Treatment of Cluster Seizures and Status Epilepticus

Chapter 230


Treatment of Cluster Seizures and Status Epilepticus



Acute-onset seizures are common presenting complaints in veterinary emergency practice. They are caused by focal groups of abnormal neurons that initiate and then propagate bursts of aberrant activity. These episodes generally are short-lived, but prolonged seizure activity or repeated seizures can be life threatening and must be treated aggressively. Treatment of cluster seizures or status epilepticus should focus on rapid treatment of the seizures, identification and treatment of systemic sequelae such as hypoperfusion, hyperthermia, and deficits in ventilation and oxygenation, and in-patient therapy targeted at achieving a 24-hour seizure-free interval. Additional workup to identify the underlying cause of the seizures should be initiated once the patient’s condition has been stabilized. Finally, an anticonvulsant treatment plan tailored to the needs of the patient and client must be devised. This chapter considers these aspects of diagnosis and therapy.



Pathophysiology


A seizure is initiated by a high-frequency burst of action potentials within a local, hypersynchronized population of neurons. When a large enough population of neurons is involved, a characteristic spike can be seen in the electroencephalogram (EEG). Within this population, individual neurons experience a sequence of events that includes the following: (1) an intracellular influx of calcium and sodium, leading to a high-frequency burst of action potentials at approximately 700 to 1000/sec; (2) a phase during which the cell remains depolarized; and finally (3) rapid influx of chloride or efflux of potassium mediated by γ-aminobutyric acid (GABA) receptors, which leads to rapid repolarization and hyperpolarization. Although the cause commonly is forebrain disease, other areas of the brain, including the thalamus, subcortical nuclei, and brainstem, can participate in the genesis and propagation of seizures.


Individual, infrequent, and short-duration seizures may not require therapy, but severe, acute seizures are life-threatening emergencies, and aggressive therapy is warranted. Cluster seizures and status epilepticus are the two most life-threatening types of seizures. A cluster of seizures is defined clinically as more than one seizure within a 24-hour period, between which the patient returns to normal mentation and activity. Status epilepticus is seizure activity that continues unabated for longer than 5 minutes or multiple seizures between which the patient does not return to normal mentation. With these types of severe seizures, direct neuronal damage is common and predisposes the patient to more frequent and severe seizures in the future. In addition, systemic sequelae such as traumatic injury to other parts of the body, hyperthermia leading to disseminated intravascular coagulation (DIC), aspiration pneumonia, and noncardiogenic pulmonary edema are common, so that close monitoring and intensive supportive care are required even after the seizures have been controlled. Aggressive management of cluster seizures and status epilepticus is essential, and both intracranial and extracranial priorities must be addressed.



Differential Diagnoses and Diagnostic Workup


Both extracranial and intracranial diseases may cause seizures. Determining the definitive cause of an individual patient’s seizures can require an extensive diagnostic workup, but development of the best treatment plan and accurate estimation of prognosis depends upon an accurate diagnosis.



Extracranial Causes of Seizure


Metabolic disturbances and systemic disease can lead to alterations in the electrophysiology of the brain, causing paroxysmal neuronal discharges and seizures. In general, these types of diseases are likely to cause widespread disturbances affecting both hemispheres. Therefore generalized seizures are more common than focal seizures.


Endogenous toxins accumulating because of hepatic or renal disease can lead to seizures. Metabolic disturbances such as hypoglycemia, hyperlipidemia, hypocalcemia, and hypermagnesemia as well as endocrine diseases such as hypothyroidism and hyperosmolar nonketotic diabetes mellitus also can lead to seizures. Many toxicoses, including bromethalin, theobromine, caffeine, lead, or organophosphate poisoning, can result in seizures.


Initial diagnostic testing should include a complete blood count to rule out systemic inflammation or infection and platelet disorders, as well as a chemistry panel and urinalysis to rule out electrolyte and glucose derangements and to assess renal and hepatic function. Taking a thorough history to rule out potential toxin exposure also is essential. For patients in which there is a high index of suspicion of extracranial disease, further diagnostic studies including abdominal ultrasonography or specific organ function testing may be warranted.



Intracranial Causes of Seizure


Once extracranial causes of seizure are ruled out, the many primary intracranial causes of seizure must be considered. In patients with localizing neurologic deficits (e.g., cranial nerve dysfunction or lateralized proprioceptive deficits), intracranial disease is more likely than extracranial disease. A classification scheme such as DAMNIT-V can be helpful for organizing this large list of disorders. See Table 230-1 for a compilation of differential diagnoses using the DAMNIT-V scheme. Definitive diagnosis of intracranial causes of seizure commonly requires advanced imaging such as magnetic resonance imaging or computed tomography and cerebrospinal fluid analysis, which usually cannot be done until the patient is in stable condition and seizures are controlled. Basic historical and signalment data can be useful in ranking the relative likelihood of each of the differential diagnoses. In dogs younger than 6 months of age, infectious or anomalous diseases are most common. In dogs between 6 months and 6 years of age, idiopathic epilepsy is most common, and in dogs older than 6 years of age, neoplasia is most likely. In younger cats, infectious and anomalous diseases are most common. In outdoor cats, parasitic diseases like cuterebriasis should be considered, and in catteries and multicat households, feline infectious peritonitis becomes more likely.




Treatment


Treatment includes emergent anticonvulsant therapy and extracranial stabilization. A number of anticonvulsant drugs are effective in the acute setting, but careful patient monitoring is important. The management of extracranial complications and support of other organ systems is also of vital importance.



Emergent Anticonvulsant Therapy


It is vital that seizure activity be stopped as soon as possible to prevent continued injury to the brain and to reduce the potential for systemic sequelae. The goal of emergent anticonvulsant therapy is to stop all seizure activity immediately and to prevent all additional seizures for a 24-hour period. It should be recommended strongly to the owner of any patient with cluster seizures or status epilepticus that the animal be admitted to the hospital for a minimum of 24 hours for intravenous anticonvulsant therapy. If the patient has additional seizures within the first 24 hours of therapy, the 24 hour time period should be restarted.



Benzodiazepines


Intravenous diazepam (0.5 to 1.0 mg/kg) or midazolam (0.066 to 0.22 mg/kg) should be considered first-line therapy for patients with severe, acute seizures. These drugs are GABA agonists and cause hyperpolarization of neurons via influx of chloride ions, which results in cessation of seizure activity. They generally are effective and safe when given intravenously in dogs and cats, and have a low likelihood of significant adverse effects, although a small number of cats have been reported to develop fatal acute hepatic necrosis when administered diazepam orally. For patients in whom intravenous access is not readily available, diazepam at a dose of 1 to 2 mg/kg can be administered rectally and is absorbed rapidly. To ensure adequate retention of the drug when administered rectally, it should be injected through a red rubber catheter passed into the colon and flushed with saline or air. Intramuscular midazolam has also recently been shown to be as effective and safe as intravenous benzodiazepines for status epilepticus in people and may be considered an alternative to rectal diazepam in patients without IV access. If the patient responds to benzodiazepine therapy but shows rapid recrudescence, an intravenous constant-rate infusion should be considered. Diazepam at 0.5 to 2.0 mg/kg/hr often is effective, but the drug should be protected from light and drawn up from a glass vial freshly every 6 hours because of its capacity to bind to plastic.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Treatment of Cluster Seizures and Status Epilepticus

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