Nonconvulsive Status Epilepticus

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Diagnosis and reasoning

The young adult who presents following a first time convulsion is a diagnostic dilemma, with the possibilities ranging from syncope with jerky movements, to nonepileptic attack disorder (NEAD), and primary and secondary seizures. However, the prolonged confusional state in this patient supplies an important diagnostic clue; in an emergency setting, this should raise concern of an acute encephalopathy - such as that secondary to central nervous system (CNS) infections, strokes, metabolic derangements, or drugs and toxins. The family history of epilepsy raises another possibility: the convulsion might have been a first epileptic seizure, with her now being in a postictal state, or more remotely, nonconvulsive status epilepticus (NCSE). Two other disorders are notable for presenting with convulsions and prolonged confusion: intermittent psychosis and hysterical fugue; however, these are not emergencies, and can be considered on a more leisurely basis. The physical examination does not reveal any significant abnormality except for a lacerated tongue and brisk knee jerks; these signs may be encountered after convulsions due to any cause. The low-grade fever in this patient might be due to a CNS infection, but is a non-specific finding. Conversely, there are no features of meningism, or a history of headache. The absence of focal neurological findings makes a stroke clinically less likely (but does not completely exclude this possibility). There is no evidence in support of drug intoxication, although this may need further evaluation. Metabolic derangements cannot be excluded via clinical findings alone. Her biochemical tests show normal glucose and electrolyte levels; the CT scan of the brain shows no mass lesions, structural anomalies or evidence of hemorrhage; the cerebrospinal fluid (CSF) analysis is not suggestive of infection or inflammation. Given the possibility of epilepsy, an electroencephalogram (EEG) can be justified; this surprisingly, reveals the presence of generalized spike and slow wave discharges, a complex of findings characteristic of absence status, a common phenotype of NCSE. NCSE is a medical emergency; fortunately, it often rapidly responds to treatment with a benzodiazepine such as Lorazepam. Note that this effect may be transient, and a longer acting antiepileptic drug may need to be administered afterwards As opposed to convulsive status epilepticus (SE), individuals with NCSE generally do not require treatment in a critical care setting. Both IV glucose and IV antibiotics are not indicated in this patient. In the long term, note that she needs further investigation as to whether this is de novo epilepsy, or whether there is an underlying trigger factor.


Discussion

Status epilepticus (SE) is a neurological emergency associated with significant mortality and morbidity. Traditionally, SE was defined as a continuous seizure lasting more than 30 minutes, or two or more seizures without full recovery of consciousness between them. However, recent guidelines recommend that 5 minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures to be defined as SE, and treated accordingly. This is because spontaneous termination becomes less likely if the seizure lasts for more than 5 minutes; in addition, the longer the seizure continues, the more difficult it is to control with antiepileptic drugs (AEDs) and the greater the degree of neuronal damage. SE can be broadly categorized into generalized convulsive SE (GCSE) and non-convulsive SE (NCSE) depending upon the clinical and EEG findings. NCSE refers to seizure activity seen on an electroencephalogram (EEG) without the clinical findings of a physical convulsion. Note that the remainder of this discussion focuses on NCSE. The etiology of NCSE is poorly understood and probably heterogenous; however in many cases, it arises de-novo or may correspond to conversion of an existing seizure or of GCSE into NSCE. Three phenotypes of NCSE are commonly seen in practice: absence status, complex focal status, and NCSE associated with coma. Absence status is characterized by confusion, diminished responsiveness with occasional blinking and twitching that may last for hours or days. Complex focal NSCE presents with prolonged or repetitive complex, partial seizures. Absence and focal NCSE can be distinguished easily by EEG, the former being characterised by generalised spike and slow wave activity, and the latter by more or less focalised discharges generally associated with the temporal or frontal lobe. Absence status is more benign in its clinical presentation and in its prognosis (as opposed to focal NCSE), and is more common in younger patients. Despite the fact NCSE makes up around one-third of all cases of status epilepticus (SE), it is still grossly underdiagnosed and undertreated. Since the diagnostic criteria of NCSE are controversial, all patients with clinical features suggestive of NCSE such as prolonged postictal confusion, unexplained coma or subtle behavioural changes should undergo EEG monitoring; this is vital for confirmation of the diagnosis. Note that EEG evaluation is also useful in excluding other differential diagnoses such as metabolic disturbances, CNS infections and transient ischemic attacks. The treatment recommendations for NCSE, though controversial, differ significantly from those of GCSE. As opposed to GCSE, non-comatose NCSE patients generally do not require ICU care; in addition, NCSE tends to show a good response to treatment, with some patients even recovering spontaneously. The general condition of the patient, possible underlying etiology and likely prognosis play a significant role in selecting the appropriate treatment option. In the vast majority of cases (particularly typical absences), benzodiazepines should be used to interrupt the NCSE. Following acute and/or diagnostic use of benzodiazepines, many patients will respond effectively to sodium valproate; this plays a key role in both acute treatment and maintenance therapy. For patients who fail to respond to valproate, an appropriate and effective antiepileptic drug (AED) regimen should be formulated with caution. It is particularly important to note that complex partial NCSE requires more aggressive treatment in the acute setting, and that such patients are less likely to remain off medication in long term. Intensive treatment should be cautiously initiated in comatose patients due to the fact that some patients may rapidly recover anyway, while more vulnerable patients may potentially deteriorate.


Take home messages

  1. Status epilepticus (SE) can present in either of the two forms: Generalized Convulsive Status Epilepticus (GCSE) with prolonged convulsions or Non-convulsive status epilepticus (NCSE) with confusion, behavioural changes, and subtle motor activity or memory defects.
  2. Despite making up an estimated one third of all SE cases, NCSE is grossly underdiagnosed resulting in undue delays in treatment and greater neurological morbidity.
  3. Where NCSE is suspected, the diagnosis should be confirmed by EEG whenever possible and treatment should be initiated at once.
  4. Unlike GCSE, the majority of patients with NCSE do not require ICU care.

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