Dr. Parag MoonSR, Dept. of Neurology,

GMC Kota.

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)

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

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 longtermcognitive dysfunction and behavioralsymptoms

3) Complement cascade

Excessive complement activation can also produce reactive oxygen species, can facilitate proinflammatory mediators and causes edema, cell necrosis or apoptosis

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

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

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.

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.

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

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

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

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.

4) Serum markers

S100B and neuron-specific enolase (NSE) are elevated in adults and children

Do not correlate with severity of SE

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.

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”,

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.

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

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.

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

Thanks

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 ClinNeurosci 23:3, Summer 2011