Case 7: Abnormal CSF findings in a 32 year old male

Chemical Pathology Class of 2011

History
“A 32-year-old man was in good health until about one year ago, when he entered an accelerated computer programming training program. Within the last year he began to notice episodic blurring of vision, mild vertigo, and headache. He attributed his complaints of sensory loss in his hands and a feeling of weakness after physical exertion to being “out of shape.”

History
“He decided to see his physician after an attack of blurred vision accompanied by a feeling of paralysis, which was followed by pins and needles in his left leg. An optic examination was negative. Neurological examination led to a spinal tap being performed for laboratory findings and myelography. The latter was negative.”

History: Lab Results
CSF = Clear, colourless fluid, apparently free of debris;culture yields no growth = Normal = 60 mg/dL (plasma =80 mg/dL)

WBC Glucose IgG/Alb ratio IgG

= 1.7 = Oligoclonal banding present

History: Lab Results
CSF = Clear, colourless fluid, apparently free of debris;culture yields no growth = Normal = 60 mg/dL (plasma =80 mg/dL)

WBC Glucose IgG/Alb ratio IgG

= 1.7 = Oligoclonal banding present

Questions

What is the significance of the normal CSF protein and IgG/Alb ratio? What pathology is consistent with these results?

Myelography
Largely superseded by CT and especially MRI. Still used in subjects in whom MRI is contraindicated (e.g. cardiac pace- maker, metallic implants, claustrophobia). Can screen whole spinal cord and cauda equina for compressive or expanding lesions. Can visualise roots and spinal vasculature abnormalities.

Myelography: Procedure
5–25mL of (usually water-soluble) radio-opaque contrast medium is injected via an LP needle in the usual location (occasionally cisternal puncture is used). By tipping the patient on a tilt table, the whole spinal sub-arachnoid space may be visualised using X-Ray.

Review: CSF
150 ml or approx. 8% of CNS cavity volume Formed at a rate of 500ml per day by: selective ultrafiltration of blood active secretion by epithelial membranes

Review: CSF
Formation: Choroid plexus ependymal cells lining the ventricles Absorption arachnoid granulation in dural venous sinuses (esp. superior sagital sinus)

Composition of CSF Compared to Plasma

Normal values for CSF
White cells: 0–4/mm3 Red blood cells: ideally none! Protein: 0.15–0.45g/L (.3-.5% of plasma proteins) Glucose: ~one-half to two-thirds of simultaneous blood glucose. Opening pressure: 8–20cm CSF Colour: Clear

History: Lab Results
CSF = Clear, colourless fluid, apparently free of debris;culture yields no growth = Normal = 60 mg/dL (plasma =80 mg/dL)

WBC Glucose IgG/Alb ratio IgG

= 1.7 = Oligoclonal banding present

Abnormal Values for CSF: Pressure
by space-occupying lesions within the cranial vault, such as oedema, masses, chronic inflammation. by increased central venous pressure, e.g. in the anxious patient with tensed abdominal muscles. if the spinal subarachnoid space is obstructed, thus impeding CSF flow.

Abnormal Values for CSF: Cells
Polymorphs (neutrophils): suggest acute bacterial infection. Lymphocytes & monocytes: viral and chronic infections or tumours. Eosinophils: tumours, parasites, foreign body reactions.

Abnormal Values for CSF: Glucose
Glucose: by non-viral processes causing meningeal inflammation and increase CNS consumption ( eg. tumor of the CNS).

Abnormal Values for CSF: Immunoglobulins

Increased with: inflammation within the theca, e.g. MS, infection, tissue damage.

Abnormal Values for CSF: Colour
Yellow color: (xanthochromia) in the supernatant of centrifuged CSF within 1 hour or less after collection is usually the result of previous bleeding Pinkish color is usually the result of a bloody tap; the color generally clears progressively from tubes 1 to 4 Turbidity: usually indicates the presence of leukocytes (bleeding introduces approximately 1 WBC/500 RBCs into the CSF).

History: Lab Results
CSF = Clear, colourless fluid, apparently free of debris;culture yields no growth = Normal = 60 mg/dL (plasma =80 mg/dL)

WBC Glucose IgG/Alb ratio IgG

= 1.7 = Oligoclonal banding present

More on CSF proteins
levels determined by: selective ultrafiltration by the CSF epithelial barrier secretory ability

Decreased CSF Protein
Decreased dialysis from plasma increased protein loss (eg. removal of excessive volumes of CSF Leakage from the CSF from a tear in dura, otorrhea or rhinorrhea

Increased CSF Protein
Lysis of contaminant blood from traumatic tap Increased permeability of the epithelial membrane (eg. bacterial or fungal infection, cerebral hemorrhage) Increased production by the CNS tissue (e.g subacute sclerosing panencephalitis or multiple sclerosis Obstruction (e.g tumor or abscess) Decrease in the rate of removal

CSF IgG Albumin Index

CSF IgG / Serum IgG = CSF index CSF albumin / serum albumin

Normal = 0.5 increased with local IgG production

History: Lab Results
CSF = Clear, colourless fluid, apparently free of debris;culture yields no growth = Normal = 60 mg/dL (plasma =80 mg/dL)

WBC Glucose IgG/Alb ratio IgG

= 1.7 = Oligoclonal banding present

Basis of CSF IgG Albumin Index
Albumin produced ONLY in the liver therefor presence in CSF is dependent on membrane transport IgG however can be produced locally by plasma cells in the CSF Therefore the CSF index is used to normalize the values for IgG to determine the source Increased CSF IgG without concomitant CSF albumin increase suggest local production Used in diagnosis of demyelinating disorders eg SSPE and MS

Oligoclonal banding
Increased CSF protein levels is an indication for protein electrophoresis Multiple banding in IgG band is termed as oligoclonal banding which is the presence of a small number of clones of IgG from the same cell type with nearly identical electrophoretic properties Associated with CNS inflammatory diseases such as SSPE and MS when banding is absent in serum seperation

Deferential Diagnoses for Oligoclonal Banding
Multiple sclerosis Devic's disease Systemic lupus erythematosus Neurosarcoidosis Subacute sclerosing panencephalitis Subarachnoid haemorrhage

Questions

What is the significance of the normal CSF protein and IgG/Alb ratio? What pathology is consistent with these results?

References

Clinical Chemistry: Principles, Procedures, Correlations By Bishop, Fody & Schoeff Oxford Handbook of Clinical and Laboratory Investigations 2nd edition

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