Glucocorticoids and Neurologic Disease Wendy Blount DVM Corticosteroids

Glucocorticoids and Neurologic Disease Wendy Blount, DVM

Corticosteroids Argument *for* use in CNS Disease • Protection from free radicals • Reduced CSF production => reduced cerebrospinal pressure • Maintaining microvascular integrity • Reduction of cerebral edema

Head Trauma Pro • Control of secondary injury by lipid peroxidation – LP results in neuronal degeneration – Which is indirectly related to prognosis • Reduces cerebral edema • Anti-inflammatory effects

Head Trauma Con • Can potentiate neuronal damage when ischemia is present • Inhibits remyelination of damaged neurons • Hyperglycemia (>200 mg/dl) has adverse effect on cerebral edema • Increased infection Current recommendation is against use of corticosteroids for head trauma

CRASH • Corticosteroid Randomization After Significant Head Injury (CRASH) study – Roberts et al, 2004 – 10, 000 human patients – Risk of death within 2 weeks slightly higher with corticosteroids (21% vs. 18%) – No evaluation of long term outcome

Acute Spinal Cord Trauma • Most common causes – TL intravertebral Disc Disease – External Trauma Pro • Studies show that methylprednisolone sodium succinate (MPSS – Solu. Medrol®) given within 8 hours of trauma may be beneficial – 30 mg/kg slowly IV – 5. 4 mg/kg/hr CRI for 24 -48 hours, or follow -up doses

Acute Spinal Cord Trauma Con • Same protocol more than 8 hours after injury has adverse effect • Interferes with regeneration • High dose MPSS can result in prolonged hospital stays due to side effects – GI erosions, ulceration • Can cause vomiting if given IV too quickly – Give over 5 -10 minutes

Acute Spinal Cord Trauma Comparisons - medical management type 1 disc disease • Confinement longer than 2 weeks did not affect outcome • No benefit or harm of prednisone administration in cervical disc dz • Dogs with TL Disc Dz did worse if treated with prednisone • NSAIDs improved outcome of cervical disc dz • Electro-acupuncture improved outcome of TL disc dz

MPSS Follow-up Dose Protocol Dogs 1. 30 mg/kg IV within 3 -8 hours 2. 15 mg/kg IV in 2 hours and 6 hours 3. Every 8 hours until 48 hours after the trauma Cats 1. 30 mg/kg IV within 3 -8 hours 2. 15 mg/kg IV in 2 hours and 6 hours 3. 2. 5 mg/kg/hr CRI until 48 hours after the trauma

CNS Trauma 1. All head and spinal cord trauma patients should receive IV fluids, even if euvolemic – Dehydration exacerbates secondary neurologic injury 2. Appropriate analgesia reduces catecholamine induced cortisol release which can delay healing 3. Glucocorticoids - Acute protective effects are weighed against catabolic effects that can delay or prevent regeneration

CNS Trauma • • • Moderate dose dexamethasone for head trauma has not been evaluated pre-surgical dexamethasone in dogs with disk herniation increased the odds of adverse events and did not improve recovery (Levine et al 2008, J Am Vet Med Assoc). Single MPSS boluses are discouraged, as they only temporarily reduce lipid peroxidation Some think corticosteroids for acute spinal cord trauma are contraindicated Others think they have dubious benefit Others think there is evidence of benefit, used judiciously

Type II Disc Protrusion Gradual Compression – vastly different pathology from acute injury Cornerstones of therapy: 1. Cage rest (4 -6 weeks) 2. analgesics 3. physiotherapy Many agree that glucocorticoids improve return to function • Minimal myelopathy, so not subject adverse catabolic effects

Type II Disc Protrusion Guidelines: • Short term anti-inflammatory regimens – 0. 5 mg/lb/day of pred x 7 days or less • Not advocated when there is pain only and no neuro deficits • Can reduce vasogenic edema when there is compression There are neurologists that think that glucocorticoids are contraindicated even for compressive myelopathy

CNS Neoplasia • Reduces peritumoral edema • Reduces tumor associated inflammation • Treats acquired hydrocephalus • Often used to treat acute exacerbation of clinical signs – Brain herniation

CNS Neoplasia • Anti-inflammatory - 0. 5 mg/lb/day or less • Also mannitol 0. 5 -1 g/kg IV over 20 minutes – Contraindicated if dehydrated or renal disease • and furosemide 0. 7 mg/kg IV, shortly after mannitol • Improvement can be dramatic within 24 hours • Relapse is inevitable, but might not come for weeks to months Experts agree this can be life saving

Infectious Meningoencephalitis Canine distemper virus Rickettsial disease Fungal Toxoplasma spp. , Neospora spp. FIP bacterial • Immunosuppressive effects must be weighed against anti-inflammatory effects

Infectious Meningoencephalitis • 0. 5 -2 mg/lb/day PO for FIP, rickettsial – Duration variable • 0. 5 mg/lb/day x 7 days for fungal • 0. 15 mg/kg IV 1 x 15 -20 minutes prior to beginning antimicrobial therapy for bacterial Human studies show beneficial outcome for bacterial meningoencephalitis

Granulomatous Meningoencephalitis • 1 -2 mg/lb/day PO, tapered over 2 -3 months or more • Add other immunsuppressives if needed – – Lomustine Azathioprine Cyclosporine Cytosar U

Necrotizing Meningoencephalitis Aka Pug Encephalitis • Various forms in Pugs, Maltese, Yorkies • Prednisone 1 -2 mg/lb/day PO has temporarily improved symptoms • Ultimate prognosis is poor, regardless of prednisone therapy

Steroid Responsive Meningitis-Arteritis Large breed dogs < 2 years of age • Nova Scotia Tolling Retrievers Another form in Beagles – “Beagle Pain Syndrome” • Fever, meningitis, neck pain • Prednisone 2 mg/lb/day x 2 days • Then 1 mg/lb/day x 2 weeks • Then gradually reduce over 2 -3 months or more, sometime long term • Relapses are not uncommon

Hydrocephalus Dilation of the ventricle system • Glucocorticoids decrease CSF production – 0. 1 -0. 25 mg/lb/day – Reduced gradually to 0. 05 mg/lb/day • As does omeprazole Above used to treat Chiari in Cavaliers

Cerebrovascular Accident • Peracute onset of focal, asymmetric brain dysfunction • May worsen for 24 -72 hours before improving – Edema and hemorrhage – Secondary neuroinjury Glucocorticoids are generally not recommended

In a Nutshell… • Everybody agrees that glucocorticoids have powerful anti-inflammatory effects on the CNS, which can be beneficial in some cases • Everybody agrees that side effects can be significant and need to be managed • General consensus amongst experts is that acute CNS injury is not helped by corticosteroid therapy, and that therapy might be contraindicated

In a Nutshell… • General consensus amongst experts is that glucocorticoids for CNS neoplasia and immune mediated disease can be life saving • Some neurologists use corticosteroids for fungal CNS disease and chronic compressive disease • Some neurologists think a single dose of reasonable dexamethasone for acute CNS trauma should not induce scheduling of a flogging for the offending vet.

GI Protection Why do dogs with corticosteroid toxicity vomit? – – Decreased mucosal cell growth and mucus production Increased gastric acid secretion High doses required for acute toxicity Chronic toxicity when other risk factors present: – – Concurrent NSAIDs, bile acid reflux spinal cord disease, liver disease, renal disease Hypotension, Addison’s disease, MCT degranulation Gastrinoma. H 2 blockers/proton pump blockers for prevention Add sucralfate for treatment of GI Ulceration

Summary Power. Points –. pptx –. pdf – 1 slide per page –. pdf – 6 slides per page Scientific Article – Levine: Glucorticoids for Neurologic Disease

Acknowledgements Curtis Dewey, ACVIM (Neurology) Ronaldo C de Costa • Practical Guide to Canine and Feline Neurology, 3 rd ed. 2016. Jon M. Levine, DVM, DACVIM • (Neurology) Assistant Professor, Neurology/Neurosurgery Texas A&M University • GLUCOCORTICOIDS FOR NEUROLOGIC DISEASE