Page 1286 - Cote clinical veterinary advisor dogs and cats 4th

648 Meningoencephalitis of Unknown Origin

○ Brainstem signs: central vestibular disease • Histopathology (surgical biopsy or necropsy): ○ Targeted whole blood concentrations,
(head tilt, ataxia) confirms GME or NE measured 1 week after initiation of
VetBooks.ir Etiology and Pathophysiology TREATMENT ○ Small size of many MUO patients may
therapy or dosage change: 800-1400 ng/
○ Meningitis: cervical pain
mL (peak), 400-600 ng/mL (trough)
• Cause is unknown; presumed autoimmune
or immune mediated Treatment Overview necessitate compounded formulations of
Glucocorticoids are the benchmark of treat-
cyclosporine; commercially available liquid
• Attempts to identify an inciting infectious ment. The choice of add-on therapy varies formulation can be used (minimum dose
cause have been unrewarding. based on clinician preference, owner finances, of 10 mg/kg PO q 12h often required
• Antibodies against neural elements (astro- proximity to a hospital capable of administer- to achieve therapeutic concentrations).
cytes, glial fibrillary acidic protein) have been ing chemotherapy, and owner health concerns The microemulsified form (Neoral/
identified in serum and cerebrospinal fluid (immune compromised/pregnant). Cytarabine, cyclosporine modified) is recommended
(CSF) of affected dogs. cyclosporine, procarbazine, azathioprine, over Sandimmune.
• Histopathology: nonsuppurative, mono- mycophenolate mofetil, and radiation therapy ○ Vaccines may be less effective in dogs
nuclear cell infiltration in the brain and/or have been used. on cyclosporine; avoid live attenuated
+
meninges, especially CD8 T lymphocytes in vaccines.
GME Acute General Treatment • Procarbazine (Matulane, Alcami) 25-50 mg/
2
• Prednisone/prednisolone is initiated at antiin- m PO q 24h decreasing to q 48h dosing
DIAGNOSIS flammatory dosages (e.g., 0.5-1 mg/kg PO q after 1-3 months
24h) pending infectious disease titers. Some • Azathioprine 2 mg/kg PO q 24h for 2-4
Diagnostic Overview advocate for immediate immunosuppression weeks, then 2 mg/kg PO q 48h
MUO should be considered based on signal- (e.g., 2 mg/kg PO q 12h) after MRI and • Mycophenolate mofetil 20 mg/kg PO or IV
ment and presenting clinical signs. Initial CSF, based on the low positive yields from q 12h, decrease to 10 mg/kg PO q 12h after
diagnostics are performed to evaluate for other infectious disease testing. 2-4 months, then 10 mg/kg PO q 24h for
causes of neurologic disease. Diagnosis often ○ If severity of neurologic signs at the 2-4 months, for a final dosing schedule of
requires referral for MRI and CSF analysis. time of diagnosis precludes the admin- 10 mg/kg PO q 48h. Capsules should not
MRI or CSF can occasionally be normal, istration of oral medications, consider be opened, and the sodium enteric-coated
highlighting the importance of a complete drugs with IV formulations (dexa- tablets should be avoided.
diagnostic workup. methasone, methylprednisolone sodium • Tapering of medication dosages is contingent
succinate, cytarabine, mycophenolate on the absence of recurrence of clinical signs.
Differential Diagnosis mofetil). • Lomustine 44-88 mg/m PO q 6 weeks (p.
2
• Infectious meningoencephalitis • Treat for common infectious diseases (doxy- 609). The use of live vaccines is discouraged.
○ Protozoal: Toxoplasma gondii, Neospora cycline 5-10 mg/kg PO q 12h, clindamycin • Radiation therapy 10 3-Gy treatments
caninum 15 mg/kg PO q 12h, fluconazole 5 mg/kg
○ Bacterial PO q 12h) while awaiting titer results. Behavior/Exercise
○ Viral: canine distemper, rabies • Seizure activity: IV benzodiazepines, then While on immunosuppressive therapy, com-
○ Tick-borne: Ehrlichia canis, Anaplasma initiate maintenance antiepileptic therapy munal areas such as dog parks and boarding
spp, Rickettsia rickettsii, Borrelia burg- with parenteral formulation of phenobarbital facilities should be avoided.
dorferi, Babesia canis, Bartonella henselae or levetiracetam. Levetiracetam tends to be
○ Fungal: Cryptococcus neoformans, Blasto- preferred and has less effect on dog’s mental Drug Interactions
myces spp, Coccidioides immitis, Aspergillus status than phenobarbital. Cyclosporine, phenobarbital, and procarbazine
spp, Histoplasma spp • Signs of elevated intracranial pressure are metabolized by the hepatic cytochrome
○ Other: Prototheca spp, Cuterebra (depressed mental attitude/poor pupillary P450 system; they alter the disposition of
• Neoplasia light reflexes): mannitol 1 g/kg IV once other drugs that depend on P450 enzymes for
• Vascular: ischemic or hemorrhagic stroke or 3% hypertonic saline 4-6 mL/kg IV metabolism, necessitating a higher dose when
• Blindness (p. 123) once. used in combination.
Initial Database Chronic Treatment Possible Complications
• Neurologic exam (p 1136): to localize lesion • Prednisone/prednisolone: immunosuppressive • Glucocorticoid side effects should be
• Testing to rule out other causes for clinical doses with a slow taper over the next year: expected: polyuria, polydipsia, polyphagia,
signs 2 mg/kg PO q 12h for 3 days, then 1-1.5 ± others (e.g., hepatopathy, iatrogenic
○ CBC, serum chemistry, urinalysis mg/kg PO q 12h for 1-3 months, then hyperadrenocorticism)
○ Bile acids, preprandial and postprandial decrease dose by 25% q 6-8 weeks until the • Gastrointestinal side effects are possible
○ Infectious disease testing (tick-transmitted/ lowest effective dose is achieved. Complete with all treatments: famotidine 1 mg/kg
protozoal/fungal infection) withdrawal is possible in some cases. PO q 24h or omeprazole 1 mg/kg PO q
2
• Cytarabine 200 mg/m IV constant-rate 24h might help prevent gastric ulceration.
Advanced or Confirmatory Testing infusion (CRI) over 8 hours (25 mg/m /h Excessive vomiting, especially with blood, or
2
2
• MRI of brain (p. 1132): focal to multifocal × 8 hours [p. 609]) or 50 mg/m SQ q anorexia necessitates a medication change.
T2- and FLAIR-weighted hyperintensities 12h for 4 doses. Repeat q 3 weeks for 4 ○ Administer cyclosporine on an empty
throughout cerebral cortex; occasional cycles, increasing the treatment interval by stomach; if excessive vomiting, freeze the
involvement of cerebellum and brainstem 1 week q 4 cycles until q 8 week treatment capsule and/or administer metoclopramide
variable contrast enhancement schedule is reached. Recent studies suggest or maropitant 30 minutes before dosing.
• CSF analysis (pp. 1080 and 1323): elevated a longer survival time with CRI than SQ • Myelosuppression: perform complete blood
nucleated cell count and total protein administration. counts to monitor
• Cytology: > 50% mononuclear, varied lower • Cyclosporine (Atopica) 5-10 mg/kg PO ○ Cytarabine: 1 week after administration
percentages of nondegenerative neutrophils q 12h and before each treatment
• Paired distemper titers (serum ± CSF): ○ To reduce cost, can be administered q 24h ○ Procarbazine: every week for the first
normal with ketoconazole 8 mg/kg PO q 24h month, then monthly

www.ExpertConsult.com