This document discusses metabolic encephalopathies, including their definition, pathophysiology, common types, diagnosis, and management. It focuses on hepatic encephalopathy caused by liver failure and uremic encephalopathy caused by kidney failure. The main mechanisms involve disruption of brain arousal centers and neurotransmitter abnormalities. Management involves treating the underlying condition, controlling seizures, reducing ammonia levels, and managing cerebral edema. Metabolic encephalopathies in critically ill patients can lead to long-term neurocognitive deficits even if the initial brain dysfunction was reversible.

1. Presented By :
Riham Hamdy Mostafa
Neurology Resident At Cairo Hospital University

2. Agenda :
 Definition of encephalopathy
 Pathophysiology of metabolic encephalopathies
 Etiology of metabolic encephalopathies
 Common types :
 hepatic encephalopathy
Uremic encephalopathy
 Diagnosis and evaluation
 Differential diagnosis of metabolic encepahlopathies
 Prognosis

3. • This term “ Encephalopathy “ is defined as altered mental
status as a result of a diffuse disturbance of brain
function .
• Or
• Any clinical condition that causes impairment in
consciousness usually accompanied by diffuse EEG
abnormalities

4. • Mainly it depends on the cause
However regardless the etiology the
main mechanism is due to disruption
of arousal and attention centers in
the brain (ARAS).
• Another mechanism including
compression or injury for areas
critical for memory ,attention and
executive functions .
• Abnormalities in
neurotransmitters such as ( (Ach ,
serotonin, GABA ,dopamine,
tryptophan ,cytokines ) also affect
these connections

7. uremicHepatic

8. • Pathogenesis of hepatic encephalopathy related to the acuity
of developing liver failure ( high risk with acute liver failure )
Ammonia
induced
neurotoxicity

9. Factors lead to hepatic encephalopathy :
• Hyper ammonia :
astrocytes swelling and dysfunction
induced vasodilation and increase
cerebral edema
• Increase sensitivity to glutamine and
GABA which are inhibitory
neurotransmitters and low the
threshold for seziures activity
• Inflammatory markers
(tumor necrosis factor ) lead to
cytotoxic edema for brain cells

12. Management :
1- cerebral edema :
• Monitoring of ICP is
indicated in patient with
grade 3&4 HE especially who
are candidate to OLT.
• The most accurate is
intraparenchymal ICP
monitoring.
• This requires reversal of
patient’s coagulopathy
during placement only .
Cerebral edema
SeziuresHyperammonia

13. Management :
1- Cerebral Edema :
• elevate the head of bed 30 degree
• Maintain head in midline position
• Control agitation and pain
• Keep Co2 between 35 mm hg to 40 mm hg
• Maintain the patient normothermic
• Maintain the patient euvolmic
• Treat shivering
• Osmotic therapy :
hypertonic saline 23%
mannitol 20%
target Na level 150 to 155meq/dl

14. Cerebral edema
SeziuresHyperammonia
2- Seziures :
• All patient with hepatic
encephalopathy should be
considered for EEG monitoring
• More common with patient of
fulminant hepatitis and Reyes
syndrome
• Any electrolytes imbalance or
hypoglyemia should be
corrected
• Common posttransplant due to
acute GABA-ergic withdrawal
• High risk if associated with
brain hge , inc ICP
• Best AEDs for these patient is
leverticitam

15. 3-Hyperammonia :
 Lactulose is the corner stone on
management of HE with
nonabsorbable antibiotics such
as neomycin , rifaximin
especially in chronic liver
failure.
 NAC is strongly recommended
in all cases of early stage acute
liver cell failure either
acetaminophen overdose or not
.
Cerebral edema
SeziuresHyperammonia

16. 3-Hyperammonia :
• NAC affecting glutathione stores in body
• Oral and iv forms
• Loading dose 150 mg/kg in 500 ml dextrose 5% for 30 min
• 50 mg/kg over 4hr
• 1000 ml of dextrose 5% over 19 hrs
• Infusion continued till INR less than 1.5

17. uremicHepatic

18. • Development of uremic encephalopathy occurred when
GFR is less than normal by 10%
• More severe with acute patients than chronic patients
• Patients with hepatorenal syndrome are at higher risks

19. Pathology :
• Dec clearance of osmotically active toxins
• Proinflammatory state lead to BBB breakage
• Electrolytes abnormailites
• Seziures and myoclonus
• Dysequilibrium syndrome
• Dialysis dementia
• Cerebral atrophy

20. 1-Seziures and myoclonus:
• Occurs in about 14% to 33% either generalized or focal
• More common in acute renal failure and exacerbated with
electrolytes abnormalities especially hyponatremia , and
hypocalcemia
myclonus

21. • Any of abnormal movement presented in renal
patient should be evaluated by EEG confirm
diagnosis of myoclonus
• Phenytoin used as AEDs in uremic patient to
control sezuires but it worse myoclonus
• Best choice for myoclonus is tiratam &valporic acid

22. 2-Dysequilibrium syndrome:
is the occurrence of neurologic signs and symptoms,
attributed to cerebral edema, during or following shortly
(8hr) after intermittent hemodialysis.
• Due to sudden clearing of nitrogenous compounds from
blood and increase urea content in brain lead to ICP
• Symptoms :
•Confusion
•Headache
•Nausea and vomiting
•Tremors
•Myclonic sezuires
• Usually resolve spontanously within days

23. 3-Dialysis dementia:
a neurological syndrome that occurs in some long term( 2.5 yr)
dialysis patients, is associated with aluminum intoxication (as
from aluminum-containing compounds in the dialysis fluid.
Symptoms :
• Permenant memory loss
• Dysarthria
• Fascial grimacing
• Myoclonus
• Mood and personality changes
• Usually lead to death within 6 m from diagnosis

27. • Metabolic encephalopathy is common in the ICU setting
• the brain dysfunction that occurs with metabolic
encephalopathy was thought to be completely reversible
• critically ill patients with metabolic encephalopathy are
often left with long-term neurocognitive deficits.
• Persistent neurologic and psychiatric deficits occur in up
to 32% of medical ICU survivors