Neurology Networks tries to offer broad exposure to various topics that may be presented on the veterinary neurology board exam.

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HUMAN PAPER: “Cyclosporine-Associated Neurotoxicity: The Need for a Better Guide for Immunosuppressive Therapy”

Leslie W. Miller, MD

Circulation. 1996; 94:1209-1211


In humans, cyclosporine can have several neurotoxic effects.  Incidence can range from 10-25% with increasing risk the longer a person is on the drug.  Clinical signs can include tremors, restlessness, dysesthesias of the palms and soles, seizures, and altered mental status with confusion and visual or auditory hallucinations; cortical blindness, encephalopathy, and coma are less common. Signs referable to the caudal fossa are most common . The signs usually resolve in the reverse order of appearance after discontinuing the drug with visible improvement in 2/3 patients within 48 hours and all patients when given several days/ weeks.  Risk factors include previous seizures or a cerebral vascular accident, hypertension, cholesterol <100 mg/mL, concomitant use of intravenous methylprednisolone, hypertension, hypomagnesemia, and high cyclosporine levels.  Diagnosis is by exclusion and response to stopping the drug.  MRI sometimes shows small, slight symmetrical hyperintensities on T2 images.  Proposed MOA include hypocholesterolemia (increases percentage of unbound lipophilic drugs and can increase LDL receptors which can lead to increased cyclosporine in the brain), hypomagnesemia(cyclosporine causes proximal tubule dysfunction and increased magnesium clearance which can lower the seizure threshold), cyclospoine-stimulated release of endothelin (causes microvascular damage and BBB permeability), and direct toxic effect which can be associated with demyelination.

**Informal note: Neurotoxicity in dogs is thus far unreported in the literature, but several anecdotal reports are present in the VIN message boards.  This article was included on this site because of a case presented to us with multifocal (predominantly caudal fossa) signs on long-term cyclosporine for dermatologic problems.  Systemic workup with additional brain MRI and CSF were inconclusive.  Cyclosporine was discontinued on 8/6/13.  Ultimate outcome is pending.



“Suspected chlorambucil-related neurotoxicity with seizures in a dog”

Antonio Giuliano

Journal of Small Animal Practice •Vol 54 •August 2013

8yr Saluki with lymphoma and nephritic syndrome.  48 hours after dosing (20mg/m2 with Prednisone) the dog developed lethargy and cervical ventroflexion.  The dog was dosed with dexamethasone and improved in 24 hours.  48 hours after the next dose, the dog showed similar signs, which only temporarily improved with dexamethasone.  The dog developed seizures and was euthanized. 

This is a letter to the editor, so is sparse in supporting evidence.  There is no neuro or systemic workup.  In humans, nephritic syndrome affects albumin levels which can impact bound/unbound levels; this was not recorded in this dog.  It is not known if the improvement in clinical signs are from drug metabolism or from the steroid administration.  Steroids can increase the brain’s sensitivity to neurotoxins (like in cyclosporine), so it was speculated that the steroids may have contributed to the development of seizures.