Encephalopathy Connectomic Collapse Atlas (ECCA-MET) | Metabolic Encephalopathy Biomarker Panel

SCF-ECCA-MET-BIO-0006

Metabolic Encephalopathy Biomarker Panel

Systemic Metabolic Connectomic Collapse Validation System

FDA-Aligned Endpoint Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-MET)

I. PURPOSE

The SCF Metabolic Encephalopathy Biomarker Panel is designed to:

Establish metabolic encephalopathy diagnostic support
Quantify metabolic-connectomic collapse severity
Identify primary metabolic drivers
Forecast neurologic deterioration
Personalize acupuncture neurocircuit selection
Monitor correction of metabolic abnormalities
Support FDA-aligned translational endpoint development
Enable precision prediction of recovery trajectories

II. SCF METABOLIC ENCEPHALOPATHY BIOMARKER DOMAINS

Domain	Function
Metabolic Homeostasis	Measures systemic metabolic stability
Electrolyte Regulation	Measures neuroelectrical integrity
Renal Function	Measures uremic neurotoxicity burden
Endocrine Function	Measures hormonal-metabolic regulation
Neuroaxonal Injury	Measures neuronal injury
Neuroglial Activation	Measures astrocytic response
Mitochondrial Function	Measures ATP-redox collapse
BBB Integrity	Measures neurovascular dysfunction
Connectomic Function	Measures network synchronization
Autonomic Function	Measures neurovisceral regulation
Cognitive Function	Measures cortical performance
Recovery Prediction	Forecasts treatment responsiveness

III. METABOLIC HOMEOSTASIS PANEL

Tier 1 Primary Metabolic Layer

Biomarker	FDA-Aligned Assay	Normal	Mild Risk	Moderate Risk	Severe Risk
Glucose	Clinical Chemistry	70–100 mg/dL	60–69 / 100–150	40–59 / 150–250	<40 / >250
HbA1c	HPLC	<5.7%	5.7–6.4%	6.5–8%	>8%
Serum Osmolality	Osmometry	275–295 mOsm/kg	295–305	305–320	>320
Anion Gap	Clinical Chemistry	8–12	12–16	16–24	>24
Bicarbonate	Chemistry	22–28 mmol/L	18–22	12–18	<12

Endpoint

Metabolic Stability Index (MSI)

IV. ELECTROLYTE COLLAPSE PANEL

Tier 2 Neuroelectrical Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Sodium	Clinical Chemistry	135–145 mmol/L	130–134 / 146–150	125–129 / 151–160	<125 / >160
Potassium	Clinical Chemistry	3.5–5.0 mmol/L	3.0–3.4 / 5.1–5.5	2.5–2.9 / 5.6–6.0	<2.5 / >6.0
Calcium	Clinical Chemistry	8.5–10.5 mg/dL	Mild abnormality	Moderate abnormality	Severe abnormality
Magnesium	Clinical Chemistry	1.7–2.2 mg/dL	Mild abnormality	Moderate abnormality	Severe abnormality
Phosphate	Clinical Chemistry	2.5–4.5 mg/dL	Mild abnormality	Moderate abnormality	Severe abnormality

Endpoint

Neuroelectrical Stability Score (NSS)

V. RENAL-UREMIC PANEL

Tier 3 Uremic Neurotoxicity Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Creatinine	Clinical Chemistry	<1.2 mg/dL	1.2–2.0	2.0–4.0	>4.0
eGFR	CKD-EPI	>90	60–89	30–59	<30
BUN	Clinical Chemistry	7–20 mg/dL	20–40	40–80	>80
Uric Acid	Chemistry	Reference	Elevated	High	Very High
Indoxyl Sulfate	LC-MS/MS	Reference	Elevated	High	Very High

Endpoint

Uremic Neurotoxicity Index (UNI)

VI. ENDOCRINE-METABOLIC PANEL

Tier 4 Hormonal Regulation Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
TSH	CLIA	0.4–4.5 mIU/L	Mild abnormality	Moderate	Severe
Free T4	Immunoassay	Reference	Mild abnormality	Moderate	Severe
Cortisol (AM)	Immunoassay	5–25 µg/dL	Mild abnormality	Moderate	Severe
ACTH	Immunoassay	Reference	Elevated	High	Very High
Insulin	Immunoassay	Reference	Elevated	High	Very High

Endpoint

Endocrine Regulation Index (ERI)

VII. NEUROAXONAL INJURY PANEL

Tier 5 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
NSE	CLIA	<12 ng/mL	12–18	18–25	>25
UCH-L1	ELISA	<100 pg/mL	100–200	200–400	>400

Endpoint

Neuroaxonal Injury Index (NAII)

VIII. GLIAL ACTIVATION PANEL

Tier 6 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)

IX. MITOCHONDRIAL FAILURE PANEL

Tier 7 Bioenergetic Collapse 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)

X. BBB INTEGRITY PANEL

Tier 8 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)

XI. CONNECTOMIC FUNCTION PANEL

Tier 9 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)

XII. AUTONOMIC FUNCTION PANEL

Tier 10 Neurovisceral 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)

XIII. COGNITIVE ENDPOINT PANEL

Tier 11 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
Delirium Rating Scale	Minimal	Mild	Moderate	Severe

Endpoint

Metabolic Connectomic Performance Score (MCPS)

XIV. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Biomarker Pattern	Predicted Dysfunction	Primary Acupuncture Network
Sodium Dysregulation	Neuroelectrical instability	GV20 + PC6 + HT7
Elevated Lactate/Pyruvate	Mitochondrial collapse	KI3 + SP6 + ST36
Elevated GFAP + S100B	Glial injury	GV20 + Sishencong + ST36
Elevated NfL + Tau	Neuroaxonal injury	GV20 + GV24 + GB20
Uremic biomarker dominance	Uremic neurotoxicity	KI3 + BL23 + ST36
Glucose instability	Hypothalamic-metabolic dysfunction	ST36 + CV6 + SP6
Reduced rs-fMRI Connectivity	Connectomic collapse	GV20 + GV24 + Sishencong
HRV suppression	Dysautonomia	PC6 + HT7 + CV17

XV. SCF PRECISION FORECASTING MODEL

Low-Risk Recovery

Criteria:

Corrected electrolyte imbalance
GFAP <250
NfL <20
MoCA >24
Preserved HRV

Predicted Response:

Rapid neurologic recovery potential.

Intermediate Risk

Criteria:

Persistent metabolic instability
GFAP 250–500
Moderate EEG slowing
MoCA 18–24

Predicted Response:

Prolonged recovery requiring ongoing metabolic correction.

High-Risk Progression

Criteria:

Severe electrolyte derangement
GFAP >500
NfL >50
Severe EEG slowing
MoCA <18

Predicted Response:

High risk for coma, recurrent encephalopathy, or permanent neurologic injury.

XVI. COMPOSITE SCF METABOLIC ENCEPHALOPATHY SCORE (SCF-MES)

Domain	Weight
Metabolic Homeostasis	15%
Electrolyte Regulation	15%
Renal-Uremic Function	15%
Endocrine Function	10%
Neuroaxonal Injury	10%
Glial Activation	10%
Mitochondrial Function	10%
BBB Integrity	5%
Connectomics	5%
Autonomics	3%
Cognition	2%

Interpretation

Score	Classification
<20	Stable
20–40	Mild Metabolic Connectomic Dysfunction
40–60	Moderate Collapse
60–80	Severe Metabolic Encephalopathy
>80	Critical Multi-System Metabolic Failure

XVII. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic-Support Endpoints

Comprehensive metabolic panel
Serum osmolality
Renal function tests
Endocrine evaluation
EEG

Predictive Endpoints

NfL
GFAP
Lactate/Pyruvate Ratio
HRV
Electrolyte Stability Index

Therapeutic Response Endpoints

Normalization of metabolic markers
Improved MoCA
Improved HRV
Reduced GFAP/NfL
Improved Connectomic Collapse Index

NEXT PANEL IN SEQUENCE

SCF-ECCA-HYP-BIO-0007

Hypoxic–Ischemic Encephalopathy Biomarker Panel

(Cerebral Hypoxia Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-MET-BIO-0006 — Metabolic Encephalopathy Biomarker Panel
SCF-ECCA-MET-ACU-0006 — Metabolic 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