Infectious diseases of the nervous system are relatively uncommon compared to other neurological abnormalities in adult animals. However, infectious diseases should be placed high on the differential diagnosis list in puppies and kittens.
Infectious diseases of the nervous system are relatively uncommon compared to other neurological abnormalities in adult animals. However, infectious diseases should be placed high on the differential diagnosis list in puppies and kittens. Poor suckling leading to malnutrition and incomplete transfer of maternal antibodies, difficult parturition, environmental stresses and concurrent disease processes such as Parvo virus can weaken the immune system increasing the chance of bacterial meningoencephalitis. Puppies with bacterial meningoencephalitis may have a fever or leukocytosis. CSF results with bacterial meningoencephalitis are neutrophilic. However, severe neutrophilic pleocytosis can also be seen with non infectious inflammatory diseases such as steroid responsive meningitis arteritis. Culturing the CSF and or urine may help identify a bacterial cause. Visualization of bacteria in the CSF allows for a more definitive diagnosis of bacterial meningoencephalitis. Staphylococcus, E. Coli and Streptococcus and various anaerobes are typically present in bacterial meningoencephalitis.1 CNS penetration is typically a consideration when choosing an antibiotic. Initially the blood brain barrier is compromised allowing better penetration into the CNS. Once the blood barrier is intact antibiotic penetration may be more difficult. Thus, a longer course of antibiotic therapy, higher dosages or choosing an antibiotic that more reliably penetrates the CNS may be required. Chloramphenicol reaches high CNS concentrations, however is not typically used due to the potential adverse effects. Doxycycline also penetrates the CNS, however its bacteriostatic nature and concerns for its use in young animals should be considered. Trimethoprim/sulfa also reaches relatively high CNS concentrations, but concerns regarding potential adverse effects have limited its use. Amoxacillin/clavulanic acid is broad spectrum, but reaches low CSF concentrations when the blood brain barrier is intact. Fluoroquinilones are good choices for Staphylococcus and E. Coli, however have variable affects on Streptococcus and also reach low CSF concentrations.2
Canine distemper virus (CDV), a single stranded RNA morbillivirus, is typically spread through an aerosol route. CDV is epitheliotropic. The respiratory system is initially infected, but spreads to the CNS, integument, bladder and intestinal tract. CDV crosses the blood brain barrier via infected mononuclear cells. Multifocal lesions are common. Primary demyelination often occurs in the white matter, although gray matter can also be affected. Commonly affected areas of the brain include the cerebellum, periventricular white matter, optic pathways and spinal cord.3,4
Clinical signs are typically seen in dogs less than 3 year of age. Persistent viral infection can lead to a chronic form, "old dog distemper." Outbreaks may be seen in animal shelters. Vaccination has reduced the incidence of infection, however 30% of cases occur in vaccinated dogs.5 Clinical signs are typically focal, despite multifocal lesions. Seizures and myoclonus are the most common neurological signs. Cerebellar and myelopathic signs may also be seen.3 Myoclonus may be due to hyperexcitability of the lower motor neuron. It may persist during sleep, but disappears with anesthesia.6
The diagnosis of CDV is often based on clinical signs. The combination of neurological abnormalities, particularly myoclonus, with extraneural signs should lead to a high suspicion of CDV. Extra neural signs include pneumonia, enteritis, conjunctivitis, rhinitis, discolored teeth and hyperkeratosis of the nasal planum and foot pads.3,5 Pulmonary infiltrates are commonly identified by thoracic radiographs. CSF commonly identifies a mononuclear pleocytosis, but can be normal. Serology is typically not helpful due to vaccine induced antibodies. Immunosupression can also decrease the antibody titer. PCR testing can be helpful. PCR testing may be done on CSF, blood or urine.3 In one study 20 of 22 dogs tested positive when PCR testing was done on the urine. Twelve asymptomatic dogs tested negative. Vaccine virus can be identified for a couple of days after vaccination.7
The prognosis for distemper infections is variable. Severely affected dogs will likely die, while mildly affected dogs may recover. Supportive care is the mainstay of therapy. Anticonvulsants should be used to treat seizures, antibiotics for pneumonia and intravenous fluids to maintain hydration. Concurrent toxoplasma infection may occur and if present should be treated.3
Neospora caninum, a protozoal parasite, is a primary CNS and neuromuscular infection in dogs. Pneumonia, encephalitis, myocarditis, hepatitis and myonecrosis are the predominant lesions in neonates. Ninety-two percent of affected dogs are less than 3 year of age. Transplacental transmission is the major route of infection. An ascending paralysis is typically the presenting sign with progression to the cervical, brainstem and cerebellar regions. Polyradiculoneuritis and polymyositis may result in hyperextension of the pelvic limbs. CSF abnormalities typically include a mononuclear pleocytosis. The diagnosis can be supported via serum immunofluorescence antibody (IFA) titers. Affected dogs have IFA titer > 3:300. However clinically normal dogs can have titers as high 3:800. Tachyzoites may be identified in cells from CSF, bronchial lavage and dermal lesions.3,8 Clindamycin therapy is recommended. Trimethoprin sulfadiazine may also be used. The prognosis is considered poor.3,8
Toxoplasma gondii is a protozoal parasite that is transmitted via ingestion of sporulated oocysts transplacentally or in undercooked meats.9 Cats are the definitive host. Transplacental infection in kittens causes the most severe signs. Kittens may be stillborn, or die within weeks. Pulmonary, CNS, hepatic, pancreatic, cardiac and ocular lesions are common in clinically infected cats. Brain lesions are very common, although neurological signs may absent in many affected cats. 3,10 Muscle involvement is uncommon in cats.11 Toxoplasmic encephalitis occurs in up to 30 % of people with acquired immune deficiency syndrome.9 Most clinical cases result from reactivated infections in cats older than 3 months of age. Positive serology may support the diagnosis. However 30% of cats and dogs have T gondii antibodies.12 Positive IgM antibodies indicate recent infection and last for up to 12 weeks after inoculation. IgM antibodies typically are not seen in healthy cats and correlate more closely with disease. IgG antibodies support more chronic infection.9 CSF in CNS toxoplasmosis typically exhibits a mixed pleocytosis with increased protein.12 PCR testing is available and can be done directly on CSF. Clindamycin is the treatment of choice.12
Feline infectious perotinitis (FIP) is a common and fatal infectious feline disease caused by a mutant form of feline enteric corona virus (FECV).13 A pyogranulomatous meningoencephalitis and meningomyelitis is seen with CNS involvement. Median age of cats with FIP affecting the CNS is 1 year of age.14 Cats with neurologic FIP may have weight loss, mentation changes, ataxia and hyperesthesia. Ocular abnormalities are not uncommon. Anterior uveitis, hyphema and retinal hemorrhage may be identified on ophthalmologic examination.13 Serum globulins, are often elevated in FIP.15 Seronegative FIP may be seen in cats with low titers, acute fulminant disease less than 10 days and from immune complex consumption.16 MRI may identify periventricular changes consistent with ependymitis. The 3rd and 4th ventricles are commonly affected. Secondary hydrocephalus may also be identified. CSF analysis indicates an elevated protein value (mean 97.3 g/dl)13 and a neutrophilic pleocytosis (mean 28 cells/ul).14 CSF antibodies are likely of serum origin, however conflicting studies make the definitive antibody origin unkown.13,14 A ratio of CSF Ab: serum Ab compared to CSF protein: serum total protein > 1 has typically suggested intrathecal antibody production.13,14 However, a value > 1 may not necessarily imply active CNS infection.14 Prednisone therapy is typically given to cats with neurologic FIP to decrease CNS inflammation and for immunosuppression. While prednisone therapy +/- other immunosuppressive medications may slow the progression of disease the prognosis is ultimately poor.
Common surgeries such as ovariohysterectomy or castration, deciduous teeth and a possible increased susceptibility to tetanus toxin increase the risk of puppies and kitten to tetanus. Tetanus results from the neurotoxin tetanospasmin derived from gram positive, anaerobic, bacteria Clostridium tetani. Tetanospasmin enters a wound, reaches the motor endplate, migrates retrograde within the motor axon to the neuronal cell body within the spinal cord and may spread to the brain. Tetanus toxin inhibits release of glycine and GABA of inhibitory interneurons of the brain and spinal cord. A presynaptic blockade occurs.17 Cats are less susceptible than dogs and are more likely to have a focal tetanus than dogs.
Diagnosis of tetanus is based on clinical signs. In the initial stages clear signs of tetanus may not be apparent. Ocular changes initially may be subtle. Lethargy, anorexia and vomiting are also common initial signs. As the disease progresses protrusion of the third eyelid and enophthalmos may be seen. The ears may become erect and the lips drawn back, known as Risus sardonicus. Contraction of the masticatory muscles may lead to trismus. Dysphagia may result. A generalized stiff gait is apparent with generalized tetanus and may progress to the extreme rigidity of a sawhorse type posture.17 Autonomic disturbance are also possible and worsen the prognosis.18 Seizures may also arise. Hiatal hernias and aspiration pneumonia are possible, thus thoracic radiographs are recommended. Abdominal ultrasound may be helpful in identifying stump pyometra if recent ovariohysterectomy has been performed.
Initial therapy consists of identification and treatment of any wounds, including removal of any foxtails/Grass awns and any infected deciduous teeth. Tetanus equine antitoxin 100-1000 U/kg IV up to a total dose of 20,000 U17 should be given once the diagnosis of tetanus is clear. Intradermal skin testing (0.1-0.2 ml antitoxin) is done prior to IV antitoxin administration. However, skin testing may not be reliable18 and thus pretreatment with diphenhydramine should be considered and close monitoring during administration and immediately following is required. Glucocorticoids or epinephrine are recommended if adverse a reaction occurs.17 Metronidazole is considered the treatment of choice to eradicate C. tetani organisms in dogs with tetanus, although penicillin G may also be used.18 Efforts to keep the animals calm and relaxed should be made. Keeping them in a dimly lit, quite room without noise helps prevent episodes of tetanic spasm. Sedatives such as ace promazine may be required. Diazepam and midazolam can provide sedation, muscle relaxation and treatment of potential seizures. Methocarbamol may be used for muscle relaxation, but is not thought to be very effective.18 Baclofen may be helpful in providing muscle relaxation. Tremors may arise with baclofen usage, particularly at higher dosages. Phenobarbital therapy is often used to prevent seizures and for its sedative properties. Supportive therapy is essential as signs progress. IV fluids are needed to maintain hydration. Parental nutrition or feeding tubes may become necessary. Patients should be kept on soft bedding and turned every 4-6 hours to prevent bed sores and should be kept clean and dry. Monitoring respiration, heart rate, temperature, urination and for seizures are important. The prognosis for tetanus can be good with intensive monitoring and therapy.
Irwin PJ, Parry BW. Streptococcal meningoenchaphalitis in a dog. J Am Anim Hosp Assoc 1999;35:417-22.
Plumb DC. Veterinary Drug Handbook. 3rd edition. Iowa State University Press, Ames, 1999.
Lavely JA. Pediatric Neurology of the dog and cat. Vet Clin Small Anim Pract 2006;36:475-501.
Vandevelde M, Zurbriggen A. Demyelination in canine distemper virus infection: a review. Acta Neuropathol (Berl) 2005;109:56–68.
Koutinas AF, Polizopoulou ZS, BaumgaertnerW, et al. Relation of clinical signs to pathological changes in 19 cases of canine distemper encephalomyelitis. J Comp Pathol 2002;126: 47–56.
Inada S. Electromyographic analysis of canine distemper myoclonus. Electromyogr Clin Neurophysiol 1989;29:323–31.
Saito TB, Alfieri AA, Wosiacki SR, et al. Detection of canine distemper virus by reverse transcriptase-polymerase chain reaction in the urine of dogs with clinical signs of distemper encephalitis. Res Vet Sci 2006;80:116–9.
Ruehlman D, Podell M, Oglesbee M, et al. Canine neosporosis: a case report and literature review. J Am Anim Hosp Assoc 1995;31:174–83.
Vollaire MR, Radecki SV, Lappin MR. Seroprevalence of toxoplasma gondii antibodies in clinically ill cats in the United States. Am J Vet Res 2005;66(5):874–7.
Dubey JP, Carpenter JL. Histologically confirmed clinical toxoplasmosis in cats: 100 cases. J Am Vet Med Assoc 1993;203(1):1556–66.
Dickinson PJ, LeCouteur RA. Feline neuromuscular disorders. Vet Clin North Am Small Anim Pract 2004;34:1307–59.
Dubey JP, Lappin MR. Toxoplasmosis and neosporosis. In: Greene CE, editor. Infectious diseases of the dog and cat. 2nd edition. Philadelphia: WB Saunders; 1998. p. 493–509.
13. Foley JE, Lapointe JM, Koblik P, et al. Diagnostic features of clinical neurologic feline infectious peritonitis. J Vet Intern Med 1998;12:415-423.
Boettcher IC, Steinberg T, Matiasek K, et al. Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats. J Am Vet Med Assoc 2007;230(2):199-205.
Hartmann K, Binder C, Hirschberger J, et al. Comparison of different tests to diagnose feline infectious peritonitis. J vet Intern Med 2003;17:781-790
Foley JE. Feline infectious peritonitis and feline enteric coronavirus. In: Ettinger, Feldman, editors. Textbook of Veterinary Internal Medicine. 6th edition. St. Louis: Elsevier; 2005. p 663-666.
Greene CE. Tetanus. In: Greene CE, editor. Infectious diseases of the dog and cat. 3rd edition. St. Louis: Elsevier; 2006. p. 395- 402.
Burkitt JM, Sturges BK, Jandrey KE et al. Risk factors associated with outcome in dogs with tetanus:38 cases (1987-2005). J Am Vet Med Assoc 2007;230(1):76-83.