19 Seizure Disorders: Diagnosis and Management

10.1055/b-0038-160249

19 Seizure Disorders: Diagnosis and Management

Vivek Ramakrishnan, Margaret Wacker, Dan E. Miulli, and Glenn Fischberg

Abstract

Seizure disorder is due to irritation of the brain from edema, compression, metabolic derangements, or other circumstances affecting the neurophysiology of the brain tissue. The irritation leads to abnormal electrical discharges of the neurons, which requires additional energy and resources. If the continuous discharge is not halted quickly the brain will not be able to replenish its resources, leading to the failure of normal brain cell homeostasis and eventual cell death. When seizures occur, adequate airway, breathing, and circulation should be maintained in order to help with the brain nutrient delivery to prevent ischemia. The seizure must be stopped as soon as possible and steps should be taken to prevent recurrence.

Case Study

A 23-year-old woman underwent a subfrontal craniotomy for craniopharyngioma. She developed transient diabetes insipidus. Several days later, her sodium level dropped abruptly from the 150 s to 131 after a dose of 1-deamino-8-D-arginine vasopressin (DDAVP, or desmopressin) as the diabetes insipidus was resolving. At the same time, her phenytoin level was found to be subtherapeutic, though this was not immediately corrected because she appeared to be doing well clinically and had no seizures. Later in the evening, her family noticed some staring spells and decreased responsiveness. This persisted, and later she was noted to have some seizure activity witnessed by the nurse. This continued, and the patient then developed nonconvulsive status epilepticus. A follow-up computed tomographic scan was obtained, which showed increased edema in the region of the tumor consistent with hypoxic injury. Despite efforts to correct the electrolytes and control the seizure activity, she went on to brain death.

See end of chapter for Case Management.

19.1 Classification of Seizures

Seizures may occur in patients in the neurosurgical intensive care unit (NICU) as evidence of either a primary or secondary neurologic disease process. In addition, seizure thresholds may be lowered due to metabolic derangements or fever, as was the case in the case study. Seizures may also add to the injury to the brain, especially if they are recurrent, through the imposition of increased metabolic demand or hypoxia due to the suppression of respirations during the seizure episodes. Untreated or unrecognized status epilepticus can be fatal or cause permanent neurologic injury. Hence efforts must be made to reduce the risk of seizures in the already neurologically compromised NICU patient.

Because many of the treatments for epilepsy are more effective for one or another seizure type, a brief review of types of seizures is necessary for choosing appropriate treatment. The International Classification of Epileptic Seizures (► Table 19.1) is included here as a basis for understanding different types of seizures. ¹ Generalized seizures, including those that have secondarily generalized, may affect respiration and thus be more dangerous to the patient, especially if they are recurrent.

**Table 19.1** International classification of epileptic seizures ¹ , ³
Generalized seizures (bilaterally symmetrical and without local onset) Tonic, clonic, or tonicoclonic (grand mal) Absence (petit mal) Simple—loss of consciousness only Complex—with brief tonic, clonic, or automatic movements Lennox–Gastaut syndrome Juvenile myoclonic epilepsy Infantile spasms (West’s syndrome) Atonic (astatic, akinetic) seizures (sometimes with myoclonic jerks) Partial, or focal, seizures (seizures beginning locally) Simple (without loss of consciousness) Motor (tonic, clonic, tonicoclonic; Jacksonian; benign childhood epilepsy; epilepsia partialis continua) Somatosensory or special sensory (visual, auditory, olfactory, gustatory, vertiginous) Autonomic Psychic Complex (with impaired consciousness) Beginning as simple partial seizures and progressing to impairment of consciousness With impairment of consciousness at outset Special epileptic syndromes Myoclonus and myoclonic seizures Reflex epilepsy Acquired aphasia with convulsive disorder Febrile and other seizures of infancy and childhood Hysterical seizures

19.2Treatment of Seizures

Anticonvulsant medications should be selected by optimizing the drug for the type of seizures the patient has or for which the patient is at risk. For partial-onset seizures, including those with secondary generalization, the preferred agents are carbamazepine and phenytoin. Alternative agents include valproate and many of the newer anticonvulsant agents, including levetiracetam. For absence seizures, first-choice agents are ethosuximide and valproate. Valproate is the first choice for atypical absence or atonic seizures. An alternative is lamotrigine for either absence or atypical absence/atonic seizures. Valproate is also the first choice for myoclonic seizures, with the alternatives of lamotrigine, clonazepam, and clorazepate. For generalized tonicoclonic seizures, valproate, carbamazepine, and phenytoin are preferred agents, though newer antiepileptic drugs, such as topiramate, lamotrigine, and zonisamide, may also be useful. In general, one agent should be chosen and increased to the maximum tolerated dose before beginning polypharmacy for the treatment of seizures. Carbamazepine is contraindicated in primary generalized epilepsy due to possible exacerbation, but may be effective for secondarily generalized epilepsy.

In the setting of the NICU, the mode of administration of agents needs to be considered because many patients are unable to take medications orally. Agents currently available in the United States for intravenous (IV) administration include lorazepam (Ativan), diazepam (Valium), phenytoin (Dilantin), fosphenytoin (Cerebyx), phenobarbital, levetiracetam (Keppra), and valproate (Depacon). In addition, diazepam is available for rectal administration.

Newer antiepileptic agents in wide use over the last several years include levetiracetam and lacosamide (Vimpat). Levetiracetam (Keppra) has a mechanism of action that is unclear; however, it is suggested that the medication might work on presynaptic calcium channels, inhibiting synaptic firing. Lacosamide (Vimpat) has been shown to work on voltage-gated sodium channels and has been approved as an adjunctive therapy for partial seizures as well as neuropathic pain syndromes.

19.3 Status Epilepticus

Status epilepticus is a special case of seizure activity historically thought of as without recovery of consciousness between seizures lasting for more than 30 minutes. It is now generally considered ≥ 5 minutes of continuous clinical and/or electrographic seizure activity, or occurrence of more than one seizure without recovery to clinical baseline between. ²

There are approximately100,000 cases per year in the United States. ³ , ⁴ In half of the cases, it is the initial manifestation of a seizure disorder. The most commonly affected groups are young children and patients over 60 years of age. Status epilepticus can be either generalized or partial. Generalized status can be convulsive and nonconvulsive.

Convulsive status includes (1) generalized: may be tonic, tonicoclonic, myoclonic (atonic would be an unusual form of generalized seizure; though without convulsions, still not generally considered either part of the nonconvulsive status epilepticus realm) and (2) focal motor status or epilepsia partialis continua.

Nonconvulsive status includes altered mentation, and despite its designation is still allowed to have subtle movements, such as some facial twitches or eye blinking or automatisms, such as lip smacking. Symptoms may be negative, such as aphasia, catatonia, or lethargy, or positive, such as, crying, laughter, or psychosis. Generalized convulsive status is the most frequent type of status epilepticus, of which 75% of cases are secondarily generalized. There are a variety of causes for status epilepticus, including febrile seizures; cerebrovascular accidents; infection, such as meningitis; idiopathic, epilepsy, or subtherapeutic anticonvulsants; electrolyte imbalance; drug intoxication, especially cocaine; alcohol or benzodiazepine withdrawal; traumatic brain injury; anoxia; and tumors.

Treatment of status epilepticus is directed to stabilizing the patient by stopping seizure activity and addressing the underlying cause of the status epilepticus. Any recurrent seizures without interval return to baseline should be treated aggressively. Historically, mortality from status epilepticus has been reported to be as high as 50%, although more recent data suggest it is on the order of 10 to 12%, to perhaps as high as 20%, of which only ~ 2% of deaths are directly attributable to the status epilepticus. ³ , ⁴ Morbidity and mortality may be due to central nervous system (CNS) injury caused by repetitive electrical discharges, systemic stress from the seizure (cardiac, respiratory, renal, or metabolic), or CNS damage from the insult that caused the status epilepticus.

Initial treatment should address airway, breathing, and circulation (ABC). This should include maintaining the airway with an oral airway or possibly intubation, the administration of supplemental oxygen, and cardiac and blood pressure monitoring. Once this has been accomplished, priorities must be to stop further seizure activity and to correct its cause. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ An IV of normal saline should be started as soon as possible, and both a benzodiazepine, such as lorazepam or diazepam, and phenytoin loading dose should be administered. Intramuscular midazolam has been shown to be as effective as IV lorazepam. ⁸ Lorazepam and midazolam have the most data, and diazepam should be used if it is the first available as rectal medication. Emergent treatment for status is Class I, Level A evidence for lorazepam and midazolam and Class IIa, Level A for diazepam. ² The role of valproate is not yet defined for use in status epilepticus, although it is a potential additional anticonvulsant that may be used. In general, except in the case of cocaine-induced seizures, a benzodiazepine alone should not be used; rather, it should be used in conjunction with a longer-acting anticonvulsant.

Concurrently, efforts should be started to identify and correct the underlying cause. This workup should include blood work consisting of electrolytes, glucose, magnesium, calcium, anticonvulsant level, and arterial blood gas. If there is any consideration of CNS infection, a lumbar puncture should be performed unless it is contraindicated. If the patient is hypoglycemic or if glucose cannot immediately be measured, 25 to 50 mL of dextrose 50 (D50) should be given. Fifty to 100 mg of thiamine should be given immediately prior to the D50 in patients in whom thiamine deficiency might be present. Likewise, naloxone (Narcan 0.4 mg IV push [IVP]) should be given in the case of patients who might have taken narcotics. An electroencephalography (EEG) monitor is helpful if available. Paralytic agents will stop the visible manifestation of the seizures, but they do not stop the dangerous electrical activity in the brain that can lead to permanent neurologic damage. Thus they should be avoided in patients with status epilepticus and those without EEG monitoring, except for the use of short-acting agents for intubation. In some cases of prolonged seizure activity, paralytic agents may be helpful in reducing the lactic acidosis and rhabdomyolysis caused by the seizure activity. In these cases, continuous EEG monitoring is necessary to determine whether electrical seizures are continuing and possibly causing further damage to the brain. In addition, narcotics and phenothiazines should be avoided in status epilepticus because they lower the seizure threshold (► Table 19.2).

**Table 19.2** Protocol for the management of status epilepticus ¹ , ³ , ⁴
Lorazepam (Ativan) 0.1 mg/kg IV up to 4 mg (average adult dose) at rate of < 2 mg/min OR Diazepam (Valium) 0.2 mg/kg (10 mg average adult dose) IV at 5 mg/min OR Valproic acid 20 mg/kg diluted in water or vegetable oil administered rectally in pediatric patients with frequent seizures and no IV access Phenytoin (Dilantin) or fosphenytoin (Cerebyx) load of 20 mg/kg IV at a maximal rate of 50 mg/min. If phenytoin is used, cardiac monitoring should be performed and the rate slowed should arrhythmias occur. If seizures continue, additional phenytoin may be given up to a total of 30 mg/kg OR Phenobarbital IV up to a total load of 20 mg/kg. (Because phenobarbital may lower blood pressure and suppress respirations, these need to be monitored during its administration.) OR Paraldehyde 0.3–0.5 mg/kg in a 1% solution diluted 1:1 in vegetable oil administered rectally If seizures continue, the patient should be intubated and general anesthesia instituted with pentobarbital to induce burst suppression. This should be started with a load of 15 mg/kg IV and continued at a rate of ~ 2.5 mg/kg/h. Blood pressure should be closely monitored, and pressors may be needed to maintain an adequate blood pressure. OR Propofol can be used as an alternative to pentobarbital to induce burst suppression. A load of 40 mg is given and repeated to an induction dose of 2.0–2.5 mg/kg and maintenance of 0.1–0.2 mg/kg/min. Similar to pentobarbital, blood pressure must be closely monitored, and pressors may be needed. OR Midazolam (Versed) 5–10 mg bolus at less than 4 mg/min, followed by a 0.05–0.40 mg/kg/h drip By this stage, continuous electroencephalographic monitoring should be used to titrate either pentobarbital or propofol to provide burst suppression. It should also be used to monitor the effect of treatment and should be instituted as early as is feasible in those patients with refractory status epilepticus who do not rapidly return to baseline function.