Expectation of protein elevation, number and proportion of patients with a specific clinical category compared with all reported cases with associated percentage change from using an invariant 0.45 g/L CSF-TP threshold (all comers with ACD) versus a threshold varying with age (‘true’ ACD)
| Clinical category | ACD expected | Traditional ACD—proportion with ACD (0.45 g/L upper limit) | True ACD—proportion with ACD (age-adjusted upper limit) | Change | P value* |
| Y/N | n (%) | n (%) | Δ% | ||
| Polyneuropathy | Y | 204 (7.8) | 127 (21.3) | 13.50 | <0.0001 |
| Tumour | Y | 139 (5.3) | 47 (7.9) | 2.60 | 0.019 |
| Encephalitis (infectious, paraneoplastic or autoimmune) | Y | 45 (1.7) | 24 (4) | 2.30 | 0.0014 |
| Seizure | Y | 191 (7.3) | 53 (8.9) | 1.60 | 0.20 |
| Central shunt | Y | 34 (1.3) | 15 (2.5) | 1.20 | 0.039 |
| CNS structural anomaly | Y | 7 (0.3) | 4 (0.7) | 0.40 | 0.13 |
| Myelopathy | Y | 47 (1.8) | 13 (2.2) | 0.40 | 0.50 |
| Hydrocephalus | Y | 34 (1.3) | 10 (1.7) | 0.40 | 0.44 |
| Trauma (eg, postneurosurgery, diffuse axonal injury, etc) | Y | 8 (0.3) | 4 (0.7) | 0.40 | 0.25 |
| Diffuse anoxic–ischaemic injury | Y | 17 (0.6) | 6 (1) | 0.40 | 0.41 |
| Infection (no CNS involvement, eg, meningitis) | Y | 67 (2.6) | 17 (2.8) | 0.20 | 0.67 |
| CNS vasculitis | Y | 19 (0.7) | 6 (1) | 0.30 | 0.44 |
| Neuroinflammation | Y | 28 (1.1) | 8 (1.3) | 0.20 | 0.52 |
| Cerebral venous occlusion | Y | 11 (0.4) | 4 (0.7) | 0.30 | 0.50 |
| Meningeal disease/process (eg, carcinomatosis, IgG4 disease, etc) | Y | 16 (0.6) | 5 (0.8) | 0.20 | 0.57 |
| CSF leak | Y | 3 (0.1) | 2 (0.3) | 0.20 | 0.23 |
| Unresolved encephalopathy | Y | 79 (3) | 19 (3.2) | 0.20 | 0.79 |
| Haemorrhage within 3 months (eg, subarachnoid, intraparenchymal, etc) | Y | 19 (0.7) | 5 (0.8) | 0.10 | 0.79 |
| Mononeuropathy multiplex (inflammatory) | Y | 7 (0.3) | 2 (0.3) | 0 | 0.68 |
| Neurotoxicity (toxin causing CNS damage, eg, heroin inhalation) | Y | 5 (0.2) | 1 (0.2) | 0 | 1 |
| Aseptic meningitis | Y | 1 (0) | 0 (0) | 0 | 1 |
| Idiopathic intracranial hypertension | Y | 24 (0.9) | 5 (0.8) | −0.10 | 1 |
| Hypertensive encephalopathy including posterior reversible encephalopathy syndrome | Y | 16 (0.6) | 3 (0.5) | −0.10 | 1 |
| Systemic inflammatory process | Y | 3 (0.1) | 0 (0) | −0.10 | 1 |
| Spinal disease | Y | 12 (0.5) | 2 (0.3) | −0.20 | 1 |
| Unresolved neurological symptoms | Y | 4 (0.2) | 0 (0) | −0.20 | 1 |
| Prior intrathecal chemotherapy | Y | 23 (0.9) | 4 (0.7) | −0.20 | 0.80 |
| Neurodegenerative | Y | 24 (0.9) | 4 (0.7) | −0.20 | 0.81 |
| Optic nerve disease | Y | 35 (1.3) | 4 (0.7) | −0.60 | 0.22 |
| All-cause major stroke | Y | 112 (4.3) | 19 (3.2) | −1.10 | 0.25 |
| Inflammatory white matter disease | Y | 240 (9.1) | 33 (5.5) | −3.60 | 0.0033 |
| Plexopathy | N | 7 (0.3) | 4 (0.7) | 0.40 | 0.13 |
| Genetic neurological illness | N | 3 (0.1) | 2 (0.3) | 0.20 | 0.23 |
| First dose prophylactic intrathecal chemotherapy | N | 2 (0.1) | 1 (0.2) | 0.10 | 0.46 |
| Motor neuron disease | N | 7 (0.3) | 2 (0.3) | 0 | 0.68 |
| Cerebrovascular disease (vasculopathy) | N | 9 (0.3) | 2 (0.3) | 0 | 1 |
| Pain benign syndromes | N | 5 (0.2) | 1 (0.2) | 0 | 1 |
| Neuropathy (focal) | N | 1 (0) | 0 (0) | 0 | 1 |
| Myopathy | N | 6 (0.2) | 1 (0.2) | 0 | 1 |
| Psychiatric/psychogenic symptoms | N | 17 (0.6) | 3 (0.5) | −0.10 | 1 |
| Ocular disease | N | 5 (0.2) | 0 (0) | −0.20 | 1 |
| Cranial neuropathy | N | 12 (0.5) | 2 (0.3) | −0.20 | 1 |
| Transient ischaemic attack | N | 9 (0.3) | 0 (0) | −0.30 | 0.38 |
| Transient neurological symptoms | N | 72 (2.7) | 9 (1.5) | −1.20 | 0.11 |
| Diagnostic testing | N | 94 (3.6) | 5 (0.8) | −2.80 | 0.0001 |
| Transient encephalopathy | N | 262 (10) | 37 (6.2) | −3.80 | 0.0037 |
| Benign headache | N | 642 (24.4) | 82 (13.7) | −10.70 | <0.0001 |
| Totals | 2627 (100) | 597 (100) |
Samples were considered to have ‘ACD expected’ after evaluating the available literature or consensus between authors where expectation of ACD was unclear from the literature review.
All-cause major stroke: includes thromboembolic disease, vasculitis of the CNS causing stroke and reversible cerebrovascular constriction syndrome.
Inflammatory white matter disease: includes multiple sclerosis, neuromyelitis optica, acute demyelinating encephalomyelitis.
Results in bold showed a significant proportionate change when age-adjusted thresholds were applied
*P values compare the change in proportion for the specific diagnostic category versus all other categories when assessing pseudo versus ‘true’ ACD.
ACD, albuminocytological dissociation; CNS, central nervous system; CSF, cerebrospinal fluid; TP, total protein.