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Objectives: To investigate dogs with acute onset of intracranial signs suspected of stroke by primary veterinary clinicians, and establish possible differential diagnoses and long‐term outcome. In addition, serum C‐reactive protein and plasma cytokines were investigated as potential biomarkers of disease. Materials and Methods: All cases were evaluated by neurologic examination, routine haematology and biochemistry and measurement of serum C‐reactive protein, plasma cytokine concentrations (interleukin‐2, ‐6, ‐8, ‐10, tumour necrosis factor) and low‐field MRI. Results: Primary veterinarians contacted the investigators with 85 suspected stroke cases. Only 20 met the inclusion criteria. Of these, two were diagnosed with ischaemic stroke. Other causes were idiopathic vestibular syndrome (n=6), brain tumour (n=5) and inflammatory brain disease (n=2); in five cases a precise diagnosis could not be determined. Median survival times were: brain tumour, 3 days, idiopathic vestibular syndrome, 315 days, ischaemic stroke, 365 days and inflammatory central nervous system (CNS) disease, 468 days. The median plasma concentrations of interleukin‐2, ‐6, ‐8, ‐10 or tumour necrosis factor were not significantly increased in any of the diagnosis groups compared to healthy controls. Serum C‐reactive protein was higher in dogs with brain tumours and inflammatory brain disease but not above the upper bound of the reference interval. Clinical Significance: Dogs that present with acute onset intracranial disease may have ischaemic stroke but are more likely to have other causes. Many dogs with such acute onset of neurological dysfunction (brain tumours excluded) may recover within a couple of weeks despite their initial severe clinical appearance. [ABSTRACT FROM AUTHOR]