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Encephalitis
Encephalitis
369
RABBITS
RABBITS
Encephalitis BASIC INFORMATION DEFINITION Encephalitis is inflammation of the brain. Meningitis is inflammation of the membranes that cover the brain and spinal cord (meninges). Meningoencephalitis is concurrent inflammation of both the brain and the meninges.
SYNONYM Encephalomeningitis
EPIDEMIOLOGY GENETICS AND BREED PREDISPOSITION • Lop-eared rabbits appear to be at increased risk for otitis externa, which may lead to meningitis in severe cases. • Dwarf rabbits may have increased risk of exhibiting clinical signs due to Encephalitozoon cuniculi infection. RISK FACTORS • Otitis externa/media (see Otitis) • Dental disease • Positive E. cuniculi titer • Exposure to toxins • Exposure to raccoon feces • Pasteurellosis (see Pasteurellosis)
CONTAGION AND ZOONOSIS • E. cuniculi is a potential zoonosis, with immune suppressed individuals at particular risk. • Pasteurella multocida contracted from a pet rabbit has resulted in fatal infection in one human. GEOGRAPHY AND SEASONALITY • Rabies is not present in the United Kingdom or Australia. • Baylisascaris procyonis is found in North America. ASSOCIATED CONDITIONS AND DISORDERS • Otitis externa may be associated with increased risk of meningitis. • E. cuniculi infection is positively associated with increased risk of seizure disorders and chronic renal disease (see Renal Disease).
CLINICAL PRESENTATION DISEASE FORMS/SUBTYPES • Meningitis may be further classified into: Pachymeningitis (inflammation of the outer meningeal membrane) Leptomeningitis (inflammation of the inner meningeal membrane)
HISTORY, CHIEF COMPLAINT • Often an acute onset of clinical signs such as head tilt/rolling/urine scalding/falling/seizures • Possible prior history of upper respiratory, dental, or aural disease • Access to outdoors may be consistent with exposure to toxins (e.g., lead) and/or parasitic encephalitis (e.g., B. procyonis, toxoplasmosis, encephalitozoonosis). PHYSICAL EXAM FINDINGS • Neurologic signs will be the prominent findings: Head tilt Rolling Ataxia Nystagmus Opisthotonus Torticollis Reduced mentation • It is important to not ignore the nonneurologic signs (e.g., presence of urine scalding, otitis externa/media, dental disease, evidence of unexplained skin trauma/scuffing of nails).
370 Encephalitis ETIOLOGY AND PATHOPHYSIOLOGY • Bacterial Common Related to dental, upper respiratory, or ear disease (pasteurellosis commonly implicated) Listeriosis (Listeria monocytogenes) is a potential cause of meningoencephalitis in weanling rabbits. • Protozoal Exposure to E. cuniculi is common, but the incidence of disease caused by this organism is unknown. Toxoplasmosis is seen sporadically. • Viral Rare Rabies after a nonfatal bite is a potential differential diagnosis in endemic areas. Herpes viral encephalitis after exposure to human herpes simplex virus has been reported. • Parasitic B. procyonis (raccoon roundworm) infestation is a possible cause in endemic areas, but occurrence is sporadic. A similar species, B. columnaris, is found in skunks but most reported cases of baylisascariasis are due to B. procyonis. • Fungal Not reported in rabbits currently, but in endemic areas should be considered • Inflammatory Heatstroke or granulomatous inflammation without evidence of causative organisms is a common postmortem finding. This has been suggested to be caused by E. cuniculi. • Neoplastic Potential differential diagnoses are pituitary adenomas and teratomas. • Traumatic • Toxic Exposure to lead or organophosphate pesticides
• Urinalysis, including trichrome stain to look for E. cuniculi spores • Skull radiography • Neurologic examination • Fecal examination
ADVANCED OR CONFIRMATORY TESTING • Aural examination under general anesthesia (using endoscope preferably) and cytologic and bacteriologic sampling from middle ear • E. cuniculi serology • Toxoplasma serology • Rabies titer • Serum lead evaluation • Cerebrospinal fluid analysis • Magnetic resonance imaging • Computed tomography • Necropsy, including histopathologic examination of the brain in cases where rabbit colonies are involved, or if rabies is suspected
TREATMENT THERAPEUTIC GOALS • To achieve sufficient neurologic function to allow good quality of life • To control seizure activity • To provide pain control as required
ACUTE GENERAL TREATMENT
DIAGNOSIS
• Provide safe, padded environment. • Establish IV access and provide fluid and nutritional support as indicated. • Control seizures with benzodiazepines (e.g., diazepam 1-5 mg/kg IV; midazolam 0.2-2 mg/kg IV IM). • Cautious use of corticosteroids may be justified in severe cases (e.g., dexamethasone 1-2 mg/kg IM, IV once; prednisolone 0.05-2 mg/kg SC, IM once). • Use of prochlorperazine (0.25-0.5 mg/ kg q 8-12 h PO) may enhance stability. • Broad-spectrum antibiotics with good central nervous system penetration (e.g., chloramphenicol 20-50 mg/kg q 8-12 h IM, IV, SC, PO; ceftazidime 50 mg/kg q 8 h IM, IV)
DIFFERENTIAL DIAGNOSIS
CHRONIC TREATMENT
• Seizures: epilepsy, uremia, hepatic encephalopathy, toxins, neoplasia, infection • Urine scalding: urinary sludging, urolithiasis, cystitis, polyuria, spinal disease • Head tilt/rolling: middle/inner ear disease • Nystagmus: peripheral or central vestibular disease (see Vestibular Disease) • Reduced mentation: sedation, uremia
• Benzimidazoles (e.g., fenbendazole 20 mg/kg q 24 h PO × 28 d for encephalitozoonosis; consider oxytetracycline 50 mg/kg q 12 h PO or enrofloxacin 5-10 mg/kg PO, SC, IM IV q 12 h in addition) • B. procyonis infection: ivermectin 0.20.4 mg/kg q 7-10 d PO, SC; or oxibendazole 60 mg/kg q 24 h PO indefinitely • Long-term antibiotics in response to culture and sensitivity results • Long-term nonsteroidal antiinflammatory (NSAIDs) medication may prove
INITIAL DATABASE • Complete blood count and blood biochemistry
beneficial (e.g., meloxicam 0.3-0.5 mg/ kg q 12-24 h PO, SC). • Supportive feeding as required • Monitor for potential ongoing problems such as perineal cecotrophal soiling, urine scalding and associated dermal and urinary problems. • Barbiturates to control chronic seizures (e.g., phenobarbital 2.5-5 mg/kg q 12 h PO; adjust accordingly) • Lead toxicity: chelation therapy via NaCa-EDTA 27.5 mg/kg SC q 12 h × 5 d, repeated after 5 days. Repeat blood lead level 5 days after last treatment. Alternatively D-penicillamine 30 mg/kg q 12 h PO.
DRUG INTERACTIONS NSAIDs and corticosteroids may interact, causing gastrointestinal ulceration.
POSSIBLE COMPLICATIONS • Deterioration despite treatment • Traumatic skeletal or ocular damage due to seizures or rolling • Urine scalding • Perineal cecotrophal soiling • Gut stasis • Status epilepticus
RECOMMENDED MONITORING • Repeated neurologic examinations at intervals determined by rapidity of resolution of clinical signs • Regular weighing and clinical examinations to ensure that the rabbit is adequately able to feed and clean itself • Regular dental examinations • Blood phenobarbital levels in rabbits receiving this drug
PROGNOSIS AND OUTCOME • Dependent on causative agent/process and severity/duration of clinical signs at presentation • Owners should be made aware of potentially prolonged recovery period and high risk of recurrence • Part of the recovery process is learning to cope with clinical signs (rabbits and owners); failure of rabbit to cope may be triggered by other (unrelated) disease.
CONTROVERSY • E. cuniculi: it is not yet known how many rabbits that are seropositive for encephalitozoonosis actually develop disease directly due to this organism • Lufenuron is an oral chitin synthesis inhibitor. Although lufenuron probably does not kill E. cuniculi, it may hinder growth of microsporidia.
PEARLS & CONSIDERATIONS COMMENTS Many rabbits with seemingly insurmountable neurologic dysfunction are able to cope well within the home environment. It is better to assess this on “home ground” by looking at video footage or making a home visit, rather than on the basis of appearance in the examination room.
PREVENTION • Avoid access to raccoon, skunk, and cat feces. • Remove potential toxins from environment. • Perform routine dental examinations to minimize the likelihood of untreated disease spreading into central nervous system. • Use elevated food bowls and water bottles to reduce ingestion of E. cuniculi spores from urine-contaminated ground.
• Consider treating “in-contact” rabbits with fenbendazole prophylactically in cases where encephalitozoonosis is suspected.
CLIENT EDUCATION
Pasteurellosis Renal Disorders Vestibular Disease AUTHOR: MOLLY VARGA EDITOR: DAVID VELLA
To recognize early signs of disease and concurrent problems such as urine scalding
SUGGESTED READINGS Carpenter JW: Diagnosing and treating common neurologic diseases in rabbits, Vet Med 101:728–736, 2006. Gruber A, et al: A retrospective study of neurological disease in 118 rabbits, J Comp Pathol 140:31–37, 2009. Keeble E: Common neurological and musculoskeletal problems in rabbits, In Pract 28: 212–218, 2006.
CROSS-REFERENCES TO OTHER SECTIONS Abscesses Encephalitozoonosis Otitis
Encephalitis Torticollis is a common clinical sign of encephalitis in the rabbit. (Photo courtesy Jörg Mayer, The University of Georgia, Athens.)
369
RABBITS
RABBITS
Encephalitis BASIC INFORMATION DEFINITION Encephalitis is inflammation of the brain. Meningitis is inflammation of the membranes that cover the brain and spinal cord (meninges). Meningoencephalitis is concurrent inflammation of both the brain and the meninges.
SYNONYM Encephalomeningitis
EPIDEMIOLOGY GENETICS AND BREED PREDISPOSITION • Lop-eared rabbits appear to be at increased risk for otitis externa, which may lead to meningitis in severe cases. • Dwarf rabbits may have increased risk of exhibiting clinical signs due to Encephalitozoon cuniculi infection. RISK FACTORS • Otitis externa/media (see Otitis) • Dental disease • Positive E. cuniculi titer • Exposure to toxins • Exposure to raccoon feces • Pasteurellosis (see Pasteurellosis)
CONTAGION AND ZOONOSIS • E. cuniculi is a potential zoonosis, with immune suppressed individuals at particular risk. • Pasteurella multocida contracted from a pet rabbit has resulted in fatal infection in one human. GEOGRAPHY AND SEASONALITY • Rabies is not present in the United Kingdom or Australia. • Baylisascaris procyonis is found in North America. ASSOCIATED CONDITIONS AND DISORDERS • Otitis externa may be associated with increased risk of meningitis. • E. cuniculi infection is positively associated with increased risk of seizure disorders and chronic renal disease (see Renal Disease).
CLINICAL PRESENTATION DISEASE FORMS/SUBTYPES • Meningitis may be further classified into: Pachymeningitis (inflammation of the outer meningeal membrane) Leptomeningitis (inflammation of the inner meningeal membrane)
HISTORY, CHIEF COMPLAINT • Often an acute onset of clinical signs such as head tilt/rolling/urine scalding/falling/seizures • Possible prior history of upper respiratory, dental, or aural disease • Access to outdoors may be consistent with exposure to toxins (e.g., lead) and/or parasitic encephalitis (e.g., B. procyonis, toxoplasmosis, encephalitozoonosis). PHYSICAL EXAM FINDINGS • Neurologic signs will be the prominent findings: Head tilt Rolling Ataxia Nystagmus Opisthotonus Torticollis Reduced mentation • It is important to not ignore the nonneurologic signs (e.g., presence of urine scalding, otitis externa/media, dental disease, evidence of unexplained skin trauma/scuffing of nails).
370 Encephalitis ETIOLOGY AND PATHOPHYSIOLOGY • Bacterial Common Related to dental, upper respiratory, or ear disease (pasteurellosis commonly implicated) Listeriosis (Listeria monocytogenes) is a potential cause of meningoencephalitis in weanling rabbits. • Protozoal Exposure to E. cuniculi is common, but the incidence of disease caused by this organism is unknown. Toxoplasmosis is seen sporadically. • Viral Rare Rabies after a nonfatal bite is a potential differential diagnosis in endemic areas. Herpes viral encephalitis after exposure to human herpes simplex virus has been reported. • Parasitic B. procyonis (raccoon roundworm) infestation is a possible cause in endemic areas, but occurrence is sporadic. A similar species, B. columnaris, is found in skunks but most reported cases of baylisascariasis are due to B. procyonis. • Fungal Not reported in rabbits currently, but in endemic areas should be considered • Inflammatory Heatstroke or granulomatous inflammation without evidence of causative organisms is a common postmortem finding. This has been suggested to be caused by E. cuniculi. • Neoplastic Potential differential diagnoses are pituitary adenomas and teratomas. • Traumatic • Toxic Exposure to lead or organophosphate pesticides
• Urinalysis, including trichrome stain to look for E. cuniculi spores • Skull radiography • Neurologic examination • Fecal examination
ADVANCED OR CONFIRMATORY TESTING • Aural examination under general anesthesia (using endoscope preferably) and cytologic and bacteriologic sampling from middle ear • E. cuniculi serology • Toxoplasma serology • Rabies titer • Serum lead evaluation • Cerebrospinal fluid analysis • Magnetic resonance imaging • Computed tomography • Necropsy, including histopathologic examination of the brain in cases where rabbit colonies are involved, or if rabies is suspected
TREATMENT THERAPEUTIC GOALS • To achieve sufficient neurologic function to allow good quality of life • To control seizure activity • To provide pain control as required
ACUTE GENERAL TREATMENT
DIAGNOSIS
• Provide safe, padded environment. • Establish IV access and provide fluid and nutritional support as indicated. • Control seizures with benzodiazepines (e.g., diazepam 1-5 mg/kg IV; midazolam 0.2-2 mg/kg IV IM). • Cautious use of corticosteroids may be justified in severe cases (e.g., dexamethasone 1-2 mg/kg IM, IV once; prednisolone 0.05-2 mg/kg SC, IM once). • Use of prochlorperazine (0.25-0.5 mg/ kg q 8-12 h PO) may enhance stability. • Broad-spectrum antibiotics with good central nervous system penetration (e.g., chloramphenicol 20-50 mg/kg q 8-12 h IM, IV, SC, PO; ceftazidime 50 mg/kg q 8 h IM, IV)
DIFFERENTIAL DIAGNOSIS
CHRONIC TREATMENT
• Seizures: epilepsy, uremia, hepatic encephalopathy, toxins, neoplasia, infection • Urine scalding: urinary sludging, urolithiasis, cystitis, polyuria, spinal disease • Head tilt/rolling: middle/inner ear disease • Nystagmus: peripheral or central vestibular disease (see Vestibular Disease) • Reduced mentation: sedation, uremia
• Benzimidazoles (e.g., fenbendazole 20 mg/kg q 24 h PO × 28 d for encephalitozoonosis; consider oxytetracycline 50 mg/kg q 12 h PO or enrofloxacin 5-10 mg/kg PO, SC, IM IV q 12 h in addition) • B. procyonis infection: ivermectin 0.20.4 mg/kg q 7-10 d PO, SC; or oxibendazole 60 mg/kg q 24 h PO indefinitely • Long-term antibiotics in response to culture and sensitivity results • Long-term nonsteroidal antiinflammatory (NSAIDs) medication may prove
INITIAL DATABASE • Complete blood count and blood biochemistry
beneficial (e.g., meloxicam 0.3-0.5 mg/ kg q 12-24 h PO, SC). • Supportive feeding as required • Monitor for potential ongoing problems such as perineal cecotrophal soiling, urine scalding and associated dermal and urinary problems. • Barbiturates to control chronic seizures (e.g., phenobarbital 2.5-5 mg/kg q 12 h PO; adjust accordingly) • Lead toxicity: chelation therapy via NaCa-EDTA 27.5 mg/kg SC q 12 h × 5 d, repeated after 5 days. Repeat blood lead level 5 days after last treatment. Alternatively D-penicillamine 30 mg/kg q 12 h PO.
DRUG INTERACTIONS NSAIDs and corticosteroids may interact, causing gastrointestinal ulceration.
POSSIBLE COMPLICATIONS • Deterioration despite treatment • Traumatic skeletal or ocular damage due to seizures or rolling • Urine scalding • Perineal cecotrophal soiling • Gut stasis • Status epilepticus
RECOMMENDED MONITORING • Repeated neurologic examinations at intervals determined by rapidity of resolution of clinical signs • Regular weighing and clinical examinations to ensure that the rabbit is adequately able to feed and clean itself • Regular dental examinations • Blood phenobarbital levels in rabbits receiving this drug
PROGNOSIS AND OUTCOME • Dependent on causative agent/process and severity/duration of clinical signs at presentation • Owners should be made aware of potentially prolonged recovery period and high risk of recurrence • Part of the recovery process is learning to cope with clinical signs (rabbits and owners); failure of rabbit to cope may be triggered by other (unrelated) disease.
CONTROVERSY • E. cuniculi: it is not yet known how many rabbits that are seropositive for encephalitozoonosis actually develop disease directly due to this organism • Lufenuron is an oral chitin synthesis inhibitor. Although lufenuron probably does not kill E. cuniculi, it may hinder growth of microsporidia.
PEARLS & CONSIDERATIONS COMMENTS Many rabbits with seemingly insurmountable neurologic dysfunction are able to cope well within the home environment. It is better to assess this on “home ground” by looking at video footage or making a home visit, rather than on the basis of appearance in the examination room.
PREVENTION • Avoid access to raccoon, skunk, and cat feces. • Remove potential toxins from environment. • Perform routine dental examinations to minimize the likelihood of untreated disease spreading into central nervous system. • Use elevated food bowls and water bottles to reduce ingestion of E. cuniculi spores from urine-contaminated ground.
• Consider treating “in-contact” rabbits with fenbendazole prophylactically in cases where encephalitozoonosis is suspected.
CLIENT EDUCATION
Pasteurellosis Renal Disorders Vestibular Disease AUTHOR: MOLLY VARGA EDITOR: DAVID VELLA
To recognize early signs of disease and concurrent problems such as urine scalding
SUGGESTED READINGS Carpenter JW: Diagnosing and treating common neurologic diseases in rabbits, Vet Med 101:728–736, 2006. Gruber A, et al: A retrospective study of neurological disease in 118 rabbits, J Comp Pathol 140:31–37, 2009. Keeble E: Common neurological and musculoskeletal problems in rabbits, In Pract 28: 212–218, 2006.
CROSS-REFERENCES TO OTHER SECTIONS Abscesses Encephalitozoonosis Otitis
Encephalitis Torticollis is a common clinical sign of encephalitis in the rabbit. (Photo courtesy Jörg Mayer, The University of Georgia, Athens.)