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 • Ataxia • 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 • Seizures • 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

• Toxoplasma gondii 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 Cats: 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

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

Neutrophils, macrophages, lymphocytes and necrosis in the cerebellum

Infection

Sarcocystis Neurona

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)

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

Infection

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. (Apicomplexa: 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 cat. 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.