What is the management of albumino-cytologic dissociation in cerebrospinal fluid (CSF)?

Management of Albumino-Cytologic Dissociation in Cerebrospinal Fluid

Albumino-cytologic dissociation (elevated CSF protein with normal cell count) is a diagnostic finding that requires identification of the underlying cause, not management of the finding itself. The appropriate approach is to diagnose and treat the specific condition causing this CSF abnormality, with Guillain-Barré syndrome being the most common etiology.

Understanding Albumino-Cytologic Dissociation

Albumino-cytologic dissociation is characterized by:

• Elevated CSF protein levels (typically >45 mg/dL)
• Normal CSF cell count (<10 cells/μL)
• No evidence of infection or inflammation in the CSF

Common Causes and Diagnostic Approach

1. Guillain-Barré Syndrome (GBS)

• Most common cause of albumino-cytologic dissociation
• CSF protein may be normal in 30-50% of patients in the first week of symptoms 1
• Protein elevation increases with time from symptom onset, with 80% showing elevation by 2 weeks 2
• Diagnostic yield is higher with longer duration from clinical onset to lumbar puncture 3
• Electrophysiologic variants show different rates of albumino-cytologic dissociation:
  • AIDP (demyelinating): 60.6% show early dissociation
  • AMAN (axonal): 21.2% show early dissociation 2

2. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Increased CSF protein is a supportive diagnostic factor, especially when electrophysiologic criteria are not definitive 4
• Typically more persistent elevation than in GBS

3. Leptomeningeal Metastases

• CSF cytology is the gold standard for diagnosis 5
• May require multiple large-volume CSF samples (10-15 mL) for cytologic analysis
• False-negative rates can be high, requiring repeated sampling 5
• MRI with gadolinium of brain and entire spine is essential 5

4. Primary Amyloidosis

• Can present with autonomic neuropathy and albumino-cytologic dissociation 6
• Requires tissue biopsy (sural nerve, rectal membrane, bone marrow) for definitive diagnosis

5. Autoimmune Encephalitis

• CSF may show normal or mild pleocytosis with elevated protein 5
• Testing for neural autoantibodies is essential even if CSF is otherwise normal 5

Diagnostic Algorithm

1. Initial CSF Analysis:

   • Obtain adequate CSF volume (10-15 mL)
   • Process promptly (within 30 minutes)
   • Measure protein, cell count, glucose, and glucose ratio
   • Consider CSF lactate (<2 mmol/L rules out bacterial disease) 5

2. Based on Clinical Presentation:

   a) If acute ascending weakness/neuropathy (suspect GBS):

   • Proceed with treatment if clinical presentation is typical, even if CSF is normal early in course 1
   • Consider repeat lumbar puncture after 1-2 weeks if diagnosis remains uncertain
   • Perform electrodiagnostic studies to support diagnosis

   b) If chronic/relapsing neuropathy (suspect CIDP):

   • Evaluate for other supportive criteria (clinical, electrophysiologic)
   • Consider nerve biopsy if diagnosis remains uncertain

   c) If cancer history or suspicious for leptomeningeal disease:

   • Perform CSF cytology (may require multiple samples)
   • Obtain MRI brain and total spine with contrast
   • Consider CSF flow studies if abnormal flow is suspected 5
   • Test for tumor markers in CSF (e.g., CEA, AFP, beta-HCG) 5

   d) If encephalopathy/encephalitis suspected:

   • Test CSF for viral PCR (HSV, VZV, enterovirus)
   • Test for neural autoantibodies (e.g., NMDAR, LGI1)
   • Obtain MRI brain with contrast
   • Consider EEG to evaluate for subclinical seizures 5

Treatment Considerations

Treatment should target the underlying cause:

1. For GBS:

   • Intravenous immunoglobulin (0.4 g/kg/day for 5 days) or plasma exchange
   • Supportive care and monitoring for respiratory failure

2. For CIDP:

   • Corticosteroids, IVIg, or plasma exchange
   • Consider maintenance therapy for relapsing forms

3. For Leptomeningeal Metastases:

   • Radiation therapy to symptomatic sites
   • Intrathecal chemotherapy for microscopic disease
   • Systemic therapy with CNS penetration 5

4. For Autoimmune Encephalitis:

   • First-line: Corticosteroids, IVIg, or plasma exchange
   • Second-line: Rituximab or cyclophosphamide if poor response 5

Important Caveats

• Normal CSF protein does not rule out GBS, especially early in the disease course 1
• Mild pleocytosis (10-50 cells/μL) can occur in GBS but should prompt consideration of alternative diagnoses 1
• Marked pleocytosis (>50 cells/μL) suggests other pathologies such as infection or malignancy 1
• Traumatic lumbar puncture can confound interpretation; subtract 1 white cell for every 700 red blood cells 5
• CSF examination alone is insufficient for diagnosis of most conditions causing albumino-cytologic dissociation; clinical features remain the cornerstone of diagnosis 1