1. Dr. Parag Moon
SR, Dept. of Neurology,
GMC Kota.

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.

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

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

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”,

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

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

28. Thanks

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