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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).
11
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.
16
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).
17
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
18
• 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
23
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).
24
25
26
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.
30
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)
31
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
33
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).
34
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).
35
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