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).

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

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 airway bloodstream subarachnoid space subcapsular constituents trigger inflammation fever, meningimus, change in MS brain/meningeal edema decreased CSF drainage hydrocephalus increased ICP 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: Brudzinskis sign (passive flexion of the neck resulting in flexion of the hips and knees) Kernigs sign (straightening of the knee with a flexed hip resulting in back and neck pain) Skin : Purpura Petechiae/splinter hem, pustular lesionsmicroemboli

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 Meningeal : Lumbar puncture Neoplasm, CNS vasculitis, SAH Brain abscess, encephalitis, toxoplasmosis

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

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).

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).

3. ALZHEIMERS 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 agestandardized 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 agespecific 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 dementiarelated 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 So 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 -amyloid (A) 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 A1 42 peptide.[4]
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Because A1 42 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 A is critical to the pathogenesis of AD,some investigators believe that A 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 Alzheimers disease does more than rob people of their memories; people with Alzheimers 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 agitation. (Cummings,2004). Many people with Alzheimers 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 familys 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. Thats why recognizing the symptoms, understanding the cause and knowing treatment options are so important. (Cummings,2004). What are behavioral and psychiatric symptoms of Alzheimers disease? The term behavioral and psychiatric symptoms refers to a large group of symptoms that occur in many but not all individuals with Alzheimers. In early stages of the disease, people may experience irritability, anxiety or depression. In later stages, other symptoms may occur, including: Sleep disturbances psychiatric symptoms, can cause personality changes and

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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). Alzheimers generally leads to impairment of cognitive and memory function, communication problems, personality changes, erratic behavior, dependence and loss of control over bodily functions. Alzheimers disease doesnt 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 Alzheimers 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. ii. iii. iv. v. vi. vii. Getting lost Difficulty managing money and paying bills Repetitive questions and conversations Taking longer than usual to finish routine daily tasks Poor judgment Losing things or misplacing them in odd places 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 Alzheimers 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 persons 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 Alzheimers 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 HUNTINGTONS 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 Huntingtons 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 cytosineadenine-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. Its 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. Its 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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