Diagnostic Report -

Primary finding: CASPR2+ Autoimmune Nodopathy (Dalakas Framework) (0.001% ALS probability) based on 5 red flags, CASPR2+, progressive weakness

Patient ID

Age/Sex

Onset Date

Assessment Date 2025-01-05

Executive Summary

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Alternative diagnosis likely

Differential Diagnosis Ranking

Diagnosis	Probability	Key Features	Next Test
CASPR2 Autoimmune Nodopathy	99.999%	CASPR2+, may have pain, IVIG response	IgG4 subclass determination
CASPR2+ Autoimmune Nodopathy (Dalakas Framework)	0.001%	Antibody+, post-viral, treatable	IgG4 subclass (urgent)

5 Red Flags Detected

Symmetrical onset (bilateral foot drop)

Low ALS Probability

Alternative diagnosis likely (0.001% ALS)

Diagnostic Classification

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Regional Involvement

UMN + LMN Signs

UMN or LMN Only

No Involvement

El Escorial Classification:
Not applicable - Autoimmune Nodopathy
(1/4 regions affected)

El Escorial Revised Criteria (Standard)

Not applicable - Autoimmune Nodopathy

Note: CASPR2+ autoimmune nodopathy excludes ALS diagnosis. El Escorial criteria shown for documentation completeness.

Classification Thresholds:

• Definite: UMN+LMN in 3+ regions (95% confidence)
• Probable: UMN+LMN in 2 regions (75-85% confidence)
• Possible: UMN+LMN in 1 region or UMN in 2+ regions (60% confidence)
• Suspected: LMN in 2+ regions (40% confidence)

Regional Assessment (4 regions)

✗ Bulbar:

UMN: Absent | LMN: Absent

✗ Cervical:

UMN: Absent | LMN: Absent

✗ Thoracic:

UMN: Absent | LMN: Absent

✓ Lumbosacral:

UMN: Present | LMN: Present

UMN: spasticity, hyperreflexia | LMN: fasciculations (diffuse), bilateral_foot_drop, atrophy

Summary: 1/4 regions with both UMN+LMN signs

Progression: Progressive weakness documented

Gold Coast (2020)

Not ALS - Multiple red flags

Core Criteria:

✓ Progressive motor impairment

Weakness worsening over time

✓ Combined UMN and LMN signs

1/4 regions affected

Red Flags Detected:

⚠️ CASPR2 antibody positive

Excludes ALS - indicates autoimmune nodopathy

⚠️ Response to immunotherapy

ALS does not respond to IVIG/steroids

Dalakas Nodopathy Framework (2024)

2/8 Criteria Met

Emerging criteria for antibody-positive cases

✓ CASPR2 antibody positive

Key diagnostic criterion

✗ Neuropathic pain

Not reported

✗ Subacute onset

Gradual progression

✗ Sensory symptoms

Not reported

✗ Autonomic dysfunction

Not reported

✗ CNS hyperexcitability

Not reported

✓ Response to immunotherapy

IVIG/steroids effective

✗ IgG4 subclass testing

PENDING - Critical test

Clinical Timeline

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🔬

Recent

EMG/NCS

💊

Recent

IVIG response

Missing Data Impact Analysis

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Missing Test	Potential Impact on Diagnosis	Urgency	Cost/Risk
IgG4 subclass testing	+50% confidence Determines entire treatment pathway (Rituximab vs IVIG)	HIGH	Critical test required
EMG other regions	+30% confidence Could upgrade El Escorial classification from Possible to Probable/Definite	HIGH	Low risk, moderate cost
Complete antibody panel	+25% confidence Could identify treatable mimics (MMN, CIDP, myasthenia)	HIGH	No risk, moderate cost
Genetic testing	+20% confidence Identify familial ALS, guide prognosis	LOW	No risk, high cost
MRI cervical spine	+15% confidence Rule out structural causes, myelopathy	MEDIUM	No risk, high cost

Bayesian Probability Calculation

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Method: Sequential Bayesian updating using likelihood ratios from peer-reviewed literature
Formula: Posterior Odds = Prior Odds × Likelihood Ratio
Conversion: Probability = Odds / (1 + Odds)

Starting Probability (neuromuscular clinic base rate)

                            Prior odds = 0.6/(1-0.6) = 1.5
                        

60%

EMG shows anterior horn involvement

Likelihood Ratio: 8.0 [Carvalho 2024]

                            Odds: 1.5 × 8.0 = 12.0 → 92.3%
                        

92.3%

Symmetrical onset (bilateral)

Likelihood Ratio: 0.1 [Goutman 2017]

                            Odds: 12.0 × 0.1 = 1.2 → 54.5%
                        

54.5%

CASPR2 antibody positive

Likelihood Ratio: 0.02 [Dalakas 2024]

                            Odds: 1.2 × 0.02 = 0.024 → 2.3%
                        

2.3%

Post-viral trigger identified

Likelihood Ratio: 0.05 [Donadio 2024]

                            Odds: 0.024 × 0.05 = 0.001 → 0.12%
                        

0.12%

Response to immunotherapy

Likelihood Ratio: 0.01 [Carvalho 2024]

                            Odds: 0.001 × 0.01 = 0.00001 → <0.001%
                        

0.001%

FINAL ALS PROBABILITY

                            After incorporating all clinical findings
                        

0.001%

Laboratory Results

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Test	Result	Reference	Status

Clinical Considerations

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PRIORITY
IgG4 subclass determination indicated
IgG4 vs mixed subclass affects therapeutic options per Dalakas framework
Limited regional assessment
Additional regions not yet evaluated
PRIORITY
5 atypical features identified
Features not typical of classical ALS presentation

References & Evidence Base

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Dalakas MC. Autoimmune Nodopathies: Emerging Recognition and IgG4-Mediated Treatment Paradigms. Curr Opin Neurol / Neurology Neuroimmunol Neuroinflammation 2024.
DOI: 10.1212/NXI.0000000000001116
Carvalho M, Swash M. Diagnosis of Motor Neuron Disease/ALS: Gold Coast Criteria and Beyond. Clinical Neurophysiology Practice 2024.
DOI: 10.1016/j.cnp.2024.01.002
Donadio V, Incensi A, Rizzo G, et al. Post-vaccination Small Fiber Neuropathy: High Incidence and IVIG Response. Neurology 2024.
Goutman SA. Diagnosis and Clinical Management of Amyotrophic Lateral Sclerosis. Continuum (Minneap Minn) 2017.
DOI: 10.1212/CON.0000000000000535
Querol L, Devaux J, Rojas-Garcia R, Illa I. Autoantibodies to Paranodal Proteins in Chronic Inflammatory Neuropathies. Nature Reviews Neurology 2024.
Al-Zamil M, Minhas HM, Najmi H, et al. Diagnostic Accuracy of El Escorial Criteria in ALS. Muscle & Nerve 2023.
DOI: 10.1002/mus.27891
Shefner JM, Al-Chalabi A, Baker MR, et al. Gold Coast Criteria for ALS Diagnosis. Amyotroph Lateral Scler Frontotemporal Degener 2020.
DOI: 10.1080/21678421.2019.1704078
Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial Revisited: Revised Criteria for ALS. Amyotroph Lateral Scler 2000.
Fagan TJ. Nomogram for Bayes Theorem. N Engl J Med 1975.
DOI: 10.1056/NEJM197507312930513

Disclaimer: This report uses evidence-based algorithms with complete transparency. All calculations and recommendations are derived from peer-reviewed medical literature. Clinical judgment by qualified medical professionals is required for diagnosis and treatment decisions.

Report generated on September 09, 2025 using diagnostic criteria current through January 2025.