Louping ill is primarily a veterinarian infection caused by the Louping Ill virus, belonging to the group of flaviviruses. Its natural reservoirs are sheep, goats, pigs and several other animals, but in rare cases, the human infection may occur. Nonspecific symptoms and rare reports of fatal encephalitis are documented, but decades have passed since the last confirmed case. Advanced molecular testing is necessary to establish the diagnosis.
No case of Louping Ill has been reported in the last 20 years, and only 31 individuals with a confirmed infection have been documented until the 1990's, but many cases are assumed to be undiagnosed due to lack of clinical suspicion and, until recently, the absence of rapid diagnostic methods that could identify the virus   . Louping Ill virus (LIV), classified into flaviviruses and considered as a similar pathogen to tick-borne encephalitis viruses (TIBV), is the causative agent of Louping Ill, and is transmitted by ixodes ricinus, known as the sheep tick  . LIV primarily causes a potentially fatal infection in livestock (sheep, cattle, pigs, goats) but also other animals (certain canine, horse, deer and red grouse species) residing in the United Kingdom (mainly Scotland and Ireland)  , but its detection in Spain, Norway, Turkey and other European countries has been documented  . Similarly to animal inoculation, humans contract the virus through a tick bite, but the occupational exposure seems to be the single most important risk factor. Sheepherders, slaughterhouse workers, veterinarians, butchers and laboratory personnel working with animal samples are at an increased risk for contracting LIV    . Human infection can present in numerous ways, and four clinical syndromes are mentioned in the literature - an influenza-like illness comprised of nonspecific constitutional symptoms and fever, hemorrhagic fever, and a central nervous system (CNS) infection, either as encephalitis, characterized by confusion, stupor, ataxia, paralysis, or even coma, or a poliomyelitis-like illness   .
Having in mind the nonspecific clinical presentation and a broad differential diagnosis, Louping Ill may be difficult to diagnose or even consider as the etiology of the symptoms. Through a properly obtained patient history, however, this rare but potentially life-threatening infection might be included as a possible cause. Details about occupancy and recent tick bites. as well as contact with livestock or other animals that were ill in patients who either visited or are residing in Scotland, Ireland, other areas in the United Kingdom, but also Spain and Norway can be of vital importance . Despite the vital role of physical examination for every patient, findings may be nonspecific and point to an infection of the central nervous system, in which case imaging studies of the brain - either computed tomography (CT) or magnetic resonance imaging (MRI), and subsequent lumbar puncture should be performed  . Detection of anti-LIV immunoglobulin (Ig) M antibodies in serum (or a four-fold increase in IgG) through serology is an efficient method to detect a possible immune response against the virus, and the same procedure should be carried out in animals with whom the patient was in contact . Recent advances in molecular techniques and the introduction of polymerase chain reaction (PCR) has greatly aided in prompt, but also more specific detection of microorganisms in humans  . More specifically, the reverse-transcriptase PCR (RT-PCR) can amplify the viral genetic material and confirm the diagnosis  , but its very high cost makes it scarcely available. Histopathological examinations of animal tissue are used as a definite method for confirming the reservoir of infection .