Causes of albuminocytological dissociation and the impact of age-adjusted cerebrospinal fluid protein reference intervals: a retrospective chart review of 2627 samples collected at tertiary care centre

Abstract

ObjectiveWe set out to test the discriminative power of an age-adjusted upper reference limit for cerebrospinal fluid total protein (CSF-TP) in identifying clinically relevant causes of albuminocytological dissociation (ACD).MethodsWe reviewed the charts of 2627 patients who underwent a lumbar puncture at a tertiary care centre over a 20-year period. Samples with CSF-TP above 45 mg/dL (0.45 g/L) were included. Samples with white cell count >5×109/L, red cell count >50×109/L and glucose <2.5 mmol/L (45 mg/dL) were excluded as were samples with incomplete data and those taken from paediatric patients (ie, age <18 years old). Patients with CSF-TP elevated above 45 mg/dL were considered to have ‘pseudo’ ACD unless their CSF-TP was in excess of age-adjusted norms in which case they were considered to have ‘true’ ACD. Adjustment for sex was not applied to the age-adjusted norms although the importance of gender has been previously described.ResultsThe presence of ACD was associated with a broad range of neurological diagnoses. Among all 2627 patients with ACD, a clinical diagnosis explaining CSF-TP elevation was identified in 57% of cases. ‘True’ ACD was associated with a suitable diagnosis in 75% of cases, whereas patients with ‘pseudo’ ACD showed an appropriate diagnosis in only 51% of cases. Use of an age-adjusted upper reference limit favoured the detection of polyneuropathy patients (13.5% proportionate increase) and excluded a larger number of patients with isolated headache (10.7% proportionate decrease; p<0.0001).ConclusionsElevated CSF-TP is a common finding, with a range of underlying causes. Use of an age-adjusted upper reference limit for the CSF-TP value improves diagnostic specificity and helps to avoid overdiagnosis of ACD.

Cerebrospinal fluid in COVID-19: A systematic review of the literature

“…These include, but are not limited to, male sex, body mass index, diabetes mellitus, hypothyroidism, hypoparathyroidism, Cushing’s disease, uremia, medications (such as phenytoin and phenothiazines) [ 287 , 288 ]. Elevated CSF protein has been observed in a wide range of neuropsychiatric disorders and we did not document past medical/neuropsychiatric history for patients included in this review [ 288 , 289 ]. Further, though perspectives on the relationship between CSF protein and age vary, it has been suggested that CSF protein may increase with age throughout adulthood and we did not take age into consideration when we reviewed CSF protein [ [287] , [288] , [289] , [290] ].…”

Cerebrospinal fluid analysis in dogs: Main patterns and prevalence of albuminocytological dissociation

“…The exact pathophysiology of ACD is unknown, but different mechanisms have been proposed, including the intrathecal production of specific proteins (IgG and myelin basic protein), dysfunction of the bloodbrain barrier, dysfunction of the blood-nerve barrier, decreased CSF flow and sequestration of CSF in spinal cord compression. [5][6][7] In veterinary medicine, several diseases, such as idiopathic polyradiculoneuritis, extradural compressive lesions, intramedullary lesions (neoplasia and inflammatory or infectious diseases), idiopathic epilepsy, degenerative myelopathy, fibrocartilaginous embolism, trauma, vasculitis, trigeminal, facial and vestibular neuropathies have been reported to cause ACD, yet the majority of them anecdotally. 3,[8][9][10][11][12] In human medicine, several conditions have been traditionally associated with ACD including infectious and non-infectious meningoencephalitis, intra and extra-axial tumours, inflammatory polyneuropathy, hydrocephalus, angiitis of the CNS, cerebral venous sinus occlusion, optic nerve disease, facial neuritis, posterior reversible encephalopathy syndrome, structural spinal disorders, nervous system toxic exposure, dementia, epileptic seizures, strokes, intrathecal chemotherapy and subarachnoid hemorrhage.…”

“…3,[8][9][10][11][12] In human medicine, several conditions have been traditionally associated with ACD including infectious and non-infectious meningoencephalitis, intra and extra-axial tumours, inflammatory polyneuropathy, hydrocephalus, angiitis of the CNS, cerebral venous sinus occlusion, optic nerve disease, facial neuritis, posterior reversible encephalopathy syndrome, structural spinal disorders, nervous system toxic exposure, dementia, epileptic seizures, strokes, intrathecal chemotherapy and subarachnoid hemorrhage. 6,13,14 In human medicine, the reported ACD prevalence is 31.4-31.8%, both analysed in large cohorts of patients with CSF collected in the LSS and using the traditional 45 mg/dL reference limit for TP concentration. 6,15 In veterinary medicine, there are no studies analysing the different causes and prevalence of ACD, and therefore it is unknown which diseases can disrupt the blood brain barrier enough to cause a leakage of proteins without affecting the cell count.…”

“…6,13,14 In human medicine, the reported ACD prevalence is 31.4-31.8%, both analysed in large cohorts of patients with CSF collected in the LSS and using the traditional 45 mg/dL reference limit for TP concentration. 6,15 In veterinary medicine, there are no studies analysing the different causes and prevalence of ACD, and therefore it is unknown which diseases can disrupt the blood brain barrier enough to cause a leakage of proteins without affecting the cell count. Understanding the prevalence or the conditions associated with ACD in dogs could improve the diagnostic performance of the CSF analysis as well as our understanding of some canine neurological conditions.…”

Dorsal cauda equina nerve root enhancement on magnetic resonance imaging due to ANNA-1-associated paraneoplastic polyneuropathy

“…Also, her findings of CSF albuminocytological dissociation were initially felt to corroborate a diagnosis of GBS, though this finding is relatively non-specific and can be seen with various inflammatory aetiologies. 8 Our patient’s experience was therefore instructive in showing that paraneoplastic polyneuropathy may overlap clinically with GBS, with regard to both symptomatology and lab findings. A similar initial misdiagnosis of GBS in a patient with ANNA-1-associated sensorimotor neuropathy has been previously reported, though this patient also had brain MRI findings of limbic encephalitis that suggested a paraneoplastic aetiology.…”