ALZHEIMER’S DISEASE

INTRODUCTION

Alzheimer's is the most common form of dementia, a general term for memory loss and other intellectual
abilities serious enough to interfere with daily life. Alzheimer's disease accounts for 50 to 80 percent of
dementia cases. This incurable, degenerative, and terminal disease was first described by German psychiatrist
and neuro-pathologist, 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.

DEFINITION

Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of
memory and eventually by disturbances in reasoning, planning, language, and perception .

INCIDENCE

 Alzheimer's disease is most common in people over 65 years of age.

 Affects slightly more women than men.
 The risk increases with age, and people who are over 80 years of age are thought to have a one in
six chance of developing the condition.
 The fastest growth in the elderly population is taking place in China, India, and their south Asian and western
Pacific neighbours.

RISK FACTORS

 head injury: Studies show that people who have suffered concussions are more likely to develop
Alzheimer's later on.
 vascular disease: Coexisting small strokes increase the risk and severity of memory problems in
Alzheimer's disease.
 inflammation: People with arthritis are less likely to get Alzheimer's. It is speculated that the
medications used to reduce inflammation in arthritis may have a beneficial effect on an inflammatory
process in the brain.
 gender: Women are nearly twice as likely as men to suffer from Alzheimer's.
 education: Research suggests that better educated people are less prone to Alzheimer's. Those who
already have the disease do better if they keep mentally active - an unused brain may deteriorate
faster.
 toxins (e.g., aluminum): A controversial and unproven theory links aluminum in drinking water to
senile plaque formation. Earlier studies hinted at a connection, but not according to recent studies
that are larger and better-designed.
 prions: Some scientists speculate that prions, tiny infectious particles made of protein, may be
involved in Alzheimer's disease by infecting the brain.

ETIOLOGY
 Ageing – Alzheimer's disease mainly affects older people (over 60yrs of age)
 a previous severe head injury
 lifestyle factors such as smoking or obesity
 diabetes
  raised blood pressure and raised blood cholesterol levels
 Genetic . Researchers have even found a gene that causes a particularly severe form of the
disease. If the patient inherit this gene from only one parent, there is an increased chance of
getting Alzheimer's disease, compared to people with the normal gene. Inheriting it from both
parents means you'll almost certainly get the disease, and at an earlier age.

 Familial autosomal dominant Alzheimer's disease (FAD) is the name given when Alzheimer's
disease is clearly passed on from generation to generation in a family. It typically comes on before
the age of 60, and the Alzheimer's gene, called APOE e4, turns up in many family members

 Plaques. These clumps of a protein called beta-amyloid may damage and destroy brain cells in
several ways, including interfering with cell-to-cell communication. Although the ultimate cause of
brain-cell death in Alzheimer's isn't known, abnormal processing of beta-amyloid is a prime
suspect.

 Tangles. Brain cells depend on an internal support and transport system to carry nutrients and
other essential materials throughout their long extensions. This system requires the normal
structure and functioning of a protein called tau. In Alzheimer's, threads of tau protein twist into
abnormal tangles, leading to failure of the transport system. This failure is also strongly implicated
in the decline and death of brain cells.

STAGES

Once you've been diagnosed with Alzheimer's, we can expect three phases of symptoms, generally
classified as mild, moderate, and severe.
 Stage I (Mild) can last two to four years. There will be minor memory loss, as well as
mood swings and personality changes. However, relative independence can be
maintained. Stage I symptoms can include:
 Getting lost easily
 Difficulty handling money and/or paying bills
 Repeating questions or bits of conversation out of context
 Taking longer to finish routine tasks
 Exercising poor judgment
 Losing or misplacing items
 Stage II (Moderate) Alzheimer's causes the brain to begin experiencing significant neural
damage. Simple tasks can still be accomplished, but people in stage II will struggle with
language, reason, sensory perception, and cognition. Stage II Alzheimer's tends to be the
longest, lasting anywhere from two to 10 years.

Symptoms may include:

 Trouble completing tasks with multiple steps, such as getting dressed or cooking a meal.

 Increased memory loss, where both recent events as well as personal history are no
longer remembered.

 Confusion as past memories blend with the present

 Difficulty recognizing familiar people or family

 Loss of ability to read and write

  Impulsive behavior and tendencies to wander

 Stage III (Severe) lasts one to three years. People with stage III Alzheimer's generally lose all
independence and most of their mental ability. At this stage, you will require constant care.
Many people remain homebound or in bed nearly all day. Symptoms can include:
 Inability to recognize anyone, including yourself
 Loss of communication, relying instead on grunts or moans
 Increased vulnerability to other diseases, such as skin or respiratory infections
 Loss of control over bodily functions, such as trouble swallowing or lack of bowel and
bladder control.
 Further decrease in memory, which becomes nearly nonexistent.

PATHOPHYSIOLOGY

The main factors causing AD are,

 Amyloid Plaques: are deposits of a protein fragment called beta-amyloid (BAY-tuh AM-uh-loyd)
that build up in the spaces between nerve cells.
 Neurofibrillary Tangles :are twisted fibers of another protein called tau that build up inside
cells.
 Loss of connection between cells and cell death

AMYLOID PLAGUES:

AGING, VASCULAR DISORDERS ETC

. AMYLOID PLAGUES ARE PRODUCED (INCREASED IN AD)

CLUSTERS OF INSOLUBLE DEPOSITS OF PROTEIN, β AMYLOID, OTHER PROTEINS,

REMNANTS OF NEURONS, NON NERVE CELLS

ATTACKS CEREBRAL CORETEX

AFFECTS MEMORY, COGNITION, REASONING

MEMORY LOSS, AGITATION, DIFFICULTY COMMUNICATING ETC

NEUROFIBRILLARY TANGLES:

‘TAU’ PROTEIN IN CNS(SUPPORTS INTRACELLULAR

MICROTUBULES AND HOLDS IT TOGETHER)

TAU PROTEIN IS ALTERED

MICRO TUBULES TWIST TOGETHER IN A HELICAL FASHION

NEURO FIBRILLARY TANGLES

LOSS OF CONNECTION BETWEEN CELLS AND CELL DEATH:

LOSS OF CONNECTION BETWEEN CELLS AND CELL DEATH

LOSS OF CONNECTION BETWEEN NEURONS

DAMAGE AND DEATH OF NEURONS

AFFECTED PART OF THE BRAIN SHRINK

BRAIN ATROPHY

CLINICAL MANIFESTATIONS
Brain changes associated with Alzheimer's disease lead to growing trouble with:

 Memory
The memory loss associated with Alzheimer's disease persists and gets worse. People with Alzheimer's may:

 Repeat statements and questions over and over

 Forget conversations, appointments or events, and not remember them later
 Routinely misplace possessions, often putting them in illogical locations
 Eventually forget the names of family members and everyday objects
 Disorientation and misinterpreting spatial relationships
People with Alzheimer's disease may lose their sense of what day it is, the time of year, where they are or
even their current life circumstances. Alzheimer's may also disrupt your brain's ability to interpret what you
see, making it difficult to understand your surroundings. Eventually, these problems may lead to getting lost
in familiar places.

 Speaking and writing

Those with Alzheimer's may have trouble finding the right words to identify objects, express thoughts or take
part in conversations. Over time, the ability to read and write also declines.

 Thinking and reasoning

Alzheimer's disease causes difficulty concentrating and thinking, especially about abstract concepts like
numbers. Many people find it challenging to manage their finances, balance their checkbooks, and keep track
of bills and pay them on time. These difficulties may progress to inability to recognize and deal with numbers.

 Making judgments and decisions

Responding effectively to everyday problems, such as food burning on the stove or unexpected driving
situations, becomes increasingly challenging.

 Planning and performing familiar tasks

Once-routine activities that require sequential steps, such as planning and cooking a meal or playing a
favorite game, become a struggle as the disease progresses. Eventually, people with advanced Alzheimer's
may forget how to perform basic tasks such as dressing and bathing.

 Changes in personality and behavior

Brain changes that occur in Alzheimer's disease can affect the way you act and how you feel. People with
Alzheimer's may experience:

 Depression

 Anxiety

 Social withdrawal

 Mood swings

 Distrust in others

 Increased stubbornness

 Irritability and aggressiveness

 Changes in sleeping habits

 Wandering
 DIAGNOSTIC EVALUATION
 History collection

 Physical examination

o Reflexes

o Muscle tone and strength

o Ability to move around

o Sense of touch and sight

o Co-ordination

o Balance

 Laboratory tests
The most common are blood tests and urinalysis. Blood tests involve a series of tests routinely done on blood
to look for abnormalities associated with various diseases and disorders. Blood tests also might be used to look
for the presence of a specific gene that has been identified as a risk factor for Alzheimer’s disease. A urinalysis is
a test in which a urine sample is evaluated to detect abnormalities, such as improper levels of sugar or protein.
 Lumbar puncture/spinal tap
A lumbar puncture, also called a spinal tap, is a procedure in which the fluid surrounding the spinal cord (called
the cerebrospinal fluid or CSF) is withdrawn through a needle and examined in a laboratory. Testing the CSF can
help your doctor diagnose disorders of the central nervous system (including multiple sclerosis) that may involve
the brain, spinal cord, or their coverings (meninges).
 Computed tomography (CT) scan
CT scans often can reveal certain changes that are characteristic of Alzheimer’s disease in its later stages. These
changes include a reduction in the size of the brain (atrophy), widened indentations in the tissues, and
enlargement of the fluid-filled chambers called cerebral ventricles.
 Magnetic resonance imaging (MRI)
MRI is beneficial in ruling out other causes of dementia, such as tumors or strokes. It also might help to show the
physical and functional changes in the brain that are associated with Alzheimer’s disease.
 Electroencephalography (EEG)
Because the EEG procedure is non-invasive and painless, it often is used to study various brain processes, such
as perception, memory, attention, language, and emotion, and is most helpful in identifying disorders that can
mimic Alzheimer's disease.

 Electrocardiogram (ECG or EKG)

 Neuropsychological testing
 Neuropsychological testing studies the relationship between the brain and behavior. It is used when the patient
is having serious problems with short- and long-term memory, attention and concentration, word and name
association, language understanding, and other symptoms that persist or worsen over time. These tests help in
the diagnosis and treatment of conditions that affect thinking, emotion, and behavior. These include Alzheimer’s
disease, various psychiatric problems (depression, anxiety disorders), medication-related conditions, substance
abuse, strokes, and tumors. Neuropsychological tests accompany a comprehensive interview with the patient,
and might include tests to assess attention, memory, language, the ability to plan and reason, and the ability to
modify behavior, as well as assessments of personality and emotional stability. Neuropsychological testing also
can help the doctor and family better understand the impact of a disorder on a patient’s everyday functioning.
 In addition, the following tests also might be done to help diagnose and monitor the progression of Alzheimer’s
disease:
 Positron emission tomography (PET) scan
 PET imaging can show the region of the brain that is causing a patient to have seizures, and is useful in
evaluating degenerative brain diseases such as Alzheimer's, Huntington's, and Parkinson's. PET scans can show
the difference in brain activity between a normal brain and one affected by Alzheimer’s disease. It can also help
differentiate Alzheimer's disease from other forms of dementia. Amyloid imaging is a special type of PET
scanning which shows deposits of amyloid, a protein, in the brain.

 Single photon emission computed tomography (SPECT) scan

 SPECT is a non-invasive technique for creating very clear, three-dimensional pictures of a major organ, such as
the brain or heart. SPECT scans use radionuclide imaging – a technique that involves the injection of a very small
amount of a radioactive substance, called a tracer.

MANAGEMENT
The collaborative management of Alzheimer’s disease is aimed at
 Improving or controlling decline in cognition
 Controlling the undesirable behavioral manifestations that the patient may exhibit.
MEDICAL MANAGEMENT
 For decreased memory and cognition:
Cholinesterase inhibitors

e.g., Rivastigmine, Galantamine, N-methyl-D-aspartate (NMDA), Memantine .

 Depression
 Selective serotonin reuptake inhibitors(SSRIs)
e.g., Sertraline, Fluvoxamine,
 Tricyclic antidepressants
e.g.,Nortryptriptyline,Amitriptyline,Imipramine.
 Behavioral problems
Conventional antipsychotics(Neuroleptics)
e.g.,Loxapine,haloperidol.
Atypical antipsychotics
e.g.,Risperidone,Olanzapine
DIETARY MANAGEMENT

 Fats: Omega 3,6 and DHA

A number of epidemiological studies have found that higher consumption of Docosaehexanoic acid (DHA), an
omega-3 fat found in fatty fish, is associated with reduced risk of developing Alzheimer’s Disease. 

Salmon, albacore tuna, whitefish,Seaweed,2 oz. walnuts

Eat fish twice a week

Supplement with fish oil with DHA and EPA

 Nitrates
Drinking 16 oz. of beet juice daily may help. There is a theory that Alzheimer’s and dementia may
be the result of decreased blood flow to the brain. Nitrates, which are in beets, may help blood cir-
culation, which could ward of the disease. Approximately 80 percent of dietary nitrates are derived
from vegetable consumption.

Good sources of nitrates include:

Beets, Cauliflower, Collard greens, Broccoli, Spinach, Root vegetables (potatoes, turnips, parsnips)

 Vitamin B
Our brains shrink as we age – especially as we get to be over 70 years old.  However, it appears that
taking a vitamin B supplement that contains folic acid and B12 may be good for our brains as we
age. According to a small British study, a daily dose of certain B vitamins may be able to reduce the
rate of brain atrophy by up to 53 percent.

Good sources B12 include:

 Clams ,Oysters ,Crab, Lobster, Caviar, Fish, Eggs, Low-fat dairy products

Good sources of B6:

 Oatmeal, Trout ,Soybeans ,Walnuts, Peanut butter ,Spinach, Tomato juice

Try the “Brain Protective” Diet

There is research that shows a “brain protective” diet may help. The participants in the study who
followed this had an 38 percent lowered risk of developing Alzheimer’s. “The brain protective diet
was noted to be rich in omega-3 fatty acids, omega-6 fatty acids, vitamin E, and folate, and relatively
lower in saturated fat and vitamin B12.” Part of the diet means a lower intake of high-fat dairy, but-
ter, red meat and organ meat.

 Beets, Olive oil, Nuts, Fish, Tomatoes ,Poultry, Cruciferous vegetables (broccoli, bok choy, cauli-
flower), Fruits, Leafy green vegetables
NURSING MANAGEMENT
Nursing Assessment
• Subjective data:
 Important health information
 Past health history
 Medications
 Functional health patterns
• Health perception-health management
• Nutritional-metabolic
• Elimination
• Activity-exercise
•Objective data:
–General
• Disheveled appearance, agitation
– Neurologic
• Early, middle, late
– Possible findings
NURSING DIAGNOSIS

 Disturbed thought process related to effect of dementia.

 Self care deficit related to memory deficit and neuro muscular impairment.
 Imbalanced nutritional status less than body requirement related to impaired muscle tone.
 Impaired elimination pattern related to neuromuscular impairment.
 Risk for injury related to impaired judgement,muscle weakness,gait instability.
 Risk for infection related to prolonged immobility,lack of hygiene.

PREVENTION

1. Regular exercise
2. Healthy diet
3. Mental stimulation
4. Quality sleep
5. Stress management
6. An active social life

HEALTH EDUCATION

 stop smoking
 avoid drinking large amounts of alcohol
 eat a healthy, balanced diet, including at least five portions of fruit and vegetables every day
 exercise for at least at least 150 minutes (2 hours and 30 minutes) of moderate-intensity aerobic activity (i.e. cycling or fast walking)
every week as this will improve both your physical and mental health
 stay mentally active, for example, by reading, writing or taking an adult education course 
 RESEARCH ABSTRACT
 September 19, 2011
 New Study Strengthens Link Between Diabetes and Alzheimer's
Diagnosis with type 2 diabetes doubled future risk of dementia for older adults.
- HealthDay
 September 16, 2011
Insulin via Nasal Spray Shows Preliminary Promise in Alzheimer's and MCI
In a small, short-term pilot study, participants receiving intranasal insulin scored better on some memory tests and had scans
showing increased brain use of glucose.
- Bloomberg

JOURNAL

ScienceDaily (Aug. 19, 2011) — A research team at Charité -- Universitätsmedizin Berlin and Universitätsklinik Freiburg has documented how
the immune system can counteract the advancement of Alzheimer's disease. In a newly published paper, they showed that certain scavenger
cells in the immune system, called macrophages, play a key role in this context. Furthermore, they were able to demonstrate how special cell-
signaling proteins, called chemokines, mediate the defense process.

The results of the study have now been published in the Journal of Neuroscience.

Prof. Josef Priller, Director of Neuropsychiatry at Campus Charité Mitte, is head of the research team. The paper was sponsored by the
German Federal Ministry of Education and Research ('BMBF') and the German Research Foundation ('DFG'). For ten years now, the scientists
have been investigating the exact role of macrophages in neurodegenerative diseases. "Macrophages can reduce harmful deposits in the
brain that are the cause of Alzheimer's disease," Prof. Priller explains.



 HUNTINGTON’S DISEASE

DEFINITION
Huntington's disease, chorea, or disorder (HD), is a neurodegenerative genetic disorder that affects muscle coordination and
leads to cognitive decline and dementia. It typically becomes noticeable in middle age.

INCIDENCE
 1 in 10,000

 Higher incidence in Europian ancestry

 In each pregnancy, an affected parent has a 50% chance of having a child with huntingtons disease

ETIOLOGY

 Huntington's disease is caused by a faulty gene that is found on chromosome number 4. The defect causes a part of DNA, called a
CAG repeat, to occur many more times than it is supposed to. Normally, this section of DNA is repeated 10 to 28 times. But in persons
with Huntington's disease, it is repeated 36 to 120 times. The larger the number of repeats, the greater your chance of developing
symptoms at an earlier age.
 The normal copy of the gene produces a protein called huntingtin, but the faulty gene is larger than normal and produces a larger
form of huntingtin. 
 Cells in parts of the brain – specifically, the basal ganglia and parts of the cortex – are very sensitive to the effects of the abnormal
huntingtin. This makes them function poorly and eventually die. 
 The brain normally sends messages through the basal ganglia. When this part of the brain is damaged, it causes problems with con-
trol of movement, behaviour and thinking.

It is still unclear exactly how abnormal huntingtin affects the brain cells and why some are more sensitive than others.
RISK FACTORS

Parents with the Disease

A child of an individual with Huntington's Disease has a 50% chance of developing the disease. Researchers refer to Huntington's as
an autosomal dominant disorder because only one parent has to possess the defective gene to pass it along to the child.

Sporadic Cases

Rarely, Huntington's disease occurs sporadically without either parent carrying the gene. Researchers believe this occurs due to
mutation in the father's sperm that results in the same level of defects as seen when a parent carries the gene. There does not
appear to be any indicator of why or how this mutation occurs.

Age

Onset of symptoms on average range 35-50 years old. A subset of juvenile cases occurs in people less than 20 years of age.

TYPES
There are two forms of Huntington's disease.

 The most common is adult-onset Huntington's disease. Persons with this form usually develop symptoms in their mid 30s
and 40s.
 An early-onset form of Huntington's disease accounts for a small number of cases and begins in childhood or adolescence.

PATHOPHYSIOLOGY

The Htt protein interacts with over 100 other proteins, and appears to have multiple biological functions.The behavior of mutated mHtt
protein is not completely understood, but it is toxic to certain types of cells, particularly in the brain. Damage mainly occurs in the
striatum, but as the disease progresses, other areas of the brain are also significantly affected. As the damage accumulates, symptoms
associated with the functions of these brain areas appear. Planning and modulating movement are the main functions of the striatum,
and difficulties with these are initial symptoms .
Htt function
Htt is expressed in all mammalian cells. The highest concentrations are found in the brain and testes, with moderate amounts in the
liver, heart, and lungs. The function of Htt in humans is unclear. It interacts with proteins which are involved in transcription, cell
signaling and intracellular transporting. In animals genetically modified to exhibit HD, several functions of Htt have been found. In these
animals, Htt is important for embryonic development, as its absence is related to embryonic death. It also acts as an anti-apoptotic agent
preventing programmed cell death and controls the production of brain-derived neurotrophic factor, a protein which protects neurons
and regulates their creation during neurogenesis. Htt also facilitates vesicular transport and synaptic transmission and controls neuronal
gene transcription. If the expression of Htt is increased and more Htt produced, brain cell survival is improved and the effects of mHtt are
reduced, whereas when the expression of Htt is reduced, the resulting characteristics are more typical of the presence of mHtt .In
humans the disruption of the normal gene does not cause the disease .It is currently concluded that the disease is not caused by
inadequate production of Htt, but by a gain of toxic function of mHtt.

Cellular changes due to mHtt

A microscope image of a neuron with inclusion (stained orange) caused by HD

There are multiple cellular changes through which the toxic function of mHtt may manifest and produce the HD pathology During the
biological process of posttranslational modification of mHtt, cleavage of the protein can leave behind shorter fragments constituted of
parts of the polyglutamine expansion.The polar nature of glutamine causes interactions with other proteins when it is overabundant in
Htt proteins. Thus, the Htt molecule strands will form hydrogen bonds with one another, forming a protein aggregate rather than folding
into functional proteins. Over time, the aggregates accumulate, ultimately interfering with neuron function because these fragments can
 then misfold and coalesce, in a process called protein aggregation, to form inclusion bodies within cells. Neuronal inclusions run indirect
interference. The excess protein aggregates clump together at axons and dendrites in neurons which mechanically stops the
transmission of neurotransmitters because vesicles (filled with neurotransmitters) can no longer move through the cytoskeleton.
Ultimately, over time, less and less neurotransmitters are available for release in signaling other neurons as the neuronal inclusions
grow.Inclusion bodies have been found in both the cell nucleus and cytoplasm. Inclusion bodies in cells of the brain are one of the
earliest pathological changes, and some experiments have found that they can be toxic for the cell, but other experiments have shown
that they may form as part of the body's defense mechanism and help protect cells.

Several pathways by which mHtt may cause cell death have been identified. These include: effects on chaperone proteins, which help
fold proteins and remove misfolded ones; interactions with caspases, which play a role in the process of removing cells; the toxic effects
of glutamine on nerve cells; impairment of energy production within cells; and effects on the expression of genes. The cytotoxic effects
of mHtt are strongly enhanced by interactions with a protein called Rhes, which is expressed mainly in the striatum.Rhes was found to
induce sumoylation of mHtt, which causes the protein clumps to disaggregate—studies in cell culture showed that the clumps were
much less toxic than the disaggregated form.

An additional theory that explains another way cell function may be disrupted by HD proposes that damage to mitochondria in striatal
cells (numerous accounts of mitochondrial metabolism deficiency have been found) and the interactions of the altered huntingtin
protein with numerous proteins in neurons leads to an increased vulnerability of glutamine, which, in large amounts, has been found to
be an excitotoxin. Excitotoxins may cause damage to numerous cellular structures. Although glutamine is not found in excessively high
amounts, it has been postulated that because of the increased vulnerability, even normal amounts glutamine can cause excitotoxins to
be expressed. Furthermore, the increase in sensitivity turn on capases are activated by the repeat expansion of polyglutamine and the
increase in sensitivity. The huntingtin protein is cleaved into tiny pieces by capases; these nuclear aggregates disrupt transcription by
interfering with the production of proteins by "slipping" into the nucleus of the neuron. Unfortunately, the cellular stress caused by the
interference causes more huntingtin to be broken up until apoptosis occurs.

Macroscopic changes due to mHtt

Area of the brain damaged by Huntington's disease – striatum (shown in purple)

 HD affects the whole brain, but certain areas are more vulnerable than others. The most prominent early effects are in a part of the
basal ganglia called the neostriatum, which is composed of the caudate nucleus and putamen.Other areas affected include the
substantia nigra, layers 3, 5 and 6 of the cerebral cortex, the hippocampus, purkinje cells in the cerebellum, lateral tuberal nuclei of the
hypothalamus and parts of the thalamus. These areas are affected according to their structure and the types of neurons they contain,
reducing in size as they lose cells.Striatal spiny neurons are the most vulnerable, particularly ones with projections towards the external
globus pallidus, with interneurons and spiny cells projecting to the internal pallidum being less affected.HD also causes an abnormal
increase in astrocytes

The basal ganglia—the part of the brain most prominently affected by HD—play a key role in movement and behavior control. Their
functions are not fully understood, but current theories propose that they are part of the cognitive executive systemand the motor
circuit.The basal ganglia ordinarily inhibit a large number of circuits that generate specific movements. To initiate a particular
movement, the cerebral cortex sends a signal to the basal ganglia that causes the inhibition to be released. Damage to the basal ganglia
can cause the release or reinstatement of the inhibitions to be erratic and uncontrolled, which results in an awkward start to motion or
motions to be unintentionally initiated, or a motion to be halted before, or beyond, its intended completion. The accumulating damage
to this area causes the characteristic erratic movements associated with HD.

Transcriptional dysregulation
CREB-binding protein (CBP), a transcription factor, is essential for cell function because as a coactivator at a significant number of
promoters, it activates the transcription of genes for survival pathways.Furthermore, the amino acids that form CBP include a strip 18
glutamines. Thus, the glutamines on CBP interact directly with the increased numbers of glutamine on the Htt chain and CBP gets pulled
away from its typical location next to the nucleus. Specifically, CRB contains a acetyltransferase domain that, in an experiment
performed by Steffan and colleagues, showed that a Htt exon 1 with 51 glutamines binded to this domain in CBP .Autopsied brains of
those who had Huntington's disease also have been found to have incredibly reduced amounts of CBP Plus, when CBP is overexpressed,
polyglutamine-induced death diminished, further demonstrating that CBP plays an important role in Huntington's disease and neurons in
general.

CLINICAL MANIFESTATION

 Behavior changes may occur before movement problems, and can include:

 Behavioral disturbances
 Hallucinations
 Irritability
 Moodiness
 Restlessness or fidgeting
 Paranoia
 Psychosis

 Abnormal and unusual movements include:

 Facial movements, including grimaces

 Head turning to shift eye position
 Quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts
 Slow, uncontrolled movements
 Unsteady gait

 Dementia that slowly gets worse, including:

 Disorientation or confusion
 Loss of judgment
 Loss of memory
 Personality changes
 Speech changes

 Additional symptoms that may be associated with this disease:

 Anxiety, stress, and tension

 Difficulty swallowing
 Speech impairment

 Symptoms in children:

 Rigidity
 Slow movements
 Tremor
 DIAGNOSTIC EVALUATION

Neurological examination
The neurologist will ask you questions and conduct relatively simple tests in the office to judge:

 Reflexes, Muscle strength, Muscle tone, Sense of touch, Vision and eye movement, Hearing, Coordination, Balance, Mental status,
Mood.

Psychiatric evaluation
A number of factors that could contribute to your diagnosis, including:

 Emotional state, Patterns of behaviors, Quality of judgment, Coping skills, Signs of disordered thinking, Evidence of substance abuse.

Brain-imaging tests.

 CT Scan
 MRI
  PET Scan

Electroencephalogram (EEG).

Genetic counseling and testing

If symptoms strongly suggest a diagnosis of Huntington's disease, your doctor may recommend a genetic test for the defective gene. This
test can confirm the diagnosis, and it may be valuable if there's no known family history of Huntington's disease or if no other family
member's diagnosis was confirmed with a genetic test.

The test won't provide information that is beneficial in determining a treatment plan.

Predictive genetic test

A genetic test can be given to someone who has a family history of the disease but shows no signs or symptoms. This is called predictive
testing. The test result has no treatment benefit, and it doesn't indicate when disease onset will begin or what symptoms are likely to
appear first.

Some people may elect to do the test because they find it more stressful not knowing. Others may want to take the test before they make
decisions about having children. Risks may include problems with insurability or future employment and the stresses of facing a fatal
disease. These tests are only performed after consultation with a genetic counselor.

MANAGEMENT

MEDICAL MANAGEMENT

There is no cure for Huntington's disease, and there is no known way to stop the disease from getting worse. The goal of treatment is
to slow down the course of the disease and help the person function for as long and as comfortably as possible.

Medications vary depending on the symptoms.

 Dopamine blockers may help reduce abnormal behaviors and movements.

 Drugs like tetrabenazine and amantadine are used to try to control extra movements.

There is a progressive need for assistance and supervision, and 24-hour care may eventually be needed.
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 depres-
sion 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.
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 prob-
lems.

 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 anti-
convulsants, 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.
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.
 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.

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.

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

NURSING MANAGEMENT

 A high calorie diet is frequently needed due to the high metabolic requirements in patients with HD.
 Provide 6 to 8 smaller meals per day instead of the usual three.
 Offer frequent snacks or liquid supplements between meals.
 Work towards creating a calm, stress free environment
 Allow extra time for comprehension, response and completion of tasks
 Encourage independence - offer assistance but don't take over
 Avoid confrontation by distracting attention
 Allow considered risk taking
 Be specific when giving time limits - keep your promises
 Positive re-enforcement - avoid criticism and praise achievements
 Invest your time
 Be self aware - verbal and none verbal communication
 Know your limits and take care of yourself
  Relaxation techniques
 Diversional activities
 Appropriate humour
 Medication

Nursing assessment

Attention to self-care and daily living skills, such as brushing your teeth, shaving, combing your hair, getting dressed, etc.,
serves three purposes: it increases your ability to perform these activities, provides overall muscle toning and increases your
range of motion.

Performing as many self-care tasks as possible will also help you develop independence and self-esteem. Feeling dependent on
others can be defeating, and a certain satisfaction can be gained from setting objectives in life and accomplishing them.

Nursing diagnosis

 Risk for aspiration

 Body image disturbance
 Bowel incontinence
 Risk for injury
 Altered nutrition less than body requirements
 Self-care deficit
 Risk for impaired skin integrity
 Impaired swallowing
 Altered thought process
 Impaired verbal communication

COMPLICATIONS

 Loss of ability to care for self

 Loss of ability to interact
 Injury to self or others
 Increased risk of infection
  Depression
 Death.

PREVENTION

Genetic counseling is advised if there is a family history of Huntington's disease. Experts also recommend genetic
counseling for couples with a family history of this disease who are considering having children.

HEALTH EDUCATION

Education regarding the following can be given:

 Caregivers of people who have HD can take steps to help the patient with daily activities. It can be helpful to the patient to keep his
or her environment as "normal" as possible
 Exercise can help the patient physically and mentally, so the person with HD should try to do as many physical activities as possible.
 Proper nutrition is very important, because the person with HD may have trouble getting enough calories. He or she may need to eat
several times a day. For patients with HD who have trouble eating and swallowing, the caregiver can cut the food into smaller bites or
puree it to make it easier to swallow. To prevent dehydration (another risk), the patient will need to get enough to drink every day.
 Caregivers can also make use of various community resources for the person with HD, including home care services, group housing,
and institutional care.

RESEARCH STUDIES

Grape Derived Polyphenols

Submitted by Marsha Miller Ph.D. on Sun, 03/27/2011

Researchers at the Mount Sinai School of Medicine in New York have investigated grape derived polyphenol extract (GDPE) as a
potential treatment for Huntington's disease. They found promising results in a cell model, a drosophila model, and the R6/2 mice.

In previous studies, the authors investigated the bioavailability of GDPE and found that although it is metabolized in the gut, it does
cross the blood brain barrier and can be detected in the brain.The researchers have also studied GDPE as a potential Alzheimer's
 treatment and found that it interferes with aggregation of the protein associated with the disease. GDPE is also an antioxidant and metal
chelator.

New Route Identified for Clearing Away the Toxic Protein that Causes Huntington’s Disease

In Huntington’s disease (HD), a toxic protein accumulates inside brain cells, leading to symptoms such as uncontrolled movements,
impaired thinking and personality changes.  Researchers have now identified a chemical tag that attaches to this protein, sends it through
a cellular waste handling system and prevents its harmful effects.  Efforts are underway to identify drugs that could stimulate tagging of
the protein and thus slow the course of HD.

HD is a genetic disease, caused by mutations that affect a protein called Huntingtin (Htt).  Those mutations elongate the protein and
cause it to build up in tangled clumps that interfere with vital cell functions.The new study, published in Cell*, shows that the attachment
of a chemical tag effectively labels mutant Htt as trash.  That tag is known as an acetyl group, and it is dealt out by proteins called
acetylases.  The tagged Htt protein is delivered to an acid-filled structure called a phagolysosome, which is the cellular equivalent of an
incinerator.

JOURNAL REFERENCE

Therapeutic Strategy for Huntington’s Disease Could Focus on Containing Cell ‘Shrapnel’

Writing in the journal Neuron,* investigators report that enzymes involved in ailments from stroke to cancer also play a role in Hunting-
ton’s disease.  Blocking the function of these enzymes, called matrix metalloproteinases (MMPs), is beneficial in cell and animal models
of Huntington’s, and could be an effective therapeutic strategy for patients

A Mitochondrial Meltdown in Huntington's Disease?

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Friday, June 17, 2011

Families with Huntington's disease know the devastation it inflicts.  The disease attacks parts of the brain essential for thinking and motor
control, leading to dementia, personality changes, and uncontrolled movements.  A lesser known and early symptom is unwanted weight
loss.  Scientists have long suspected, but could not prove, that the weight loss might reflect a metabolic problem – perhaps a breakdown
of the cellular energy factories known as mitochondria.
 Now, a study published in Nature Medicine* suggests that defects in the number, size and distribution of mitochondria play an early,
critical role in Huntington's disease. 

AMYOTROPHIC LATERAL SCLEROSIS

DEFINITION

Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably fatal neurological
disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles.

MEANING

ALS is named for its underlying pathophysiology. Amyotrophy refers to the atrophy of muscle fibers, which are denervated as their
corresponding anterior horn cells degenerate. Lateral sclerosis refers to hardening of the anterior and lateral columns of the spinal
cord as motor neurons in these areas degenerate and are replaced by fibrous astrocytes (gliosis).

INCIDENCE

ALS affects approximately 5 out of every 100,000 people worldwide.Males are affected more than females(1.5:1 in western countries,3:1 in In-
dia) .The disease usually strikes between age 40 and 60.

ETIOLOGY

Potential factors in mechanisms that might play a role in ALS and their relevance to the development of therapies are currently as follows:

􀂄 Environmental Factors: Although ALS is age dependant, and is on the increase as the average age of the population increases, the
rate of increase is greater than would be predicted based on the aging population alone. This suggests the role of an environmental
factor–an idea supported by several examples in which clusters of ALS cases have occurred in a particular geographic area or environ -
mental environmental situation. Although no single environmental agent has been shown to directly cause ALS, worldwide epidemio-
logical studie consistently sugges environmental triggers are important enough to continue to study to better understand the rela -
tionships.

􀂄 Genetic Factors and Inherited Variants of ALS:Approximately 90% of ALS cases are sporadic and do not show inheritance. How-
ever, scientists assume that for many people who develop ALS, a genetic
predisposition may interact with other factors suc as environmental variables to produce the disease. In less than 10% of people with
ALS, the disease is inherited. Seven genetic loci have been implicated in familial forms of ALS, each producing different features of the
disease in the families affected. Every newly identified and located ALS gene provides scientists a piece of the ALS puzzle and creates
the opportunity to develop new mouse models and cell lines that simulate these genetic abnormalities to research mechanisms that
may occur in ALS.

􀂄 Free Radicals and Oxidative Stress: Canadian researchers have documented the existence of excessive levels of proteins damaged
by free oxygen radicals within neurons in ALS, suggesting that either neuron synthesizes excessive levels of free radicals,or that it is
incapable of "venting" those that are normally produced. Therapies geared to reducing oxidative stress are in development, including
gene therapy and new pharmacotherapy .

􀂄 Immunological Factors: In recent years, researchers have considered how injured motor neurons might spur an immune response
that could contribute to, and even perpetuate, a cascade of cell death in the nervous system. The immune cells called microglial cells
and astrocytes can respond to neural injury in a way that can either be beneficial or harmful. This microglial response has been impli-
cated
as a trigger of programmed cell death (PCD), a mechanism that is useful on a small scale to clear away damage, but devastating on a
large scale as it ripples through the nervous system killing motor neurons.

Neurotrophic Factors: Although it is not clear how deficiencies of neurotrophic factors may affect human motor neurons, several at-
tempts have been made to determine whether neurotrophic factors can slow the rate of progression of ALS by first testing these
agents in animal models of the disease. Researchers are also investigating how the neurotrophic factors including brain derived neu-
rotrophic factor (BDNF) and cytokine ciliary neurotrophic factor (CNTF) interact with metal ions in the cell, and how metal ions can
thereby have extremely toxic effects in a cell depending on the neurotrophic factors present. Gene therapies are also in development
to promote the levels of beneficial neurotrophic factors. The gene for insulin-like growth factor 1 (IGF-1) was successfully delivered
in ALS mice using a viral vector, resulting in prolonging survival.

􀂄 Altered Protein and Neurofilament Metabolism:A signature feature of ALS is the accumulation of neurofilaments in the motor
neurons. These key neuronal proteins are believed to be responsible for maintaining the normal neuronal structure and shape. Stud-
ies making use of transgenic mouse models to alter neurofilament expression reveal that abnormalities in the metabolism of neurofil-
 aments, or the way in which neurofilaments interact with each other or with other proteins, could play a role in the development of
ALS.
􀂄 Glutamate Excitotoxicity: Abnormalities in the handling of excitatory amino acids by the nervous system, particularly glutamate,
may be critical to the occurrence of ALS. Through damage to the normal "transporter" mechanisms by which glutamate is removed
from the nervous system, excessive glutamate accumulates. When motor neurons receive glutamate at their receptors, there is an in-
flux in calcium ions into the cell. The motor neurons may not be able to deal with the excessive levels of calcium flooding in, resulting
in damage. Researchers are investigating ways to help the nervous system handle calcium and glutamate. Riluzole, the single drug
currently. available for the treatment of ALS, shows very modest results. Its action is not well understood but is thought to perhaps
affect glutamate mechanisms.

RISK FACTORS

 Heredity. Up to 10 percent of the people who have ALS inherited it from their parents. If you have this type of ALS, your children have
a 50-50 chance of developing the disease.

 Age. ALS most commonly occurs in people between the ages of 40 and 60.

 Sex. Before the age of 65, slightly more men than women develop ALS. This sex difference disappears after age 70.

Environmental factors under study that may modify a person's individual risk of ALS include:

 Smoking. Smoking cigarettes appears to increase a person's risk of ALS to almost twice the risk of nonsmokers. The more years spent
smoking, the greater the risk. On the other hand, quitting smoking can eventually lower this increased risk to that of a nonsmoker.

 Lead exposure. Some evidence suggests that exposure to lead in the workplace may be associated with the development of ALS.

 Military service. Recent studies indicate that people who have served in the military are at higher risk of ALS. Exactly what about mili-
tary service may trigger the development of ALS is uncertain, but it may include exposure to certain metals or chemicals, traumatic in -
juries, viral infections and intense exertion.

CLASSIFICATION
 Epidemiological and genetic factors permit classifying
 ALS as:
  􀂄 Classical sporadic ALS (90% of cases)
 􀂄 Familial ALS [5-10% of cases in which 20% of
 these are connected to a mutation of copper zinc
 superoxide dismutase 1 (SODI) in chromosome 2

PATHOPHYSIOLOGY
Each neuron whether motor or sensory has a cell body and then has a process called the axon (think of it as a body and its tail). The
motor neurons which control the movements of the arms and legs are located in the spinal cord (we refer to them as the anterior horn
cells becuase they lie anterioly in the spinal cord). We also have motor neurons which control other movements like that of
swallowing, speech etc. These neurons lie in the brain stem (the lower part of the brain). MND’s like ALS cause the death of these
motor neurons in the spinal cord (anterior horn cells) and those in the brain stem. In its classical form, ALS does not affect the sensory
neurons hence it is called a motor neuron disease. Once the motor neurons in the anterior horn cells and the brainstem die they do
not regenerate again and hence ALS is also a neurodegenerative disease causing progressive elentless degeneration of motor neurons.
CLINICAL MANIFESTATIONS
ALS may begin as weakness, awkwardness, or atrophy in one or more limbs. It may start as a difficulty swallowing or speaking. The
symptoms may be very subtle at first, and may be overlooked. Common symptoms include the following:

 Difficulty standing, walking, or running

 Clumsiness - Frequent tripping or falls

 Difficulty with fine hand motions such as buttoning, writing, turning a key in a lock

 Atrophy of hand muscles

 Atrophy of tongue

 Difficulty chewing food

 Difficulty swallowing (dysphagia)

 Difficulty speaking

 Oversensitive gag reflex

  Difficulty forming words (dysarthria)

 Weakness and atrophy in specific muscles

 Tight, stiff muscles (spasticity)

 Muscle cramps

 Muscle twitching visible under skin (fasciculations )

DIAGNOSTIC EVALUATION

 Electromyography (EMG)
 Nerve conduction velocity (NCV)
 Magnetic resonance imaging (MRI)
 CT Scan
 Blood and urine tests

 Muscle biopsy.
 Spinal tap:- inserts a needle into the spinal canal and removes fluid (cerebrospinal fluid) for testing.

MEDIACAL MANAGEMENT

 Medications
 Riluzole (Rilutek) is the only medication approved for treating ALS, but it only slows the progression. It is not a cure.
 Treatment is focused on symptom relief, maintenance of function, and extending life. ALS is not painful, but there may be pain
associated with prolonged immobility. Counseling for families and patients is recommended.
 There are no preventive measures, largely because the cause of ALS is unknown. The only prevention is genetic counseling for
families with a history of ALS.

 Physical and occupational therapy..

  Speech therapy

 . Assistive devices

 Nutritional support

 Mental health care.

 Family support.

 Follow-up care.

NURSING MANAGEMENT

Nursing assessment:

PHYSICAL

I. Muscle Weakness/Skin Status

1. Assessment
o Assess motor strength; presence of spasticity of flaccidity.
o Assess for presence of contracture.
o Assess skin daily, especially those areas susceptible to breakdown

II. Urinary Function

1. Assessment
o Assess urination pattern and patterns of fluid intake.
o Assess ability to transfer to toilet or commode, or standing ability for a male.
o Assess for signs and symptoms of urinary tract infection; frequency, urgency, painful urination, fever, etc. (urinary tract infections are rare in ALS).

III. Altered Bowel Function

1. Assessment
o Assess bowel pattern (for constipation, diarrhea, impaction.
o Assess diet, fluid intake, and swallowing ability.
o Assess activity level.

NUTRITION
I. Nutritional Needs
A. Assessment

1. Anthropometric Measures:
a) Height
b) Pre-morbid “usual” weight
c) Current Weight
d) Weight gain/loss pattern since onset of disease
e) “Ideal body weight”

2. Laboratory Test – indicated if patient has lost ten percent or more of body weight in the last two months or weighs fifteen percent or more below “ideal
body weight”.

3. Hydration status – determined by careful recording of fluid intake and output and by test of urine specific gravity. The average person needs 35cc fluid/kg
body weight for adequate renal function. This figure can be used to calculate fluid requirements.

B. Dysphagia (difficulty in swallowing)

1. Assessment
a) Assess gag, cough and swallowing reflexes, and chewing.
b) Assess patient’s ability to swallow liquids and solids.
c) Assess weight serially.
2. Common Nursing Diagnoses
a) Potential for injury.
b) Impaired nutritional status.

RESPIRATORY
A. Assessment
1. History: subjective symptoms (starving for air, shortness of breath and relation to position changes, fatigue).
2. Assess: changes from baseline respiratory rate, depth, pattern, chest expansion; adequacy of respiratory exchange and effort; retraction of intercostals
 spaces; abdominal breathing; diaphragmatic breathing; nasal flaring and use of cervical accessory muscles of respiration; color (cyanosis); cough, gag, and
swallow reflexes.
3. Auscultate: decreased breath sounds, presence of extra or adventitious sounds (i.e., sales, wheezes)

Communication
A. Assessment
1. Assess volume and clarity of speech.

2. Assess ability to communicate needs to family/significant others.

Psychological Adaptation
A. Assessment
1. Evaluate the patient and family’s support systems and coping
patterns with awareness that with ongoing loss of independence,

there will b

e ongoing grieving by patient and family.

NURSING DIAGNOSIS

 Ineffective airway clearances related to impaired/absent gag reflex

 Impaired gas exchange related to aspiration secondary to impaired/absent gag, swallowing and cough/sneeze relexes.
 Self care deficit related to impaired physical mobility
 Impaired nutritional status
 Impaired bowel elimination.
 Impaired urinary elimination related to progressive loss of mobility and dehydration
 Potential for injury related to impaired physical mobility.
 Knowledge deficit regarding airway clearance and gas
exchange.,diet,self care etc.

COMPLICATIONS
  Breathing in food or fluid (aspiration)
 Loss of ability to care for self
 Lung failure (See: Adult respiratory distress syndrome)
 Pneumonia
 Pressure sores
 Weight loss

PREVENTION
The only prevention is genetic counseling for families with a history of ALS.

HEALTH EDUCATION

It can be given on the following aspects:

 Emotional support is vital in coping with the disorder, because mental functioning is not affected. Groups such as the ALS
Association may be available to help people who are coping with the disorder.
 Support for people who are caring for someone with ALS is also available, and may be very helpful.
 Gentle, low-impact aerobic exercise such as walking, swimming, and stationary bicycling can strengthen unaffected mus-
cles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exer-
cises can help prevent painful spasticity and shortening (contracture) of muscles. Physical therapists can recommend exer-
cises that provide these benefits without overworking muscles.
 Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve
energy and remain mobile.
 As ALS progresses, speech therapists can help patients develop ways for responding to yes-or-no questions with their eyes
or by other nonverbal means and can recommend aids such as speech synthesizers and computer-based communication
systems. These methods and devices help patients communicate when they can no longer speak or produce vocal sounds.
 Patients and caregivers can learn from speech therapists and nutritionists how to plan and prepare numerous small meals
throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow.
 Patients may begin using suction devices to remove excess fluids or saliva and prevent choking.
  When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the
stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids
into the lungs.

RESEARCH STUDIES

 Landmark studies identify new gene as the most common cause of ALS and FTD
 Two studies published in the September 21 online issue of Neuron report the identification of the long-sought genetic abnormality
which authors say is the most common cause of two different but related forms of neurodegenerative disease: FTD and ALS.

The first study, entitled “Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked
frontotemporal dementia and amyotrophic lateral sclerosis” was led by neurogeneticist Rosa Rademakers, PhD, at the Mayo Clinic in
Florida. The researchers identified a short DNA sequence repeated hundreds to thousands of times in almost 12 per cent of familial
FTD and more than 22 per cent of familial ALS of samples studied. Ian Mackenzie, MD, neuropathologist at Vancouver General Hospi -
tal and professor in the department of pathology and laboratory medicine at the University of British Columbia (UBC) also served as a
lead investigator in this study

SYRINGOMYELOMA
DEFINITION

Syringomyelia is damage to the spinal cord due to the formation of a fluid-filled area within the cord.
 Syringomyelia is a generic term referring to a disorder in which a cyst or cavity forms within the spinal cord. This cyst, called a syrinx, can
expand and elongate over time, destroying the spinal cord.

INCIDENCE

 Although an older study had suggested that 20% of patients died at an average of 47 years, mortality rates are likely lower in today's
patients as a result of surgical interventions and better treatment of complications associated with significant paresis, such as pul-
monary embolism.
 Occurrence of syringomyelia in different races is unknown.
 Familial cases have been described.
 Syringomyelia occurs more frequently in men than in women.
 The disease usually appears in the third or fourth decade of life, with a mean age of onset of 30 years.
 Rarely, syringomyelia may develop in childhood or late adulthood.

ETIOLOGY

The following conditions and diseases can lead to syringomyelia:

 Chiari malformation — a condition in which brain tissue protrudes into your spinal canal

 Meningitis — an inflammation of the membranes surrounding your brain and spinal cord

 Spinal cord tumor — which may interfere with the normal circulation of cerebrospinal fluid

 Tethered spinal cord syndrome — a disorder caused when tissue attached to your spinal cord limits its movement

 Spinal injury — which may cause symptoms months or even years after the initial injury

 Spinal scar tissue — which can develop after surgery.

RISK FACTORS

The fluid buildup seen in syringomyelia may be a result of

 spinal cord trauma

  tumors of the spinal cord

 birth defects (specifically, "chiari malformation,"

PATHOPHYSIOLOGY

The progression of syringomyelia associated with Chiari I malformation is produced by the action of the cerebellar tonsils, which partially occlude the subarachnoid

space at the foramen magnum and act as a piston on the partially enclosed spinal subarachnoid space. This creates enlarged cervical subarachnoid pressure waves

that compress the spinal cord from without, not from within, and propagate syrinx fluid caudally with each heartbeat, which leads to syrinx progression.

CLINICAL MANIFESTATIONS
There may be no symptoms, or symptoms may include:

 Gradual loss of muscle mass (wasting, atrophy)

 Headache
 Muscle function loss, loss of ability to use arms or legs
 Numbness or decreased sensation
o Decreased sense of pain or temperature
o Lessened ability to sense that the skin is being touched
o Neck, shoulders, upper arms, trunk -- in a cape-like pattern
o Slowly, but progressively, gets worse
 Pain down the arms, neck, or into the upper back
 Weakness (decreased muscle strength, independent of exercise) in the arms or legs

Additional symptoms that may be associated with this disease:

 Muscle contractions
  Rashes
 Spasms in or tightness of the leg muscles
 Uncoordinated movement

DIAGNOSTIC EVALUATION

 History collection
 Physical findngs
 MRI
 CT Scan
 Myelogram
 3D CTs
 High definition imaging

MEDICAL MANAGEMENT

Surgery is the only viable treatment for syringomyelia. Not all patients will advance to the stage where surgery is needed.
Evaluation of the condition is often difficult because syringomyelia can remain stationary for long periods of time, and in
some cases progress rapidly.

SURGICAL MANAGEMENT
 Monitoring
If syringomyelia is discovered on an MRI scan that's done for an unrelated reason, and it's not causing signs or symptoms, monitoring with periodic MRI and neurological exams
may be all that's necessary. In rare cases, a syrinx may resolve on its own without treatment.

Surgery
If syringomyelia is causing signs and symptoms that interfere with your daily life, or if signs and symptoms rapidly worsen, surgery is usually recommended. The goal of surgery
is to remove the pressure the syrinx places on your spinal cord and to restore the normal flow of cerebrospinal fluid. The type of surgery you'll need depends on the underlying
cause of syringomyelia.

Typically, surgery for syringomyelia includes one or more of the following:

 Treating Chiari malformation. If syringomyelia is caused by Chiari malformation, your doctor may recommend surgery that involves enlarging the opening at the base of your
skull (suboccipital craniectomy) and expanding the covering of your brain (dura mater). This surgery can reduce pressure on your brain and spinal cord, restore the normal flow
of cerebrospinal fluid and, in most cases, resolve syringomyelia.
 Draining the syrinx. To drain the syrinx, your doctor may surgically insert a drainage system, called a shunt. It consists of a flexible tube with a valve that keeps fluid from the sy -
rinx flowing in the desired direction. One end of the tubing is placed in the syrinx, and the other is placed just outside your spinal cord. The shunt remains inside your spine after
surgery. In some cases, your doctor may be able to drain the syrinx during surgery with a small tube (catheter), and a shunt is not required.
 Removing the obstruction. If something within your spinal cord is hindering the normal flow of cerebrospinal fluid, such as a tumor or a bony growth, surgically removing the
obstruction may restore the normal flow and allow fluid to drain from the syrinx.
 Correcting the abnormality. If a spinal abnormality is hindering the normal flow of cerebrospinal fluid, surgery to correct it — such as releasing a tethered spinal cord — may re-
store normal fluid flow and allow the syrinx to drain.

NURSING MANAGEMENT

* Determines knowledge level assesses readiness to learn,identifies barriers to communication

* Explains sequence of events,and reinforces teaching about syringomyelia, expected disease and available treatment options.

* Provides instruction (ie.,verbal, written) for surgical procedure and discharge based
on age and identified needs patient and family to include:
* wound care,
* activity level,
* safety measures,
 * signs and symptoms to
report, and
* when to call the surgeon.
* Evaluates response to instruction.

* Identifies baseline tissue perfusion and preoperative neurovascular status of extremities.

* Assesses factors related to risk for ineffective tissue perfusion (eg, syringomyelia).

* Positions the patient neutrally and anatomically correct and pads pressure
points.

* Evaluates for signs and symptoms of positioning injury by comparing the patient's
extremity neurovascular status with baseline status.

* Identifies physical alterations that require additional precautins.

* Identifies approaches to minimize risk of injury atpatient's home and work place.

* Identifies potential risks for injury.

* Assists the patient and family members to identity additional strategies to prevent
postoperative injury.

* Evaluates response to safety management interventions.

* Assesses pain control.

* Implements pain guidelines * Identifies cultural and value components related to pain.

* Provides pain management instruction.

* Implements alternative methods of pain control

(eg, perioperative sedation, patient-controlled analgesia).
NURSING DIAGNOSIS
Pre operative

 Pain in the extremities related to muscle spasms

 Ineffective breathing pattern related to respiratory muscle spasm.
 Impaired tissue perfusion
 Disturbed thought process related to neurologic impairment
 Self care deficit related to muscle spasm
 Imbalanced nutrition less than body requirement related to dysphagia
 Impaired verbal communication

Post operative
 Pain related to surgical incision
 Self care deficit related to surgical procedure
 High risk for infection related to

COMPLICATIONS
Without treatment, the condition will lead to:

 Continued or progressive loss of neurologic function

 Permanent disability

Possible complications of surgery include:

 Postoperative infection and other complications common to all surgeries

PREVENTION
 There is no known prevention, other than avoiding trauma to the spinal cord.

Prompt treatment reduces progression of the disorder.

HEALTH EDUCATION

 Postoperative care
o Provide appropriate care of the surgical wound.
o Check for CSF leakage from tubes exiting the dura.
o Provide neck collar as needed for patient comfort.
 Reported postoperative complications include the following:
o Worsening of neurological deficit
o Low-pressure headache
o Shunt infection or obstruction
 MRI is recommended during the early postoperative period as a baseline for further studies.

RESEARCH ARTICLES

Investigators have found that as the heart beats, syrinx fluid is forced downward. This finding suggests a role for the cardiovascular sys-
tem in syringomyelia.

Surgical techniques are also being refined by the neurosurgical research community. It is also important to understand the role of birth
defects in the development of hindbrain malformations that can lead to syringomyelia. Dietary supplements of folic acid during preg -
nancy have already been found to reduce the number of cases of certain birth defects.

JOURNAL REFERENCE

An efficacy analysis of posterior fossa decompression techniques in the treatment of Chiari malformation with associated
syringomyelia:
A retrospective study of the efficacy of posterior fossa decompression (PFD) was carried out in 132 patients with Chiari malformation (CM) with associ-
ated syringomyelia (SM). Of these 132 patients, 69 received extended PFD (large craniotomy group), and the other 63 patients received only local PFD
(small craniotomy group). At the short-term postoperative evaluation (1-4weeks) the extended PFD appeared to be more effective than the local PFD
(p<0.05). However, there was no significant difference in long-term analysis (6months-11years) (p>0.05). In the large craniotomy group, there was no
difference between the short-term and long-term efficacy (p>0.05). However, in the small craniotomy group, long-term efficacy clearly improved
(p<0.05). Furthermore, patients who had undergone local PFD exhibited more obvious radiological improvement of SM (p<0.05) and fewer postopera-
tive complications compared to patients undergoing extended PFD (p<0.05). Therefore, local PFD is preferable for the surgical treatment of CM with as-
sociated SM.

Diffusion-Weighted MR Imaging in a Rat Model of Syringomyelia after Excitotoxic Spinal Cord Injury
Eric D. Schwartz,a, Robert P. Yezierskia, Pradip M. Pattanya, Robert M. Quencera and Raymond G. Weavera

BACKGROUND AND PURPOSE: Recent experimental data have shown that an increase of excitatory amino acids and the initiation of
inflammatory responses within the injured spinal cord may play a role in post-traumatic syringomyelia. The purpose of this study was to
determine whether diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) maps could provide earlier evidence of spinal
cord cavitation in a rat model of syringomyelia than available with conventional MR imaging.