Steroids in Neurological Disease: The Good, The Bad, and the

Miraculous!

Dr. Andrea FinnenDVM, DES, MSc, DACVIM (Neurology)

Lipid soluble

Protein bound – free portion important

Interact with receptor IN cell

Transcribe genes

or protein

Affect biological action

Back to school…..

Effect Site of action

Gluconeogenesis LiverHepatic glycogen LiverBlood glucose LiverLipolysis Adipose tissueWater excretion KidneyGastric acid secretion StomachCatabolic Muscle, liver−ve feedback CRH HypothalamusBlock inflammatory response DiffuseSuppress immune system Macro, lymphs

Physiological Effects

Inhibit synthesis of inflammatory mediators (prostaglandins, thromboxanes, leukotrienes)

The Good

Phospholipids

Arachidonic Acid

Prostaglandins Prostaglandins

Leukotrienes

Physiological Functions Inflammation

Inflammation

STEROIDS

NSAIDS

Inhibit synthesis of inflammatory mediators (prostaglandins, thromboxanes, leukotrienes)

Stabilize lysosomal membranes - rupture and release of proteolytic enzymes

Attenuates fever by Il-1, reduces vasodilation

Pain relief via anti-inflammatory actions

The Good

permeability of capilliaries

migration WBC into tissues

Suppresses immune system by Tcell lymphocytes and Tcell antibody production

Prevent fibrin deposition and connective tissue synthesis

The Good

Adverse Effects – The Bad

Common Dermatologic

PU/PD PP, weight gain Potbelly Panting Lethargy Muscle

atrophy/weakness

Alopecia Thin skin Comedones Bruising Hyperpigmentation Calcinosis cutis Pyoderma Seborrhea 2° demodex

Adverse Effects – The Bad

Renal/endocrine Blood work abnormalities

Proteinuria urine glucose Recurrent UTI

Diabetes mellitus Euthyroid sick

TT4, T3, TSH Hyperglycemia Hyperlipidemia Hypercholesterolemia ALP Lymphopenia Neutrophila Eosinopenia Hypokalemia Hyperlactatemia

Vomiting Diarrhea Gastric ulceration Colonic perforation Urinary tract infection *

Adverse Effects – The Ugly!

Glucocorticoids

Dexamethasone Prednisone

30x more potent than cortisol

7x more potent than Prednisone

2x mineralocorticoid effects

Greater penetration into CSF

Biologic effect ≤48hr

4x more potent than cortisol

Minimal mineralocorticoid effects

Prednisolone in cats better absorbed

Biologic effect 12-36hr

Doses

Anti-Inflammatory Immunosuppressive

Prednisone0.5-1mg/kg/day

Dexamethasone0.075-0.15mg/kg/day

Prednisone1-2mg/kg/day DOGup to 4mg/kg/day CAT

Dexamethasoneup to 0.3mg/kg/day

Many neurological diseases have an inflammatory or immune etiology

Sometimes steroids are the only treatment

If you think it’s inflammatory and it’s not…

Think about what you are treating before Rx - Diagnosis is key!

Why use steroids?

Degenerative myelopathy (DM)

FCEM

Coonhound paralysis

Trigeminal neuritis

Ischemic infarct (stroke)

Bengal polyneuropathy

Steroids - NO

Steroid responsive meningitis-arteritis (SRMA)

Meningoencephalitis of unknown etiology (MUE)

Intracranial neoplasia

IVDD Type I and II

Cervical spondylomyelopathy (Wobblers)

COMS + syringomyelia (SM)

Hydrocephalus

Steroids – YES!

Steroid responsive meningitis-arteritis (SRMA)

Meningoencephalitis of unknown etiology (MUE)

Intracranial neoplasia

IVDD Type I and II

Cervical spondylomyelopathy (Wobblers)

COMS + syringomyelia (SM)

Hydrocephalus

Steroids – Miraculous!

Head trauma

Spinal trauma

Infectious encephalitis/abscess

Lumbosacral disease

Myasthenia Gravis

Steroids – Maybe…

Signalment + clinical signs Imaging – MRI preferred for CNS +/-CSF +/- biopsy, culture

But……client have only $100 to spend…..

Diagnosis is KEY

4 yo FS Miniature poodle Presenting complaint: walking funny

◦ Hind end ataxia (grade 2)◦ Delayed paw placement both HL◦ Back pain at TL junction ◦ Appetite decreased ◦ Lethargic, not moving around much

Top 2 differentials:◦ IVDD◦ Meningomyelitis◦ +/- Others (trauma, infectious, neoplasia, FCEM, etc)

Clinical practice

What are you treating? Inflammatory

◦ IVDD◦ Other spinal cord/nerve compression ◦ CSF over-production◦ Unknown dx

Immune◦ Definitively diagnosed ◦ Hard to justify high dose steroids if no definitive dx!

Go read a book!

“Evaluation of the Success of Medical Management for Presumptive Thoracolumbar IVDD in Dogs”

Levine, VS 2007

Conclusion: ◦ “…glucocorticoids may negatively impact success and

QOL.”

Discussion:◦ “…possible that glucocorticoids have a negative impact on

dogs with medically managed presumptive disk herniation.”

In the Literature…

“Evaluation of the Success of Medical Management for Presumptive Cervical IVDD in Dogs”

Levine, VS 2007

Conclusions: ◦ “NSAIDs should be considered as part of the therapeutic regimen.” ◦ “…glucocorticoid administration does not appear to benefit these

dogs..”

Discussion: ◦ “…glucocorticoids were less likely to have a successful outcome

but this association was also not statistically significant.”◦ NSAIDs seem to be associated with success in dogs with

presumptive cervical disk herniation..”

In the Literature…

“Recurrence rate of presumed thoracolumbar disc disease in ambulatory dogs with spinal hyperpathia treated with anti-inflammatory drugs: 78 cases (1997-2000).”

Mann et al., JVECC 2007

Conclusions: ◦ “Dogs treated with NSAIDs or MPSS were less likely to experience

recurrence than dogs treated with corticosteroids other than MPSS.”

Discussion: ◦ “…impossible to determine whether any of the drugs used are

necessary for recovery of the initial episodes of presumed IVDD…”

In the Literature…

“Adverse effects and outcome associated with dexamethasone administration in dogs with acute thoracolumbar intervertebral disk herniation: 161 cases (2000-2006).”

Levine, JAVMA 2008

Conclusions: ◦ “…treatment with dexamethasone before surgery is associated with

more adverse effects, compared with treatment with glucocorticoids other than dexamethasone or no treatment with glucocorticoids…”

DOSE 1-30mg/kg!!!!! 3.4x more likely to develop AE 66% non treatment had AE too

In the Literature…

CVT XV Chapter 233 Canine IVDH

◦ Medical therapy: 2-4 weeks cage rest and analgesia with NSAID and opioids

+/- drugs for neuropathic pain

◦ “The use of corticoids such as Dexamethasone is strongly discouraged for acute SCI from IVDH.”

◦ “..glucocorticoid therapy was negatively associated with improved functional outcome.” (Levine, 2007)

Reference texts any better?

Inhibit platelet aggregation Aspirin has irreversible action! Risk of gastric ulceration and GI effects Can lead to renal damage Need 48-72 hour wash-out

NSAIDS can be bad too!

My recipe - IVDD Ideally – MRI +

decompressive surgery

Dexamethasone 0.1-0.15mg/kg/day for 3-5 days

+/- Prednisone anti-inflammatory tapering for 1 week

No diagnosis?

Dexamethasone 0.1mg/kg/day x 1 week then 0.05mg/kg/day x 1 week

Recheck – better?

STOP or switch to Prednisone for longer maintenance

My recipe

Steroids are not all bad! Think about what you are treating Use appropriate doses Follow up and D/C when possible Don’t use steroids with NSAIDS!

Take home message

Questions?