SCF-HEP-MNSS-TEMP-0006
Temporal Windows of Hepatic Encephalopathy (HE)
SCF Multi-Neurosystems Shock State (MNSS) Atlas
Pre-Hepatic Encephalopathy → Overt Hepatic Encephalopathy → Post-Hepatic Neurocognitive Recovery
Integrated Neuroimmune, Neurocardiac, Neurovascular, Neurometabolic, Neuroendocrine, Astrocytic, Glymphatic, Neuroaxonal, and Connectomic Biomarker Framework
I. SCF HEPATIC ENCEPHALOPATHY SHOCK CASCADE
Primary Pathophysiologic Flow
Chronic Liver Injury
↓
Portal Hypertension
↓
Hepatic Detoxification Failure
↓
Hyperammonemia
↓
Astrocytic Glutamine Accumulation
↓
Astrocyte Swelling
↓
BBB Dysfunction
↓
Neuroimmune Activation
↓
Neurometabolic Failure
↓
Connectomic Dysregulation
↓
Thalamocortical Dysfunction
↓
Hepatic Encephalopathy
↓
Post-HE Cognitive Syndrome
II. MASTER TEMPORAL PROGRESSION TABLE
SCF Phase | Temporal Window | Dominant Shock State | Clinical Status | Reversibility |
MNSS-0 | Months–Years | Compensated Liver Disease | Asymptomatic | Very High |
MNSS-IA | Weeks–Months | Hyperammonemic Priming | Minimal symptoms | Very High |
MNSS-IB | Days–Weeks | Neuroimmune-Astrocytic Priming | Brain fog | Very High |
MNSS-II | Days Before Overt HE | Astrocytic-Neurometabolic Shock | Minimal HE | High |
MNSS-IIIA | Hours–Days | Early Hepatic Encephalopathy | Grade I–II HE | High |
MNSS-IIIB | Days–Weeks | Established HE | Grade II–III HE | Moderate |
MNSS-IV | Hours–Days | Global Multi-Neurosystems Shock | Grade III–IV HE | Limited |
MNSS-R1 | Days–Weeks | Resolution Phase | Recovery initiation | High |
MNSS-R2 | Weeks–Months | Connectomic Reconstruction | Cognitive recovery | Moderate–High |
MNSS-R3 | Months–Years | Neuroadaptive Compensation | Residual cognitive dysfunction | Variable |
III. PRE-ENCEPHALOPATHY WINDOW 1
MNSS-IA
Hyperammonemic Priming State
Temporal Window
Weeks–Months Before Clinical HE
Dominant Shock States
- Neurometabolic Shock (NMS-1)
- Neuroendocrine Shock (NES-1)
Neurometabolic Biomarkers
Biomarker | Baseline | Alert Threshold |
Plasma Ammonia | <50 µmol/L | >60 µmol/L |
Glutamine | Normal | Elevated |
Lactate/Pyruvate Ratio | <20 | >25 |
cf-mtDNA | Low | Elevated |
Neuroendocrine Biomarkers
Biomarker | Alert Threshold |
Cortisol Rhythm | Flattening |
IGF-1 | Declining |
DHEA-S | Reduced |
Neurocardiac Biomarkers
Biomarker | Alert Threshold |
SDNN | <90 ms |
RMSSD | <25 ms |
Clinical Features
- Fatigue
- Sleep disturbance
- Mild concentration deficits
Therapeutic Objective
Prevent astrocytic injury
IV. PRE-ENCEPHALOPATHY WINDOW 2
MNSS-IB
Neuroimmune-Astrocytic Priming
Temporal Window
Days–Weeks Before Minimal HE
Dominant Shock States
- Neuroimmune Shock (NIS-1)
- Neuroglial Shock (NGS-1)
- Neurovascular Shock (NVS-1)
Neuroimmune Biomarkers
Biomarker | Alert Threshold |
IL-6 | >10 pg/mL |
TNF-α | >10 pg/mL |
IL-1β | Elevated |
HMGB1 | Elevated |
Astrocytic Biomarkers
Biomarker | Alert Threshold |
GFAP | >120 pg/mL |
YKL-40 | >80 ng/mL |
S100B | >0.1 ng/mL |
Neurovascular Biomarkers
Biomarker | Alert Threshold |
MMP-9 | >200 ng/mL |
VEGF | Elevated |
Albumin Quotient | Rising |
Clinical Features
- Brain fog
- Mild executive dysfunction
- Reduced psychomotor speed
Therapeutic Objective
Prevent progression to minimal HE
V. PRE-OVERT HEPATIC ENCEPHALOPATHY
MNSS-II
Astrocytic-Neurometabolic Shock
Temporal Window
Days Before Clinical HE
Dominant Shock States
- Neuroglial Shock (NGS-2)
- Neurometabolic Shock (NMS-2)
Astrocytic Injury Biomarkers
Biomarker | Threshold |
GFAP | >180 pg/mL |
S100B | >0.15 ng/mL |
YKL-40 | >120 ng/mL |
Neurometabolic Biomarkers
Biomarker | Threshold |
Ammonia | >80 µmol/L |
Glutamine | Elevated |
Lactate | >2 mmol/L |
ATP Production | ↓20–30% |
Connectomic Biomarkers
Biomarker | Threshold |
EEG Theta | Increased |
EEG Alpha | Reduced |
qEEG Connectivity | >10% decline |
Clinical Features
Minimal Hepatic Encephalopathy
- Attention deficits
- Sleep inversion
- Slowed processing speed
Therapeutic Objective
Prevent overt HE
VI. EARLY HEPATIC ENCEPHALOPATHY
MNSS-IIIA
Temporal Window
Hours–Days Following Overt HE
Dominant Shock States
- Neuroglial Shock (NGS-3)
- Neuroimmune Shock (NIS-2)
Neuroimmune Biomarkers
Biomarker | Threshold |
IL-6 | >20 pg/mL |
TNF-α | >15 pg/mL |
HMGB1 | Elevated |
Astrocytic Biomarkers
Biomarker | Threshold |
GFAP | >250 pg/mL |
S100B | >0.2 ng/mL |
Connectomic Biomarkers
Biomarker | Threshold |
EEG Delta | Increased |
EEG Theta | Increased |
qEEG Connectivity | >15% reduction |
Clinical Features
West Haven Grade I–II
- Confusion
- Disorientation
- Impaired attention
Therapeutic Objective
Preserve network integrity
VII. ESTABLISHED HEPATIC ENCEPHALOPATHY
MNSS-IIIB
Temporal Window
Days–Weeks
Dominant Shock States
- Neuroaxonal Shock (NAS-1)
- Neurocardiac Shock (NCS-1)
- Neurometabolic Shock (NMS-3)
Neuroaxonal Biomarkers
Biomarker | Threshold |
NfL | >20 pg/mL |
UCH-L1 | Elevated |
NSE | Elevated |
Total Tau | Elevated |
Neurocardiac Biomarkers
Biomarker | Threshold |
SDNN | <80 ms |
RMSSD | <15 ms |
QTc | Prolonged |
Neurometabolic Biomarkers
Biomarker | Threshold |
Ammonia | >120 µmol/L |
Lactate | >3 mmol/L |
ATP Production | ↓40% |
Clinical Features
West Haven Grade II–III
- Marked confusion
- Asterixis
- Executive dysfunction
- Dysautonomia
Therapeutic Objective
Prevent cerebral edema and coma
VIII. ACUTE MULTI-NEUROSYSTEMS SHOCK
MNSS-IV
Temporal Window
Hours–Days
Dominant Shock States
- Neuroimmune Shock (NIS-4)
- Neurovascular Shock (NVS-3)
- Neurometabolic Shock (NMS-4)
- Neuroendocrine Shock (NES-3)
- Neurocardiac Shock (NCS-3)
Peak Biomarker Panel
Neuroimmune
- IL-6 Peak
- TNF-α Peak
- HMGB1 Peak
Neurocardiac
Biomarker | Threshold |
SDNN | <50 ms |
RMSSD | Severely reduced |
Troponin | Elevated |
NT-proBNP | Elevated |
Neurovascular
- MMP-9 Peak
- S100B Peak
- Albumin Quotient Peak
Neurometabolic
Biomarker | Threshold |
Ammonia | >150–200 µmol/L |
Lactate | >4 mmol/L |
cf-mtDNA | Peak |
Neuroendocrine
- Cortisol dysregulation
- ACTH dysregulation
- IGF-1 suppression
Neuroaxonal
- NfL Peak
- Tau Peak
- UCH-L1 Peak
Clinical Features
West Haven Grade III–IV
- Stupor
- Coma
- Cerebral edema risk
- Respiratory compromise
Therapeutic Objective
Life preservation
IX. POST-ENCEPHALOPATHY RECOVERY WINDOW
MNSS-R1
Resolution Phase
Temporal Window
Days–Weeks
Recovery Biomarkers
Biomarker | Trend |
Ammonia | ↓ |
IL-6 | ↓ |
TNF-α | ↓ |
GFAP | ↓ |
Lactate | ↓ |
HRV | ↑ |
Clinical Features
- Improved attention
- Reduced confusion
- Restored sleep
Therapeutic Objective
Accelerate neurocognitive recovery
X. CONNECTOMIC RECONSTRUCTION WINDOW
MNSS-R2
Temporal Window
Weeks–Months
Reconstruction Biomarkers
Biomarker | Desired Trend |
GFAP | ↓ |
NfL | ↓ |
qEEG Connectivity | ↑ |
DTI FA | ↑ |
HRV SDNN | ↑ |
Cortisol Rhythm | Restored |
IGF-1 | Improving |
Clinical Features
- Cognitive recovery
- Executive function restoration
- Improved autonomic function
Therapeutic Objective
Restore thalamocortical and executive networks
XI. POST-HEPATIC ENCEPHALOPATHY SYNDROME
MNSS-R3
Temporal Window
Months–Years
Persistent Risk Biomarkers
System | Biomarkers |
Neuroimmune | HMGB1, IL-6, YKL-40 |
Neurocardiac | Persistent SDNN suppression |
Neurovascular | MMP-9 elevation |
Neurometabolic | Residual mitochondrial dysfunction |
Neuroendocrine | Cortisol rhythm abnormalities, IGF-1 deficiency |
Neuroglial | GFAP |
Neuroaxonal | NfL, Tau |
Connectomic | Persistent qEEG dysconnectivity |
Clinical Features
- Residual cognitive impairment
- Executive dysfunction
- Sleep disorders
- Fatigue
- Recurrent HE susceptibility
XII. MASTER SCF PRE/POST HEPATIC ENCEPHALOPATHY BIOMARKER MATRIX
Stage | Neuroimmune | Neurocardiac | Neurovascular | Neurometabolic | Neuroendocrine |
MNSS-IA | IL-6 | SDNN ↓ | MMP-9 ↑ | Ammonia ↑ | Cortisol ↑ |
MNSS-IB | HMGB1 ↑ | LF/HF ↑ | Albumin Quotient ↑ | Glutamine ↑ | DHEA-S ↓ |
MNSS-II | IL-6 ↑↑ | HRV ↓↓ | S100B ↑ | Lactate ↑ | Circadian disruption |
MNSS-IIIA | Cytokine surge | Dysautonomia | BBB dysfunction | ATP loss | HPA activation |
MNSS-IIIB | Persistent inflammation | QTc prolongation | Endothelial dysfunction | Hyperammonemia | IGF-1 suppression |
MNSS-IV | Peak cytokines | Severe autonomic collapse | Peak BBB injury | Peak ammonia/lactate | HPA collapse |
MNSS-R1 | Resolution | HRV recovery | BBB repair | Ammonia normalization | Endocrine recovery |
MNSS-R2 | Low inflammation | SDNN ↑ | Vascular repair | ATP restoration | Circadian restoration |
MNSS-R3 | Residual inflammation | Persistent dysautonomia | Residual dysfunction | Chronic bioenergetic deficits | Neuroendocrine maladaptation |
XIII. HEPATIC ENCEPHALOPATHY THERAPEUTIC TEMPORAL WINDOW MATRIX
Window | SCF Phase | Reversibility | Primary Therapeutic Objective |
Window 1 | MNSS-IA | Very High | Control hyperammonemia before astrocytic injury |
Window 2 | MNSS-IB | Very High | Suppress neuroimmune priming |
Window 3 | MNSS-II | High | Prevent overt HE |
Window 4 | MNSS-IIIA | High | Preserve connectomic integrity |
Window 5 | MNSS-IIIB | Moderate | Prevent cerebral edema and axonal injury |
Window 6 | MNSS-IV | Limited | Preserve life and neurological function |
Window 7 | MNSS-R1 | High | Accelerate recovery |
Window 8 | MNSS-R2 | Moderate–High | Promote connectomic reconstruction |
Window 9 | MNSS-R3 | Variable | Prevent recurrent HE and chronic cognitive impairment |
XIV. SCF EARLIEST PREDICTIVE BIOMARKER PANEL FOR HEPATIC ENCEPHALOPATHY
The earliest biomarkers preceding overt hepatic encephalopathy are:
- Plasma Ammonia
- Glutamine
- IL-6
- HMGB1
- GFAP
- YKL-40
- HRV SDNN Decline
- Lactate/Pyruvate Ratio
- Albumin Quotient
- Cortisol Circadian Distortion
- IGF-1 Reduction
- cf-mtDNA Elevation
These biomarkers define the highest-value intervention window before development of Minimal Hepatic Encephalopathy and overt West Haven Grade I–IV disease.
MASTER REGISTRY INDEX
- SCF-HEP-MNSS-TEMP-0006 — Hepatic Encephalopathy Disease Progression Timeline Mapping
- SCF-ECCA-HEP-0001 — Hepatic Encephalopathy Module
- SCF-ECCA-HEP-BIO-0002 — Hepatic Encephalopathy Biomarker Panel
- SCF-MNSS-0001 — Multi-Neurosystems Shock State Framework
- SCF-CONNECTOMIC-RECONSTRUCTION-0001 — Neuroimmune Connectomic Reconstruction Framework
- SCF-BIOMARKER-ENDPOINTS-0001 — Biomarker Endpoint Validation Framework
- SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
- SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema