DAVAO MEDICAL SCHOOL FOUNDATION INC.

College of Nursing

Medical School Drive, Bajada, Davao City

A RESEARCH ON

NEUROLOGICAL DISORDERS

In Partial Fulfillment of the Requirements in

NCM 104- LECTURE

Submitted to:

MS. MARY JANE GUIANG R.N.

Clinical Instructor

Submitted by:

Kimberly Anne Gonzaga

BSN- 4B

October 4, 2010
ALZHEIMER’S DISEASE

Alzheimer’s disease is the most common form of dementia. This incurable, degenerative, and terminal disease was
first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. Most
often, it is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur
much earlier. The specific cause is unknown. Research indicates that the disease is associated with plaques
and tangles in the brain.

The disease course is divided into four stages, with progressive patterns of cognitive and functional impairments.

1. Pre-dementia

2. Early dementia

3. Moderate dementia

4. Advanced dementia

Signs and Symptoms .

o Gradual loss of memory

o Lack of concentration becomes apparent

o Inability to acquire new memories

o Problem solving, mathematical ability and judgment are poor

o Managing ADL becomes difficult

o Confusion

o Irritability and aggression

o Mood swings

o Language breakdown

o Does not recognize family

 o Long-term memory loss

o Senses decline

Pathophysiology .

Typical changes in Alzheimer’s disease include progressive cortical atrophy, which leads to dilated
ventricles, widening of the sulci. Neurofibrillary tangles in the neurons and senile plaques are found in
large numbers in the affected parts of the brain. The plaques, which disrupt neural conduction, contain
fragments from beta-amyloid precursor protein (β APP); the role of this protein is a focus of research.
Some neurofibrils and plaques have been found in the brains of elderly people whose cognitive function
is not impaired, therefore it appears that the numbers and distribution of the plaques are significant
factors. A deficit of the neurotransmitter Ach also occurs in the affected brain.

Disease mechanism. Exactly how disturbances of production and aggregation of the beta amyloid
peptide gives rise to the pathology of AD is not known. The amyloid hypothesis traditionally points to the
accumulation of beta amyloid peptides as the central event triggering neuron degeneration. Accumulation
of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for
disrupting the cell's calcium ion homeostasis, induces programmed cell death (apoptosis.) It is also known
that Aβ selectively builds up in the mitochondria in the cells of Alzheimer's-affected brains, and it also
inhibits certain enzyme functions and the utilisation of glucose by neurons.

Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer's
disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to
tissue damage in AD or a marker of an immunological response. Alterations in the distribution of
different neurotrophic factors and in the expression of their receptors such as the brain derived
neurotrophic factor (BDNF) have been described in AD.

Genetics.The vast majority of cases of Alzheimer's disease are sporadic, meaning that they are not
genetically inherited although some genes may act as risk factors. On the other hand, around 0.1% of the
cases are familial forms of autosomal-dominant inheritance, which usually have an onset before age 65.

Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: amyloid
precursor protein (APP) and presenilins 1 and 2. Most mutations in the APP and presenilin genes increase
the production of a small protein called Aβ42, which is the main component of senile plaques. Some of the
mutations merely alter the size ratio between Aβ42 and the other major forms—e.g., Aβ40—without
increasing Aβ42 levels. This suggests that presenilin mutations can cause disease even if they lower the
 total amount of Aβ produced and may point to other roles of presenilin or a role for alterations in the
function of APP and/or its fragments other than Aβ.

Most cases of Alzheimer's disease do not exhibit autosomal-dominant inheritance and are termed sporadic
AD. Nevertheless genetic differences may act as risk factors. The best known genetic risk factor is the
inheritance of the ε4 allele of the apolipoprotein E (APOE). Between 40 and 80% of patients with AD
possess at least one apoE4 allele. The APOE4 allele increases the risk of the disease by three times in
heterozygotes and by 15 times in homozygotes. Geneticists agree that numerous other genes also act as
risk factors or have protective effects that influence the development of late onset Alzheimer's
disease. Over 400 genes have been tested for association with late-onset sporadic AD, most with null
results.

Diagnostic Tools .

Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from
relatives, and clinical observations, based on the presence of
characteristic neurological and neuropsychological features and the absence of alternative
conditions. Advanced medical imaging with computed tomography (CT) or magneti resonance
imaging (MRI), and with single photon emission computed tomography(SPECT) or positron
emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of
dementia. Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to
Alzheimer's disease.

Neuropsychological tests such as the mini-mental state examination (MMSE), are widely used to
evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for
high reliability of results, particularly in the earliest stages of the disease. Neurological examination in
early AD will usually provide normal results, except for obvious cognitive impairment, which may not
differ from that resulting from other diseases processes, including other causes of dementia.

Further neurological examinations are crucial in the differential diagnosis of AD and other
diseases. Interviews with family members are also utilised in the assessment of the disease. Caregivers can
supply important information on the daily living abilities, as well as on the decrease, over time, of the
person's mental function. A caregiver's viewpoint is particularly important, since a person with AD is
commonly unaware of his own deficits. Many times, families also have difficulties in the detection of
initial dementia symptoms and may not communicate accurate information to a physician.
 Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau
proteins, both total tau protein and phosphorylated tau protein concentrations. Searching for these proteins
using a spinal tap can predict the onset of Alzheimer's with a sensitivity of between 94% and 100%. When
used in conjunction with existing neuroimaging techniques, doctors can identify patients with significant
memory loss who are already developing the disease. Spinal fluid tests are commercially available, unlike
the latest neuroimaging technology. Alzheimer's was diagnosed in one-third of the people who did not
have any symptoms in a 2010 study, meaning that disease progression occurs well before symptoms occur.

Supplemental testing provides extra information on some features of the disease or is used to rule out other
diagnoses. Blood tests can identify other causes for dementia than AD—causes which may, in rare cases,
be reversible. It is common to perform thyroid function tests, assess B12, rule out syphillis, rule out
metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels
of heavy metals (e.g. lead, mercury) and anemia. Psychological tests for depression are employed, since
depression can either be concurrent with AD an early sign of cognitive impairment, or even the cause.

Management .

There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefit
but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and
caregiving.

Specific problems such as depression or anxiety are treated symptomatically. Many drugs are
contraindicated because they add to mental confusion. Anticholinesterase drugs, such as donepezil
(Aricept), have led to some temporary improvement resulting from improved cholinergic transmission.

Since Alzheimer's has no cure and it gradually renders people incapable of tending for their own needs,
care giving essentially is the treatment and must be carefully managed over the course of the disease.

During the early and moderate stages, modifications to the living environment and lifestyle can
increase patient safety and reduce caretaker burden. Examples of such modifications are the adherence to
simplified routines, the placing of safety locks, the labeling of household items to cue the person with the
disease or the use of modified daily life objects. The patient may also become incapable of feeding
themselves, so they require food in smaller pieces or pureed. When swallowing difficulties arise, the use of
feeding tubes may be required. In such cases, the medical efficacy and ethics of continuing feeding is an
important consideration of the caregivers and family members. The use of physical restraints is rarely
indicated in any stage of the disease, although there are situations when they are necessary to prevent harm
to the person with AD or their caregivers.
As the disease progresses, different medical issues can appear, such as oral and dental disease, pressure
ulcers, malnutrition, hygiene problems, or respiratory, skin, or eye infections. Careful management can
prevent them, while professional treatment is needed when they do arise. During the final stages of the
disease, treatment is centered on relieving discomfort until death.

A small recent study in the US concluded that patients whose caregivers had a realistic understanding of
the prognosis and clinical complications of late dementia were less likely to receive aggressive treatment
near the end of life.
MYASTHENIA GRAVIS

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of
the skeletal (voluntary) muscles of the body. The name myasthenia gravis, which is Latin and Greek in origin, literally
means "grave muscle weakness." With current therapies, however, most cases of myasthenia gravis are not as "grave"
as the name implies. In fact, for the majority of individuals with myasthenia gravis, life expectancy is not lessened by
the disorder.

Myasthenia gravis is an autoimmune disorder that impairs the receptors for acetylcholine (Ach) at the neuromuscular
junction. The specific cause is not known, although many patients have thymus disorders, such as hyperterplasia or
benign tumors. Women are more frequently affected than men, and the age of onset is between ages 20 – 30 for
women and over age 50 for men.

Types of Myasthenia Gravis:

1. Generalized Myasthenia Gravis – characterized by weakness in the trunk, arms and legs.

2. Occular Myasthenia Gravis – weakness only in muscles that control eye movement.

3. Congenital Myasthenia Gravis – inherited condition caused by genetic defect.

4. Transient Myasthenia Gravis – a temporary condition in infants born to mothers who have
myasthenia gravis.

Myasthenic Crisis which may occur when there is added stress, such as infection, trauma or alcohol intake, involves
an increase in weakness and fatigue and respiratory impairment may develop.

Signs and Symptoms .

o Muscle weakness

o Fatigue

o Diplopia

o Ptosis
 o Impaired Vision

o Nasal-monotone-speech

o Face droop with sadness

o Difficulty in chewing and swallowing

o Head droops

o Difficulty performing ADL

Pathophysiology .

Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs
when normal communication between the nerve and muscle is interrupted at the neuromuscular
junction - the place where nerve cells connect with the muscles they control. Normally when impulses
travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine.
Acetylcholine travels through the neuromuscular junction and binds to acetylcholine receptors which
are activated and generate a muscle contraction.

In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the
neuromuscular junction which prevents the muscle contraction from occurring. These antibodies are
produced by the body's own immune system. Thus, myasthenia gravis is an autoimmune disease
because the immune system - which normally protects the body from foreign organisms - mistakenly
attacks itself.

Autoantibodies (immunoglobulin G [IgG]) develop against ACh nicotinic postsynaptic receptors for
unknown reasons, although certain genotypes are more susceptible.

Cholinergic nerve conduction to striated muscle is impaired by a mechanical blockage of the binding
site by antibodies and, ultimately, by destruction of the postsynaptic receptor.

Patients become symptomatic once the number of ACh receptors is reduced to approximately 30% of
normal. The cholinergic receptors of smooth and cardiac muscle have a different antigenicity than
skeletal muscle and are not affected by the disease.

The role of the thymus in the pathogenesis of myasthenia gravis is not entirely clear, but 75% of
patients with myasthenia gravis have some degree of thymus abnormality (eg, hyperplasia in 85% of
 cases, thymoma in 15% of cases). Given the immunologic function of the thymus and the
improvement in the clinical condition of patients following thymectomy, the thymus is suspected to be
the site of autoantibody formation. However, the stimulus that initiates the autoimmune process has
not been identified.

Diagnostic Tools .

Several tests are available, including electromyography, to test for muscle fatigue and an assay serum
antibodies. One test uses edrophonium chloride (Tensilon), a short-acting anticholinesterase inhibitor, to
prolong the action of Ach at the myoneural junction, resulting in a short period of increased skeletal
muscle function.

A special blood test can detect the presence of immune molecules or acetylcholine receptor antibodies.
Most patients with myasthenia gravis have abnormally elevated levels of these antibodies. However,
antibodies may not be detected in patients with only ocular forms of the disease

Management .

Myasthenia gravis is one of the most treatable neuromuscular disorders. The choice of treatment depends
on several factors, including age, overall health, severity of disease, and rate of disease progression.

Anticholinesterase medications such as neostigmine (Prostigmin®) and pyridostigmine (Mestinon®) are

usually prescribed. These drugs prevent ACh destruction and increase the accumulation of ACh at
neuromuscular junctions, improving the ability of the muscles to contract.

Side effects include excessive salivation, involuntary muscle twitching (fasciculation), abdominal pain,
nausea, and diarrhea. A drug called kaolin may be used with anticholinesterase medications to reduce
gastrointestinal side effects.

Corticosteroids (e.g., prednisone) suppress the antibodies that block AChR at the neuromuscular junction
and may be used in conjunction with anticholinesterase. Corticosteroids improve symptoms within a few
weeks and once improvement stabilizes, the dose is slowly decreased.
 A low dosage may be used indefinitely to treat MG; however, side effects such as gastric ulcers,
osteoporosis (bone thinning), weight gain, high blood sugar (hyperglycemia), and increased risk for
infection may develop over the long term.

Immunosuppressants such as azathioprine (Imuran®) and cyclophosphamide (Neosar®) are used to treat
generalized MG when other medications fail to reduce symptoms. Side effects may be severe and include
low white blood cell count (leukopenia), liver dysfunction, nausea, vomiting, and hair loss.

Immunosuppressants are not used to treat congenital MG because this condition is not the result of an
immune system malfunction.

Plasmapheresis, or plasma exchange, is used to modify the immune system malfunction. It can be used to
treat severe worsening of symptoms (exacerbations) or in preparation for surgery (thymectomy) in
patients who have myasthenia gravis.

n this procedure, blood is removed from the body and blood cells are separated from the liquid portion of
the blood (plasma). Then, AChR antibodies are removed and blood cells are diluted with artificial plasma
(usually a solution of saline and sterilized human albumin protein) and infused back into the body.

Typically, 2 to 3 liters of plasma is removed and replaced during a single treatment, which takes several
hours. Most patients undergo several sessions over the course of 2 weeks or more. Plasmapheresis
improves MG symptoms within days and improvement lasts 6–8 weeks.

Risks include low blood pressure, dizziness, blurred vision, and formation of blood clots (thrombosis).

Thymectomy is surgical removal of the thymus gland. It is usually performed on patients with a tumor of
the thymus (thymoma) and patients younger than age 55 with generalized MG. Benefits of thymectomy
develop gradually and most improvement occurs years after the procedure is performed.

Medications can block the neuromuscular junction and cause symptoms similar to MG. These drugs
include the following:

o Antibiotics (e.g., ciprofloxacin, erythromycin, ampicillin)

o Antispasmodic drugs (e.g., trihexyphenidyl; used to treat movement disorders)

o Beta-adrenergic receptor blocking agents (e.g., propranolol, timolol)

o Cardiac drugs (e.g., procainamide, verapamil, quinidine)

o Lithium (used to treat bipolar disorder)

o Penicillamine (penicillin product; used to treat metal poisoning)

TIC DOULOUREUX

Tic douloureux or trigeminal neuralgia is a severe, stabbing pain to one side of the face. It stems from one or more
branches of the nerve that supplies sensation to the face, the trigeminal nerve. It is considered one of the most painful
conditions to affect people.

Most people feel the pain in their jaw, cheek, or lip on one side of the face only. Pain is usually triggered by a light
touch of the face or mouth on the same side as the pain. The pain is so severe that people can become afraid to talk,
eat, or move during periods of attacks.

Tic douloureux is generally a disease of middle age or later life. Women are affected more often than men. People
with multiple sclerosis are affected much more frequently than the general population.

Signs and Symptoms .

o Facial pain triggered by eating, talking, shaving and brushing teeth.

o Facial pain described as electric shocks, burning, pressing, crushing, exploding or

shooting pain.

Pathophysiology .

The trigeminal nerve is the T1, T2, T3 and possibly the fifth cranial nerve, a mixed cranial nerve
responsible for sensory data such as tactition (pressure), thermoception (temperature), and
nociception (pain) originating from the face above the jawline; it is also responsible for the motor
function of the muscles of mastication, the muscles involved in chewing but not facial expression.

Several theories exist to explain the possible causes of this pain syndrome. It was once believed that
the nerve was compressed in the opening from the inside to the outside of the skull; but newer leading
research indicates that it is an enlarged blood vessel - possibly the superior cerebellar artery -
compressing or throbbing against the microvasculature of the trigeminal nerve near its connection with
the pons. Such a compression can injure the nerve's protective myelin sheath and cause erratic and
hyperactive functioning of the nerve. This can lead to pain attacks at the slightest stimulation of any
area served by the nerve as well as hinder the nerve's ability to shut off the pain signals after the
 stimulation ends. This type of injury may rarely be caused by an aneurysm (an outpouching of a blood
vessel); by a tumor by an arachnoid cyst in the cerebellopontine angle; or by a traumatic event such as
a car accident or even a tongue piercing.

A large portion of multiple sclerosis patients have TN, but not everyone with TN has MS. Only two to
four percent of patients with TN, usually younger, have evidence of multiple sclerosis, which may
damage either the trigeminal nerve or other related parts of the brain. It has been theorized that this is
due to damage to the spinal trigeminal complex. Trigeminal pain has a similar presentation in patients
with and without MS.

Postherpetic Neuralgia, which occurs after shingles, may cause similar symptoms if the trigeminal
nerve is damaged.

When there is no [apparent] structural cause, the syndrome is called idiopathic.

Diagnostic Tools .

There is no single medical test to diagnose tic douloureux. The diagnosis is made based on the
description of the pain, physical examination, and exclusion of other causes of facial pain.

The pain of tic douloureux is unique. A history of bursts of shooting pain in one side of the face along
with a trigger zone will give the doctor good clues to the cause of your pain.

The physical examination is normal in tic douloureux. If numbness, decreased hearing, dizziness,
visual changes, or dysfunction of the muscles of the face is found, then other disorders may be
considered. Additionally, other causes of facial pain such as a sinus infection, dental infection, or a
jaw disorder, such as TMJ, can often be found by physical examination.

Special x-ray images, such as a CT scan or MRI of the head, can look for other causes of facial pain.
They can also help delineate blood vessels or tumors that might be pressing on the nerve and irritating
it.

• Management .
The primary treatment of tic douloureux is medication to control the pain. Surgery may be necessary when
drug therapy is not effective or side effects from the medications are not tolerable.

A number of medications are effective in helping control the pain of tic douloureux. The most commonly
prescribed medications are anticonvulsants (seizure medications). Anticonvulsants help to stop the irritated
trigeminal nerve from firing pain impulses.

The most frequently prescribed anticonvulsant medication for tic douloureux is carbamazepine (Tegretol).
Other anticonvulsants used include phenytoin(Dilantin) and gabapentin (Neurontin). These medications are
generally started at a low dose and then increased until pain is controlled or side effects occur. Common side
effects include drowsiness, dizziness, double vision, and nausea. Rarely, serious liver or bone
marrow problems can occur.

Baclofen (Lioresal), a muscle relaxant, is useful for some people who either do not respond to
anticonvulsants or who suffer serious side effects.

Opioid pain medications can be useful during episodes of severe pain.

Medication is 80% effective. For the other 20%, drug therapy either fails to provide adequate pain control or
adverse side effects are intolerable. Unfortunately, up to 50% of people who initially respond to
anticonvulsants eventually develop resistance to the medications.
MULTIPLE SCLEROSIS

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and
spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and
symptoms. Disease onset usually occurs in young adults, and it is more common in females. It has aprevalence that
ranges between 2 and 150 per 100,000. MS was first described in 1868 by Jean-Martin Charcot. There are number of
types of MS with considerable variation I the effects, severity and progression in any one individual.

Signs and Symptoms .

The manifestations of MS are determined by the areas that are demyelinated in each individual.

o Changes in sensation

o Loss of sensitivity

o Tingling

o Pricking or numbness

o Muscle weakness

o Muscle spasms

o Ataxia

o Dysathria

o Dysphagia

o Nystagmus

o Diplopia

o Fatigue

o Acute pain
 o Bladder and bowel difficulties

o Cognitive impairment

o Depression or unstable mood

o Uhthoff’s phenomenon

o Lhermitte’s sign

Pathophysiology .

Loss of myelin interferes with the conduction of impulses in the affected fibers. It affects all types of
nerve fibers – motor, sensory and autonomic – and occurs in diffuse patches throughout the nervous
system. Intellectual functions are not usually affected.

The earliest lesion occurs as an inflammatory response, with loss of myelin in the white matter of the
brain or spinal cord. Later, larger areas of inflammation and demyelination, termed plaques, become
visible, frequently beside the lateral ventricles in the brain, in the brainstem, and I the optic nerves.

Initially, the area of plaque appears pinkish and edematous, but then it becomes gray and firm. Each
plaque varies in size, and several may coalesce into a single patch. The initial inflammation may subside,
and neural function may return to normal for a short time, until another exacerbation occurs. In time,
neural degeneration becomes irreversible and function is lost permanently. With each recurrence,
additional areas of the central nervous system (CNS) are involved. Multiple sclerosis varies in severity,
occurring in mild and slowly progressive patterns in some individuals and in rapidly progressive forms
in others.

Diagnostic Tools .

Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to other
medical problems. Medical organizations have created diagnostic criteria to ease and standardize the
diagnostic process especially in the first stages of the disease. Historically, the Schumacher and Poser
criteria were both popular. Currently, the McDonald criteria focus on a demonstration with clinical,
laboratory and radiologic data of the dissemination of MS lesions in time and space.

Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate
episodes of neurologic symptoms characteristic of MS. Since some people seek medical attention after
 only one attack, other testing may hasten and ease the diagnosis. The most commonly used diagnostic
tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance
imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be
administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the
existence of historical lesions not associated with symptoms at the moment of the evaluation. Testing
of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of
the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on
electrophoresis, which are an inflammation marker found in 75–85% of people with MS. The nervous
system of a person with MS responds less actively to stimulation of the optic nerve and sensory
nerves due to demyelination of such pathways. These brain responses can be examined using visual and
sensory evoked potentials.

• Management .

There is as yet no cure for MS. Many patients do well with no therapy at all,
especially since many medications have serious side effects and some carry
significant risks. However, three forms of beta interferon (Avonex, Betaseron, and
Rebif) have now been approved by the Food and Drug Administration for treatment
of relapsing-remitting MS. Beta interferon has been shown to reduce the number of
exacerbations and may slow the progression of physical disability. When attacks do
occur, they tend to be shorter and less severe. The FDA also has approved a
synthetic form of myelin basic protein, called copolymer I (Copaxone), for the
treatment of relapsing-remitting MS. Copolymer I has few side effects, and studies
indicate that the agent can reduce the relapse rate by almost one third. An
immunosuppressant treatment, Novantrone (mitoxantrone), is approved by the
FDA for the treatment of advanced or chronic MS. The FDA has also approved
dalfampridine (Ampyra) to improve walking in individuals with MS.

One monoclonal antibody, natalizumab (Tysabri), was shown in clinical trials to

significantly reduce the frequency of attacks in people with relapsing forms of
 MS and was approved for marketing by the U.S. Food and Drug Administration
(FDA) in 2004. However, in 2005 the drug’s manufacturer voluntarily
suspended marketing of the drug after several reports of significant adverse
events. In 2006, the FDA again approved sale of the drug for MS but under
strict treatment guidelines involving infusion centers where patients can be
monitored by specially trained physicians.

While steroids do not affect the course of MS over time, they can reduce the
duration and severity of attacks in some patients. Spasticity, which can occur
either as a sustained stiffness caused by increased muscle tone or as spasms
that come and go, is usually treated with muscle relaxants and tranquilizers
such as baclofen, tizanidine, diazepam, clonazepam, and dantrolene. Physical
therapy and exercise can help preserve remaining function, and patients may
find that various aids -- such as foot braces, canes, and walkers -- can help
them remain independent and mobile. Avoiding excessive activity and
avoiding heat are probably the most important measures patients can take to
counter physiological fatigue. If psychological symptoms of fatigue such as
depression or apathy are evident, antidepressant medications may help. Other
drugs that may reduce fatigue in some, but not all, patients include amantadine
(Symmetrel), pemoline (Cylert), and the still-experimental drug aminopyridine.
Although improvement of optic symptoms usually occurs even without
treatment, a short course of treatment with intravenous methylprednisolone
(Solu-Medrol) followed by treatment with oral steroids is sometimes used.

CEREBROVASCULAR ACCIDENT (CVA)

A stroke, known medically as a cerebrovascular accident (CVA), is the rapidly developing loss of brain function(s)
due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood flow) caused by
blockage (thrombosis, arterial embolism), or ahemorrhage (leakage of blood). As a result, the affected area of the
brain is unable to function, leading to inability to move one or more limbs on one side of the body, inability
to understand or formulate speech, or an inability to see one side of the visual field.
Ischemic stroke

In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that
area. There are four reasons why this might happen:

1. Thrombosis (obstruction of a blood vessel by a blood clot forming locally)

2. Embolism (obstruction due to an embolus from elsewhere in the body, see below),

3. Systemic hypoperfusion (general decrease in blood supply, e.g. in shock

4. Venous thrombosis

Hemorrhagic stroke

Intracranial hemorrhage is the accumulation of blood anywhere within the skull vault. A distinction is made
between intra-axial hemorrhage (blood inside the brain) and extra-axial hemorrhage (blood inside the skull but outside
the brain). Intra-axial hemorrhage is due to intraparenchymal hemorrhage orintraventricular hemorrhage (blood in the
ventricular system). The main types of extra-axial hemorrhage are epidural hematoma (bleeding between the dura
mater and the skull), subdural hematoma (in the subdural space) and subarachnoid hemorrhage (between
the arachnoid mater and pia mater). Most of the hemorrhagic stroke syndromes have specific symptoms
(e.g. headache, previous head injury).

Signs and Symptoms .

o Sudden transient weakness

o Numbness

o Tingling in the face, an arm or leg or one side of the body

o Temporary loss of speech

o Failure to comprehend
 o Confusion

o Sudden loss of vision

o Sudden severe headache

o Unusual dizziness or unsteadiness

o Flaccid paralysis

o Spastic paralysis

o Coma

o Loss of consciousness

o Loss of problem solving skills

o Personality changes

o Aphasia

o Visual loss

Pathophysiology .

Ischemic

Ischemic stroke occurs due to a loss of blood supply to part of the brain, initiating the ischemic cascade
Brain tissue ceases to function if deprived of oxygen for more than 60 to 90 seconds and after
approximately three hours, will suffer irreversible injury possibly leading to death of the tissue,
i.e., infarction. (This is why TPA's (e.g. Streptokinase, Altapase) are given only until three hours since
the onset of the stroke.) Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood
vessels leading to a reduction of blood flow, by causing the formation of blood clots within the vessel,
or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic
infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a
consequence of atrial fibrillation, or in the carotid arteries, break off, enter the cerebral circulation, then
lodge in and occlude brain blood vessels. Since blood vessels in the brain are now occluded, the brain
becomes low in energy, and thus it resorts into using anaerobic respiration within the region of brain
tissue affected by ischemia. Unfortunately, this kind of respiration produces less ATP but releases a by-
product called lactic acid. Lactic acid is an irritant which could potentially destroy cells since it is an
acid and disrupts the normal acid-bace balance in the brain. The ischemia area is referred to as the
"ischemic penumbra".

Then, as oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy
phosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-
dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off a series of
interrelated events that result in cellular injury and death. A major cause of neuronal injury is release of
the excitatory neurotransmitter glutamate. The concentration of glutamate outside the cells of the
nervous system is normally kept low by so-called uptake carriers, which are powered by the
concentration gradients of ions (mainly Na+) across the cell membrane. However, stroke cuts off the
supply of oxygen and glucose which powers the ion pumps maintaining these gradients. As a result the
transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing
glutamate into the extracellular space. Glutamate acts on receptors in nerve cells (especially NMDA
receptors), producing an influx of calcium which activates enzymes that digest the cells' proteins, lipids
and nuclear material. Calcium influx can also lead to the failure of mitochondria, which can lead further
toward energy depletion and may trigger cell death due to apoptosis.

Ischemia also induces production of oxygen free radicals and other reactive oxygen species. These react
with and damage a number of cellular and extracellular elements. Damage to the blood vessel lining or
endothelium is particularly important. In fact, many antioxidant neuroprotectants such as uric
acid and NXY-059 work at the level of the endothelium and not in the brain per se. Free radicals also
directly initiate elements of the apoptosis cascade by means of redox signaling.

These processes are the same for any type of ischemic tissue and are referred to collectively as
the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little
respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs.

Brain tissue survival can be improved to some extent if one or more of these processes is inhibited.
Drugs that scavenge reactive oxygen species, inhibit apoptosis, or inhibit excitatory neurotransmitters,
for example, have been shown experimentally to reduce tissue injury due to ischemia. Agents that work
in this way are referred to as being neuroprotective. Until recently, human clinical trials with
neuroprotective agents have failed, with the probable exception of deep barbiturate coma. However,
more recently NXY-059, the disulfonyl derivative of the radical-
scavenging spintrap phenylbutylnitrone, is reported to be neuroprotective in stroke.This agent appears
 to work at the level of the blood vessel lining or endothelium. Unfortunately, after producing favorable
results in one large-scale clinical trial, a second trial failed to show favorable results.

In addition to injurious effects on brain cells, ischemia and infarction can result in loss of structural
integrity of brain tissue and blood vessels, partly through the release of matrix metalloproteases, which
are zinc- and calcium-dependent enzymes that break down collagen, hyaluronic acid, and other
elements of connective tissue. Other proteases also contribute to this process. The loss of vascular
structural integrity results in a breakdown of the protective blood brain barrier that contributes
to cerebral edema, which can cause secondary progression of the brain injury.

As is the case with any type of brain injury, the immune system is activated by cerebral infarction and
may under some circumstances exacerbate the injury caused by the infarction. Inhibition of
the inflammatory response has been shown experimentally to reduce tissue injury due to cerebral
infarction, but this has not proved out in clinical studies.

Hemorrhagic

Hemorrhagic strokes result in tissue injury by causing compression of tissue from an expanding
hematoma or hematomas. This can distort and injure tissue. In addition, the pressure may lead to a loss
of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage
appears to have direct toxic effects on brain tissue and vasculature.

Diagnostic Tools .

Stroke is diagnosed through several techniques: a neurological examination (such as the Nihss), CT
scans (most often without contrast enhancements) or MRI scans, Doppler ultrasound, and arteriography.
The diagnosis of stroke itself is clinical, with assistance from the imaging techniques. Imaging
techniques also assist in determining the subtypes and cause of stroke. There is yet no commonly
used blood test for the stroke diagnosis itself, though blood tests may be of help in finding out the likely
cause of stroke

• Management_____________________________________________________
An ischemic stroke is caused by a thrombus (blood clot) occluding blood flow to an artery supplying the
brain. Definitive therapy is aimed at removing the blockage by breaking the clot down (thrombolysis), or
by removing it mechanically (thrombectomy). The more rapidly blood flow is restored to the brain, the
fewer brain cells die.

Other medical therapies are aimed at minimizing clot enlargement or preventing new clots from forming.
To this end, treatment with medications such as aspirin, clopidogrel anddipyridamole may be given to
prevent platelets from aggregating.

In addition to definitive therapies, management of acute stroke includes control of blood sugars, ensuring
the patient has adequate oxygenation and adequate intravenous fluids. Patients may be positioned with
their heads flat on the stretcher, rather than sitting up, to increase blood flow to the brain. It is common
for the bloo pressure to be elevated immediately following a stroke. Although high blood pressure may
cause some strokes, hypertension during acute stroke is desirable to allow adequate blood flow to the
brain.

Patients with intracerebral hemorrhage require neurosurgical evaluation to detect and treat the cause of
the bleeding, although many may not need surgery. Anticoagulants and antithrombotics, key in treating
ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are
monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.

Stroke rehabilitation is the process by which patients with disabling strokes undergo treatment to help
them return to normal life as much as possible by regaining and relearning the skills of everyday living.
It also aims to help the survivor understand and adapt to difficulties, prevent secondary complications
and educate family members to play a supporting role.

A rehabilitation team is usually multidisciplinary as it involves staff with different skills working
together to help the patient. These include nursing staff, physiotherapy, occupational therapy, speech and
language therapy, and usually a physician trained in rehabilitation medicine. Some teams may also
include psychologists, social workers, and pharmacists since at least one third of the patients
manifest post stroke depression. Validated instruments such as the Barthel scale may be used to assess
the likelihood of a stroke patient being able to manage at home with or without support subsequent to
discharge from hospital.

Good nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, and
monitoring vital signs such as temperature, pulse, and blood pressure. Stroke rehabilitation begins almost
immediately.
 For most stroke patients, physical therapy (PT) and occupational therapy (OT) are the cornerstones of
the rehabilitation process, but in many countries Neurocognitive Rehabilitation is used, too.
Often, assistive technology such as a wheelchair, walkers, canes, and orthosis may be beneficial. PT and
OT have overlapping areas of working but their main attention fields are; PT involves re-learning
functions as transferring, walking and other gross motor functions. OT focusses on exercises and training
to help relearn everyday activities known as theActivities of daily living (ADLs) such as eating,
drinking, dressing, bathing, cooking, reading and writing, and toileting. Speech and language therapy is
appropriate for patients with problems understanding speech or written words, problems forming speech
and problems with swallowing.

Patients may have particular problems, such as complete or partial inability to swallow, which can cause
swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve
with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly
into the stomach. If swallowing is still unsafe after a week, then a percutaneous endoscopic gastrostomy
(PEG) tube is passed and this can remain indefinitely.

Stroke rehabilitation should be started as quickly as possible and can last anywhere from a few days to
over a year. Most return of function is seen in the first few months, and then improvement falls off with
the "window" considered officially by U.S. state rehabilitation units and others to be closed after six
months, with little chance of further improvement. However, patients have been known to continue to
improve for years, regaining and strengthening abilities like writing, walking, running, and talking. Daily
rehabilitation exercises should continue to be part of the stroke patient's routine. Complete recovery is
unusual but not impossible and most patients will improve to some extent : proper diet and exercise are
known to help the brain to recover.

•
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