3. Defined as brain dysfunction due to sepsis
and SIRS
Also called sepsis-associated delirium
Clinically, acute impairment in the level of
consciousness and confusion (manifested by
alteration in attention, disorientation and
concentration up to deep coma in more
severe cases)
4. 9 -71% of patients with sepsis develop SE
Patients With known CNS pathology are at
greater risk for SE
Often described as a reversible syndrome
New studies show prolonged cognitive
impairment and depressive symptoms in
sepsis survivors
63% mortality rate reported in SE patients
with reduced Glasgow Coma Scale to 3-8
points
5. 1) Oxidative stress
occurs early (<6h)
2) Cytokines
Pro-inflammatory cytokines (tumor necrosis
factor (TNF), Interleukin (IL)-1ß, IL-6) are
significantly increased in SE
Contribute to the development of longterm
cognitive dysfunction and behavioral
symptoms
6. 3) Complement cascade
Excessive complement activation can also
produce reactive oxygen species, can
facilitate proinflammatory mediators and
causes edema, cell necrosis or apoptosis
7. Diminished cholinergic innervation -
hippocampal, parietal and prefrontal cortex-incapacities
of memory functions
Dysfunction of the neural circuits between
medial temporal lobe, posterior parietal
cortex and dorsal prefrontal cortex by
disconnection from general activating
projections from the ascending reticular
activating system (ARAS)- delirium and long-term
impairment in SE patients
8. Cerebral endothelial dysfunction,
microvasculature and blood-brain-barrier
(BBB) changes
Impaired nutrition delivery and removal of
metabolic waste products as well as increased
permeability
Inappropriate blood supply to neurons may
play an important role for SE
9. Aromatic amino acids (AAA)
Normally restricted by BBB
Increased in SE patients and correlate with
severity of encephalopathy
May act as false neurotransmitter and/or
disturb neurotransmitter synthesis
Increased serum levels of phenylalanine,
ammonia, and tryptophan with influence on
procalcitonin and IL-6 levels contributing to
SE development.
10.
11. Mild patients demonstrate a fluctuating
confusional state and inappropriate behavior.
Inattention and writing errors (including
spelling, writing full sentences, orientation of
writing on the page).
More severely affected show delirium, an
agitated confusional state or coma.
12. Most common motor sign is paratonic
rigidity or gegenhalten, a resistance to passive
movement of limbs that is velocity-dependent
Asterixis, multifocal myoclonus, seizures and
tremor are relatively infrequent
Cranial nerve functions are almost invariably
spared.
Lateralized features are almost never
encountered
13. Clinical or laboratory evidence of peripheral
nerve dysfunction, namely critical illness
polyneuropathy, is found in 70% patients.
It is axonal type, later in onset and much
slower to recover than the encephalopathy
14.
15. No specific test available
1) Electroencephalography (EEG)
Most sensitive diagnostic tool
Normal, diffuse slowing, excessive theta,
predominantly delta, triphasic waves, and
suppression or burst suppression
Non-specific
16.
17. 2) Short-latency and long-latency-SEP
measurement provide a valuable estimation
of SE severity
3) CSF examination
Total protein may be elevated in severe SE
cases, cell counts and microbiological
cultures remain normal
Used to exclude direct infection in suspected
meningoencephalitis.
18. 4) Serum markers
S100B and neuron-specific enolase (NSE) are
elevated in adults and children
Do not correlate with severity of SE
19. 1)CT scans mostly normal
White matter hypodensities are reported
2)MR imaging
Various degrees of leukencephalopathy as well
as multiple ischemic strokes
Patients without MR abnormalities survived
without sequelae, while those who died showed
clear MRI lesions
Mainly within the white matter
Corresponded to vasogenic edema, probably
reflecting blood–brain barrier breakdown.
20. Infarction of basal ganglia secondary to
fibrinoid necrosis and thrombosis of small
vessels neuropathologically
a posterior reversible encephalopathy
syndrome (PRES)
MR angiography in this study revealed
vasospasm and
vessel “pruning”,
21.
22.
23. Cerebral hemorrhage, ischemic infarcts and
central pontine Myelinolysis(17%)
Disseminated micro-abscesses (~67%)
Ischemic and apoptotic neurons were found
in paraventricular and supraoptic nuclei as
well as in locus coeruleus.
24. No specific treatment options for SE.
Most importantly, adequate and immediate
therapy of the underlying sepsis syndrome
and supportive intensive care are required
Administration of a mixture of amino acids
with high concentrations of branched-chain
amino acids
25.
26. Activated protein C, that affect or counteract
the procoagulant state in sepsis may be
directly or indirectly beneficial to brain
function in sepsis
Ascorbate (ascorbic acid 20mg/kg) is
antioxidant. Found useful in animal model.
27. Experimental treatment-Magnesium,
glutamate release inhibitor riluzole or an
antioxidant treatment, selective antagonists
of pro-inflammatory cytokine receptors
Coupled plasma filtration adsorption, an
extracorporal therapy, aimed at the
nonspecific removal of cytokines and
mediators involved in systemic inflammation
29. Neurological Sequelae of Sepsis: I) Septic
Encephalopathy; The Open Critical Care Medicine
Journal, 2011, Volume 4
Sepsis-associated encephalopathy; Neurol J
Southeast Asia 2003; 8 : 65 – 76
Understanding brain dysfunction in sepsis;
Sonneville et al.; Annals of Intensive Care 2013,
3:15
Sepsis-Associated Encephalopathy: Review of the
Neuropsychiatric Manifestations
and Cognitive Outcome; J Neuropsychiatry Clin
Neurosci 23:3, Summer 2011
