SCF-AE-MNSS-TEMP-0008
Temporal Windows of Autoimmune Encephalopathy (AE)
SCF Multi-Neurosystems Shock State (MNSS) Atlas
Pre-Autoimmune Encephalopathy → Active Autoimmune Encephalopathy → Post-Encephalopathy Neuroimmune Reconstruction
Integrated Neuroimmune, Neurocardiac, Neurovascular, Neurometabolic, Neuroendocrine, Neuroglial, Neuroaxonal, Lymphatic, and Connectomic Biomarker Framework
I. SCF AUTOIMMUNE ENCEPHALOPATHY SHOCK CASCADE
Etiopathogenic Core
Genetic Susceptibility
↓
Immune Trigger
(Infection, Malignancy, Autoimmunity, Molecular Mimicry)
↓
Loss of Immune Tolerance
↓
Autoantibody Production
↓
BBB Dysfunction
↓
CNS Immune Infiltration
↓
Microglial Activation
↓
Astrocytic Activation
↓
Synaptic Dysfunction
↓
Neurotransmitter Receptor Disruption
↓
Neuroimmune Amplification
↓
Connectomic Instability
↓
Autoimmune Encephalopathy
↓
Neuroaxonal Injury
↓
Post-Encephalopathy Neurocognitive Syndrome
II. MASTER TEMPORAL PROGRESSION TABLE
SCF Phase | Temporal Window | Dominant Shock State | Clinical Status | Reversibility |
MNSS-0 | Months–Years | Immune Homeostasis | Asymptomatic | Very High |
MNSS-IA | Weeks–Months | Autoimmune Priming | Subclinical autoimmunity | Very High |
MNSS-IB | Days–Weeks | Neuroimmune Propagation | Early neurocognitive symptoms | Very High |
MNSS-II | Days Before Overt Disease | Neurovascular-Neuroglial Shock | Prodromal AE | High |
MNSS-IIIA | Hours–Days | Early Autoimmune Encephalopathy | Mild AE | High |
MNSS-IIIB | Days–Weeks | Established AE | Moderate-Severe AE | Moderate |
MNSS-IV | Hours–Days | Global Multi-Neurosystems Shock | Fulminant AE | Limited |
MNSS-R1 | Days–Weeks | Immune Resolution | Recovery initiation | High |
MNSS-R2 | Weeks–Months | Connectomic Reconstruction | Functional recovery | Moderate–High |
MNSS-R3 | Months–Years | Neuroadaptive Compensation | Post-AE syndrome | Variable |
III. PRE-ENCEPHALOPATHY WINDOW 1
MNSS-IA
AUTOIMMUNE PRIMING STATE
Temporal Window
Weeks–Months Before Neurological Symptoms
Dominant SCF Shock States
- Neuroimmune Shock (NIS-1)
- Neuroendocrine Shock (NES-1)
SCF Biomarker Panel
Neuroimmune Biomarkers
Biomarker | Baseline | Alert Threshold |
ANA | Negative/Low | Positive |
CXCL13 | <20 pg/mL | >50 pg/mL |
IL-6 | <2 pg/mL | >10 pg/mL |
TNF-α | <5 pg/mL | >10 pg/mL |
IFN-γ | Normal | Elevated |
Autoantibody Biomarkers
Biomarker | Alert Threshold |
NMDAR-IgG | Positive |
LGI1-IgG | Positive |
CASPR2-IgG | Positive |
AMPAR-IgG | Positive |
GABA-BR-IgG | Positive |
DPPX-IgG | Positive |
Neuroendocrine Biomarkers
Biomarker | Alert Threshold |
Cortisol Rhythm | Flattening |
DHEA-S | ↓15% |
Melatonin | Reduced |
Clinical Manifestations
- Fatigue
- Mild anxiety
- Sleep disruption
- Subjective cognitive slowing
Therapeutic Objective
Prevent CNS autoimmunity establishment.
IV. PRE-ENCEPHALOPATHY WINDOW 2
MNSS-IB
NEUROIMMUNE PROPAGATION PHASE
Temporal Window
Days–Weeks Before Overt AE
Dominant Shock States
- Neuroimmune Shock (NIS-2)
- Neurovascular Shock (NVS-1)
SCF Biomarker Panel
Neuroimmune Biomarkers
Biomarker | Alert Threshold |
IL-6 | >15 pg/mL |
TNF-α | >15 pg/mL |
CXCL13 | >100 pg/mL |
IFN-γ | Elevated |
HMGB1 | Elevated |
Neurovascular Biomarkers
Biomarker | Alert Threshold |
MMP-9 | >250 ng/mL |
ICAM-1 | Elevated |
VCAM-1 | Elevated |
Albumin Quotient | Rising |
Neurocardiac Biomarkers
Biomarker | Alert Threshold |
SDNN | <90 ms |
RMSSD | <25 ms |
Clinical Manifestations
- Memory lapses
- Mood changes
- Sleep disturbance
- Reduced concentration
Therapeutic Objective
Prevent BBB penetration and CNS immune activation.
V. PRODROMAL AUTOIMMUNE ENCEPHALOPATHY
MNSS-II
NEUROVASCULAR-NEUROGLIAL SHOCK
Temporal Window
Days Before Overt Disease
Dominant Shock States
- Neurovascular Shock (NVS-2)
- Neuroglial Shock (NGS-1)
- Neurometabolic Shock (NMS-1)
SCF Biomarker Panel
Neurovascular Biomarkers
Biomarker | Threshold |
MMP-9 | >300 ng/mL |
Albumin Quotient | Elevated |
S100B | >0.15 ng/mL |
Neuroglial Biomarkers
Biomarker | Threshold |
GFAP | >150 pg/mL |
YKL-40 | >100 ng/mL |
sTREM2 | Elevated |
Neurometabolic Biomarkers
Biomarker | Threshold |
Lactate | >2 mmol/L |
ATP Production | ↓20% |
cf-mtDNA | Elevated |
Clinical Manifestations
- Mild cognitive impairment
- Executive dysfunction
- Personality changes
Therapeutic Objective
Prevent receptor-mediated neuronal dysfunction.
VI. EARLY AUTOIMMUNE ENCEPHALOPATHY
MNSS-IIIA
Temporal Window
Hours–Days After Clinical Recognition
Dominant Shock States
- Neuroimmune Shock (NIS-3)
- Neuroglial Shock (NGS-2)
SCF Biomarker Panel
Autoantibody Activity
Biomarker | Threshold |
NMDAR-IgG | Rising titer |
LGI1-IgG | Rising titer |
CASPR2-IgG | Rising titer |
AMPAR-IgG | Rising titer |
Neuroimmune Biomarkers
Biomarker | Threshold |
IL-6 | >20 pg/mL |
TNF-α | >20 pg/mL |
CXCL13 | >150 pg/mL |
Neuroglial Biomarkers
Biomarker | Threshold |
GFAP | >250 pg/mL |
S100B | >0.20 ng/mL |
Connectomic Biomarkers
Biomarker | Threshold |
qEEG Connectivity | >15% decline |
EEG Theta | Increased |
EEG Delta | Increased |
Clinical Manifestations
- Memory impairment
- Psychiatric symptoms
- Confusion
- Early seizures
Therapeutic Objective
Preserve synaptic and network integrity.
VII. ESTABLISHED AUTOIMMUNE ENCEPHALOPATHY
MNSS-IIIB
Temporal Window
Days–Weeks
Dominant Shock States
- Neuroaxonal Shock (NAS-1)
- Neurocardiac Shock (NCS-1)
- Neurometabolic Shock (NMS-2)
SCF Biomarker Panel
Neuroaxonal Biomarkers
Biomarker | Threshold |
NfL | >20 pg/mL |
UCH-L1 | Elevated |
Tau | Elevated |
NSE | Elevated |
Neurocardiac Biomarkers
Biomarker | Threshold |
SDNN | <80 ms |
RMSSD | <15 ms |
QTc | Prolonged |
Neurometabolic Biomarkers
Biomarker | Threshold |
Lactate | >3 mmol/L |
ATP Production | ↓40% |
cf-mtDNA | High |
Clinical Manifestations
- Seizures
- Cognitive decline
- Dysautonomia
- Psychosis
- Behavioral dysregulation
Therapeutic Objective
Prevent irreversible neuroaxonal injury.
VIII. ACUTE MULTI-NEUROSYSTEMS SHOCK
MNSS-IV
Temporal Window
Hours–Days
Dominant Shock States
- Neuroimmune Shock (NIS-4)
- Neurocardiac Shock (NCS-3)
- Neurovascular Shock (NVS-3)
- Neurometabolic Shock (NMS-3)
- Neuroendocrine Shock (NES-3)
Peak Biomarker Panel
Neuroimmune
- IL-6 Peak
- TNF-α Peak
- CXCL13 Peak
- IFN-γ 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
- Lactate >4 mmol/L
- ATP failure
- cf-mtDNA Peak
Neuroendocrine
- Cortisol dysregulation
- ACTH dysregulation
- Melatonin suppression
Neuroglial
- GFAP Peak
- YKL-40 Peak
Neuroaxonal
- NfL Peak
- Tau Peak
- UCH-L1 Peak
Clinical Manifestations
- Refractory seizures
- Status epilepticus
- Severe psychosis
- Catatonia
- Coma
- Autonomic instability
Therapeutic Objective
Life preservation and neuronal salvage.
IX. POST-ENCEPHALOPATHY RECOVERY WINDOW
MNSS-R1
IMMUNE RESOLUTION PHASE
Temporal Window
Days–Weeks
Recovery Biomarker Panel
Domain | Biomarker Trend |
Neuroimmune | IL-6 ↓, TNF-α ↓, CXCL13 ↓ |
Neurocardiac | SDNN ↑, RMSSD ↑ |
Neurovascular | MMP-9 ↓ |
Neuroglial | GFAP ↓ |
Neuroaxonal | NfL stabilization |
Therapeutic Objective
Suppress residual neuroinflammation.
X. CONNECTOMIC RECONSTRUCTION WINDOW
MNSS-R2
Temporal Window
Weeks–Months
Reconstruction Biomarker Panel
Domain | Desired Trend |
Neuroglial | GFAP ↓ |
Neuroaxonal | NfL ↓ |
Connectomic | qEEG Connectivity ↑ |
Connectomic | DTI FA ↑ |
Neurocardiac | HRV SDNN ↑ |
Neuroendocrine | Cortisol rhythm restoration |
Neuroimmune | Autoantibody titers declining |
Therapeutic Objective
Restore cognitive and autonomic network function.
XI. POST-AUTOIMMUNE ENCEPHALOPATHY SYNDROME
MNSS-R3
Temporal Window
Months–Years
Persistent Risk Biomarkers
Shock Domain | Persistent Biomarkers |
Neuroimmune | CXCL13, IL-6, HMGB1 |
Neurocardiac | SDNN suppression |
Neurovascular | MMP-9 elevation |
Neurometabolic | Residual mitochondrial dysfunction |
Neuroendocrine | Cortisol rhythm abnormalities |
Neuroglial | GFAP elevation |
Neuroaxonal | NfL, Tau |
Connectomic | Persistent qEEG dysconnectivity |
Autoimmune | Persistent low-level autoantibody positivity |
Clinical Manifestations
- Persistent memory deficits
- Executive dysfunction
- Fatigue
- Dysautonomia
- Mood disorders
- Relapse susceptibility
XII. MASTER SCF AUTOIMMUNE ENCEPHALOPATHY BIOMARKER MATRIX
SCF Phase | Neuroimmune Shock | Neurocardiac Shock | Neurovascular Shock | Neurometabolic Shock | Neuroendocrine Shock |
MNSS-IA | IL-6, CXCL13 | SDNN ↓ | ICAM-1 ↑ | ATP ↓ | Cortisol ↑ |
MNSS-IB | HMGB1 ↑ | LF/HF ↑ | MMP-9 ↑ | cf-mtDNA ↑ | 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 | Mitochondrial impairment | Melatonin suppression |
MNSS-IV | Peak cytokines | Severe autonomic collapse | Peak BBB injury | Peak metabolic failure | HPA collapse |
MNSS-R1 | Resolution | HRV recovery | BBB repair | ATP recovery | Endocrine recovery |
MNSS-R2 | Low inflammation | SDNN ↑ | Vascular repair | Bioenergetic restoration | Circadian restoration |
MNSS-R3 | Residual inflammation | Persistent dysautonomia | Residual dysfunction | Chronic bioenergetic deficit | Neuroendocrine maladaptation |
XIII. HIGHEST-VALUE THERAPEUTIC WINDOWS
Rank | Window | SCF Phase | Reversibility | Therapeutic Goal |
1 | Autoimmune Priming | MNSS-IA | Very High | Prevent CNS autoimmunity |
2 | Neuroimmune Propagation | MNSS-IB | Very High | Preserve BBB integrity |
3 | Prodromal AE | MNSS-II | High | Prevent receptor-mediated dysfunction |
4 | Early AE | MNSS-IIIA | High | Preserve connectomic integrity |
5 | Established AE | MNSS-IIIB | Moderate | Prevent neuroaxonal injury |
6 | Fulminant AE | MNSS-IV | Limited | Preserve life and brain function |
7 | Connectomic Reconstruction | MNSS-R2 | Moderate–High | Restore cognition and autonomics |
XIV. EARLIEST PREDICTIVE SCF BIOMARKER PANEL FOR AUTOIMMUNE ENCEPHALOPATHY
Tier 1 — Autoimmune Drivers
- NMDAR-IgG
- LGI1-IgG
- CASPR2-IgG
- AMPAR-IgG
- GABA-BR-IgG
- DPPX-IgG
Tier 2 — Neuroimmune Predictors
- CXCL13
- IL-6
- TNF-α
- IFN-γ
- HMGB1
Tier 3 — Neurovascular Predictors
- MMP-9
- ICAM-1
- VCAM-1
- Albumin Quotient
Tier 4 — Neuroglial Predictors
- GFAP
- YKL-40
- S100B
- sTREM2
Tier 5 — Neurocardiac Predictors
- HRV SDNN
- RMSSD
- LF/HF Ratio
Tier 6 — Neuroendocrine Predictors
- Cortisol Circadian Rhythm
- DHEA-S
- Melatonin
These biomarkers collectively define the highest-value intervention window before overt autoimmune encephalopathy, seizure evolution, and connectomic collapse.
MASTER REGISTRY INDEX
- SCF-AE-MNSS-TEMP-0008 — Autoimmune Encephalopathy Disease Progression Timeline Mapping
- SCF-ECCA-AE-0001 — Autoimmune Encephalopathy Module
- SCF-ECCA-AE-BIO-0004 — Autoimmune 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