Multi-focal localization focusing on infectious disease

Martin Young DVM, MS, DACVIM Video case

Hannah, 3 yr, FS, Mastiff Localization

• Spinal cord – C1-5, C6-T2, T3-L3, L4-S1

• Lower Motor Neuron – nerve, neuromuscular junction and muscle (L4-S1)

• Brain – forebrain, brainstem, cerebellum

Spinal cord signs (UMN)

• Paresis to plegia • Long stride • • Normal to increased reflexes • Increased muscle tone Lower Motor Neuron

• Rapid loss of muscle • Decreased reflexes • Weakness • Proprioception may be intact

Brain signs

• Behavior changes • Altered mentation • Cranial nerve deficits • Gait changes • Proprioceptive deficits • • Pacing/circling Multifocal localization

• History – rate and sequence of changes

• Exposures – outdoor, wildlife, other animals

• Exam – signs of both UMN and LMN signs – Long stride with ataxia and rapid loss of muscle (5-10d) – PL weakness/short stride and cranial nerve deficits – Multifocal/diffuse discomfort Causes of multifocal localization

• Infection – protozoal, fungal/algea, ricketsial

• Immune mediated – GME/MUE

• Neoplasia Infection - protozoa

• Neospora caninum . Meningoencephalitis, neuritis, myositis • Path: Normally will affect lumbosacral spinal nerves and pelvic limb muscles of young dogs. Adult dogs tend to get brain involvement (specifically cerebellum) • Dx: serum (and/or CSF) antibody test. CSF variable • Tx: Clindamycin 15mg/kg/q12 + TMS 15mg/kg/q12 • Px: may be able to stop progression Infection - protozoa

• . Meningoencephalitis - any age • Often other body systems affected – muscle and pancreas • Path: Focal or multifocal encephalopathy. Have a tendency to form large granulomas in the brain. • Dx: IgG and IgM antibody test. • Tx: Dogs: Clindamycin ~12.5 mg/kg PO q8-12hrs x 30 days : may add TMS 30 mg/kg PO q 12hrs x 14 days, and pyrimethmine 0.25-0.5 mg/kg PO q12hrs x 14 days • Px: Guarded Infection - protozoa

• Sarcocyst neurona . Meningoencephalitis and myositis

• Limited reports, titer levels have been reported (Ellison and Young) • Unknown frequency • Path: Sarcocyst neurona has been previously reported as causing myositis and encephalitis (Lichtensteiger, Speer, Chapman • Dx: serum (and/or CSF) antibody test. • Tx: Ponazuril 15mg/kg/q24, TMS 15mg/kg/Q12 • Px: unknown at this time Infection

Neutrophils, macrophages, lymphocytes and necrosis in the cerebellum

Sarcocystis Neurona

Cooley AJ, et al. Sarcocystis neurona Encephalitis in a Dog.Vet Pathol 44: 956-961 (2007) Infection - Rickettsial

• Rickettsia rickettsii (Rocky Mountain spotted fever) • Ehrlichia canis (erhlichiosis) . Obligate intracellular parasites transmitted via tick bites . Not reported in cats • Path: Cause vasculitis and/or hemorrhage . Thrombocytopenia and platelet dysfunction • Signs: Focal or multifocal signs . Systemic illness, Central vestibular disease common • Dx: Titers effective in diagnosis • Tx: Doxycycline 8-10 mg/kg PO q12hrs for 4 weeks Enrofloxacin 10 mg/kg PO q24hrs (effective for RMSF) Infection - fungal

• Cryptococcus neoformans . Dogs and cats. Carries in pigeon poop. • Coccidiodes immitus (“Valley Fever”) . SW United States • Blastomyces . Usually systemic involvement, may affect eyes • Histoplasma . Fairly rare. Near river valleys • Aspergillus . More commonly causes discospondylitis . If meningoencephalitis, likely fatal. Infection - fungal

• Meningoencephalitis and or myelitis • Commonly respiratory and bone lesions • Dx: Antibodies, antigens, identification on fluid/tissue samples • Tx: Typically for months 4-12 – oral vs intrathecal . Fluconazole 5-10 mg/kg PO q12hrs for extended time (~4-6 months) . Voriconazole . Intrathecal Amphotericin B (Young et al) Infection

Inflammation & necrosis of caudate nucleus and adjacent lining of lateral ventricle

Prototheca zopfii

Martin Young, et al. Serial MRI and CSF in a dog with intrathecal amphotericin for Protothecosis Journ Amer Anim Hosp Assoc 2012: 48: 125-131 Multi-focal infection images Characteristic UMN LMN

Gait Long-strided Short-strided

Ataxia Yes No

Postural deficit Yes No

Tone & Reflex Increased Decreased

Atrophy Mild, slow Marked, fast

Laryngeal / Pharyngeal No Yes

Palpebral Normal Weak

Painful Often Seldom

Fatigue No Yes Reference

• 1. Vashisht K, Lichtensteiger CA, Miller LA, Gondim LFP, McAllister MM: Naturally occurring Sarcocystis neurona-like infection in a dog with myositis. Vet. Parasitol. 2005;133(1):19-25. • 2. Dubey JP Speer CA: Sarcocystis canis n. sp. (: Sarcocystidae), the etiologic agent of generalized coccidiosis in dogs. J. Parasitol. 1991;77(4):522-7. • 3. Dubey JP, Chapman JL, Rosenthal BM, Mense M, Schueler RL: Clinical Sarcocystis neurona, Sarcocystis canis, Toxoplasma gondii, and Neospora caninum infections in dogs. Vet. Parasitol. 2006;137(1-2):36-49. • 4. Cooley AJ, Barr B, Rejmanek D: Sarcocystis neurona Encephalitis in a Dog. Vet. Pathol. 2007;44(6):956-961. • 5. Ellison SP, Omara-Opyene AL, Yowell CA, Marsh AE, Dame JB: Molecular characterisation of a major 29 kDa surface antigen of Sarcocystis neurona. Int. J. Parasitol. 2002;32(2):217-25. • 6. Howe DK, Gaji RY, Mroz-Barrett M, Gubbels MJ, Striepen B, Stamper S: Sarcocystis neurona Merozoites Express a Family of Immunogenic Surface Antigens That Are Orthologues of the Toxoplasma gondii Surface Antigens (SAGs) and SAG-Related Sequences. Infect. Immun. 2005;73(2):1023-1033. • 7. Crowdus CA, Marsh AE, Saville WJ, et al.: SnSAG5 is an alternative surface antigen of Sarcocystis neurona strains that is mutually exclusive to SnSAG1. Vet. Parasitol. 2008;158(1-2):36-43. • 8. Wendte JM, Miller MA, Nandra AK, et al.: Limited genetic diversity among Sarcocystis neurona strains infecting southern sea otters precludes distinction between marine and terrestrial isolates. Vet. Parasitol. 2010;169(1-2):37-44. • 9. Greene, Craig E. Infectious disease of the dog and . 3rd ed. Philadelphia (PA): Saunders; 2006: 659-65 • 10. Ellison S Lindsay DS: Decoquinate Combined with Levamisole Reduce the Clinical Signs and Serum SAG 1, 5, 6 Antibodies in Horses with Suspected Equine Protozoal Myeloencephalitis. International Journal of Applied Research in Veterinary Medicine 2012;10(1):1-7.