Reactive seizures are the reaction of a normal brain to a systemic metabolic, nutritional or exogenous toxic disorder (Podell, 1995). Reported prevalence of reactive seizures in dogs and cats varies among studies ranging from 7 to 32% in dogs and from 4 to 28% in cats (Bateman and Parent, 1999; Platt and Haag, 2002; Rusbridge, 2005; Pákozdy et al., 2008, 2010; Zimmermann et al., 2009; Brauer et al., 2011; Steinmetz et al., 2013) (see Chapters 7 and 8). In a recent study the most frequent cause of reactive seizures were intoxications (37/96, 39% of dogs) and hypoglycaemia (31/96, 32% of dogs) (see Fig. 7.2, Chapter 7); 49% (47/96) of dogs had generalized tonic-clonic seizures with loss of consciousness and 41% (39/96) of dogs were presented in status epilepticus (Brauer et al., 2011). Dogs with reactive seizures caused by exogenous toxicity have a significantly higher risk to develop status epilepticus, particularly as first manifestation of a seizure disorder, than dogs with other seizure aetiologies (Zimmermann et al., 2009). In cats with reactive seizures and structural epilepsy, status epilepticus is significantly more common than in cats with idiopathic epilepsy (see Schriefl et al., 2008; Pákozdy et al., 2010; Chapter 3).

      Clinical presentation in animals with systemic metabolic, nutritional and toxic disorders is variable depending on the underlying aetiology. Toxic disorders generally have an acute (less than 24 h) onset and neurological signs may be preceded or accompanied by gastrointestinal, cardiovascular or respiratory signs. However, chronic lead intoxication may result in recurrent seizures. Metabolic and nutritional disorders can present with an acute, subacute, or chronic onset and may be progressive or relapsing remitting. The neurological examination generally reveals diffuse, bilateral and often symmetrical neurological deficits, however seizures can sometimes be the only neurological abnormality. Diagnostic investigations (see Chapter 10) are aimed at identifying the underlying aetiology of the seizures and, if present, of the other clinical signs. Treatment is aimed at the underlying aetiology and seizure control with anti-epileptic medications (AEMs).

      This chapter describes disorders commonly resulting in reactive seizures. For detailed information on specific AEMs, as well as management of cluster seizures and status epilepticus, the reader is referred to Chapters 12 to 24.

       Systemic Metabolic Disorders Causing Seizures

      Metabolic diseases can cause seizures by interfering with energy metabolism, altering osmolality, acid-base status, or producing endogenous toxins (O’Brien, 1998). The metabolic disorders most commonly reported to cause seizures in the veterinary literature are described below.

       Hypoglycaemia

       Overview

      The blood glucose concentration is of prime importance for normal neuronal metabolism. Glucose is the single most important source of energy in the brain and carbohydrate storage in neural tissue is limited (Hess, 2010). Therefore cerebral function depends on a continuous supply of glucose. Glucose enters the brain by noninsulin dependent facilitated transport mechanisms, which requires a minimum blood glucose level to operate effectively. Persistent hypoglycaemia results in neuronal adenosine triphosphate (ATP) depletion, Na-K-ATPase dysfunction, cytotoxic oedema, excitatory neurotransmitter release (especially glutamate), activation of glutamate receptors, increased intracellular calcium, zinc, and nitric oxide synthase activity, reactive oxygen species generation, lipid peroxidation, DNA damage and cellular necrosis.

       Clinical presentation

      Hypoglycaemia at glucose concentrations of less than 60 mg/dl (<3 mmol/l) can result in neurologic signs including seizures. Clinical signs vary depending on the rate of decrease, magnitude and duration of hypoglycaemia and include behavioural changes, altered mental status, nervousness, tremors, generalized weakness and seizures. Severe brain damage, coma and death may occur with glucose concentrations of less than 18 mg/dl (<1 mmol/l). As with other homeostatically regulated parameters, the onset and severity of neurological signs may depend more on the rate of decrease than the actual concentration of glucose. Clinical signs may be triggered by fasting or exercise. There are multiple causes of hypoglycaemia (Box 4.1).

       Diagnosis

      The diagnosis of hypoglycaemic encephalopathy is based on documenting hypoglycaemia in an animal with neurological signs that improve or resolve following normalization of blood glucose concentration. Specific diagnosis of the underlying disorder requires additional investigations. The reader is referred to internal medicine textbooks for further details on diagnosis and treatment of underlying aetiologies of hypoglycaemia. When hypoglycaemia is suspected in animals presenting with seizures or other neurological signs a blood sample should be taken. Falsely low glucose concentrations may result from use of human point-of-care glucometers in haemo-concentrated animals or from delayed separation of serum from blood cells (which continue to consume glucose).

Box 4.1. Underlying causes of hypoglycaemia.

      Overproduction of endogenous insulin or insulin-like substances (e.g. insulin-like growth factor):

      • Pancreatic insulinoma;

      • Islet cell hyperplasia;

      • Extrapancreatic neoplasms including intestinal smooth-muscle tumours, hepatic tumours, or lymphoma.

      Exogenous insulin overdose in animals with diabetes mellitus (especially in cats).

      Decreased glucose production:

      • Severe hypoadrenocorticism;

      • Hypopituitarism;

      • Growth hormone deficiency;

      • Hepatic failure;

      • Glycogen storage disease;

      • Glycogen depletion in young puppies (usually of toy or miniature breeds) and kittens.

      Excess glucose consumption:

      • Sepsis;

      • Hunting dog hypoglycaemia syndrome associated with inadequate caloric intake and strenuous exercise.

      Drug associated: