. Which symptoms appear first varies greatly

among affected people. During the course of the disease, some disorders appear to be more

dominant or have a greater effect on functional ability.(Crauford, 2002)

Movement disorders

The movement disorders associated with Huntington's disease can include both involuntary

movements and impairments in voluntary movements:

Involuntary jerking or writhing movements (chorea)

Involuntary, sustained contracture of muscles (dystonia)

Muscle rigidity

Slow, uncoordinated fine movements

Slow or abnormal eye movements

Impaired gait, posture and balance

Difficulty with the physical production of speech

Difficulty swallowing

Impairments in voluntary movements — rather than the involuntary movements — may have

a greater impact on a person's ability to work, perform daily activities, communicate and

remain independent. (Crauford, 2002)

Cognitive disorders

Cognitive impairments often associated with Huntington's disease include:

Difficulty planning, organizing and prioritizing tasks

Inability to start a task or conversation

Lack of flexibility, or the tendency to get stuck on a thought, behavior or action

(perseveration)

Lack of impulse control that can result in outbursts, acting without thinking and

sexual promiscuity

Problems with spatial perception that can result in falls, clumsiness or accidents

Lack of awareness of one's own behaviors and abilities

Difficulty focusing on a task for long periods

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Slowness in processing thoughts or "finding" words

Difficulty in learning new information (Crauford, 2002)

Psychiatric disorders

The most common psychiatric disorder associated with Huntington's disease is depression.

This isn't simply a reaction to receiving a diagnosis of Huntington's disease. Instead,

depression appears to occur because of injury to the brain and subsequent changes in brain

function. Signs and symptoms may include:

Feelings of sadness or unhappiness

Loss of interest in normal activities

Social withdrawal

Insomnia or excessive sleeping

Fatigue, tiredness and loss of energy

Feelings of worthlessness or guilt

Indecisiveness, distractibility and decreased concentration

Frequent thoughts of death, dying or suicide

Changes in appetite

Reduced sex drive (Crauford, 2002)

Other common psychiatric disorders include:

Obsessive-compulsive disorder, a condition marked by recurrent, intrusive thoughts

and repetitive behaviors

Mania, which can cause elevated mood, overactivity, impulsive behavior and inflated

self-esteem

Bipolar disorder, or alternating episodes of depression and mania (Crauford, 2002)

Other changes in mood or personality, but not necessarily specific psychiatric disorders, may

include:

Irritability

Apathy

Anxiety

Sexual inhibition or inappropriate sexual behaviours (Crauford, 2002)

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Symptoms of juvenile Huntington's disease

The onset and progression of Huntington's disease in younger people may be slightly

different from that in adults. Problems that often present themselves early in the course of the

disease include:

Loss of previously learned academic or physical skills

Rapid, significant drop in overall school performance

Behavioral problems

Contracted and rigid muscles that affect gait (especially in young children)

Changes in fine motor skills that might be noticeable in skills such as handwriting

Tremors or slight involuntary movements

Seizures (Crauford, 2002).

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4.6 Treatment

No treatments can alter the course of Huntington's disease. But medications can lessen

some symptoms of movement and psychiatric disorders. And multiple interventions can help

a person adapt to changes in his or her abilities for a certain amount of time.

Medication management is likely to evolve over the course of the disease, depending on the

overall treatment goals. Also, drugs to treat some symptoms may result in side effects that

worsen other symptoms. Therefore, the treatment goals and plan will be regularly reviewed

and updated. (Walker, 2007)

Medications for movement disorders

Drugs to treat movement disorders include:

Tetrabenazine (Xenazine) is specifically approved by the Food and Drug

Administration to suppress the involuntary jerking and writhing movements

associated with Huntington's disease (chorea). A serious side effect is the risk of

worsening or triggering depression or other psychiatric conditions. Other possible side

effects include insomnia, drowsiness, nausea and restlessness.

Antipsychotic drugs, such as haloperidol (Haldol) and clozapine (Clozaril), have a

side effect of suppressing movements. Therefore, they may be beneficial in treating

chorea. These drugs may, however, worsen involuntary contractions (dystonia) and

muscle rigidity.

Other medications that may help suppress chorea, dystonia and muscle rigidity

include antiseizure drugs such as clonazepam (Klonopin) and antianxiety drugs such

as diazepam (Valium). These medications can significantly alter consciousness, and

they have a high risk of dependence and abuse. (Walker, 2007)

Medications for psychiatric disorders

Medications to treat psychiatric disorders will vary depending on the disorders and

symptoms. Possible treatments include the following:

Antidepressants include such drugs as escitalopram (Lexapro), fluoxetine (Prozac,

Sarafem) and sertraline (Zoloft). These drugs may also have some effect on treating

obsessive-compulsive disorder. Side effects may include nausea, diarrhea, insomnia,

and sexual problems.

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Antipsychotic drugs may suppress violent outbursts, agitation and other symptoms

of mood disorders or psychosis.

Mood-stabilizing drugs that can help prevent the highs and lows associated with

bipolar disorder include lithium (Lithobid) and anticonvulsants, such as valproic acid

(Depakene), divalproex (Depakote) and lamotrigine (Lamictal). Common side effects

include weight gain, tremor and gastrointestinal problems. Periodic blood tests are

required for lithium use because it can cause thyroid and kidney problems. (Walker,

2007)

Psychotherapy

A psychotherapist — a psychiatrist, psychologist or clinical social worker — can provide talk

therapy to help a person manage behavioral problems, develop coping strategies, manage

expectations during progression of the disease and facilitate effective communication among

family members. (Walker, 2007)

Speech therapy

Huntington's disease can significantly impair control of muscles of the mouth and throat that

are essential for speech, eating and swallowing. A speech therapist can help improve your

ability to speak clearly or teach you to use communication devices — such as a board

covered with pictures of everyday items and activities. Speech therapists can also address

difficulties with muscles used in eating and swallowing. (Walker, 2007)

Physical therapy

A physical therapist can teach you appropriate and safe exercises that enhance strength,

flexibility, balance and coordination. These exercises can help maintain mobility as long as

possible and may reduce the risk of falls. Instruction on appropriate posture and the use of

supports to improve posture may help lessen the severity of some movement problems.

When the use of a walker or wheelchair is required, the physical therapist can provide

instruction on appropriate use of the device and posture. Also, exercise regimens can be

adapted to suit the new level of mobility. (Walker, 2007)

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Occupational therapy

An occupational therapist can assist the person with Huntington's disease, family members

and caregivers on the use of assistive devices that improve functional abilities. These

strategies may include:

Handrails at home

Assistive devices for activities such as bathing and dressing

Eating and drinking utensils adapted for people with limited fine motor skills

(Walker, 2007)

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5. NEURAL TUBE DEFECTS

Neural tube defects is one of risk disease from central nervous systems. It’s include

anencephaly ,encephalocele, spina bifida are among the most frequently happens. It is

reasonable to assume that factors contribute this disease from happens is probably from

genetic and environmental. Between 5 and 6 weeks gestation, the neural tube forms from the

neural plate. (Hashimoto, 2002).

Classification

The term neural tube defect refers to a group of malformations including sepina bifida,

anencephaly and cephaloceles. (Frezal,2003).

i) Spina bifida

A midline defect of the vertebrae results in exposure of the contents of the neural canal.

In the most majority of the cases, the defect localized to the posterior arch of the vertebrae. In

rare cases,the defect consists of splitting of the vertebral body. (Frezal,2003).

ii)Anencephaly

Anencephaly is an anomaly characterized by the absence of cerebral hemispheres and

cranial vault. (Frezal,2003).

iii) Cephalocele

Cephalocele is a protrusion of the intracranial contents through bony defect of the skull.

The term “cranial meningoecele” is used when only meninges are herniated. The term

“encephalocele” defines the presences of brain tissue in the herniated sac. (Frezal,2003).

5.1 Epidemiology

Neural tube defects are known to exhibit wide geographic, ethnic, sex, and secular

variation. Based on some research, Europe and United States whites have lowest average

incidence for anencephaly and spina bifida which is about the same. It’s about one per 1000

for each malformation. Ireland, South Wales and Scotland which in British Isles have

recorded as the highest incidence which is about 5 to 6 per 1000 for each malformation. In

Australia the cases that recorded is lower which is 0.7 per 1000 births, But for Japan,the cases

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happen is more lower than others country which is 0.64 among the 1000 births and for spina

is 0.2 per 1000 births. (Nicolaides K,2002).

World Health Organization (WHO) shows that incidence of encephalocele is about one

in 5000 births and in contrast to anencephaly and spina bifida shows that very little

ethic,geographic or sex variation. This is remarkably constatnt. (Nicolaides K,2002).

In the presence of study, among 53 257 singleton births including stillbirths and neonatal

deaths, 71 children or 13.33 per 10 000had at least one non-syndromal neural tube defect and

a total of 85 neural tube defects. (Nicolaides K,2002).

5.2.Etiology

The cause of most NTDs is unknown. Recurrence risks during period shows the large

number with NTDs. The factors have been proven to be major casual significance.

However ,studies of reccurence risk during this period have resulted in large number of

associations with NTDs factors mostly related to the maternal environment before and during

pregnancy. (Raghavendra, 2004).

This is reported that during past years include the hyperthermia, valproic acid nutritional

deficiency, particurlaly of certain vitamins and abnormalities of zinc metabolism.

(Raghavendra, 2004).

Adverse effect from antihistamines shows that this drug is quite toxic to the central and

peripheral nervous system and also bloch nerve action. That means they cause a disturbance t

the central nervous systems development by disturb the impairment of the GABA pathway.

(Raghavendra, 2004).

5.3 Pathology

Subdivided into two which is ventral and dorsal defects. The ventral defects are

extremely rare whic is characterized by splitting of vertebral body and occurance of a cyst

that is neuroenteric in origin. The lesion is generally seen in the lower cervical or upper

thoracic vertebra. Dorsal defect are most common and subdivided into spina bifida occulta

and spina bifida aperta. Spina bifida occulta (15%) is characterised by small defect and

completely covered by skin and in many cases it is asymptomatic and is diagnosed only

incidentally by rasiographic examination of the spine. (Hashimoto, 2002).

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The diencephalic and mesencephalic structures are either completely or partially

destroyed. Besides that, others is strokes and hemmorhage. There also an area that have

hypertrichiosis, pigmented and dimpled skin or the presence of subcutaneous lipoma. The

diancephalic and mesencephalic structurs either completely or partially destroyed. Most of

the brain tissues is contained in herniated sac. Frontal cephaloceles occurs more frequently

between the frontl and ethmoidal bones. (Hashimoto, 2002).

5.4 Diagnosis

Identified in utero wth ultrasound. The diagnosis relies on the failure to demonstrate the

cranial vault. Diagnosis probably be made by early as 12-13 week. In third trimester, the

diagnosis is quite obvious when the fetus has transverse or breach presentation.

Polyhydramnious is frequently asscocated with anencephaly, the mechanism is unclear and

several hypotheses have been suggested including failure to swallow because of brain stem

lesion, excessive micturition and failurebof reabsorption of CSF. (Hashimoto, 2002).

Besides that,demonstrial of paracranial mass. However, the criterion is unsufficient to

distinguish them from other non neural masses, such as scalp edema. (Frezal,2003).

Some is based upon soft tissue and bony sign. The soft tissue signs are ‘Absence o the

skin covering the back, Presence of bulging sac’. The bony signs are derived from the

vertebral abnormalities associated with sipina bifida. There are 3 main planes used in the

evaluation of the spine : Sagittal, Coronal and Transverse. (Hashimoto, 2002).

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