IMPORTANT WARNING:

Taking metoclopramide may cause you to develop a muscle problem called tardive dyskinesia. If you develop tardive
dyskinesia, you will move your muscles, especially the muscles in your face in unusual ways. You will not be able to control
or stop these movements. Tardive dyskinesia may not go away even after you stop taking metoclopramide. The longer you
take metoclopramide, the greater the risk that you will develop tardive dyskinesia. Therefore, your doctor will probably
tell you not to take metoclopramide for longer than 12 weeks. The risk that you will develop tardive dyskinesia is also
greater if you are taking medications for mental illness, if you have diabetes, or if you are elderly, especially if you are a
woman. Call your doctor immediately if you develop any uncontrollable body movements, especially lip smacking, mouth
puckering, chewing, frowning, scowling, sticking out your tongue, blinking, eye movements, or shaking arms or legs.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin
treatment with metoclopramide and each time you refill your prescription. Read the information carefully and ask your
doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website
(http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication
Guide.
Talk to your doctor about the risks of taking metoclopramide.
Why is this medication prescribed?
Metoclopramide is used to relieve heartburn and speed the healing of ulcers and sores in the esophagus (tube that
connects the mouth to the stomach) in people who have gastroesophageal reflux disease (GERD; condition in which
backward flow of acid from the stomach causes heartburn and injury of the esophagus) that did not get better with
other treatments. Metoclopramide is also used to relieve symptoms caused by slow stomach emptying in people who have
diabetes. These symptoms include nausea, vomiting, heartburn, loss of appetite, and feeling of fullness that lasts long
after meals. Metoclopramide is in a class of medications called prokinetic agents. It works by speeding the movement of
food through the stomach and intestines.
How should this medicine be used?
Metoclopramide comes as a tablet, an orally disintegrating (dissolving) tablet, and a solution (liquid) to take by mouth. It
is usually taken 4 times a day on an empty stomach, 30 minutes before each meal and at bedtime. When metoclopramide
is used to treat symptoms of GERD, it may be taken less frequently, especially if symptoms only occur at certain times
of day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part
you do not understand. Take metoclopramide exactly as directed. Do not take more or less of it or take it more often
than prescribed by your doctor.
If you are taking the orally disintegrating tablet, use dry hands to remove the tablet from the package just before you
take your dose. If the tablet breaks or crumbles, throw it away and remove a new tablet from the package. Gently
remove the tablet and immediately place it on the top of your tongue. The tablet will usually dissolve in about one minute
and can be swallowed with saliva.
If you are taking metoclopramide to treat the symptoms of slow stomach emptying caused by diabetes, you should know
that your symptoms will not improve all at once. You may notice that your nausea improves early in your treatment and
continues to improve over the next 3 weeks. Your vomiting and loss of appetite may also improve early in your treatment,
but it may take longer for your feeling of fullness to go away.
Continue to take metoclopramide even if you feel well. Do not stop taking metoclopramide without talking to your doctor.
You may experience withdrawal symptoms such as dizziness, nervousness, and headaches when you stop taking
metoclopramide.

Other uses for this medicine

Return to top
Metoclopramide is also sometimes used to treat the symptoms of slowed stomach emptying in people who are recovering
from certain types of surgery, and to prevent nausea and vomiting in people who are being treated with chemotherapy
for cancer. Ask your doctor about the risks of using this medication to treat your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Return to top
Before taking metoclopramide,

tell your doctor and pharmacist if you are allergic to metoclopramide, any other medications, or any of the
ingredients in metoclopramide tablets or solution. Ask your doctor or pharmacist or check the Medication
Guide for a list of the ingredients.

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional
supplements and herbal products you are taking or plan to take. Be sure to mention any of the following:
acetaminophen (Tylenol, others); antihistamines; aspirin; atropine (in Lonox, in Lomotil); cyclosporine (Gengraf,
Neoral, Sandimmune); barbiturates such as pentobarbital (Nembutal), phenobarbital (Luminal), and
secobarbital (Seconal); digoxin (Lanoxicaps, Lanoxin); haloperidol (Haldol);insulin; ipratropium (Atrovent);
lithium (Eskalith, Lithobid); levodopa (in Sinemet, in Stalevo); medications for anxiety, blood pressure, irritable
bowel disease, motion sickness, nausea, Parkinson's disease, ulcers, or urinary problems; monoamine oxidase
(MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar),
and tranylcypromine (Parnate); narcotic medications for pain; sedatives; sleeping pills; tetracycline
(Bristacycline, Sumycin); or tranquilizers. Your doctor may need to change the doses of your medications or
monitor you more carefully for side effects.

tell your doctor if you have or have ever had blockage, bleeding, or a tear in your stomach or intestines;
pheochromocytoma (tumor on a small gland near the kidneys); or seizures. Your doctor will probably tell you not
to take metoclopramide.

tell your doctor if you have or have ever had Parkinson's disease (PD; a disorder of the nervous system that
causes difficulties with movement, muscle control, and balance); high blood pressure; depression; breast
cancer; asthma;glucose-6-phosphate dehydrogenase (G-6PD) deficiency (an inherited blood disorder); NADH
cytochrome B5 reductase deficiency (an inherited blood disorder); or heart, liver, or kidney disease.

tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant
while taking metoclopramide, call your doctor.

if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking
metoclopramide.

you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you
know how this medication affects you.

ask your doctor about the safe use of alcohol while you are taking this medication. Alcohol can make the side
effects of metoclopramide worse.

What special dietary instructions should I follow?

Return to top
Unless your doctor tells you otherwise, continue your regular diet.
What should I do if I forget a dose?
Return to top
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose
and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Return to top
Metoclopramide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

drowsiness

excessive tiredness

weakness

headache

dizziness

diarrhea

nausea

vomiting

breast enlargement or discharge

missed menstrual period

decreased sexual ability

frequent urination

inability to control urination

Some side effects can be serious. If you experience any of the following symptoms, or those mentioned in the
IMPORTANT WARNING section, call your doctor immediately:

tightening of the muscles, especially in the jaw or neck

speech problems

depression

thinking about harming or killing yourself

fever

muscle stiffness

confusion

fast, slow, or irregular heartbeat

sweating

restlessness

nervousness or jitteriness

agitation

difficulty falling asleep or staying asleep

pacing

foot tapping

slow or stiff movements

blank facial expression

uncontrollable shaking of a part of the body

difficulty keeping your balance

rash

hives

swelling of the eyes, face, lips, tongue, mouth, throat, arms, hands, feet, ankles, or lower legs

sudden weight gain

difficulty breathing or swallowing

high-pitched sounds while breathing

vision problems

Metoclopramide may cause other side effects. Call your doctor if you have any unusual problems while you are taking
this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's
(FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/Safety/MedWatch] or by phone [1800-332-1088].
What storage conditions are needed for this medicine?
Return to top
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room
temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is
outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose
Return to top
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not
breathing, call local emergency services at 911.
Symptoms of overdose may include

drowsiness

confusion

seizures

unusual, uncontrollable movements

lack of energy

bluish coloring of the skin

headache

shortness of breath

What other information should I know?

Return to top
Keep all appointments with your doctor.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your
prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines
you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list
with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with
you in case of emergencies.

Background
Tardive dyskinesias (TDs) are involuntary movements of the tongue, lips, face, trunk, and extremities
that occur in patients treated with long-term dopaminergic antagonist medications. Although they are
associated with the use of neuroleptics, TDs apparently existed before the development of
neuroleptics. People with schizophrenia and other neuropsychiatric disorders are especially
vulnerable to developing TDs after exposure to conventional neuroleptics, anticholinergics, toxins,
substances of abuse, and other agents. TDs are most common in patients with schizophrenia,
schizoaffective disorder, or bipolar disorder who have been treated with antipsychotic medication for
long periods, but TDs occasionally occur in other patients as well. For example, people with fetal
alcohol syndrome, other developmental disabilities, and other brain disorders are vulnerable to the
development of tardive dyskinesias, even after receiving a single dose of the causative agent.
TDs may be differentiated from acute movement disorders that commonly occur in the same patient
groups. The acute movement disorders that occur as manifestations of effects of neuroleptics and
other dopamine antagonists include akathisia, acute dystonia, and other hyperkinetic dyskinesias.
Acute effects of dopamine antagonists also include Parkinsonian syndromes manifested by
bradykinesia, rigidity, and pill rolling tremor. The acute movement disorders resulting from exposure to
dopamine antagonists are commonly termed extrapyramidal syndromes (EPS).
The occurrence of acute movement disorders upon exposure to dopamine antagonists is increased in
female patients and older patients. Use of potent dopamine antagonists, prolonged exposure to
dopamine antagonists, and prior occurrence of acute movement disorders on exposure to dopamine
antagonists are also associated with an increased risk for the occurrence of acute movement adverse
effects. Withdrawal dyskinesias may also occur as treatment with dopamine antagonists is decreased
or withdrawn. They are often refractory to all therapeutic modalities. In addition to the prototypic
orofacial dyskinesia, tardive syndromes also include a spectrum of hyperkinesias occurring during or
after prolonged treatment with dopamine antagonists.
Bishnoi and colleagues provided evidence of the involvement of the adenosinergic receptor system in
the development of TD in rodents. Haloperidol induced vacuous chewing movements, orofacial
movements, and facial stereotypies in rate. These changes were reversed after treatment with
adenosine or caffeine. These findings provide evidence that adenosine, a major inhibitory
neurotransmitter in the central nervous system, plays a role in TD. Additionally, these results suggest
potential therapeutic agents for clinical trials.[1]
Bishnoi and colleagues have demonstrated a beneficial effect of progesterone on an animal model of
tardive dyskinesia. They hypothesize that the favorable effect of progesterone is modulated by means
of the GABAergic and neuroprotective actions of alloprogesterone, a metabolite of progesterone. [3]
TD has been associated with polymorphisms of both the dopamine receptor D2 (DRD2) gene[2] , TaqI
A and TaqI B and associated haplotypes[4] , and of the dopamine receptor D3 (DRD3) gene[2, 5] , the
dopamine transporter (DAT) gene, and the manganese superoxide dismutase (MnSOD) gene.
Dysfunction of the dopamine transporter has been hypothesized to play a role in the development of
TD. However, Lafuente and colleagues did not find evidence of involvement of a polymorphism with a

variable number of tandem repeats (VNTD) in the DAT gene (SLC6A3) in dyskinesias induced by
antipsychotics.[6] Thus, further research is needed to investigate the role of the dopamine transporter in
the development and maintenance of TD.
Galecki and colleagues have reported the association of a polymorphism of the manganese
superoxide dismutase (MnSOD) gene and TD.[7]
Please find the following tools associated with this article: Abnormal Involuntary Movement
Scale, Psychoactive Medication Quality Assurance Rating Survey, Psychoactive Medication Quality
Assurance Rating Survey Screening Criteria, Hillside Akathisia Scale, Movement Disorders
Checklist,Definitions of Indicator Functions Utilizing the Items of theMovement Disorders
Checklist, Algorithms to Classify Movement Disorders, Timed Stereotypies Rating Scale, Audio
Segment.

Pathophysiology
For most of the past century, movement disorders (ie, abnormal adventitious movements) have been
categorized as extrapyramidal syndromes (EPSs) due to lesions of the extrapyramidal system of the
central nervous system. The pyramidal system, controlling voluntary movements, includes precise
anatomic pathways from the cortex to muscle. Voluntary movements through the pyramidal systems
are visible. By contrast, extrapyramidal motor activities result in automatic movement and static,
postural movement activities that are not noticeable. The extrapyramidal system includes theorized
connections within the basal ganglia, the striatopallidonigral system, and other structures of the
central nervous system that contribute to the regulation of movement, including related brainstem
nuclei and the cerebellum.
An example of a classic disorder of the pyramidal system is a stroke, resulting in paralysis of an
extremity. Corticospinal lesions above the pyramidal decussation typically result in paralysis of
volitional movements of the contralateral half of the body and a fixed posture with flexion of the upper
extremity and extension of the lower extremity. Bilateral corticospinal lesions of the upper pons and
midbrain typically cause extension of all 4 extremities and decerebrate rigidity with dorsiflexion of the
cervical and thoracolumbar spine. Unilateral lesions of the upper pons and midbrain often result in
extension of the ipsilateral arm and leg.

Extrapyramidal dysfunction
Classic disorders of the extrapyramidal system include a variety of involuntary movement disorders.
Some of these movement disorders include dyskinesias such as akathisia, chorea, dystonia,
myoclonus, stereotypy, tic, and tremor.
Table 1. Classic Characterization of the Pyramidal and Extrapyramidal Systems (Open Table in a new
window)
Characteristi
c

Pyramidal

Extrapyramidal

Anatomy

Precisely demarcated
pathways from cortex to
muscle

Hypothesized pathways among basal

ganglia and other structures of the central
nervous system

Physiologic

Voluntary

Involuntary

movements
Pathologic
movements

Paralysis, paresis,
hyperreflexia, and
spasticity

Akathisia, athetosis, ballism, chorea,

dystonia, myoclonus, stereotypy, tic, and
tremor

The pathophysiology of extrapyramidal disorders has been disputed because some extrapyramidal
disorders may not involve lesions of the basal ganglia and, in addition, may not be involuntary.
Because of the problems inherent in the concept of the extrapyramidal system, caution must be
exercised in the classification of movement disorders as EPSs, and new approaches to the
classification of movement disorders may be helpful.
Dyskinesia is a type of movement disorder that is subdivided into bradykinesias and hyperkinesias.
Bradykinesias are characterized by abnormal slowness (eg, rigidity), difficulty initiating and
terminating actions, and the masked facial expression of patients with Parkinson disease.
Hyperkinesias are purposeless movements, including akathisia, chorea, dystonia, myoclonus,
stereotypy, tic, and tremor.
The classification of movement disorders as bradykinesias and hyperkinesias is based on the
observed phenomenology, etiology, and topography. Practitioners and researchers may be
confounded by these classifications of movement disorders and may prefer instead to use clinical
impressions. Methods of data analysis, including linear and logistic regression, linear discriminant
function analysis, factor analysis, inverted factor analysis, tree approaches, dynamic clusters analysis,
and principal component analysis, may facilitate the classification of these diseases.

Dopamine system
The pathophysiology of TD is not well understood. Central dopamine blockade is hypothesized to play
a role in the pathogenesis of TD. Acute movement disorders are also hypothesized to result, in part,
from the blockade of dopamine receptors by dopamine antagonists.
Several hypotheses have been proposed for the development of TD.

Striatal dopamine receptor supersensitivity may be responsible.

Chronic dopamine blockade may result in up-regulation of dopamine receptor
responsiveness.
TD is hypothesized to result from compensatory supersensitivity of dopamine receptors
following chronic blockade. Long-term blockade of dopamine D 2 receptors in the basal ganglia by
dopamine D2antagonists (eg, neuroleptics) may produce TD.
When dopamine D2 -receptor blockade is reduced (even slightly), an exaggerated response of
the postsynaptic dopamine D2 -receptor (even to low concentrations of dopamine) may result.
Striatal disinhibition of the thalamocortical pathway from imbalance of D 1 and D2 receptors
may be involved.
Neurodegeneration secondary to lipid peroxidation or excitotoxic mechanisms may be
responsible.
Although the dopamine D2 receptor has traditionally been implicated in the pathogenesis of TD,
mounting evidence indicates that, in some individuals, the dopamine D 3, D4, and D5 receptors are
involved.
Most likely, genetic traits produce a vulnerability to develop TD when a susceptible individual is
exposed to particular agents. For example, the MscI polymorphism of the dopamine D 3 receptor gene

has been associated with the development of TD. Support for the hypothesis that TD may result from
blockade of postsynaptic dopamine receptors in the basal ganglia and other parts of the brain exists in
the form of the beneficial effects of increasing doses of neuroleptics for some patients with TD. Thus,
dopamine antagonists may mask TD.
Increased dopamine transport (DAT) uptake after treatment with quetiapine has been reported with
the amelioration of TD in a 67-year-old woman.[8]
Nicotine may play a role in the pathophysiology of TS. Cigarette smokers appear to have increased
metabolism of dopamine D2 antagonists. Nicotinic agonists appear to relieve dyskinesias in some
people with Tourette syndrome (see Tourette Syndrome), a condition characterized by the presence of
motor and phonic tics (see Tourette Syndrome and Other Tic Disorders). The relationship between TD
and the use of cigarettes and other nicotinic agonists remains to be clarified.
In 2005, Tan and colleagues reported an inverse correlation of plasma levels of brain-derived
neurotrophic factor and dyskinetic movements in people with schizophrenia with TD. [9] Thus, brainderived neurotrophic factor appears to have a protective effect in the nervous system against TD with
people with schizophrenia.
Modestin and colleagues have observed that a fluctuating course of the illness characterizes people
with tardive dyskinesia. They also report that length of illness is highly correlated with tardive
dyskinesia.[10]
Bishoi and colleagues have noted that curcumin, an antioxidant, may prevent the development of
dyskinesias induced in animals by dopamine receptor blocking drugs. [11]

Clinical presentation
Patients often have movement disorders that may actually represent a mixture or overlap of several
dyskinesia disorders, as depicted in the diagram below.

Tardive dyskinesia. Venn diagram of the classification of movement disorders.

Individuals treated with neuroleptics may demonstrate both acute and chronic effects, manifested by
acute dyskinesias and TD. Individuals may simultaneously manifest akathisia and tics after long-term
treatment with neuroleptics.
The diagnosis of acute and chronic dyskinesias may be difficult without a past history when seeing a
patient for the first time. Precise documentation of a patient's complete movement history and
medication history may facilitate accurate delineation of movement disorders. Therefore, a full
neurologic and pharmacologic history may provide the basis to distinguish idiopathic Tourette disorder
from acute medication-induced tardive tics.

Patients and families often cannot provide accurate histories; thus, firm diagnoses may be impossible.
Because acute and tardive medication effects may occur simultaneously, the distinction may be
challenging in a clinical setting. Observing patients carefully on a regular basis with precise
documentation at each visit, through structured rating instruments, of the phenomenology and
topography of movements and the pharmacologic treatments helps to provide a basis for accurate
future diagnosis of acute and TDs.

Genetic influences
A genetic basis for TD has not been identified. In particular, a functional polymorphism of the gene
coding for human glutathione S-transferase P1 (GSTP1) does not appear to be associated with TD.
[12]
Additionally, CYP3A4 and CYP2D6 gene polymorphisms are apparently unassociated with TD. [13]TD
has been associated with polymorphisms of the dopamine D3 receptor Ser9Gly [14] and of the serotonin
2A[2] and 2C receptor genes[14, 2] .
Reports of associations between TD and polymorphisms of NADPH quinine oxidoreductase 1 (NQO1)
and superoxide dismutase 2 (SOD2, MnSOD) genes have not consistently been confirmed by
subsequent studies.[15]

General diagnosis
TD is common in individuals with psychotic disorders (eg, schizophrenias, schizoaffective disorders,
bipolar disorders) who are treated with antipsychotic medications, especially dopamine antagonists,
for many years.
Generally, TD is diagnosed if one of the following circumstances is present. Criteria for neurolepticinduced tardive dyskinesia are listed in the image below.

Diagnostic criteria for neuroleptic-induced tardive dyskinesia.

A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 2 movements of at least mild intensity while taking a neuroleptic.
A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 1 movement of at least moderate intensity while taking a neuroleptic.
A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 2 movements of at least mild intensity within 4 weeks of the discontinuation of the
neuroleptic.
A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 1 movement of at least moderate intensity within 4 weeks of the discontinuation of the
neuroleptic.
A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 2 movements of at least mild intensity within 8 weeks of the discontinuation of a depot
neuroleptic.
A person who has taken neuroleptics for at least 3 months (1 mo if older than 60 y) develops
at least 1 movement of at least moderate intensity within 8 weeks of the discontinuation of a depot
neuroleptic.

Epidemiology
Frequency
United States
In 1997, Goetz estimated that tardive dyskinesia (TD) occurs in approximately 15-30% of persons
who receive long-term treatment with neuroleptics.[16] TD is more likely to occur in individuals who have
manifested acute adverse effects of exposure to dopamine antagonists. Frequency of the various
subtypes varies markedly. For example, orofacial, buccolingual, and masticatory dyskinesias are
common, but only 1-2% of people treated with dopamine antagonists develop tardive dystonia.
Orofacial TDs differ from peripheral TDs in the occurrence of comorbid acute movement disorders.
Acute tremor, acute akathisia, and acute Parkinsonism are more common in people with peripheral
TD. Distinguishing acute and TDs in an individual patient can represent a serious diagnostic
challenge.
The prevalence of TD is higher in cigarette smokers.[17]
International
The international frequency is apparently similar to that of the United States.

Race
Tardive dyskinesia (TD) occurs in persons of every race.[18]

Studies in different populations have identified overall prevalences of 1-65%.

Africans and African Americans appear to be especially vulnerable to TD after exposure to
low doses of neuroleptics for short durations.
However, drawing any conclusions on the basis of these results is difficult because different
investigators conducted the studies in different settings. A number of other variables, such as
therapeutic approaches, methodologic inconsistencies, diet, weather, and varied assessments, may
also contribute to the differences in various racial groups.

Sex
Elderly female patients appear to be particularly susceptible. [18] Young men are prone to develop
tardive blepharospasm and tardive dystonia.

Age
TD occurs in all ages.

In 2001, Connor et al found that 5.9% of 95 young people aged 7-21 years receiving
dopamine antagonist treatment for 3 months had TD.[19]
Advanced age is a major risk factor for TD.[18] The prevalence of TD is 29% in elderly patients
receiving dopamine antagonist treatment for 3 months and 26-67% in patients treated long term

MIASTENIA GRAVIS
BAB I
PENDAHULUAN
A. Latar Belakang Masalah
Saraf perifer, taut neuromuskular, dan otot rangka merupakan komponen akhir neuron motorik
perifer. Penyakit yang mengenai struktur-struktur ini dapat mengakibatkan terjadinya kelemahan
otot. Sedangkan secara spesifik, kelemahan otot terbagi menjadi tiga macam yaitu:
- Penyakit neurologik yang mengenai neuron motorik atas atau bawah. Paralisis neuron motorik
bawah ditandai dengan atrofi otot dan hilangnya refleks tendon dan secara klinis penyakit ini
menyerupai otot primer. Sedangkan paralisis neuron motorik atas menyebabkan spastisitas dan
refleks cepat tanpa atrofi otot yang signifikan
Kegagalan transmisi neuromuskuler
- Penyakit yang mengenai otot rangka itu sendiri, antara lain miositis, distrofi dan miopati.
(Chandrasoma dan Taylor, 2005)
Salah satu penyakit kelemahan otot yang sering dijumpai dalam klinis adalah gangguan transmisi
neuromuskuler myasthenia gravis. Myasthenia Gravis adalah penyakit neuromuskuler yang
menggabungkan kelelahan cepat otot volunter dan waktu penyembuhan yang lama. Myathenia gravis
merupakan penyakit kronis yang disebabkan oleh gangguan transmisi neuromuskuler asetilkolin pada
membran postsinaps. Pada kasus ringan, myasthenia menyebabkan kelemahan otot-otot pada mata
dan menimbulkan ptosis. Sedangkan pada moderate kasus, myasthenia menyebabkan kesulitan
berbicara, mengunyah, menelan, bernafas, dan kelemahan pada anggota gerak badan. (Hartwig,
2005)
Miastenia gravis adalah salah satu penyakit kelemahan otot yang ditimbulkan oleh reaksi autoimun.
Dari penelitian yang telah dilakukan pada penderita miastenia, ditemukan adanya defisiensi dari
acetylcholine receptor (AchR) pada neuromuscular junction. Defisiensi ini disebabkan oleh timbulnya
antibodi terhadap AchR. Sehingga, terdapat perkembangan dalam pengertian tentang struktur dan
fungsi dari AchR serta interaksinya dengan antibodi AchR. Hubungan antara konsentrasi, spesifisitas,
dan fungsi dari antibodi terhadap manifestasi klinik pada miastenia gravis saat ini telah dianalisis
dengan sangat hati-hati, dan mekanisme dimana antibodi AchR mempengaruhi transmisi
neuromuskular telah diinvestigasi lebih jauh. (Dewabenny, 2008)
Myasthenia gravis dapat terjadi pada berbagai usia. Prevalensi penyakit ini diperkirakan 14 per
100.000 populasi, dengan 36.000 kasus terjadi di Amerika Serikat. Puncak usia awitan adalah 20

tahun, dengan rasio perbandingan antara perempuan dan laki-laki adalah 3:1. Puncak kedua
walaupun lebih rendah daripada yang pertama, terjadi pada laki-laki tua usia dalam dekade tujuh
puluhan atau delapan puluhan. (Hartwig, 2005)
B. Rumusan Masalah
Seorang wanita umur 25 tahun datang di RS dengan keluhan beberapa bulan ini mengeluh kelemahan
pada otot, apabila melakukan kegiatan anggota gerak cepat capai, kelopak mata sulit dibuka, bila
melihat cepat capai dan pandangan menjadi double. Dan semua keluahn tersebut semakin memberat
waktu sore hari. Pada pagi hari, terutama setelah bangun tidur keluhan tersebut hilang atau
berkurang. Dalam beberapa minggu ini keluhan semakin bertambah, anggota gerak semakin capai
dan cepat membaik setelah istirahat, bila berbicara semakin lemah. Belum mengeluh perasaan tidak
enak di dada atau sesak nafas, tidak ada gangguan sensibilitas dan gerakan abnormal. Tidak
ditemukan juga keluhan ini dalam keluarganya. Pada pemeriksaan penunjang didapatkan bahwa hasil
pemeriksaan elektrolit darah dalam batas normal, hasil pemeriksaan EMG dengan merangsang salah
satu saraf secara terus menerus ditemukan penurunan reaksi abnormal, dan tes endorphonium
positif. Dokter menjelaskan kelainannya pada motor end plate sehingga diberikan obat prostigmin
dan keluhan berkurang.
1. Bagaimana anatomi, fisiologi neuromuscular junction, fisiologi dan histologi otot lurik?
2. Bagaimana penegakkan diagnosis dan apa penyakit pasien?
3. Bagaimana patofisiologi dari gejala-gejala yang dialami pasien?
4. Apakah kelainan yang diderita pasien bersifat progresif?
5. Apakah penyakit pasien bersifat kongenital?
6. Mengapa keluhan yang dialami memberat pada sore hari dan berkurang setelah istirahat?
7. Akankah di kemudian hari pasien akan mengalami sesak napas? mengapa?
8. Mengapa pemeriksaan penunjangnya dipilih elektrolit darah, tensilon test, dan EMG? Apakah ada
pemeriksaan lain?
9. Bagaimana interpretasi hasil dari EMG ?
10. Apakah pemberian prostigmin memberi prognosis yang baik? Bagaimana farmakokinetik,
farmakodinamik, dan indikasi pengobatan?
11. Bagaimana penatalaksanaan dan prognosisnya?
C. Tujuan Penulisan
Tujuan Umum
Menerapkan konsep-konsep dan prinsip ilmu-ilmu biomedik, klinik, perilaku, epidemiologi, dan
kesehatan masyarakat pada problem klinik serta penatalaksanaan pasien penyakit dalam bidang
muskuloskeletal.
Tujuan Khusus
1. Mengidentifikasi dan menerapkan prinsip-prinsip ilmu dasar yang relevan untuk memahami

etiologi, patofisiologi, dan patogenesis mengenai gangguan muskuloskeletal

2. Menangani suatu permasalahan klinis secara mandiri dengan kemampuan menetapkan diagnosis
klinik berdasarkan anamnesis, pemeriksaan fisik dan pemeriksaan penunjang
3. Mampu menjelaskan secara rasional dan ilmiah dalam menentukan penanganan pasien baik klinik,
epidemiologis, farmakologis, fisiologis, dan perubahan perilaku
D. Manfaat Penulisan
1. Sebagai upaya memahami dasar homeostatis tubuh dari tingkat sel hingga sistem organ tubuh.
2. Sebagai upaya memahami mekanisme gangguan pada penghantaran sel dan motor end plate
3. Sebagai langkah upaya dalam memahami etiologi dan menifestasi klinis myasthenia gravis
4. Untuk memahami langkah-langkah dalam penegakan diagnosis, pemeriksaan penunjang dan
pengobatan yang terkait dengan myasthenia gravis

BAB II
TINJAUAN PUSTAKA
A. Histologi dan Fisiologi Neurmoscular Junction
Bagian terminal dari saraf motorik melebar pada bagian akhirnya yang disebut terminal bulb, yang
terbentang diantara celah-celah yang terdapat di sepanjang serat saraf. Membran presinaptik
(membran saraf), membran post sinaptik (membran otot), dan celah sinaps merupakan bagianbagian pembentuk neuromuscular junction. Celah sinaps merupakan jarak antara membran
presinaptik dan membran post sinaptik. Lebarnya berkisar antara 20-30 nanometer dan terisi oleh
suatu lamina basalis, yang merupakan lapisan tipis dengan serat retikular seperti busa yang dapat
dilalui oleh cairan ekstraselular secara difusi. Terminal presinaptik mengandung vesikel yang
didalamnya berisi asetilkolin (ACh). Asetilkolin disintesis dalam sitoplasma di bagian terminal,
namun dengan cepat diabsorpsi ke dalam sejumlah vesikel sinaps yang kecil, yan terdapat di bagian
terminal suatu lempeng akhir motorik (motor end plate). Bila suatu impuls saraf tiba di
neuromuscular junction, sekitar 125 kantong asetilkolin akan dilepaskan dari terminal bub masuk ke
dalam celah sinaps. Bila potensial aksi menyebar ke seluruh terminal, maka akan terjadi difusi dari
ion-ion kalsium ke bagian dalam terminal. Ion-ion kalsium ini mempunyai pengaruh tarikan terhadap
vesikel asetilkolin. Beberapa vesikel akan bersatu ke membran saraf dan mengeluarkan asetilkolinnya
ke dalam celah sinaps. Asetilkolin yang dilepaskan berdifusi sepanjang sinaps dan berikatan dengan
reseptor asetilkolin (AChRs) pada membran post sinaptik. Secara biokimiawi keseluruhan, proses
pada neuromuscular junction dianggap berlangsung dalam 6 tahap, yaitu: (Ngoerah, 1991; Howard,
2008)
1. Sintesis asetil kolin terjadi dalam sitosol terminal saraf dengan menggunakan enzim kolin
asetiltransferase yang mengkatalisis reaksi berikut ini:

Asetil-KoA + Kolin Asetilkolin + KoA

2. Asetilkolin kemudian diinkorporasikan/ disatukan ke dalam partikel kecil terikat membran yang
disebut vesikel sinap dan disimpan di dalam vesikel tersebut.
3. Pelepasan asetilkolin dari vesikel ke dalam celah sinaps merupakan tahap berikutnya. Peristiwa ini
terjadi melalui eksositosis yang melibatkan fusi vesikel dengan membran presinaptik. Dalam keadaan
istirahat, kuanta tunggal (sekitar 10.000 molekul transmitter yang mungkin sesuai dengan isi satu
vesikel sinaps) akan dilepaskan secara spontan sehingga menghasilkan potensial endplate miniature
yang kecil. Kalau sebuah akhir saraf mengalami depolarisasi akibat transmisi sebuah impuls saraf,
proses ini akan membuka saluran Ca2+ yang sensitive terhadap voltase listrik sehingga
memungkinkan aliran masuk Ca2+ dari ruang sinaps ke terminal saraf. Ion Ca2+ ini memerankan
peranan yang esensial dalam eksositosis yang melepaskan asitilkolin (isi kurang lebih 125 vesikel) ke
dalam rongga sinaps.
4. Asetilkolin yang dilepaskan akan berdifusi dengan cepat melintasi celah sinaps ke dalam reseptor di
dalam lipatan taut (junctional fold), merupakan bagian yang menonjol dari motor end plate yang
mengandung reseptor asetilkolin (AChR) dengan kerapatan yang tinggi dan sangat rapat dengan
terminal saraf. Jika 2 molekul asetilkolin terikat pada sebuah reseptor, maka reseptor ini akan
mengalami perubahan bentuk dengan membuka saluran dalam reseptor yang memungkinkan aliran
kation melintasi membran. Masuknya ion Na+ akan menimbulkan depolarisasi membran otot
sehingga terbentuk potensial end plate. Keadaan ini selanjutnya akan menimbulkan depolarisasi
membran otot di dekatnya dan terjadi potensial aksi yang ditransmisikan disepanjang serabut saraf
sehingga timbul kontraksi otot.
5. Jika saluran tersebut menutup, asetilkolin akan terurai dan dihidrolisis oleh enzim
asetilkolinesterase yang mengkatalisis reaksi berikut:
Asetilkolin + H2O Asetat + Kolin
Enzim yang penting ini terdapat dengan jumlah yang besar dalam lamina basalis rongga sinaps
6. Kolin didaur ulang ke dalam terminal saraf melalui mekanisme transport aktif di mana protein
tersebut dapat digunakan kembali bagi sintesis asetilkolin. (Murray et al, 2003)
Setiap reseptor asetilkolin merupakan kompleks protein besar dengan saluran yang akan segera
terbuka setelah melekatnya asetilkolin. Kompleks ini terdiri dari 5 protein subunit, yaitu 2 protein
alfa, dan masing-masing satu protein beta, delta, dan gamma. Melekatnya asetilkolin memungkinkan
natrium dapat bergerak secara mudah melewati saluran tersebut, sehingga akan terjadi depolarisasi
parsial dari membran post sinaptik. Peristiwa ini akan menyebabkan suatu perubahan potensial
setempat pada membran serat otot yang disebut excitatory postsynaptic potential (potensial lempeng
akhir). Apabila pembukaan gerbang natrium telah mencukupi, maka akan terjadi suatu potensial aksi
pada membran otot yang selanjutnya menyebabkan kontraksi otot. (Murray et al, 2003)
B. Histologi dan Fisiologi Otot Lurik

Pada penampang membujur, otot serat lintang (otot lurik) mempunyai garis-garis atau pita-pita
melintang secara bergantian antara gelap terang. Pita yang gelap disebut pita A (anisotrop) yang
tersusun dari filament tebal yang masih disertai sedikit filament tipis yang overlapping, sedangkan
pita yang terang disebut pita I (Isotrop) yang tersusun dari filament tipis. Di tengah-tengah pita I
terdapat satu pita tipis gelap yang disebur garis Z. Bagian dari serat otot yang dibatasi oleh garis Z
yang berurutan disebut dengan sarkomer. Di tengah-tengah pita A masih terdapat satu garis terang
yang disebut garis H, yang hanya tersusun atas filament tebal saja. Setiap filament tebal terdiri dari
beberapa ratus molekul miosin yang terkemas dalam susunan tertentu. Miosin adalah suatu protein
yang terdiri dari dua subidentik dengan masing-masing berbentuk seperti tongkat golf. Ekor dari
miosisn berorientasi kearah bagian tengah filament, sedangkan kepala globulernya menonjol keluar
membentuk jembatan silang antara filament tebal dan tipis. Setiap jembatan silang memiliki dua
tempat penting untuk proses kontraktil, yaitu tempat pengikatan aktin (actin binding site) dan tempat
ATPase miosin (Myosin ATPase site). (Sherwood, 2001)
Filamen tipis terdiri dari tiga protein: aktin, tropomiosin, dan troponin. Tulang punggung filament
tipis dibentuk oleh molekul-molekul aktin yang menyatu membentuk dua untaian yang saling berjalin
dan membelit satu sama lain. Setiap molekul aktin memiliki tempat pengikatan khusus untuk melekat
dengan jembatan silang miosin. Pengikatan molekul aktin dan miosin di jembatan silang
menghasilkan kontraksi serat otot yang mengonsumsi energi. Dengan demikian, protein aktin dan
miosin disebut dengan protein kontraktil. Saat relaksasi, aktin tidak bisa berikatan dengan miosin
karena dihalangi oleh molekul tropomiosin dan dan troponin. Tropomiosin adalah protein berbentuk
seperti benang yang terletak di sepanjang yang terletak di sepanjang alur spiral aktin bersambungan
ujung ke ujung. Dan dalam posisi menghambat ini, troponin distabilisasi oleh troponin, yang akan
berikatan dengan ujung-ujung setiap molekul tropomiosin. Troponin adalah suatu kompleks protein
yang terdiri dari tiga jenis unit polipeptida: polipeptida T berikatan dengan tropomiosin, polipeptida I
mengikat aktin, dan polipeptida C berikatan dengan Ca2+. Tropomiosin dan triponin sering disebut
sebagai protein regulator karena peran mereka dalam menutupi (mencegah kontraksi) atau
memajankan (memungkinkan kontraksi) tempat-tempat pengikatan untuk interaksi jembatan silang
antara aktin dan miosin. Adapun mekanisme kontraksi otot adalah: (Sherwood, 2001)
- Asetilkolin yang dikeluarkan dari ujung terminal neuron motorik mengawali potensial aksi di sel
otot yang merambat ke seluruh permukaan membran. Dan aktivitas listrik ini dibawa ke bagian
tengah otot oleh tubulus T
- Penyebaran potensial aksi di tubulus T mencetuskan pelepasan simpanan Ca2+ dari kantungkantung lateral retikulum sarkoplasmik didekat tubulus.
- Ca2+ yang dilepaskan akan berikatan dengan troponin, sehingga kompleks troponin-tropomiosin
secara fisik tergeser ke samping, membuka tempat pengikatan jembatan silang aktin.
- Bagian aktin yang telah terpajan tersebut berikatan dengan jembatan silang miosin, yang

sebelumnya telah mendapat energi dari penguraian ATP menjadi ADP + Pi +energi oleh ATPase
miosin
- Pengikatan aktin dan miosin menyebabkan jembatan silang menekuk, menghasilkan suatu gerakan
mengayun kuat yang menarik filamen tipis ke arah dalam. Pergeseran ke arah dalam dari semua
filamen tipis akan memperpendek sarkomer. Dan selama gerakan mengayun kuat tersebut, ADP dan
Pi dibebaskan dari jembatan silang
- Perlekatan ATP baru memungkinkan terlepasnya jembatan silang dan Ca2+ akan terdorong masuk
kembali ke retikulum sarkoplasmik. Namun, penguraian ATP dan pengikatan Ca2+ berulang akan
mengulangi ikatan jembatan silang ini. (Sherwood, 2001)

C. Myasthenia Gravis
Miastenia gravis merupakan sindroma klinis akibat kegagalan transmisi neuromuskuler yang
disebabkan oleh hambatan dan destruksi reseptor asetilkolin oleh autoantibodi. Sehingga dalam hal
ini, miastenia gravis merupakan penyakit autoimun yang spesifik organ. Antibodi reseptor asetilkolin
terdapat didalam serum pada hampir semua pasien. Antibodi ini merupakan antibodi IgG dan dapat
melewati plasenta pada kehamilan. (Chandrasoma dan Taylor, 2005)
Miastenia gravis ditandai dengan kelemahan otot yang secara tipikal diperberat dengan adanya
kontraksi berulang. Pada 90% pasien gejala awal melibatkan otot olukar yang menyebabkan diplopia
dan ptosis. Selain itu, otot wajah, laring, dan faring juga sering terlibat dalam mistenia gravis.
Keterlibatan ini dapat mengakibatkan regugirtasi melalui hidung ketika berusaha menelan (otot
palatum); bicara hidung yang abnormal; dan tidak dapat menutup mulut (hanging jaw sign). Otot
pernafasan juga dapat terlibat dalam penyakit ini. Keterlibatan ini ditandai dengan adanya batuk
lemah, serangan dispnea, dan ketidakmampuan pasien untuk membersihkan mukus dari cabang
trakheobronkial. (Hartwig, 2005) . Klasifikasi myasthenia gravis yaitu :
1. Myasthenia okuler (I)
2. Myasthenia umum (II)
a. Myasthenia umum derajat ringan (II A): progesivitasnya lambat, tidak terjadi krisis, dan respon
terhadap obat baik.
b. Myasthenia umum derajat sedang (II B) : terjadi kelemahan pada otot skeletal dan bulber, tidak
terjadi krisis, tetapi respon terhadap obat kurang memuaskan.
3. Myasthenia fulminasi akut (III) : gejala memberat dengan sangat cepat, terjadi krisis pernafasan,
respon terhadap obat sangat buruk, sering ditemukan adanya timoma, mortalitas tinggi.
4. Myasthenia berat yang sedang berkembang lamban (IV) : klinis seperti golongan III, tetapi
memerlukan waktu lebih dari dua tahun untuk beralih dari golongan I atau II.
Diagnosis klinis miastenia gravis dapat dipastikan dengan uji terapeutik, EMG, dan uji serologik.
a. Endrofonium (Tensilon) test, yaitu tes dengan pemberian obat antikolinesterase kerja singkat yang

menghasilkan perbaiakn segera pada kelemahan otot bila diberikan secara intravena.
b. Uji Kinin, merupakan uji dimana diberikan 3 tablet kinina masing-masing 200 mg. 3 jam kemudian
diberikan 3 tablet lagi (masing-masing 200 mg per tablet). Pada miastenia gravis, gejala seperti
ptosis, strabismus, dan lain-lain akan bertambah berat. Untuk uji ini, sebaiknya disiapkan juga injeksi
prostigmin, agar gejala-gejala miastenik tidak bertambah berat.
c. EMG (Elektromiografi), alat tes uji dengan mempelajari aktivitas listrik yang timbul pada otot
sewaktu istirahat dan sewaktu kontraksi. Pada penderita miastenia gravis terlihat penurunan
progresif amplitudo potensial aksi otot ketika pasien melakukan kontraksi volunter berulang.
d. Pemeriksaan serum untuk antibodi reseptor asetilkolin, merupakan uji yang sangat baik karena
bersifat spesifik terdapat pada 80% pasien miastenia gravis. Uji yang positif bersifat diagnostik untuk
penyakit miastenia gravis. Dan titer antibodi yang tinggi tidak berhubungan dengan beratnya
penyakit. (Chandrasoma dan Taylor, 2005)
D. Lambert-Eaton Myasthenic Syndrome
Sindrom miastenik merupakan sindrom paraneoplastik yang berkaitan dengan kanker, terutama
karsinoma sel kecil paru. Sindrom miastenik sangat jarang terjadi pada pasien tanpa kanker. Sindrom
miastenik terjadi akibat kelainan pelepasan asetilkolin oleh ujung saraf pada lempeng akhir motorik
yang disebabkan oleh autoantibodi pada saluran kalsium di terminal saraf motorik. Sindrom ini
secara klinis ditandai dengan kelemahan otot yang sama dengan mistenia gravis, yaitu mengenai otot
mata. Namun kelemahan otot tidak diperberat oleh usaha. Selain itu, pada elektromiografi
menunjukkan peningkatan progresif amplitudo potensial aksi pada kontraksi berulang (efek yang
berlawanan dengan mistenia gravis). (Chandrasoma dan Taylor, 2005)
E. Pengobatan Myasthenia Gravis
1. Terapi jangka pendek untuk Intervensi keadaan akut
a. Plasma Exchange, efektif digunakan pada situasi dimana terapi jangka pendek yang
menguntungkan menjadi prioritas. Terapi ini digunakan pada pasien yang akan memasuki atau
sedang mengalami masa krisis. PE dapat memaksimalkan tenaga pasien yang akan menjalani
thymektomi atau pasien yang kesulitan menjalani periode postoperative.
b. Intravenous Immunoglobulin, merupakan produk dimana 99% merupakan IgG adalah
complement-activating aggregates yang relatif aman untuk diberikan secara intravena. Mekanisme
kerja dari IVIG belum diketahui secara pasti, tetapi IVIG diperkirakan mampu memodulasi respon
imun. Reduksi dari titer antibody tidak dapat dibuktikan secara klinis, karena pada sebagian besar
pasien tidak terdapat penurunan dari titer antibodi.
c. Intravenous Methylprednisolone (IVMp),
2. Pengobatan Farmakologi jangka panjang
a. Kortikosteroid, memiliki efek yang kompleks terhadap sistem imun. Kortikosteroid diperkirakan
memiliki efek pada aktivasi sel T helper dan pada fase proliferasi dari sel B. Dan pasien yang berespon

terhadap kortikosteroid akan mengalami penurunan dari titer antibodinya. Tapi, obat ini
diindikasikan pada penderita dengan gejala klinis yang sangat menggangu, yang tidak dapat di
kontrol dengan antikolinesterase.
b. Azathioprine, biasanya digunakan pada pasien miastenia gravis yang secara relatif terkontrol tetapi
menggunakan kortikosteroid dengan dosis tinggi
c. Cyclosporine, berpengaruh pada produksi dan pelepasan interleukin-2 dari sel T-helper. Supresi
terhadap aktivasi sel T-helper, menimbulkan efek pada produksi antibodi
d. Cyclophosphamide, merupakan suatu alkilating agent yang berefek pada proliferasi sel B, dan
secara tidak langsung dapat menekan sintesis imunoglobulin. Secara teori CPM memiliki efek
langsung terhadap produksi antibodi dibandingkan obat lainnya.
3. Timektomi (terapi bedah)
Tujuan neurologi utama dari Thymectomi ini adalah tercapainya perbaikan signifikan dari kelemahan
pasien, mengurangi dosis obat yang harus dikonsumsi pasien, serta idealnya adalah kesembuhan yang
permanen dari pasien.
BAB III
PEMBAHASAN
Dalam kasus di skenario, disebutkan bahwa pasien mengalami kelemahan otot. Kelemahan otot ini
tergolong dalam kelemahan pada LMN (lower motor neuron) yang melanda segenap bagian perifer
susunan neuromuskular. Susunan neuromuskuler ini tersusun oleh motoneuron yang membentuk
inti motorik saraf kranial dan inti motorik di kornu anterior medula spinalis, motor end plate, serta
otot skeletal di bagian efektornya. Karena dalam skenario disebutkan bahwa penderita mengalami
gangguan pada motor end plate, maka kemungkinan besar kelainan yang diderita berawal dari
abnormalitas neuromuscular junction. Selain itu, dari berbagai pemeriksaan fisik yang telah
dilakukan dan pemeriksaan penunjang (seperti EMG dan endorphonium test) maka dapat
disimpulkan bahwa pasien menderita miastenia gravis.
Miastenia gravis merupakan gangguan neuromuskular junction yang disebabkan oleh gangguan
transmisi asetilkolin (Ach) untuk berikatan dengan reseptornya di permukaan membran sel otot.
Kelainan ini disebabkan oleh terbentuknya antibodi berupa IgG yang nantinya akan berikatan secara
inhibitor kompetitif pada reseptor asetilkolin (AchR). Adanya antibodi yang terikat ini nantinya akan
menyebabkan lisis fokal yang ditandai dengan rusaknya reseptor. Reseptor yang rusak akan
mempercepat proses turn over dan mengurangi jumlahnya pada permukaan membran sel.
Mekanisme pembentukan antibodi terhadap reseptor Ach ini masih belum dimengerti. Namun,
mekanisme ini tergolong dalam proses autoantibodi tipe II (reaksi kompleks imun). Selain itu,
antibodi yang terbentuk (IgG) dapat melewati plasenta. Sehingga, kelainan miastenia gravis dapat
ditularkan secara kongenital dari ibu yang menderita miastenia gravis.
Pada miastenia gravis, gangguan yang terjadi terletak pada bagian membran post sinaptik. Gangguan

ini menyebabkan asetilkolin tidak akan berikatan dengan reseptor sehingga asetilkolin akan terlihat
berenang didalam celah sinaptik. Kondisi asetilkolin bebas ini akan memudahkan asetilkolin
dihidrolisis oleh enzim asetilkolinesterase. Sehingga, jumlah asetilkolin yang terikat reseptor akan
semakin sedikit dan hal ini menimbulkan depolarisasi membran sel otot yang sifatnya tidak sekuat
normal. Depolarisasi berjenjang sel otot akan semakin menurun jumlahnya sehingga nantinya akan
bermanifes pada kelemahan otot dalam kontraksi.
Kelainan miastenia gravis ditandai pada kelemahan otot-otot volunter. Pada awalnya gejala ini timbul
pada serat otot dengan satuan motorik terkecil seperti otot-otot penggerak bola mata. Dan seringkali
kelainan ini menyerang otot yang dipersarafi nervvus kranial. Pada skenario, penderita mengalami
keluhan berupa kelopak mata sulit dibuka serta bila melihat cepat capai dan tampak double. Hal ini
disebabkan oleh kelemahan otot-otot pada kelopak mata yaitu m. orbikularis okuli yang berjalan
melingkar di dalam kelopak atas dan bawah, dan terletak di bawah kulit kelopak, yang berfungsi
dalam menutup bola mata yang dipersarafi n. VII. Sedangkan m. levator palpebra yang dipersarafi
oleh n. III berfungsi untuk mengangkat kelopak mata atau membuka mata.
Selain itu, kelemahan akibat gangguan neurotransmiter ini juga terjadi di berbagai otot volunter
tubuh. Kelemahan otot penyangga leher, nantinya akan bermanifes pada kesulitan menegakkan
kepala, gangguan pada otot menelan bulbair ditandai dengan kesulitan menelan dan suara yang
makin melemah. Sedangkan kelemahan otot-otot ekstremitas ditandai dengan kelemahan yang
bersifat layuh (misalnya bila mengangkat tangan selama 2-3 menit, tangan akan semakin menurun).
Keluhan pada miastenia gravis ini semakin memburuk pada sore hari dan membaik setelah istirahat
karena hal ini terkait dengan penggunaan ATP dan perangsangan yang timbul. Miastenia gravis
merupakan kelainan yang bermanifes pada otot volunter/ otot skelet. Dan otot skelet ini diinervasi
pada persarafan somatik yang timbul oleh adanya rangsangan eksitatorik di otak. Pada keadaan
istirahat dan tidur, tidak ada rangsangan yang timbul sehingga produksi asetilkolin berjumlah banyak
tersimpan dalam vesikel. Dan pada saat memulai aktivitas (rangsangan aksi awal), asetilkolin yang
berikatan dengan reseptornya masih dalam kadar yang cukup banyak sehingga mampu menimbulkan
depolarisasi membran dalam jumlah cukup. Namun, lama kelamaan keadaan ini tidak akan
terkompensasi dengan semakin lamanya aktivitas yang dicetuskan karena terkait pada jumlah
reseptor Ach yang semakin sedikit dan Ach yang banyak dihidrolisis.
Miastenia gravis merupakan penyakit yang bersifat progresif. Baik progresif lambat ataupun cepat,
tergantung pada kondisi autoimun yang diderita. Akibatnya, keluhan yang dialami semakin lama akan
makin berat. Pada kasus di skenario, penderita belum mengalami sesak nafas/ perasaan tidak enak di
dada. Dalam hal ini, penderita masih belum mengalami gangguan pernafasan yang nantinya dapat
menimbulkan krisis miastenik. Dan bila sudah timbul kondisi ini, maka penderita sudah berada
dalam kondisi kritis yang memerlukan penanganan secepat mungkin.
Dalam miastenia gravis, pemeriksaan darah menunjukkan hasil normal karena tidak terjadi kenaikan

kadar kreatin kinase. Kadar kreatin kinase ini biasanya timbul bila terjadi kerusakan otot sedangkan
pada miastenia, tidak timbul kerusakan otot melainkan gangguan pada neurotransmiternya.
Sehingga, otot pada pasien miastenia tampak normal. Akan tetapi, bila otot pasien yang mengalami
kelemahan tidak digunakan, lama kelamaan akan timbul disuse atrophy.
Sebenarnya, gangguan pada neurotransmiter dapat ditemukan pada myathenia gravis dan sindrom
Eaton-Lambert. Pada myasthenia gravis, asetilkolin tidak dapat diterima oleh reseptor pada membran
postsinaptik karena antibodi telah menduduki reseptor itu. Pada sindrom Eaton-Lambert, asetilkolin
di dalam gelembung presinaptik tidak dapat dituangkan (eksositosis) di celah sinaptik karena
membran presinaptiknya terganggu oleh adanya antibodi pada kanal kalsium.
Penanganan miastenia gravis dapat dilakukan dengan terapi farmakologik berupa pemberian obat
imunosupresif, kortikosteroid ataupun obat antikolinesterase. Selain itu, dapat pula dilakukan operasi
pengangkatan timus karean sekitar 15% penderita miastenia gravis mengalami hiperplasia kelenjar
timus (timoma). Obat antikolinesterase memiliki spektrum kerja dalam menghambat efek kerja enzim
asetilkolinesterase (enzim yang terlibat dalam penguraian asetilkolin/ Ach). Obat ini akan secara
efektif meningkatkan konsentrasi Ach pada motor end plate dan memperpanjang masa kerjanya.
Telah diketahui bahwa kerusakan reseptor karena antibodi bersifat reversibel, sehingga terjadi
pengurangan jumlah reseptor dalam satu permukaan membran sel otot. Namun, dengan penggunaan
obat antikolinesterase, Ach akan tidak langsung dihidrolisis oleh enzim asetilkolinesterae. Sehingga,
Ach yang berada dalam celah sinaps akan memiliki waktu paruh panjang dalam menemukan reseptor
yang sehat (tidak terikat antibodi) dan nantinya menimbulkan pembukaan saluran Na-K.
Komplikasi yang dapat terjadi pada pada penderita myasthenia gravis sesudah mendapat pengobatan
antikolinesterase yaitu krisis miastenik yang timbul karena underdose obat antiasetilkolinesterase
sehingga gejala-gejala lebih memburuk, biasanya terjadi karena gangguan resorpsi obat
antiasetilkolinesterase atau karena infeksi berat. Selain itu, dapat juga terjadi krisis kolinergik yang
timbul karena obat antikolinesterase yang merusak sinaps sehingga asetilkolin tidak dapat bekerja
lagi sebagai neurotransmiter.
BAB IV
PENUTUP
A. Kesimpulan
1. Penderita dalam skenario menderita miastenia gravis dan belum mengalami krisis miastenik
sehingga prognosisnya baik bila diberikan penaganan terpeutik yang tepat.
2. Miastenia gravis adalah suatu kelainan autoimun yang ditandai oleh suatu kelemahan abnormal
dan progresif pada otot rangka yang dipergunakan secara terus-menerus dan disertai dengan
kelelahan saat beraktivitas
3. Mekanisme imunogenik memegang peranan yang sangat penting pada patofisiologi miastenia
gravis, dimana antibodi yang merupakan produk dari sel B nantinya akan melawan reseptor

asetilkolin
B. Saran
1. Hendaknya dilakukan terapi awal berupa pemberian obat-obat farmakologik berupa obat
antikolienesterase seperti prostigmin atau neostigmin. Selain itu, kortikosteroid atau obat
imunosupresif juga dapat diberikan tetapi harus dalam kadar tepat mengingat efek samping yang
ditimbulkan.
2. Diharapkan pasien memperbanyak istirahat namun juga tidak boleh dilakukan penghentian
aktivitas total karena nantinya dapat menimbulkan disuse atrofi.

What is Myotonia?
Myotonia is a medical term that refers to a neuromuscular condition in which the relaxation of a
muscle is impaired. It can affect any muscle group. Repeated effort will be needed to relax the
muscle, although the condition usually improves after the muscles have warmed-up. Individuals with
myotonia may have trouble releasing their grip on objects or may have difficulty rising from a seated
position. They may walk with a stiff, awkward gait. Myotonia is caused by an abnormality in the
muscle membrane, and is often associated with inherited neurological disorders. Myotonia is
commonly seen in individuals with myotonic muscular dystrophy, myotonia congenita, and in people
who have one of a group of neurological disorders called the channelopathies, which are inherited
diseases that are caused by mutations in the chloride sodium or potassium channels that regulate the
muscle membrane. Myotonia may also be triggered by exposure to cold.

Is there any treatment?

Treatment for myotonia may include mexelitine, quinine, phenytoin, and other anticonvulsant drugs.
Physical therapy and other rehabilitative measures may help muscle function.

What is the prognosis?

Myotonia is a chronic disorder. Symptoms may improve later in life.

What research is being done?

The National Institute of Neurological Disorders and Stroke supports and conducts an extensive
research program on neuromuscular disorders. The goals of this research are to learn more about
these disorders and to find ways to treat, prevent, and cure them.

Myotonic Dystrophy
History
Myotonic dystrophy is an inherited disorder of muscle weakness and wasting characterized by sustained
involuntary muscle contractions. These involuntary contractions arise in response to voluntary muscle
use or percussion of the muscle. The disease was described by Steinert in 1909; it is also called
myotonia atrophica. Clinically myotonic dystrophy is classified as a muscular dystrophy although the
disease mechanism is distinct from that of the other muscular dystrophies. The familial pattern of
inheritance is similar to that of myotonia congenita (Thomsen, 1876) and paramyotonia congenita
(Eulenburg, 1886). Myotonic dystrophy is distinct in having widespread effects throughout the systems
of the body. That this disease primarily affects muscle and not nerve was shown by Denny-Brown and
Nevin in 1941. The tendency of the disease to become more severe with successive generations, called
anticipation, was recognized by Fleischer in 1918. The genetic basis for the disease was elicited in 1992.

Clinical Presentation
Epidemiology

Myotonic dystrophy occurs in one per 8,000 live births. It is among the more common inherited
neurological disorders and occurs equally in men and women. The disease most often affects members
of the same family, often becoming more severe with successive generations - this is most true when
the disorder is passed on from the mother, when passed on from the father the disease may become
less severe. There are rare sporadic cases of myotonic dystrophy.
Clinical Features

Myotonic dystrophy has effects throughout most of the body. Although chiefly characterized by muscle
weakness and wasting there are associated cardiac, hormonal, respiratory, digestive and mental effects.

Typically the disease first develops in the early teen years with hand weakness and a tendency towards
foot drop. The patient may notice difficulty releasing a firm grasp especially in the cold. Handling objects
such as keys, a hammer or the vacuum cleaner can be problematic. The characteristic appearance of a
"haggard" or "mournful" face is caused by facial muscle wasting, frontal hair loss, drooping eyelids and
an open mouth. In middle age the patient may develop frequent falls, minor difficulty swallowing, voice
changes and recurrent jaw dislocations. The tendency towards falling results because a sudden
movement may produce a sustained muscle contraction leading to the loss of balance. Muscle atrophy

sometimes becomes pronounced and there may be early infertility. Often the disease is mild,
progressing slowly and producing weakness only later in life. When severe the disease causes
progressive disability over ten to twenty years and may lead to death in the sixth decade from
respiratory failure or cardiac disease. Many live a normal life span.

There are many systemic features. Subcapsular cataracts, which may be asymptomatic, are detectable
in 90% of those with the gene. Potentially life threatening arrythmias can result from defects in cardiac
conduction. The precise cause of premature death is not always known but has been speculated to be
due to arrythmia or weakness in the walls of the heart. There are many hormonal effects. These include
reproductive abnormalities: atrophy of the testicles, loss of sex drive, early menopause in women and
habitual abortion. Thyroid function may be disordered and insulin resistance without frank diabetes is
not uncommon. Abnormalities in the respiratory system leads to excessive sleepiness and sensitivity to
sedation. The patient with myotonic dystrophy is at increased risk from anesthesia and has abnormal
sensitivity to drugs which decrease respiratory drive (barbiturates and morphine). Effects on the
digestive system produce chronic constipation, pancreatic enzyme dysfunction and increased gall
bladder inflammation.

Congenital myotonic dystrophy has typical features present at birth. These include extremely decreased
tone, shark mouth appearance due to facial weakness, a feeble cry, feeding difficulties, failure to thrive
and club feet. The usual course is one of disability and severe mental retardation. Almost all children
with congenital myotonic dystrophy are born to mothers with myotonic dystrophy and display a
substantial increase in the size of the gene defect.
Pathophysiology

The structure of the affected gene suggests that it is a serine threonine protein kinase. The messenger
RNA of the gene is not properly transported to the cytoplasm when the defect is present. This protein
kinase may have a role in the normal function of skeletal muscle sodium channels.

Microscopic observation reveals changes in skeletal and heart muscle. Skeletal muscle shows type I
(slow twitch) muscle fiber atrophy, internalized nuclei, ring fibers and fibrosis. Heart muscle shows
fibrosis of the conducting system, myocyte hypertrophy and fatty infiltration.

Diagnosis
Standard evaluation

Evaluation of a patient for myotonic dystrophy includes neurological examination, EMG assessment and
obtaining serum for genetic testing. These are described in detail below. The differential diagnosis of

myotonic dystrophy includes causes of myotonia: paramyotonia, congenital myotonia, mild tetanus and
the rare stiff man syndrome. At later stages the myotonic dystrophy may resemble limb-girdle atrophy,
polymyositis or dermatomyositis.
Neurological examination

Examination is often diagnostic because the findings of myotonic dystrophy are uniquely characteristic.
The key diagnostic feature is a marked transient increase in muscle tone elicited by percussion or use of
a muscle. Other disease features are a "haggard" facies, muscle weakness, muscle atrophy and in males
testicular atrophy. Distal muscle involvement precedes proximal muscle involvement. Late in the disease
course increased tone becomes a less prominent feature and diagnosis may not be as easily made on
the basis of exam alone.
Electromyography (EMG)

Before genetic testing was available EMG was more important for confirming the diagnosis of myotonic
dystrophy. The EMG shows a typical myotonic discharge which has a waxing and waning quality giving
rise to the descriptive term, the "divebomber" sound. The predictable variability in amplitude and
frequency of the myotonic muscle action potential distinguishes it from that of complex repetitive
discharge (CRD), which displays a continuous frequency and amplitude.
Genetic testing

DNA testing is definitive. Compared with the normal population, there is a part of chromosome 19 which
is expanded in those with myotonic dystrophy. This expansion is readily detectable using standardized
tests of the genetic material. (see below)

Genetics
Myotonic dystrophy is an autosomal dominant disorder. The gene for myotonic dystrophy is located on
the short arm of chromosome 19 (19q). The genetic defect producing myotonic dystrophy was
characterized in 1992. Several papers were published that year demonstrating that a small part of the
genetic sequence (a CTG trinucleotide) was repeated many times over. In the unaffected population
there are typically from five to 30 repeats of this "CTG" sequence. In individuals with myotonic
dystrophy the repeat region expands until there are dozens or hundreds of these "CTG" repeats. This
defect is present in a part of the genome which controls to production of a protein identified as
"myotonic dystrophy protein kinase" or DMPK. The defect decreases the amount of protein made. The
messenger RNA instructing the cell how to make the protein is trapped inside the cell nucleus. The
repetitive nature of the CTG expansion region initially presented a barrier to sequencing the gene. By

combining the restriction fragment length polymorphism (RFLP) method with the polymerase chain
reaction (PCR) method the gene defect was characterized. Prior to sequencing linkage analysis was used
demonstrate the heritable nature of the disease.

Anticipation describes the tendency of myotonic dystrophy to become symptomatic at a younger age
with each generation. This occurs because at the time of fertilization the genetic defect frequently grows
larger during recombination. As a result of the enlarged defect, the disease becomes more pronounced
and begins earlier in life.

Treatment
Efforts to find a cure for myotonic dystrophy are ongoing. At present treatment is symptom oriented.
The increased muscle tone for which the disease is named is often not debilitating however the excess
tone may respond to medication. Genetic counseling is important especially since prenatal diagnosis is
possible. Ankle-foot-orthotics (AFOS) are used for foot drop, wrist braces can be recommended for wrist
weakness. Cataracts are removed when symptomatic. Special attention to cardiac complications is
warranted; recommendations have included yearly electrocardiograms. Because cardiac arrythmias have
been detected in as many as 50% of those with myotonic dystrophy, holtor monitoring is an important
diagnostic modality. Pulmonary hygiene includes breathing exercises and postural drainage. Genetic
counseling is important especially since prenatal diagnosis is possible. Patients with myotonic dystrophy
should be aware of a special vulnerability when undergoing anesthesia.

What is myotonia congenita?

Myotonia congenita is a disorder that affects muscles used for movement (skeletal
muscles). Beginning in childhood, people with this condition experience bouts of
sustained muscle tensing (myotonia) that prevent muscles from relaxing normally.
Although myotonia can affect any skeletal muscles, including muscles of the face
and tongue, it occurs most often in the legs. Myotonia causes muscle stiffness that
can interfere with movement. In some people the stiffness is very mild, while in
other cases it may be severe enough to interfere with walking, running, and other
activities of daily life. These muscle problems are particularly noticeable during
movement following a period of rest. Many affected individuals find that repeated
movements can temporarily alleviate their muscle stiffness, a phenomenon known
as the warm-up effect.

The two major types of myotonia congenita are known as Thomsen disease and
Becker disease. These conditions are distinguished by the severity of their
symptoms and their patterns of inheritance. Becker disease usually appears later in
childhood than Thomsen disease and causes more severe muscle stiffness,
particularly in males. People with Becker disease often experience temporary
attacks of muscle weakness, particularly in the arms and hands, brought on by
movement after periods of rest. They may also develop mild, permanent muscle
weakness over time. This muscle weakness is not seen in people with Thomsen
disease.
How common is myotonia congenita?

Myotonia congenita is estimated to affect 1 in 100,000 people worldwide. This

condition is more common in northern Scandinavia, where it occurs in
approximately 1 in 10,000 people.
What genes are related to myotonia congenita?

Mutations in the CLCN1 gene cause myotonia congenita.

The CLCN1 gene provides instructions for making a protein that is critical for the
normal function of skeletal muscle cells. For the body to move normally, skeletal
muscles must tense (contract) and relax in a coordinated way. Muscle contraction
and relaxation are controlled by the flow of charged atoms (ions) into and out of
muscle cells. Specifically, the protein produced from the CLCN1 gene forms a
channel that controls the flow of negatively charged chlorine atoms (chloride ions)
into these cells. The main function of this channel is to stabilize the cells' electrical
charge, which prevents muscles from contracting abnormally.
Mutations in the CLCN1 gene alter the usual structure or function of chloride
channels. The altered channels cannot properly regulate ion flow, reducing the
movement of chloride ions into skeletal muscle cells. This disruption in chloride
ion flow triggers prolonged muscle contractions, which are the hallmark of
myotonia.
Read more about the CLCN1 gene.
How do people inherit myotonia congenita?

The two forms of myotonia congenita have different patterns of inheritance.

Thomsen disease is inherited in an autosomal dominant pattern, which means one

copy of the altered gene in each cell is sufficient to cause the disorder. In most
cases, an affected person has one parent with the condition.
Becker disease is inherited in an autosomal recessive pattern, which means both
copies of the gene in each cell have mutations. Most often, the parents of an
individual with an autosomal recessive condition each carry one copy of the
mutated gene, but do not show signs and symptoms of the condition.
Because several CLCN1 mutations can cause either Becker disease or Thomsen
disease, doctors usually rely on characteristic signs and symptoms to distinguish
the two forms of myotonia congenita.

Myotonia congenita is an inherited condition that affects muscle relaxation. It is congenital, meaning
that it is present from birth.

Causes
Myotonia congenita is caused by a genetic change (mutation). It is passed down from either one or
both parents to the children (inherited).
Myotonia congenita is caused by a problem in the part of the muscle cells that are needed for muscles
to relax. Abnormal repeated electrical discharges occur in the muscles, causing a stiffness called
myotonia.

Symptoms
The hallmark of this condition is the myotonia -- the inability of the muscle to quickly relax after
contracting. For example, after a handshake, the person is only very slowly able to open and pull
away his hand.
Early symptoms may include:

Difficulty in swallowing

Gagging

Stiff movements that improve when they are repeated

Shortness of breath or tightening of the chest at the beginning of exercise

Children with myotonia congenita often appear to be muscular and well-developed. The child may not
have symptoms of myotonia congenita until age 2 or 3.

Exams and Tests

The doctor may ask if there is a family history of myotonia congenita.

Tests include:

Genetic testing

Muscle biopsy

Test of the electrical activity in muscles (EMG)

Treatment
Treatment for symptoms includes:

Mexiletine

Phenytoin

Procainamide

Outlook (Prognosis)
People with this condition can do well. Symptoms only occur when a movement is first started. After a
few repetitions, the muscle relaxes and the movement becomes normal. Symptoms may improve later
in life.

Possible Complications

Aspiration pneumonia caused by swallowing difficulties

Frequent choking, gagging, or difficulty swallowing in an infant

Abdominal muscle weakness

Chronic joint problems

When to Contact a Medical Professional

Call your health care provider if your child has symptoms of myotonia congenita.

Prevention
Genetic counseling may be of interest to couples who want to have children and have a family history
of myotonia congenita.

Alternative Names
Thomsen's disease; Becker's disease

Overview of Movement Disorders

Movement disorders are neurological conditions that affect the speed, fluency,
quality, and ease of movement. Abnormal fluency or speed of movement
(dyskinesia) may involve excessive or involuntary movement (hyperkinesia) or
slowed or absent voluntary movement (hypokinesia).
Movement disorders include the following conditions:

Ataxia (lack of coordination, often producing jerky movements)

Dystonia (causes involuntary movement and prolonged muscle contraction)

Huntington's disease (also called chronic progressive chorea)

Multiple system atrophies (e.g., Shy-Drager syndrome)

Myoclonus (rapid, brief, irregular movement)

Parkinson's disease

Progressive supranuclear palsy (rare disorder that affects purposeful movement)

Restless legs syndrome (RLS) and reflex sympathetic dystrophy/periodic limb

movement disorder (RSD/PLMD)

Tics (involuntary muscle contractions)

Tourette's syndrome

Tremor (e.g., essential tremor, resting tremor)

Wilson disease (inherited disorder that causes neurological and psychiatric symptoms
and liver disease)

Common dystonias include spasmodic torticollis, which affects muscles of the

head, face, and neck, andblepharospasm, which causes involuntary closing of
the eyelids.
Tourette's syndrome is an inherited disorder characterized by multiple motor and
vocal tics (repeated muscle contractions). Symptoms of Tourette's usually
develop during childhood or early adolescence. Patients with the disorder often
develop behavioral problems such as hyperactivity, inattention, impulsivity,
obsessions, and compulsions. In most cases, symptoms vary in frequency and in
severity.

are involuntary muscle contractions that interrupt normal activities. They

often are preceded by a strong sensation or urge that is temporarily relieved
following the muscle contraction. Examples of common tics include the following:
Tics

Blinking

Clearing the throat

Facial twitching

Grunting

Shrugging the shoulders

Sighing

Signs and Symptoms of Movement Disorders

Signs and symptoms of movement disorders vary and depend on the type
and severity of the conditon. The severity of movement disorder symptoms
can be affected by factors such as anxiety, fatigue, medication, and stress.
Some movement disorders cause hyperkinesia (i.e., excessive

spontaneous movement or abnormal involuntary movement) and others

cause hypokinesia (i.e., absent or reduced ability to perform purposeful
movement).

Abnormal movements may be rhythmical (e.g.,

essential tremor)

or irregular

and may be rapid and jerky (e.g., tics) or slowed and sustained
(e.g., Parkinson's disease, dystonia). In most cases, irregular movement
cannot be consciously controlled or suppressed.

Treatment for Movement Disorders

Treatment for movement disorders depends on the underlying cause. In most
cases, the goal of treatment is to relieve symptoms. Treatment may include
medication, botulinum toxin injection therapy (BOTOX therapy), and surgery.
Medications that may be used include the following:

Antiepileptics (e.g., carbamazepine [Tegretol], valproate [Depakote])

Antiseizure medications (e.g., primidone [Mysoline], gabapentin [Neurontin])

Beta-blockers (e.g., propranolol [Inderal])

Dopamine agonists (e.g., bromocriptine [Parlodel], pergolide [Permax])

Tranquilizers (benzodiazepines such as diazepam [Valium] and clonazepam

[Klonopin])

Side effects of antiepileptics include dizziness, drowsiness, nausea, and

vomiting. Antiseizure medications may cause a lack of coordination and balance

(ataxia), dizziness, nausea, and fatigue.Benzodiazepines may cause blood clots

(thrombosis), drowsiness, and fatigue. Side effects caused bybetablockers include slowed heart rate (bradycardia), depression, light-headedness,
and nausea.Dopamine agonists may cause nausea, headache, dizziness, and
fatigue.
Parkinson's disease may be treated using a number of different medications.
Botulinum toxin injection therapy (BOTOX therapy) is used to treat some types of
movement disorders (e.g., spasmodic torticollis, blepharospasm, myoclonus,
tremor). In this treatment, a potent neurotoxin (produced by the bacterium
Clostridium botulinum) is injected into a muscle to inhibit the release of
neurotransmitters that cause muscle contraction.
In some cases, treatment is repeated every 3 to 4 months. Patients may develop
antibodies to the toxin over time, causing treatment to become ineffective. Side
effects include temporary weakness in the group of muscles being treated and
rarely, flu-like symptoms.
When medication is ineffective, severe movement disorders may require surgery.
In deep brain stimulation (DBS), a surgically implanted, battery-operated
medical device (neurostimulator) is used to deliver electrical stimulation to areas
of the brain that control movement. The electrical charge blocks nerve signals
that trigger abnormal movement.
In DBS, an electrode (lead) is inserted through a small incision in the skull and is
implanted in the targeted area of the brain. An insulated wire (extension) is then
passed under the skin in the head, neck, and shoulder, connecting the lead to the
neurostimulator, which is surgically implanted in the chest or upper abdomen.
Side effects of deep brain stimulation include:

Bleeding at the implantation site

Depression

Impaired muscle tone

Infection

Loss of balance

Slight paralysis (paresis)

Slurred speech (dysarthia)

Tingling (parethesia) in the head or the hands

locates, targets, and then destroys (ablates) the clearly defined

area of the brain that produces chemical or electrical impulses that cause
abnormal movements.
Ablative surgery

In this surgery, a heated probe or electrode is inserted into the targeted area. The
patient remains awake during the procedure to determine if the problem has been
eliminated. A local anesthetic is used to dull the outer part of the brain and skull.
The brain is insensitive to pain, so the patient does not feel the actual procedure.
In some cases, it may be difficult to estimate how much tissue to destroy and the
amount of heat to use.

This type of surgery involves either ablation in the part of the brain called the
globus pallidus (calledpallidotomy) or ablation of brain tissue in the thalamus
(called thalamotomy). A related procedure, cryothalamotomy, uses a
supercooled probe that is inserted into the thalamus to freeze and destroy areas
that produce tremors.
Pallidotomy may be used to eliminate uncontrolled dyskinesia (e.g., jerky,
involuntary movements) and thalamotomy may be performed to eliminate tremor.
These procedures are successful in approximately 75% of cases.

Causes and Risk Factors for Movement Disorders

Movement disorders occur as a result of damage or disease in a region located
at the base of the brain (basal ganglia). The basal ganglia is comprised of
clusters of nerve cells (neurons) that send and receive electrical signals and are
responsible for involuntary movement. Movement disorders can result from the
following:

Age-related changes

Environmental toxins

Genetic disorders (e.g., Huntington's disease, Wilson disease)

Medications (e.g., antipsychotic drugs)

Metabolic disorders (e.g., hyperthyroidism)

Parkinson's disease

Stroke

Diagnosis of Movement Disorders

Diagnosis of movement disorders involves taking a family history and a
history of symptoms, and performing a physical examination
(including neurological examination) and various tests (e.g., blood tests,
imaging tests).

Blood tests

may include a complete blood count (CBC), a creatine kinase

test, and a DNA analysis. In some cases, a cerebrospinal fluid (CSF)

analysis also is performed.
Cerebrospinal fluid analysis involves performing a spinal tap, or lumbar
puncture. In this procedure, about 2 tablespoons of cerebrospinal fluid is
drawn into a needle inserted between two lumbar vertebrae and then
examined under a microscope.
Imaging tests, including computed tomography (CT scan), magnetic
(MRI scan), and positron emission tomography (PET
scan), may be used to detect damage (e.g., shrinkage) in the basal
ganglia, structural abnormalities, and stroke.
resonance imaging

An electromyogram (EMG) and anelectroencephalogram (EEG) also may

be performed. These tests are used to monitor electrical activity within the
body and can help detect nerve and muscle disorders. EMG involves
placing electrodes on the skin (surface EMG) or into the muscle
(intramuscular EMG) to record electrical activity of the muscle. In an EEG,
electrodes are attached to the scalp and connected to a machine that
records electrical impulses in the brain.
A muscle biopsy may also be performed to distinguish between nerve and
muscle disorders. This procedure, which is performed under local
anesthesia, involves making a small incision and removing a sample of
muscle for microscopic evaluation. Following the procedure, patients may
experience minor pain and bruising at the biopsy site for about 1 week.