Ms. M, aged 73 years, was brought to the neuroscience clinic by her daughters. She was alert, pleasantly confused, and using a wheelchair for mobility because of concurrent right knee antalgia and edema. The initial physical exam was unremarkable. Ms. M’s daughters provided details about her medical history, which was significant for an idiopathic transnasal cerebrospinal fluid (CSF) leak that was repaired via bifrontal craniotomy 20 years ago. Since that time, she has experienced recurrent episodes of bacterial meningitis. The last episode occurred approximately two weeks earlier, and she was admitted to the hospital for treatment. After discharge, she and her daughters reported colorless transnasal drainage consistent with CSF.
At the neuroscience clinic, MRI revealed a 3.4-cm peripherally enhancing extra-axial fluid collection within the anterior aspect of the left middle cranial fossa (likely representing abscess or infected arachnoid cyst) and areas of leptomeningeal enhancement within the skull. MRI indicated possible incomplete treatment of Ms. M’s recent bacterial meningitis. Additionally, a right sphenoid sinus surgical defect at the base of the skull was identified as a potential source of the current CSF leak.
Ms. M was admitted to the neurosurgical nursing ward in anticipation of repair of the CSF leak. She was placed in contact isolation. After an infectious disease consultation, IV antibiotics (vancomycin, cefepime, and metronidazole [Flagyl]) were started. Ms. M remained pleasantly confused with increased episodes of restlessness and agitation, which were consistent with sundown syndrome.
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On the evening prior to surgery, the patient was less agitated and nonverbal. She underwent an endonasal repair of the CSF leak. Postoperatively, Ms. M was admitted to the neurologic intensive care unit with a lumbar drain in place to drain 10 cc/hr. She remained nonverbal with the exception of forced one-word responses. Her extremities moved spontaneously, and the only verbal command the patient would follow was to open her mouth to be fed. She ate 75% of all meals but continued to keep her eyes closed and occasionally would have brief myoclonic jerks. Ms. M’s daughter informed nursing staff that this current obtunded state was identical to her most recent hospital stay.
Labs were negative. Electroencephalogram (EEG) was ordered on postoperative day two. A 21-channel digital EEG revealed bifrontal, central-predominant, continuous, high-amplitude 1-2 Hz rhythmic spikes and slow waves with triphasic morphology, which confirmed nonconvulsive status epilepticus (NCSE). Lorazepam (Ativan) 2 mg IV transiently ablated the generalized status epilepticus (SE). Phenytoin load with subsequent scheduled doses and long-term EEG monitoring was initiated. Over the course of several days, EEG results were consistent with ongoing seizure activity. Additional anti-epileptic medications were prescribed. EEG remained abnormal, but the NCSE was resolved. The patient, however, continued to be unchanged clinically.
1. Etiology
Physiologically, epileptic seizure has been defined as a sudden alteration of the central nervous system function, resulting in a paroxysmal high-frequency or synchronous low-frequency, high-voltage electrical discharge.1 SE is a common, life-threatening neurologic disorder that is essentially an acute prolonged epileptic crisis. In early studies, SE was defined by its duration (i.e., continuous seizures occurring for longer than one hour). According to the Epilepsy Foundation, SE is continuous seizure activity lasting more than thirty minutes or more sequential seizures without full recovery of consciousness between seizures. Lowenstein defined SE as any seizure activity lasting longer than five minutes since natural history data show typical generalized convulsive seizure activity resolves spontaneously after three to five minutes.2
SE can be divided into three categories: Generalized convulsive (the most prevalent category) and dangerous, nonconvulsive, or partial. NCSE is further divided into two categories: absence and complex partial. Distinguishing subtypes is important because treatment, causes, and prognosis vary with each.3 All forms of epilepsy can develop into SE (convulsive and/or nonconvulsive).
2. Incidence and prevalence
Approximately 1.5 million persons in the United States suffer from a seizure disorder. The annual incidence for all types of seizures is 1.2 per 1,000 and 0.54 per 10,000 for recurrent. It is estimated that more than 45 million people in the world experience seizures, which affect men and women equally.
NCSE is more common than previously thought and has a bimodal peak and highest incidence in children and the elderly. High-risks groups include those with a history of brain injury or lesions. NCSE constitutes 20%-23% of SE cases, occurring in about 8% of all comatose patients without signs of seizure activity and persisting in 14% of patients after controlling generalized convulsive SE. EEG is undoubtedly the most sensitive and indispensable tool for the diagnosis of NCSE. At the very least, EEG evidence of seizures is necessary. Without EEG, only presumptive diagnosis is possible.4
Approximately 10% of adults with childhood-onset absence seizures experience NCSE. About 75% of all cases of NCSE occur before age 20 years. When NCSE occurs in adults, the patients are often elderly. The mean age of onset in adults is 51 years.5
3. Pathophysiology
Adult seizures usually have specific causes, ranging from cerebral tumors and old cerebrovascular foci to such suppurative diseases as thrombophlebitis, abscesses, and neurosyphilis. A number of chemical mechanisms have been proposed, including activation of glutamate receptors, influx of calcium ions, mitochondrial dysfunction, reactive oxygen and nitrogen species, and activation of intracellular proteases and lipases, all of which indicate excitotoxicity. Whether structural or chemical, all underlying processes point toward cortical irritation or injury. NCSE based on clinical features typically does not accurately reflect its underlying cause, but its tempo suggests an aggressive etiology. Seizures are a prominent feature of all varieties of bacterial meningitis.
4. Electroencephalogram
EEG characteristics of NCSE are heterogeneous, and the morphology varies. Morphology includes typical and atypical spike-wave discharges, multiple or poly spike-wave discharges, and rhythmic delta activity with intermixed spikes. The predominant EEG patterns in comatose patients do not fall into ictal or non-ictal categories. Obtunded and comatose patients have more complex and controversial EEG patterns. These electrographic variables can be defined as generalized spike-wave discharges at >3 Hz. Clearly evolving discharges of any type can reach frequencies as high as ±4 Hz.
5. Discussion
Unresponsive and behavioral arrest and abnormal muscular movements of the extremities, face, and/or eyelids characterize NCSE. EEG to rule out NCSE is warranted in patients with a clear change in consciousness or those who are not comatose but lethargic and confused with decreased spontaneous speech, slow speech, or myoclonic jerks. Diagnosis can be difficult because EEG may show a variety of rhythmic or periodic patterns, some of which are of unclear significance. NCSE is frequently more difficult to treat than convulsive SE. NCSE is often diagnosed late and may have already been occurring for days or even weeks. Recognition and diagnosis of NCSE is also often delayed because people, including health-care personnel, are either unaware or fail to consider the diagnosis in a timely manner.
Current evidence suggests the common clinical denominator associated with NCSE is mental status impairment. Relying on clinical symptoms alone can delay diagnosis because the clinical presentation can range from subtle clinical signs or encephalopathy to frank coma. Duration of ictal activity and length of delay prior to diagnosis are independent predictors of poor outcome.4 It has been suggested that there is no definite evidence that NCSE causes harm because studies are confounded by inconsistent definitions.
Ms. M never regained her pre-admission level of consciousness, consumed all nutrition via syringe, and frequently thrashed about in her hospital bed. Repeat EEG monitoring was negative for NCSE. Her family was encouraged to delay discharge and allow referrals to a subacute facility. Prior to this hospital stay, Ms. M told her family she did not want aggressive medical care. On postoperative day 12, Ms. M was discharged home. Her daughter called to report convulsive seizure activity unresponsive to rectal diazepam. Abiding by her mother’s wishes, further medical care was not sought, and Ms. M expired three days after discharge. n
Ms. Christian-Lobley is a nurse practitioner with the Medical College of Wisconsin. She works in the department of neurosurgery at Froedtert Memorial Lutheran Hospital in Milwaukee.
References
- M Victor and AH Ropper AH, eds. Adams and Victor’s Principles of Neurology, 7th ed., New York, N.Y.: McGraw-Hill Professional; 2001:331.
- Lowenstein DH. Treatment options for status epilepticus. Curr Opin Pharmacol. 2003;3:6-11.
- Emedicine. Status epilepticus.
- Murthy JM. Nonconvulsive status epilepticus: an under diagnosed and potentially treatable condition. Neurol India. 2003;51:453-454.
- Porter RJ, Penry JK. Petit mal status. Adv Neurol. 1983;34:61-67.
All electronic documents accessed June 16, 2010.
