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Luisa De Risio. Canine and Feline Epilepsy
Canine and Feline Epilepsy
Contents
Preface
1 Pathophysiology of Seizure Activity
The Electrical Basis of Nerve Cell Function
Synaptic Transmission
Synchronization
Kindling and Epileptogenesis
Ictogenesis
Excitability arising from individual neurons
Excitability arising from neuronal microenvironment
The epileptic cell population
Mechanisms of Interictal–Ictal Transition
Nonsynaptic mechanisms. Alterations in ionic microenvironment
Active ion transport
Presynaptic terminal bursting
Ephaptic interaction
Synaptic mechanisms
Neurochemical Mechanisms Underlying Epilepsy. GABA
Glutamate
Glutamate receptors
AMPA
NMDA
Metabotropic receptors
Glutamate transporters
Targets for treatment
The Veterinary Perspective
Catecholamines
Opioid peptides
Inflammatory Mechanisms Underlying Epilepsy
Do seizures cause inflammation?
Does inflammation cause seizures?
Does inflammation cause cell loss?
Mechanistic insights
Immune and anti-inflammatory therapies
Disorders of Neuronal Migration and Seizures
How Do Seizures Stop?
Mechanisms acting at the level of single neurons
Intracellular ion-activated potassium currents
Transmembrane ion gradients
Energy failure
Mechanisms acting on a local network of neurons
Glutamate depletion
The intra- and extracellular environments
Glial buffering of glutamate
Increased GABA-ergic inhibition
References
2 Pathophysiology of Pharmacoresistant Epilepsy
Introduction
Definition
Risk Factors for Pharmacoresistant Epilepsy. Genetic risk factors
Clinical risk factors
Pseudoresistance
Mechanisms of Pharmacoresistant Epilepsy
Drug-target hypothesis
Multidrug transporter hypothesis
Conclusion
References
3 Classification of Seizures and Epilepsies
Classification of Seizures and Epilepsies in Human Medicine
Classification of Seizures and Epilepsies in Veterinary Medicine
Veterinary classification of seizures based on clinical manifestations. Generalized-onset seizures
Focal-onset seizures
Veterinary classification of seizures and epilepsies based on underlying aetiology. Reactive seizures
Structural (symptomatic or secondary) epilepsy
Probable symptomatic or cryptogenic epilepsy
Idiopathic or primary epilepsy
Precipitated seizures
Reflex seizures
References
4 Reactive Seizures
Systemic Metabolic Disorders Causing Seizures
Hypoglycaemia. Overview
Clinical presentation
Diagnosis
Management
Insulinoma. Overview
Clinical presentation
Diagnosis
Management
Hepatic encephalopathy. Overview
Clinical presentation
Diagnosis
Management
Renal-associated encephalopathy. Overview
Clinical presentation
Diagnosis
Management
Hyponatraemia. Overview
Clinical presentation
Diagnostic investigation
Management
Hypernatraemia. Overview
Clinical presentation
Diagnosis
Management
Hypocalcaemia. Overview
Clinical presentation
Diagnosis
Management
Nutritional Disorders Causing Seizures. Thiamine (vitamin B1) deficiency. Overview
Clinical presentation
Diagnosis
Management
Exogenous Toxic Disorders Causing Seizures. Overview
Clinical presentation
Diagnosis
Management
Decontamination
Cutaneous absorbed toxins
Gastrointestinal absorbed toxins
Urinary excreted toxins
Intravenous lipid emulsion infusion
Insecticides. Pyrethrin and pyrethroid (permethrin) Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Organophosphates and carbamates. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Chlorinated hydrocarbons. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Molluscicides. Metaldehyde. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Rodenticides. Strychnine. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Bromethalin. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Zinc phosphide. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Sodium monofluoroacetate (Compound 1080) Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Automotive Products. Ethylene glycol. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Detergents and Disinfectants. Hexachlorophene. Overview
Clinical presentation
Management
Prognosis
Heavy Metals. Lead. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Poisonous Plants
Blue-green algae (cyanobacteria) Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Mycotoxins. Penitrem A and roquefortine. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Animal-related Poisoning
Toad. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Therapeutic Agents and Supplements. Metronidazole. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Ivermectin and other macrocyclic lactones. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Levamisole. Overview
Mechanism of action
Clinical presentation
Management
Methylxanthines. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Amphetamine and amphetamine-like compounds. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Selective serotonin reuptake inhibitors. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
5-Hydroxytryptophan. Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
Guarana (Paullinia cupana) and ma huang (Ephedra sinica) Overview
Mechanism of action
Clinical presentation
Diagnosis
Management
Prognosis
References
5 Structural Epilepsy
Vascular. Cerebrovascular accidents (ischaemic, haemorrhagic)
Clinical signs
Post-stroke seizures and epilepsy
Diagnostic investigations
Treatment
Prognosis
Inflammatory/infectious
Clinical signs
Encephalitis-related seizures and post-encephalitic epilepsy
Diagnostic investigations
Treatment
Prognosis
Canine distemper
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Feline infectious peritonitis
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Bacterial diseases of the CNS in dogs and cats
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Granulomatous meningoencephalomyelitis
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Traumatic Brain Injury
Pathophysiology of TBI
Initial assessment and emergency treatment
Post-traumatic seizures and epilepsy
Diagnostic investigations
Treatment
Prognosis
Anomalous and Developmental
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Hydrocephalus. Pathophysiology and classification
Clinical signs
Diagnostic investigations
Treatment
Prognosis
Neoplastic
Intracranial neoplasia
Incidence
Clinical signs
Tumour-related seizures and epilepsy
Diagnostic investigations
Treatment and survival times
Prognosis
Meningioma
Incidence
Clinical signs
Diagnostic investigations
Treatment and survival times
Pathological findings and classification
Astrocytoma
Incidence
Clinical signs
Diagnostic investigations
Treatment and survival times
Pathological findings and classification
Oligodendroglioma
Incidence
Clinical signs
Diagnostic investigations
Treatment and survival times
Pathological findings and classification
CNS lymphoma
Incidence
Clinical signs
Diagnostic investigations
Treatment and survival times
Pituitary tumours
Incidence
Clinical signs
Diagnostic investigations
Treatment and survival times
Degenerative
Lysosomal storage diseases
Organic acidurias
Mitochondrial encephalopathies and encephalomyelopathies
Leukodystrophies
Spongy degenerations
Multisystem neuronal degeneration/abiotrophy
References
6 Idiopathic Epilepsy and Genetics
Clinical Overview of Canine Idiopathic Epilepsy
Interictal Signs
Lifespan and Canine Idiopathic Epilepsy
Genetics and Human Epilepsy. Epilepsies with complex inheritance
Monogenic epilepsies
Genetics and Canine Epilepsy
Idiopathic Epilepsy Seizure Disorders with Known Mutations
The Effect of Genetics on Anti-epileptic Medication Response
Genetics and Feline Epilepsy
References
7 Epidemiology of Canine Seizures
Prevalence of Canine Seizures Based on Semiological Classification
Prevalence of Canine Seizures Based on Aetiological Classification. Idiopathic epilepsy
Cryptogenic epilepsy
Symptomatic (structural) epilepsy
Inflammation
Intracranial neoplasia
Head trauma
Vascular disease
Reactive Seizures
Signalment and Canine Seizure Disorders. Breed
Gender
Age
Neurological Examination and Canine Seizure Disorders
Prognosis of Canine Seizure Disorders
References
8 Epidemiology of Feline Seizures
Prevalence of Seizures in Cats
Prevalence of Feline Seizures Based on Semiological classification
Prevalence of Feline Seizures Based on Aetiological Classification
Signalment and Feline Seizure Disorders. Breed
Gender
Age
Neurological Examination and Feline Seizure Disorders
Aetiologies of Feline Seizure Disorders
Prognosis of Feline Seizure Disorders
References
9 Mimics of Seizure Activity: Disorders Confused with Epilepsy
Initial Event Description
Diagnosis of Epilepsy. The importance of the history
Neurological evaluation of a patient with paroxysmal events
Paroxysmal events to consider as possible seizure mimics
Neuromuscular Collapse
Confirming exercise/activity relationship to the problem described
Confirming whether the lesion is upper or lower motor neuron in origin
Confirming whether the disease is focal versus diffuse
Confirming whether the disease is affecting peripheral nerve, muscle or neuromuscular junction
Differential diagnosis for neuromuscular collapse
Specific diagnostic tests for neuromuscular collapse
Involuntary Movement Abnormalities
Types of involuntary movements
Myoclonus
Tremor
Myokymia and neuromyotonia
Dyskinesia
Diagnostic approach for involuntary movement disorders
Establishing the aetiology using clinical characteristics
Localized tremor syndromes. Localized limb tremors/myoclonus
Localized head tremors
Non-ataxic head tremors
Ataxic head tremors
Generalized tremor syndromes
Essential tremors/geriatric (senile) canine tremors
Paroxysmal dyskinesias
Scotty cramp
Episodic hypertonicity in cavalier King Charles spaniels
Startle disease in Irish wolfhounds
Generalized muscle stiffness in male Labrador retrievers
Paroxysmal dyskinesia in Chinooks
Dancing doberman disease
Syncope
Pathophysiology of syncope
Approach to the patient with syncope
Treatment of syncope
Narcolepsy/Cataplexy and Sleep Disorders
Rapid eye movement sleep disorders
Compulsive Behavioural Disorders
Presenting signs of compulsive disorder
Causes of compulsive disorder. Stress
Genotype
Medical problems
Conditioning
Pathophysiology of compulsive disorder
Homogeneity of compulsive disorder
Development
Level of cognition involved
Ease of distraction
Clinical approach to compulsive disorder. Diagnosis
Treatment options
Prognosis
References
10 Clinical and Diagnostic Investigation of the Seizure Patient
Signalment
Medical History
General Physical Examination
Neurological Examination
Level of consciousness and behaviour
Posture
Gait
Involuntary movement abnormalities and cataplexy
Cranial nerve (CN) examination
Postural reactions
Muscle mass and tone
Spinal nerve reflexes
Evaluation of nociception
Palpation of the head, spine and muscles
Seizure and AEM-associated neurological deficits
Neuroanatomic Diagnosis
Differential Aetiologic Diagnoses
Diagnostic Investigations
Haematology, serum biochemistry and urinalysis
Survey radiography of the thorax and ultrasography of the abdomen
Magnetic resonance imaging
Seizure-associated MRI changes
Diffusion tensor imaging
Magnetic resonance volumetry
Functional neuroimaging
Magnetic resonance spectroscopy
Seizure-associated MRS changes
Positron emission tomography and single-photon emission computed tomography
Functional MRI
Cerebrospinal fluid analysis
Seizure-associated CSF changes
Infectious disease testing
Genetic testing
Electroencephalography
References
11 Introduction to Electroencephalography
Principles of Electroencephalography
Electrophysiological basis
Electroencephalography instrumentation
Electrode types
Montage
Patient handling
Electroencephalography Interpretation
Vigilance state and the EEG
Age and the EEG
Artefacts in the EEG
Capacitance
Impedance
Pathological waveforms
Clinical Applications of Electroencephalography
Acknowledgements
References
12 Principles of Anti-epileptic Treatment
Aims of Anti-epileptic Treatment
When to Start Anti-epileptic Treatment
Choice of Anti-epileptic Medication
Initial anti-epileptic treatment
Adjunctive anti-epileptic treatment
Alternative anti-epileptic treatment
Efficacy of AEMs
Choice of Anti-epileptic Medication Dosage
Therapeutic Monitoring of AEMs and Treatment Modulation
Reference ranges and individualization of AEM dosage
Timing of therapeutic monitoring
Therapeutic monitoring and change of AEM formulation
Therapeutic monitoring and pharmacokinetic interactions
Therapeutic monitoring and pathological states
Salivary therapeutic monitoring
When Can Anti-epileptic Treatment be Discontinued?
Pet Owner Education
References
13 Phenobarbital
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Pharmacokinetic interaction with benzodiazepines
Pharmacokinetic interaction with levetiracetam
Pharmacokinetic interaction with zonisamide
Pharmacokinetic interaction with CYP450 inhibitors
Other pharmacokinetic interactions
Transient and Dose-Related Adverse Effects of PB in Dogs and Cats
Suspected Idiosyncratic Adverse Effects of PB in Dogs
Hepatotoxicity
Haematologic abnormalities (cytopenias)
Superficial necrolytic dermatitis
Pancreatitis
Dyskinesia
Hypoalbuminaemia
Suspected Idiosyncratic Adverse Effects of PB in Cats
Alternative AEMs in dogs and cats requiring discontinuation of PB due to life-threatening adverse effects
Cytoprotective agents
PB-related Laboratory Changes
Increased hepatic enzyme activity
Hypercholesterolaemia
Effect on thyroid function testings
Effect on pituitary-adrenal axis and adrenal function testing
Dosing and Monitoring Recommendations. Routine initiation
Loading dose regimen
Reference serum PB concentrations
Monitoring serum PB concentrations
Timing of blood sampling for therapeutic monitoring
Concurrent administration of Br
Change in PB formulation
Efficacy
Summary Recommendations
References
14 Bromide
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Transient and dose-related adverse effects of Br in dogs
Bromide toxicity (bromism)
Suspected idiosyncratic adverse effects of Br in dogs
Personality changes
Pruritic dermatologic lesions
Panniculitis
Persistent cough
Pancreatitis
Br-associated lower airway disease in cats
Br-related laboratory changes. Factitious hyperchloraemia (pseudohyperchloraemia)
Effect on thyroid function tests
Dosing and Monitoring Recommendations. Routine initiation
Effect of diet
Bromide used concurrently with PB
Loading dose regimen
Reference serum Br concentrations
Monitoring serum Br concentrations
Timing of blood sampling for therapeutic monitoring
Br-induced pseudohyperchloraemia as predictor of serum Br concentration
Efficacy
Summary Recommendations
References
15 Zonisamide
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dose-related adverse effects of ZNS
Suspected idiosyncratic adverse effects of ZNS
ZNS-related laboratory changes
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
16 Levetiracetam
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
17 Gabapentin and Pregabalin
Gabapentin
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Pregabalin
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
18 Felbamate
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
19 Topiramate
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
20 The New Additions: Lacosamide, Brivaracetam and Rufinamide
Lacosamide
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
Brivaracetam
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
Rufinamide
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
21 Benzodiazepines
General Mechanism of Action
General Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and General Adverse Effects
Tolerance
Diazepam
Metabolism and pharmacokinetics
Pharmacokinetic interactions and adverse reactions
Dosing and monitoring recommendations
Efficacy
Midazolam
Metabolism and Pharmacokinetics
Pharmacokinetic interactions and adverse reactions
Dosing and monitoring recommendations
Efficacy
Lorazepam. Metabolism and pharmacokinetics
Pharmacokinetic interactions and adverse reactions
Dosing and monitoring recommendations
Efficacy
Clorazepate
Metabolism and pharmacokinetics
Pharmacokinetic interactions and adverse reactions
Dosing and monitoring recommendations
Efficacy
Summary Recommendations
References
22 Imepitoin (Pexion®)
Mechanism of Action
Metabolism and Pharmacokinetics
Pharmacokinetic Interactions and Adverse Reactions
Dosing and Monitoring Recommendations
Efficacy
Summary Recommendations
References
23 Pathophysiology and Management of Cluster Seizures
The Timing of Seizures
Mechanisms of Seizure Clustering
Defining Seizure Clustering
Seizure Periodicity
Prevalence of Seizure Clustering
Risk Factors for Experiencing Seizure Clusters
Risks and Implications of Seizure Clustering
Therapeutic Considerations
Short-Acting Treatment at the Time of a Cluster Event. Rectal benzodiazepines
Nasal benzodiazepines
Long-Acting Treatment at the Time of a Cluster Event
Oral clorazepate
Oral levetiracetam
Vagal nerve stimulation
Summary
References
24 Pathophysiology and Management of Status Epilepticus
Definition
Pathophysiology of Status Epilepticus
Causes of SE. Dogs
Cats
Outcome of SE
Clinical Features of SE
Systemic Features of SE
Management of SE
Identification and treatment of underlying causal factors
Maintain vital functions
Oxygenation, airway and patient acid-base status
Intravenous access
Temperature regulation
Termination of the seizure activity
Principles of AEM Treatment
Benzodiazepines
Phenytoin sodium (Diphenylhydantoin)
Fosphenytoin (FOS)
Barbiturates. Phenobarbital
Treatment of Refractory SE
Continuous benzodiazepine infusion
Levetiracetam
Propofol
Ketamine
Barbiturates
Inhalational anaesthesia
Lacosamide
Transition to Maintenance Therapy
Continuous EEG Monitoring in SE
Summary
References
25 Novel and Adjunctive Treatments
Neurostimulation
Vagus nerve stimulation
Mechanism of Action
Efficacy
Side effects and safety
Non-invasive vagus nerve stimulation
Transcranial magnetic brain stimulation
Thalamic stimulation
Dietary Therapy. Essential fatty acid supplementation
Hypoallergenic diet
Ketogenic diet
Mechanism of action
Efficacy
Side Effects
Acupuncture
Mechanism of action
Efficacy
Side effects
Surgical Therapy
Disorders of the mesial temporal lobe
Lesional neocortical epilepsy
‘Non-lesional’ neocortical epilepsy
Hemispheric epilepsy syndromes
Surgical therapy in veterinary patients
Herbal Medicine
Traditional Chinese medicine
Commonly used herbs
American Hellebore
Betony
Blue Cohosh
Kava
Mistletoe
Pipsissewa
Skullcap
Valerian
Melatonin
Herbal and homeopathic therapy for seizures in dogs and cats
Side effects
References
Glossary of Pharmacological Terminology
Glossary
References
Index
