Encephalopathy Connectomic Collapse Atlas (ECCA-AE) | Autoimmune Encephalopathy Biomarker Panel

SCF-ECCA-AE-BIO-0004

Autoimmune Encephalopathy Biomarker Panel

Neuroimmune Connectomic Collapse Validation System

FDA-Aligned Endpoint Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-AE)

I. PURPOSE

The SCF Autoimmune Encephalopathy Biomarker Panel is designed to:

Establish autoimmune encephalopathy diagnosis support
Quantify neuroimmune-connectomic collapse severity
Stratify autoimmune subtypes
Predict disease progression and relapse
Personalize acupuncture neurocircuit selection
Monitor immunotherapy and neuromodulation response
Support FDA-aligned translational endpoint development
Enable precision forecasting of neuroimmune instability

II. SCF AUTOIMMUNE ENCEPHALOPATHY BIOMARKER DOMAINS

Domain	Function
Autoantibody Activity	Measures pathogenic immune targeting
Neuroimmune Activation	Measures cytokine amplification
Neuroaxonal Injury	Measures neuronal injury
Glial Activation	Measures astrocyte/microglial response
BBB Integrity	Measures neurovascular dysfunction
Connectomic Function	Measures network synchronization
Autonomic Function	Measures neuro-autonomic stability
Mitochondrial Function	Measures ATP-redox collapse
Cognitive Function	Measures cortical performance
Relapse Prediction	Forecasts flare risk

III. AUTOANTIBODY PANEL

Tier 1 Autoimmune Driver Layer

Biomarker	Assay	Baseline	Mild Risk	Moderate Risk	Severe Risk
NMDAR IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
LGI1 IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
CASPR2 IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
GABA-BR IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
AMPAR IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
DPPX IgG	Cell-Based Assay	Negative	Low Positive	Moderate Positive	High Positive
ANA	Immunofluorescence	Negative	1:80	1:160	≥1:320
Anti-dsDNA	ELISA	Negative	Borderline	Positive	High Positive

Endpoint

Autoimmune Driver Index (ADI)

IV. NEUROIMMUNE ACTIVATION PANEL

Tier 2 Cytokine Amplification Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
IL-6	Multiplex	<2 pg/mL	2–10	10–50	>50
TNF-α	Multiplex	<5 pg/mL	5–15	15–30	>30
IL-1β	Multiplex	<1 pg/mL	1–5	5–15	>15
IFN-γ	Multiplex	Reference	Elevated	High	Very High
CXCL13	ELISA	Low	Elevated	High	Very High

Endpoint

Neuroimmune Amplification Score (NIAS)

V. NEUROAXONAL INJURY PANEL

Tier 3 Connectomic Injury Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
NfL	Simoa	<10 pg/mL	10–20	20–50	>50
Total Tau	Simoa	<2 pg/mL	2–4	4–8	>8
UCH-L1	ELISA	<100 pg/mL	100–200	200–400	>400
NSE	CLIA	<12 ng/mL	12–18	18–25	>25

Endpoint

Neuroaxonal Injury Index (NAII)

VI. GLIAL ACTIVATION PANEL

Tier 4 Neuroglial Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
GFAP	Simoa	<120 pg/mL	120–250	250–500	>500
S100B	Immunoassay	<0.1 ng/mL	0.1–0.2	0.2–0.5	>0.5
YKL-40	ELISA	<60 ng/mL	60–100	100–150	>150
sTREM2	ELISA	Normal	Elevated	High	Very High

Endpoint

Glial Activation Severity Score (GASS)

VII. BBB INTEGRITY PANEL

Tier 5 Neurovascular Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Albumin Quotient	CSF/Serum	<6.5	6.5–8	8–12	>12
S100B	Immunoassay	<0.1	0.1–0.2	0.2–0.5	>0.5
MMP-9	ELISA	<150 ng/mL	150–250	250–400	>400
VEGF	ELISA	Normal	Elevated	High	Very High

Endpoint

BBB Permeability Index (BBPI)

VIII. CONNECTOMIC FUNCTION PANEL

Tier 6 Connectomic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
EEG Delta Power	qEEG	Normal	+20%	+50%	+100%
EEG Theta Excess	qEEG	Normal	Mild	Moderate	Severe
Alpha Connectivity	qEEG	Normal	↓10%	↓25%	↓50%
rs-fMRI Connectivity	MRI	↓10%	↓25%	↓50%	↓75%
DTI Fractional Anisotropy	MRI-DTI	Normal	↓5%	↓10%	↓20%

Endpoint

Connectomic Collapse Index (CCI)

IX. AUTONOMIC FUNCTION PANEL

Tier 7 Neuro-Autonomic Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
HRV SDNN	ECG	>100 ms	80–100	50–80	<50
RMSSD	ECG	>30 ms	20–30	10–20	<10
LF/HF Ratio	HRV	1–2	2–3	3–5	>5
COMPASS-31	Clinical Tool	<10	10–25	25–45	>45

Endpoint

Autonomic Collapse Index (ACI)

X. MITOCHONDRIAL FUNCTION PANEL

Tier 8 Bioenergetic Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Lactate	Clinical Chemistry	0.5–2.0 mmol/L	2–3	3–5	>5
Pyruvate	LC-MS/MS	Normal	Elevated	High	Very High
Lactate/Pyruvate Ratio	LC-MS/MS	<20	20–30	30–40	>40
ATP Production Rate	Seahorse	Normal	↓10%	↓25%	↓50%

Endpoint

Bioenergetic Failure Index (BFI)

XI. COGNITIVE ENDPOINT PANEL

Tier 9 Functional Layer

Endpoint	Normal	Mild	Moderate	Severe
MoCA	≥26	22–25	16–21	<16
Trail Making Test-B	<75 sec	75–120	120–180	>180
Digit Symbol Substitution	>90	75–90	50–75	<50
Neuropsychiatric Inventory	Minimal	Mild	Moderate	Severe

Endpoint

Autoimmune Connectomic Performance Score (ACPS)

XII. RELAPSE PREDICTION PANEL

Tier 10 Forecast Layer

Biomarker	Low Risk	Intermediate Risk	High Risk
NMDAR/LGI1 Titer Trend	Stable	Rising	Rapidly Rising
GFAP	<250	250–500	>500
NfL	<20	20–50	>50
IL-6	<10	10–25	>25
EEG Connectivity	Stable	Mild Decline	Major Decline

Endpoint

Autoimmune Relapse Forecast Score (ARFS)

XIII. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Biomarker Pattern	Predicted Dysfunction	Primary Acupuncture Network
Elevated IL-6 + TNF-α	Neuroimmune hyperactivation	ST36 + LI11 + LI4
Elevated GFAP + S100B	Glial injury	GV20 + Sishencong + ST36
High NfL + Tau	Neuroaxonal injury	GV20 + GV24 + GB20
HRV suppression	Dysautonomia	PC6 + HT7 + CV17
Reduced rs-fMRI Connectivity	Connectomic collapse	GV20 + GV24 + Sishencong
Limbic antibody dominance (NMDAR/LGI1)	Limbic-connectomic dysfunction	HT7 + Yintang + LV3
Elevated Lactate/Pyruvate Ratio	Mitochondrial collapse	KI3 + SP6 + ST36

XIV. SCF PRECISION FORECASTING MODEL

Low-Risk Recovery

Criteria:

Autoantibody titers stable
GFAP <250
NfL <20
MoCA >24
Preserved HRV

Predicted Response:

High likelihood of neuromodulation responsiveness.

Intermediate Risk

Criteria:

Rising antibody titers
GFAP 250–500
Moderate EEG slowing
MoCA 18–24

Predicted Response:

Partial response requiring prolonged immunologic stabilization.

High-Risk Progression

Criteria:

Rapidly rising titers
GFAP >500
NfL >50
Severe connectivity loss
MoCA <18

Predicted Response:

High relapse probability; intensive medical management required.

XV. COMPOSITE SCF AUTOIMMUNE ENCEPHALOPATHY SCORE (SCF-AES)

Weighted Domains

Domain	Weight
Autoantibody Activity	20%
Neuroimmune Activation	15%
Neuroaxonal Injury	15%
Glial Activation	15%
BBB Integrity	10%
Connectomics	10%
Autonomics	5%
Mitochondrial Function	5%
Cognition	5%

Interpretation

Score	Classification
<20	Stable
20–40	Mild Autoimmune Connectomic Dysfunction
40–60	Moderate Collapse
60–80	Severe Autoimmune Encephalopathy
>80	Critical Neuroimmune Failure

XVI. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic-Support Endpoints

Autoimmune encephalitis antibody panel
MRI brain
EEG
CSF analysis
MoCA

Predictive Endpoints

NfL
GFAP
Autoantibody titer trajectory
HRV
rs-fMRI connectivity

Therapeutic Response Endpoints

Reduction in antibody titers
Improvement in MoCA
Reduction in GFAP/NfL
Improved HRV
Improved Connectomic Collapse Index

NEXT PANEL IN SEQUENCE

SCF-ECCA-SEP-BIO-0005

Septic Encephalopathy Biomarker Panel

(Systemic Inflammatory Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-AE-BIO-0004 — Autoimmune Encephalopathy Biomarker Panel
SCF-ECCA-AE-ACU-0004 — Autoimmune Encephalopathy Acupoint Neuro-Circuit Mapping Atlas
SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema