Characterisation of the cerebrospinal fluid of horses with West Nile virus neuroinvasive disease

Abstract

West Nile virus (WNV) is a zoonotic arbovirus transmitted by mosquitoes between wild birds (natural hosts) and other vertebrates. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Owing to the close contact of cerebrospinal fluid (CSF) with the extracellular fluid of the brain, the analysis of CSF composition can reflect central nervous system (CNS) impairments enabling the diagnosis and understanding of various neurodegenerative CNS disorders. Our objective was to compare the findings from the CSF samples of horses with neuroinvasive WNV infection with those of healthy controls. We compared findings from fifteen CSF samples of 13 horses with acute WNV encephalomyelitis with those of 20 healthy controls. Protein, particular enzymes and ions, glucose and lactate showed abnormal levels in a significant number of WNV cases. None of the six horses with elevated glucose concentrations survived. Rather neutrophilic than mononuclear pleocytosis was identified with WNV infection. Neutrophils probably play a role in the development of inflammatory response and brain damage. Although elevated glucose levels reliably predicted the outcome, they might be the consequence of increased plasma levels and reflect general stress rather than CNS pathophysiology. The CSF findings of WNV encephalomyelitis patients are non-specific and variable but facilitate the differential diagnosis.

Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance

“…In a study of 427 patients in Italy, the case-fatality rate was 22% [ 115 ], while the case-fatality rate was 8.8% in a cluster of 57 cases in a study from Romania [ 137 ]. The overall mortality was 28% in pooled data of 2993 horses from selected studies [ 9 , 22 , 24 , 116 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 134 , 135 , 136 , 138 , 139 , 140 ]. Mortality rates calculated using this same data were similar in horses infected with either L1a or L2 viruses, averaging 29% and 34%, respectively.…”

“…Parkinsonian-like features are also prominently displayed in equine disease. Fasciculations manifest as coarse or fine tremors of the upper limbs, neck, and face and occur in approximately 80% of diagnosed horses [ 9 , 24 , 54 , 116 , 126 , 128 , 129 , 131 , 134 , 135 , 136 , 138 , 139 , 140 ]. Similar to humans, these are postural and not noted when lying down.…”

“…Locomotor deficits are typically multifocal, asymmetric, and may include components of ataxia (approximately 70%) [ 9 , 21 , 24 , 54 , 116 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 134 , 135 , 136 , 138 ] and weakness (45%) [ 21 , 24 , 54 , 116 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 134 , 135 , 136 , 138 ]. These two clinical signs reflect both brain and spinal cord disease causing interruption of the sensory and motor tracts in the hindbrain and the spinal cord.…”

European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe

“…Muscle enzymes can be elevated in horses experiencing trauma or prolonged periods of recumbency. CSF analysis is often nonspecific and variable with elevated nucleated cell count (mononuclear or neutrophilic pleocytosis) and/or protein concentration and mild xanthochromia 123,124 . The antemortem detection of WNV in blood and/or CSF via culture and qPCR is rarely achieved because of the short‐lived and low‐level viremia reported in equids 34,125 …”

“…WNV-L2 is divided in 2 clades, the Central Southern European (CSE) clade and the Romanian/Russian (R/R) clade 87 CSF analysis is often nonspecific and variable with elevated nucleated cell count (mononuclear or neutrophilic pleocytosis) and/or protein concentration and mild xanthochromia. 123,124 The antemortem detection of WNV in blood and/or CSF via culture and qPCR is rarely achieved because of the short-lived and low-level viremia reported in equids. 34,125 Neutralizing antibodies have a critical role in the long-term protection from disease and, presently, their measurement provides the best correlate of flavivirus immunity and can be used for WNV field surveillance and for clinical diagnostics.…”