ENCEPHALOPAT

HY
Dr.Muhammad
Yusuf,SpS

Definisi
Encephalopathy adalah istilah yang
berarti penyakit, kerusakan, atau
malfungsi otak.

> Gejala ringan :

kehilangan memori, perubahan
kepribadian
> Gejala berat :
dementia, seizures, koma, atau
kematian.

Encephalopathy dimanifestasikan oleh keadaan

mental yang berubah dan adakalanya bersamaan
oleh manifestasi-manifestasi fisik (koordinasi
yang buruk dari gerakan-gerakan anggota tubuh).

Penyebab
infeksi-infeksi (bakteri, virus,parasit, atau prions),
anoxia (kekurangan oksigen pada otak),
alkohol,
gagal hati,
gagal ginjal,
penyakit metabolik,
tumor otak,
kimia
Perubahan pada tekanan dalam otak
nutrisi yang buruk.

Gejala-Gejala
Keadaan mental yang berubah
kelesuan,
dementia,
seizures,
tremor-tremor,
kejang otot, dan
koma.

Diagnosa Encephalopathy
Status mental, tes memori, tes koordinasi
Complete blood count (CBC ) , infeksi,
Tekanan darah
Pemeriksaan metabolik (elektrolit, glucose,
lactate, ammonia, oksigen, dan enzim hati)
Obat-obatan atau racun (alkohol, cocaine,
amphetamines, DLL)
Kultur darah dan cairan tubuh (infeksi)
Creatinine (fungsi ginjal)
CT dan MRI scans
Doppler ultrasound
Encephalogram atau EEG
Auto-antibody

Penanganan
Bervariasi tergantung penyebab primer yang
mendasarinya
Anoxia : terapi oksigen
Keracunan alkohol jangka pendek: cairan-cairan IV
(intravena)
Penyalahgunaan alkohol jangka panjang (sirosis atau
gagal hati kronis: oral lactulose, diet rendah protein,
antibiotik
Uremic encephalopathy (gagal ginjal): mengkoreksi
penyebab fisiologi yang mendasarinya, dialysis,
transplantasi ginjal
Diabetic encephalopathy: glucose hypoglycemia
Hypo- atau hypertensive encephalopathy

Gejala dan Komplikasi

Hepatic (hati) encephalopathy
pembengkakan otak dengan herniation, koma,
kematian
Metabolic encephalopathy
sifat iritabel, kelesuan, depresi, gemetar;
adakalanya koma atau kematian
Anoxic encephalopathy
perubahan kepribadian, kerusakan otak yang
parah sampai kematian pada kejadian-kejadian
anoxic jangka panjang)
Uremic encephalopathy
kelesuan, halusinasi, pingsan, kejang otot,
seizures, kematian

Hashimoto's encephalopathy
kebingungan, dementia
Wernicke's encephalopathy
kebingungan mental, memori, kemampuan
yang berkurang untuk menggerakan mata
Bovine spongiform encephalopathy atau "Mad
Cow disease"
ataxia, dementia dan myoclonus atau kejang
Shigella encephalopathy
sakit kepala, leher yang kaku, delirium,
seizures, koma
infeksius dari pediatric encephalopathy
lekas marah, anoreksia, hypotonia atau floppy
baby syndrome, seizures, kematian

Hepatic Encephalopathy

Definition (1)
Hepatic encephalopathy
(HE)
It represents a reversible
decrease in neurologic
function, based upon the
disorder of metabolism which
are caused by severe

Incidence/prevalence

Universal feature of
acute liver failure
50%~70% in chronic
hepatic failure
Difficult to estimate

Etiology
Fulminant hepatic failure
acute severe viral hepatitis,
drug/toxin
acute fatty liver of pregnancy
Due to acute hepatocellular
necrosis
Chronic liver disease
cirrhosis of all types (70%),
primary liver cancer surgically
induced portal-cava shunts
Due to one or more potentially

HE---common
precipitating factors
Nitrogenous
Nitrogenous

Non-Nitrogenous
Non-Nitrogenous

Encephalopathy
Encephalopathy

Encephalopathy
Encephalopathy

Uremia/azotemia
Gastrointestinal
bleeding
Dehydration
Metabolic alkalosis
Hypokalemia
Constipation
Excessive dietary
protein
Infection

Sedative
Benzodiazepines
Hypoxia
Hypoglycemia
Hypothyroidism
Anemia

Pathogenesis (1)
Toxic materials derived from
nitrogeneous substrate in the
gut and bypass the liver
Caused by several factors
act synergistically
Several putative gut-derived
toxins identified

Pathogenesis (2)
Postulated factors/mechanisms:
Ammonnia neurotoxicity
Synergistic neurotoxins
Excitatory inhibitory
neurotransmitters and plasma
amino acid imbalance
hypothesis
-Aminobutyric acid

Ammonia neurotoxicity
Ammonia production
resulting from the degradation of urea
or protein
primary site:
gut
other site:
kidney and skeletal
muscles
Gut-generating ammonia: 4g/day
Equilibrium of ammonia and
ammonium:

Ammonia neurotoxicity
Ammonia elimination
Transfer to the liver
Metabolized by series of urea
cycle enzymes
Comsumpted by brain, liver,
kidney: to
synthesize glutamic acid and
glutamine
Excreted into the urine

Ammonia neurotoxicity
Over production and/or hypoeccrisis
Poor hepato-cellular function:
incomplete metabolism
Portal-systemic encephalopathy:
bypass
Ammonia intoxication
Interfere with cerebral metabolism:
Depletion of glutamic acid, aspartic
acid and ATP
Depression cerebral blood flow and

Ammonia neurotoxicity
Elevation of ammonia:
detected in 60%~80%
Absolute concentration of
ammonia, ammonia
metabolites in blood or
cerebrospinal fluids, correlates
only roughly with the presence
or severity of HE
Few cases: within normal

Synergistic neurotoxins

Ammonia
Mercaptans
Short-chain fatty
acids
Phenols

Excitatory inhibitory
neurotransmitter
Neurotransmission:

Mediated by both excitatory and inhibitory

neurotransmitters
Their synthesis controlled by brain concentration
of the precursor amino acids
Increased aromatic amino acids (AAAs)
Tyrosine Phenylalanine Tryptophan
Due to the failure of hepatic deamination
Decreased branched-chain amino acids (BCAAs)
Valine
Leucine
Isoleucine
Due to increased metabolism by skeletal
muscle
and kidneys or increased insulin

Excitatory inhibitory
neurotransmitter
Imbalance of plasma amino acid:
More AAAs enter into blood-brain barrier and
CNS
Decreased synthesis of normal
neurotransmitters
L-Dopa
Dopamine
Noradrenoline
Enhanced synthesis of false
neurotransmitters
Octopamine
Tryptophan
Serotonin

- Aminobutyric acid hypothesis

- Aminobutyric acid (GABA):
Principle inhibitory neurotransmitters
Generated in the gut by bacteria
Bypasses the diseased or shunted liver
GABA-receptor complex: Localized to postsynaptic
membranes
Key contributor to neuronal inhibition in HE
GABA-ergic:25% ~ 65% of nerve endings
Increased blood-brain barrier permeability
Increased number of binding sites
Endogenous ligands for the BZ receptor:unknown
VEP = induced by BZ or barbiturate
Substances in the brain: bind to BZ receptor
GABA/BZs receptors antagonists:improve HE
symptoms

- Aminobutyric acid
hypothesis
Endogenous ligands for the BZ
receptor: unknown
VEP = induced by BZ or
barbiturate
Substances in the brain: bind
to BZ receptor
GABA/BZs receptors
antagonists:
improve HE symptoms

Pathohistology
Brain may be normal or cerebral edema
Particularly in fulminant heptic failure
Cerebral edema is likely the secondly
changes
In patients with chronic liver disease
Astrocytes: increase in number and
enlargement
In a very long-standing case
Thin cortex, loss of neurons fibers,
laminar

PathoPhisIology
CT/MRI :
- Cerebral atrophy related to
the severity of the liver
dysfunction
- Marked in chronic persistent
encephalopathy

Clinical manifestation
In acute liver failure
Spontaneously appearing
Severe fatal hepatic dysfunction +
abrupt mental
deterioration + coma/death
high fever ,tachycardia ,
tachypnea
hyperventilation

Clinical manifestation
In chronic liver disease
Insidious onset
Characterized by subtle and/or intermittent
changes in consciousness personality intelligence
speech
Disturbed consciousness:
slowness,
somnolence,
disorientation, confusion deep coma
Personality changes: childishness
irritability
Intellectual deterioration: inability to produce
simple designs
with blocks or matches
Speech: slow
slurred
monotonous voice

Clinical manifestation
Criteria for clinical stages
Personality and mental
changes
Abnormal EEG patterns
Asterixis

Clinical stages of HE

Clinical stages of HE

Laboratory and other tests

Serum ammonia
Elevation of serum ammonia:
60%~80%
particularly in chronic HE
(with portosystemic shunting)
Electroencephalogram (EEG)
Severe slowing with frequencies in
the theta
and delta
Evoked potentials

Differential diagnosis
Hypoglycemia
Uremia
Diabetic ketoacidosis
Nonketotic hyperosmolar
syndrome
Subdural hematoma
Cerebrospinal infection

Treatment
Strategy for the management of
HE
Identify and correct the
precipitating cause(s)
Initiate ammonia-lowering
therapy
Minimize the potential medical
complications
of cirrhosis and depressed

Initiate ammonia-lowing
therapy

Dietary protein restriction:

In patients with chronic HE
permanent protein restriction:
40~60g/D
In patients with acute HE
more restricted protein intake: < 40, 20,
10 or 0 g/D
Relapse return to the former regime
Vegetable protein in priority
lower rate of ammonia production
contain small amounts of methionine

Initiate ammonia-lowing
therapy
Antibiotics
Neomycin: 2~4g/D (4~6g/D)
Litter is absorbed Impaired
hearing or deafness (in long term
use) Long term use (>1 month) is
not advisable
Metronidozol: 0.2g qid as
effective as neomycin

Prognosis
HE results from fulminant
hepatic failure (FHF): Poor 20%
survival rates
HE results from chronic liver
disease
Short-term: better than FHF
Long-term: guarded

Hypoxic encephalopathy

Brain perfusion

15% of the resting cardiac output

20% of the total body oxygen consumption.
50 ml per minute for each 100 gm of tissue
Breathing 10% O2 for 15 to 30 minutes
increases the CBF by 35%
Breathing 7% O2 (PaO2 35 mm Hg) for 15
minutes increases CBF by 75%
Goetz: Textbook of Clinical Neurology, 2nd ed.,
Copyright 2003 Elsevier

Mekanisme hipoksik

The cause of hypoxic encephalopathy

Current Opinion in critical care Volume 8(2) April 2002 pp 115-120

Symptoms & signs of hypoxic

encephalopathy
New skill learning and the processing of complex
information are the most vulnerable to hypoxia
PaO2
80 mm Hg impaired dark adaptation
55 to 45 mm Hg impaired learning and shortterm memory
40 to 30 mm Hg loss of judgment, euphoria,
delirium,

perception

and muscular incoordination

twice light for visual

Goetz:
of Clinical Neurology,
ed.,
< 25 to 20 mm
Hg :Textbook
consciousness
is rapidly2nd
lost
Copyright 2003 Elsevier

Postanoxic encephalopathy syndroms

Myoclonus
Delayed anoxic encephalopathy
an unexplained phenomenon
during recovery (1 to 4 weeks) from an anoxic insult
irritability, confusion, apathy, and occasionally
agitation or mania
serious mental and motor disturbances, diffuse
rigidity, spasticity, weakness, a shuffling gait,
incontinence, coma, and death after 1 to 2 weeks
major pathological finding : cerebral demyelination.

Parkinsonism
Cerebral palsy

Goetz: Textbook of Clinical Neurology, 2nd ed.,

Copyright 2003 Elsevier

Treatment
Initial resuscitation and stabilization,
Supportive treatment of hypoxicischemic
Perfusion and Blood Pressure
Management
fluid management,
hypoglycemia and hyperglycemia
treatment of seizures

Encephalopathy,
Hypertensive

 hypertensive encephalopathy to
describe the encephalopathic
findings associated with the
accelerated malignant phase of
hypertension.

 Hypertensive crisis
1. hypertensive emergency :
Acute or ongoing vital target organ
damage, such as damage to the brain,
kidney, or heart, in the setting of severe
hypertension is considered a hypertensive
emergency. It requires a prompt reduction
in blood pressure within minutes or hours.
2. hypertensive urgency.
The absence of target organ damage in
the presence of severe elevation of blood
pressure with diastolic blood pressure
frequently greater than 120 mm Hg is
considered hypertensive urgency, and it
requires reduction in blood pressure within
24-48 hours.

 The morbidity and mortality

associated with hypertensive
encephalopathy are related to the
degree of target organ damage.
Without treatment, the 6-month
mortality rate for hypertensive
emergencies is 50%, and the 1-year
mortality rate approaches 90%.

Manifestasi klinik
neurologic symptoms :headache,
confusion, visual disturbances, seizures,
nausea, and vomiting. Headaches are
usually anterior and constant in nature.
The onset of symptoms usually occurs
over 24-48 hours, with neurologic
progression over 24-48 hours.
end organ damage. :
Cardiovascular symptoms of aortic dissection,
congestive heart failure, angina, palpitations,
irregular heart beat, and dyspnea , Renal

hematuria and acute renal failure

Physical examination
Funduscopic examination: papilledema,
hemorrhage, exudates, and cotton-wool spots.
Neurologic examination :neurological nonfocal
deficits nystagmus to weakness ,mental status
ranging from confusion to coma.
vascular examination
Other target organ damage that may be found
includes the following:
Cardiovascular - S3, elevated neck veins, peripheral
edema, murmurs, abdominal pulsations, and
diminished pulses
Renal - Acute renal failure, pulmonary edema, and
peripheral edema
Pulmonary - Pulmonary edema, rales, and wheezes

Terapi
Medical Care
CBF ---60-90 mm Hg
Lowering the mean arterial pressure by
25% and the diastolic blood pressure to
100-110 mm Hg
Pharmacologic agents selected for use in
hypertensive encephalopathy should
have few or no CNS adverse effects.
Avoid agents such as clonidine,
reserpine, and methyldopa.