BAB I

PENDAHULUAN

Myelinolysis adalah kelainan neurologis yang dapat terjadi pasca koreksi

hiponatremia secara cepat.
Penyakit ini sudah dikenal lebih dari 50 tahun yang lalu. Saat itu penyakit ini dikenal dengan
nama central pontine myelinolysis (CPM). Akan tetapi akhir-akhir ini diketahui bahwa
penyakit ini mengenai pons dan juga beberapa struktur lainnya.
Central pontine myelinolysis adalah demielinisasi simetris non inflamasi yang terjadi
di sentral basis pons. Demielinisasi dapat juga terjadi di luar pons (misalnya pada
mesensefalon, talamus, nuklei basalis, dan serebelum) disebut extrapontine myelinolysis
(EPM). Bila proses patologis mengenai pons dan struktur di luar pons disebut osmotic
demyelination syndrome(ODS). Perubahan patologis EPM identik dengan CPM; dari sebuah
laporan kasus otopsi, setengahnya ditemukan hanya CPM saja, 2/5 kasus hanya ditemukan
EPM saja, sedangkan ODS ditemukan pada 3/5 kasus.
Sejarah myelinolysis dimulai pada tahun 1949, saat seorang pria 38 tahun dirawat di
rumah sakit Boston dengan diagnosis delirium tremens dan pneumonia. Saat perawatan
terjadi kuadriplegia, kelemahan saraf wajah, disfagia, mutism, dan tanda Babinski bilateral.
Setelah 22 hari, pasien meninggal dunia. Pada otopsi ditemukan lesi simetris bilateral basis
pons. Pada pemeriksaan mikroskopik dijumpai kerusakan mielin hebat, sedangkan neuron
dan akson tidak mengalami kerusakan berarti. Setelah observasi selama 10 tahun, Adams
dkk. mendeskripsikan central pontine myelinolysis sebagai entitas klinis pada tahun 1959.
Mereka menekankan lokasi lesi pada basis pons dan bersifat simetris; oleh karena itu mereka
menduga penyebab CPM adalah gangguan metabolik dan mencurigai kemungkinan
gangguan nutrisi karena ditemukan pada pasien pecandu alkohol dan kurang gizi. Hubungan
kelainan ini dengan koreksi natrium yang cepat pada pasien hiponatremia baru ditemukan
pada tahun 1982.
 BAB II
TINJAUAN PUSTAKA

2.1 Definition
Central pontine myelinolysis (CPM) is a neurological disorder that most frequently
occurs after too rapid medical correction of sodium deficiency (hyponatremia). The rapid rise
in sodium concentration is accompanied by the movement of small molecules and pulls water
from brain cells. Through a mechanism that is only partly understood, the shift in water and
brain molecules leads to the destruction of myelin, a substance that surrounds and protects
nerve fibers. Nerve cells (neurons) can also be damaged. Certain areas of the brain are
particularly susceptible to myelinolysis, especially the part of the brain stem called
the pons. Some individuals will also have damage in other areas of the brain, which is
called extrapontine myelinolysis (EPM). Experts estimate that 10 percent of those with CPM
will also have areas of EPM.
The initial symptoms of myelinolysis, which begin to appear 2 to 3 days after
hyponatremia is corrected, include a depressed level of awareness, difficulty speaking
(dysarthria or mutism), and difficulty swallowing (dysphagia). Additional symptoms often
arise over the next 1-2 weeks, including impaired thinking, weakness or paralysis in the arms
and legs, stiffness, impaired sensation, and difficulty with coordination. At its most severe,
myelinolysis can lead to coma, “locked-in” syndrome (which is the complete paralysis of all
of the voluntary muscles in the body except for those that control the eyes), and death.
Although many affected people improve over weeks to months, some have permanent
disability. Some also develop new symptoms later, including behavioral or intellectual
impairment or movement disorders like parkinsonism or tremor.
Anyone, including adults and children, who undergoes a rapid rise in serum sodium
is at risk for myelinolysis. Some individuals who are particularly vulnerable are those with
chronic alcoholism and those who have had a liver transplant. Myelinolysis has occurred in
individuals undergoing renal dialysis, burn victims, people with HIV-AIDS, people over-
using water loss pills (diuretics), and women with eating disorders such as anorexia or
bulimia. The risk for CPM is greater if the serum (blood) sodium was low for at least 2 days
before correction.
2.2 Causes
Conditions predisposing patients to central pontine myelinolysis include alcoholism,
liver disease, malnutrition, and hyponatremia.
Risk factors for central pontine myelinolysis in the hyponatremic patient include the
following:
 Serum sodium of less than 120 mEq/L for more than 48 hours
 Aggressive IV fluid therapy with hypertonic saline solutions
 Development of hypernatremia during treatment
Many patients who have hyponatremia that is corrected rapidly do not develop
central pontine myelinolysis. Thus, other less obvious risk factors probably exist. Central
pontine myelinolysis reportedly occurs occasionally in patients who are treated for
hypernatremia.
[8]
Central pontine myelinolysis may complicate liver transplantation surgery.
Consider central pontine myelinolysis when confusion and/or weakness complicate the liver
transplant patient's postoperative recovery. The author provided consultation for a liver
transplant patient who developed central pontine myelinolysis and critical illness
neuromyopathy. The typical exam findings for central pontine myelinolysis were masked by
peripheral nerve and muscle disease. MRI studies provided conclusive evidence for brain
stem demyelination.
Burn patients with a prolonged period of serum hyperosmolality are prone to
developing central pontine myelinolysis. Central pontine myelinolysis also has occurred
concurrently with Wilson disease and neoplasia.

2.3 Epidemiology
The exact incidence of central pontine myelinolysis is unknown. A study by Singh et
al demonstrated that central pontine myelinolysis was present in 29% of postmortem
examinations of liver transplant patients. Two thirds of these patients had serum sodium
fluctuations of only ± 15-20 mEq/L. [9] Central pontine myelinolysis occurs more frequently
in females than in males.
2.4 Pathophysiology
Central pontine myelinolysis is a concentrated, frequently symmetric,
noninflammatory demyelination within the central basis pontis. In at least 10% of patients
with central pontine myelinolysis, demyelination also occurs in extrapontine regions,
including the mid brain, thalamus, basal nuclei, and cerebellum. The exact mechanism that
strips the myelin sheath is unknown.

2.5 Symptoms
Symptoms may include any of the following:
 Confusion, delirium, hallucinations
 Balance problems, tremor
 Problem swallowing
 Reduced alertness, drowsiness or sleepiness, lethargy, poor responses
 Slurred speech
 Weakness in the face, arms, or legs, usually affecting both sides of the body

One theory proposes that in regions of compact interdigitation of white and gray
matter, cellular edema, which is caused by fluctuating osmotic forces, results in compression
of fiber tracts and induces demyelination. Prolonged hyponatremia followed by rapid sodium
correction results in edema. During the period of hyponatremia, the concentration of
intracellular charged protein moieties is altered; reversal cannot parallel a rapid correction of
electrolyte status. The term osmotic myelinolysis is more appropriate than central pontine
myelinolysis for demyelination occurring in extrapontine regions after the correction of
hyponatremia. [4, 5, 6, 7]

2.6 Differential diagnosis

General imaging differential considerations include:
 demyelination including multiple sclerosis (MS)
 infarction from basilar perforators can be central, although usually brainstem infarcts
stop at the midline
 pontine neoplasms including astrocytomas
2.7 Diagnostic Tests
1. Cerebral spinal fluid (CSF) probably is not necessary when the etiology and diagnosis
are obvious. CSF studies may demonstrate increased opening pressure, elevated protein,
or mononuclear pleocytosis.
2. Radiographic features
 CT
CT may demonstrate low attenuation crossing the midline in the lower pons,
although streak artifact frequently degrades this region and beam hardening
phenomenon.
 MRI
MRI is the imaging modality of choice (see the image below). According to one
study, serial brain imaging is of value because a substantial proportion of patients
[13]
have normal findings on initial MRI. Typically, T2-weighted MRI images
demonstrate hyperintense or bright areas where demyelination has occurred and has
been caused by relatively increased water content in those regions. MRI or CT
imaging of the brain stem may not reveal an obvious anatomic disturbance. A
thorough neurologic exam therefore is indispensable. [14]
 T2-weighted MRI scan of the brain demonstrating patchy areas of signal change
within the pons that are consistent with demyelination or central pontine myelinolysis.
Courtesy of Dr Andrew Waclawik, Department of Neurology, University of Wisconsin,
Madison.
Electroencephalography in central pontine myelinolysis may demonstrate diffuse
bihemispheric slowing. Brainstem-evoked potentials may reveal abnormalities when
neuroimaging is unrevealing.
Relative preservation of axons and surrounding neurons within areas of
demyelination and an associated reduction in oligodendroglia is present.
The earliest change is seen on DWI with restriction in the lower pons. This is seen
within 24 hours of the onset of quadriplegia 3. This same region demonstrates eventual high
T2 signal and later low T1 signal. The T1 and T2 changes may take up to two weeks to
develop. This region has a classic trident shaped appearance. Occasionally gadolinium
enhancement is also demonstrated, just as in the acute phase of a multiple sclerosis
(MS) plaque. The peripheral fibres (ventrolateral longitudinal fibres), as well as the
periventricular and subpial regions, are typically spared.
Similar appearances are seen in other parts of the brain: basal ganglia, midbrain and
subcortical white matter.
Signal characteristics of affected region include:
 T1: mildly or moderately hypointense
 T2: hyperintense, sparing the periphery and corticospinal tracts
 PD: hyperintense
 FLAIR: hyperintense
 DWI: hyperintense
 ADC: signal low or signal loss
 T1 C+ (Gd): usually there is no enhancement, but some authors reported that it may
occur 5-6
 PET :Affected regions may demonstrate initial high uptake followed by subsequent low
uptake with 18-FDG.
3. Blood sodium level and other blood tests
4.Brainstem auditory evoked response (BAER)

2.8 Possible Complications

Complications may include:
 Decreased ability to interact with others
 Decreased ability to work or care for self
 Inability to move, other than to blink eyes ("locked in" syndrome)
 Permanent nervous system damage

2.9 Prevention
In the hospital, slow, controlled treatment of a low sodium level may reduce the risk
for nerve damage in the pons. Being aware of how some medicines can change sodium levels
can prevent the level from changing too quickly.

2.10 Treatment
The ideal treatment for myelinolysis is to prevent the disorder by identifying
individuals at risk and following careful guidelines for evaluation and correction of
hyponatremia. These guidelines aim to safely restore the serum sodium level, while
protecting the brain. For those who have hyponatremia for at least 2 days, or for whom the
duration is not known, the rate of rise in the serum sodium concentration should be kept
below 10 mmol/L during any 24-hour period, if possible.
For those who develop myelinolysis, treatment is supportive. Some physicians have
tried to treat myelinolysis with steroid medication or other experimental therapies, but none
has been proven effective. Individuals are likely to require extensive and prolonged physical
therapy and rehabilitation. Those individuals who develop parkinsonian symptoms may
respond to the dopaminergic drugs that work for individuals with Parkinson’s disease.

2.11 Prognosis
The prognosis for myelinolysis varies. Some individuals die and others recover
completely. Although the disorder was originally considered to have a mortality rate of 50
percent or more, improved imaging techniques and early diagnosis have led to a better
prognosis for many people. Most individuals improve gradually, but still continue to have
challenges with speech, walking, emotional ups and downs, and forgetfulness.
 BAB III
KESIMPULAN