REVIEW ARTICLE
Diagnosis, Etiology, and Treatment of Nonconvulsive Status Epilepticus, a Semiological Oriented Review Pedro Beleza, MD,* Joa˜o Rocha, MD,w and Joa˜o Pinho, MDw
Background: Nonconvulsive status epilepticus (NCSE) defines a prolonged electrographic seizure activity resulting in nonconvulsive symptoms. Semiology is a crucial element in diagnosis, etiological evaluation, and treatment plan of NCSE. It includes mostly generalized myoclonic status (GMS), focal simple motor status (FSMS), and dyscognitive status (DS). Review Summary: This review aims to guide clinicians in diagnosis, etiological evaluation, and treatment of patients with NCSE based on semiological presentation. Conclusions: Diagnosis of GMS and FSMS is based mainly on semiology, whereas DS often requires EEG for differential diagnosis with nonepileptic events. GMS and FSMS etiological investigation may be readily prioritized based on semiological type, whereas DS requires EEG for further classification in psychomotor status and absence status. Choice of appropriate treatment is dictated by the semiological presentation, EEG findings, and etiology. Surgery and other interventions including electroconvulsive therapy and vagal nerve stimulation should be considered in patients refractory to medical treatment. Key Words: nonconvulsive status epilepticus, semiology, diagnosis, treatment, prognosis
(The Neurologist 2015;19:160–167)
S
tatus epilepticus (SE) was defined by the International League Against Epilepsy task force on classification and terminology as “a seizure that shows no clinical signs of arresting after a duration encompassing the great majority of seizures of that type in most patients or recurrent seizures without interictal resumption of baseline central nervous system function,”1 the latter including not just a disturbance of consciousness, but any kind of neurological deficit persisting between seizures. Clinical studies have considered 5,2 10,3 or 30 minutes of ongoing epileptic activity to define SE,4 mostly based on the knowledge that spontaneous cessation of generalized convulsive seizures is unlikely after 5 minutes5,6 and on experimental studies that have shown irreversible neuronal damage after about 30 minutes of continuing epileptic activity.7 Initial management of generalized convulsive status epilepticus, usually considered as a generalized tonic-clonic SE, has obtained a large consensus among authors.8 However, the diagnosis and treatment of nonconvulsive status epilepticus (NCSE) remains a challenge. NCSE is a term used to denote a
range of conditions in which electrographic seizure activity is prolonged, usually considering a cut-off of 30 minutes, and results in nonconvulsive symptoms.9 A delay in diagnosis of NCSE may contribute to drug resistance10 and bad outcome.11 Classification of NCSE is not straightforward. Shorvon’s12 proposal for classification of NCSE takes into consideration age of onset, type of epilepsy syndrome, etiology, and seizure semiology, which although interesting in their completeness becomes exceedingly complicated, so that their everyday use is difficult. Other authors subdivide NCSE according to semiology, other clinical features, and EEG findings.13,14 A purely semiological classification of NCSE has been proposed15 and its practical application in the acute setting may prove to be of easier application. In this review, aiming at a pragmatical clinical approach, a semiological approach of NCSE is first considered followed by auxiliary tests findings and treatment. The most frequent subtypes of NCSE according to semiological SE classification are discussed: generalized myoclonic status (GMS), focal simple motor status (FSMS), and dyscognitive status (DS).9,15 Other rarer subtypes of NCSE include complex motor status, aura status, autonomic status, and special status.15 Myoclonic status was categorized as NCSE as proposed by the Epilepsy Research Foundation report on NCSE9 and different reviews on SE.16,17 In accordance, it has been suggested as clinical criteria of NCSE the absence of continuous major seizures either tonic or clonic seizures.9 Etiological investigations of NCSE might be prioritized based on the semiological type and EEG findings. Choice of appropriate treatment is dictated by the semiological presentation, EEG findings, and etiology. The correction of the underlying cause of NCSE often results in resolution of NCSE. Decision on aggressiveness of treatment should balance presumed morbidity of NCSE, prognosis of underlying condition, expected morbidity, and efficacy of treatment.18 Some authors recommend that surgery (eg, focal cortical resection, multiple subpial transection, corpus callosotomy) should be considered after 2 weeks of failed medical treatment.19 In addition, palliative interventions including electroconvulsive therapy (ECT) and vagal nerve stimulation (VNS) may be helpful in selected patients. This review aims to guide clinicians in the diagnosis, etiological evaluation, and treatment of adult patients with NCSE based on semiological presentation.
DIAGNOSIS OF NCSE From the *EEG Unit, Department of Neurology, Luz Saude-Arrabida Hospital and Clipovoa, Po´voa de Varzim; and wDepartment of Neurology, Braga Hospital, Braga, Portugal. The authors declare no conflict of interest. Reprints: Pedro Beleza, MD, EEG Unit, Department of Neurology, Luz Saude-Arrabida Hospital and Clipovoa, Rua Dom Manuel I, 183, Po´voa de Varzim 4490-592, Portugal. E-mail: [email protected]. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1074-7931/15/1906-0160 DOI: 10.1097/NRL.0000000000000031
160 | www.theneurologist.org
The diagnosis of NCSE requires clinical suspicion and EEG confirmation. FSMS and GMS are usually promptly identified during clinical observation, but important semiological differential diagnosis such as hemiballism, hemichorea, coreoathethosis, tremor, subcortical myoclonus, dissociative reactions, and malingering, should be considered. DS is often unrecognized and mistaken for behavioral or psychiatric disturbances. DS should be suspected in patients with (1) acutely The Neurologist
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 19, Number 6, June 2015
The Neurologist
Volume 19, Number 6, June 2015
NCSE, a Semiological Oriented Review
impaired or fluctuating consciousness interrupted by normal alertness; (2) impaired consciousness with facial myoclonus, nystagmus, lip smacking, and other automatisms; (3) episodic aphasia; (4) cyclic behavioral changes; and (5) other acutely altered behavior without obvious etiology.20,21 Psychogenic status typically includes a very gradual onset or termination, pseudosleep, discontinuous (stop-and-go) and irregular or asynchronous (out-of-phase) activity, side-to-side head shaking, opisthotonic posturing, and stuttering and weeping.22 Diagnosis of NCSE is favored in the following clinical settings: (1) acute brain insult—mostly intracerebral lobar hemorragic, infection, severe trauma, subarachnoid hemorrhage or neurosurgery; (2) after tonic-clonic seizures; and (3) history of epilepsy23 or remote symptomatic brain lesions.24 EEG findings supporting NCSE include: (1) repetitive focal or generalized epileptiform activity (interictal epileptiform discharges or rhythmic waveforms) Z3 Hz lasting >10 seconds; or (2) similar discharges
Diagnosis, Etiology, and Treatment of Nonconvulsive Status Epilepticus, a Semiological Oriented Review Pedro Beleza, MD,* Joa˜o Rocha, MD,w and Joa˜o Pinho, MDw
Background: Nonconvulsive status epilepticus (NCSE) defines a prolonged electrographic seizure activity resulting in nonconvulsive symptoms. Semiology is a crucial element in diagnosis, etiological evaluation, and treatment plan of NCSE. It includes mostly generalized myoclonic status (GMS), focal simple motor status (FSMS), and dyscognitive status (DS). Review Summary: This review aims to guide clinicians in diagnosis, etiological evaluation, and treatment of patients with NCSE based on semiological presentation. Conclusions: Diagnosis of GMS and FSMS is based mainly on semiology, whereas DS often requires EEG for differential diagnosis with nonepileptic events. GMS and FSMS etiological investigation may be readily prioritized based on semiological type, whereas DS requires EEG for further classification in psychomotor status and absence status. Choice of appropriate treatment is dictated by the semiological presentation, EEG findings, and etiology. Surgery and other interventions including electroconvulsive therapy and vagal nerve stimulation should be considered in patients refractory to medical treatment. Key Words: nonconvulsive status epilepticus, semiology, diagnosis, treatment, prognosis
(The Neurologist 2015;19:160–167)
S
tatus epilepticus (SE) was defined by the International League Against Epilepsy task force on classification and terminology as “a seizure that shows no clinical signs of arresting after a duration encompassing the great majority of seizures of that type in most patients or recurrent seizures without interictal resumption of baseline central nervous system function,”1 the latter including not just a disturbance of consciousness, but any kind of neurological deficit persisting between seizures. Clinical studies have considered 5,2 10,3 or 30 minutes of ongoing epileptic activity to define SE,4 mostly based on the knowledge that spontaneous cessation of generalized convulsive seizures is unlikely after 5 minutes5,6 and on experimental studies that have shown irreversible neuronal damage after about 30 minutes of continuing epileptic activity.7 Initial management of generalized convulsive status epilepticus, usually considered as a generalized tonic-clonic SE, has obtained a large consensus among authors.8 However, the diagnosis and treatment of nonconvulsive status epilepticus (NCSE) remains a challenge. NCSE is a term used to denote a
range of conditions in which electrographic seizure activity is prolonged, usually considering a cut-off of 30 minutes, and results in nonconvulsive symptoms.9 A delay in diagnosis of NCSE may contribute to drug resistance10 and bad outcome.11 Classification of NCSE is not straightforward. Shorvon’s12 proposal for classification of NCSE takes into consideration age of onset, type of epilepsy syndrome, etiology, and seizure semiology, which although interesting in their completeness becomes exceedingly complicated, so that their everyday use is difficult. Other authors subdivide NCSE according to semiology, other clinical features, and EEG findings.13,14 A purely semiological classification of NCSE has been proposed15 and its practical application in the acute setting may prove to be of easier application. In this review, aiming at a pragmatical clinical approach, a semiological approach of NCSE is first considered followed by auxiliary tests findings and treatment. The most frequent subtypes of NCSE according to semiological SE classification are discussed: generalized myoclonic status (GMS), focal simple motor status (FSMS), and dyscognitive status (DS).9,15 Other rarer subtypes of NCSE include complex motor status, aura status, autonomic status, and special status.15 Myoclonic status was categorized as NCSE as proposed by the Epilepsy Research Foundation report on NCSE9 and different reviews on SE.16,17 In accordance, it has been suggested as clinical criteria of NCSE the absence of continuous major seizures either tonic or clonic seizures.9 Etiological investigations of NCSE might be prioritized based on the semiological type and EEG findings. Choice of appropriate treatment is dictated by the semiological presentation, EEG findings, and etiology. The correction of the underlying cause of NCSE often results in resolution of NCSE. Decision on aggressiveness of treatment should balance presumed morbidity of NCSE, prognosis of underlying condition, expected morbidity, and efficacy of treatment.18 Some authors recommend that surgery (eg, focal cortical resection, multiple subpial transection, corpus callosotomy) should be considered after 2 weeks of failed medical treatment.19 In addition, palliative interventions including electroconvulsive therapy (ECT) and vagal nerve stimulation (VNS) may be helpful in selected patients. This review aims to guide clinicians in the diagnosis, etiological evaluation, and treatment of adult patients with NCSE based on semiological presentation.
DIAGNOSIS OF NCSE From the *EEG Unit, Department of Neurology, Luz Saude-Arrabida Hospital and Clipovoa, Po´voa de Varzim; and wDepartment of Neurology, Braga Hospital, Braga, Portugal. The authors declare no conflict of interest. Reprints: Pedro Beleza, MD, EEG Unit, Department of Neurology, Luz Saude-Arrabida Hospital and Clipovoa, Rua Dom Manuel I, 183, Po´voa de Varzim 4490-592, Portugal. E-mail: [email protected]. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1074-7931/15/1906-0160 DOI: 10.1097/NRL.0000000000000031
160 | www.theneurologist.org
The diagnosis of NCSE requires clinical suspicion and EEG confirmation. FSMS and GMS are usually promptly identified during clinical observation, but important semiological differential diagnosis such as hemiballism, hemichorea, coreoathethosis, tremor, subcortical myoclonus, dissociative reactions, and malingering, should be considered. DS is often unrecognized and mistaken for behavioral or psychiatric disturbances. DS should be suspected in patients with (1) acutely The Neurologist
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 19, Number 6, June 2015
The Neurologist
Volume 19, Number 6, June 2015
NCSE, a Semiological Oriented Review
impaired or fluctuating consciousness interrupted by normal alertness; (2) impaired consciousness with facial myoclonus, nystagmus, lip smacking, and other automatisms; (3) episodic aphasia; (4) cyclic behavioral changes; and (5) other acutely altered behavior without obvious etiology.20,21 Psychogenic status typically includes a very gradual onset or termination, pseudosleep, discontinuous (stop-and-go) and irregular or asynchronous (out-of-phase) activity, side-to-side head shaking, opisthotonic posturing, and stuttering and weeping.22 Diagnosis of NCSE is favored in the following clinical settings: (1) acute brain insult—mostly intracerebral lobar hemorragic, infection, severe trauma, subarachnoid hemorrhage or neurosurgery; (2) after tonic-clonic seizures; and (3) history of epilepsy23 or remote symptomatic brain lesions.24 EEG findings supporting NCSE include: (1) repetitive focal or generalized epileptiform activity (interictal epileptiform discharges or rhythmic waveforms) Z3 Hz lasting >10 seconds; or (2) similar discharges
