HHS Public Access Author manuscript Author Manuscript
Seizure. Author manuscript; available in PMC 2017 August 25. Published in final edited form as: Seizure. 2016 August ; 40: 102–107. doi:10.1016/j.seizure.2016.06.009.
Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome) Marta Drake-Péreza, Enrique Marco de Lucasa,b, John Lyoc, and José L. FernándezTorreb,d,e aDepartment
of Radiology, Marqués de Valdecilla University Hospital, Santander, Cantabria,
Spain
Author Manuscript
bBiomedical
Research Institute (IDIVAL), Santander, Spain
cDepartment
of Neuroradiology, Memorial Sloan Kettering Cancer Center, New York, New York,
USA dDepartment
of Clinical Neurophysiology, Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain
eDepartment
of Physiology and Pharmacology, University of Cantabria (UNICAN), Santander, Cantabria, Spain
Abstract Author Manuscript
Purpose—To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). Methods—We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. Results—Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%.
Author Manuscript
Conclusions—SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.
*
Corresponding author: Marta Drake Pérez. Department of Radiology. Marqués de Valdecilla University Hospital. Avda. Valdecilla, s/n. 39008 Santander. Cantabria. SPAIN. Tel: +34 942202520; [email protected]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Drake-Pérez et al.
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INTRODUCTION The diagnosis of acute neurological disorders occurring in patients with a history of alcohol abuse may be challenging. An unusual picture of subacute encephalopathy with seizures (SESA syndrome) in chronic alcoholics was initially characterized by Niedermeyer et al. [1] and Freund and Niedermeyer [2] in 1981. SESA syndrome represents a distinct subtype of localization-related non-convulsive status epilepticus (NCSE) in which recurrent complex partial seizures occur in alcoholic adult individuals, with transient neurologic deficits, interictal periodic lateralized discharges (PLDs) on the electroencephalography (EEG), and chronic multifocal vascular cerebral pathology [3]. This syndrome can be precipitated by alcohol abuse or alcohol withdrawal, and chronic treatment with antiepileptic drugs is necessary because recurrences are frequent. Only a few cases have been reported, with the reports mainly focusing on clinical and electroencephalographic features.
Author Manuscript
The aim of this clinical report is to better characterize the full spectrum of neuroimaging findings in SESA syndrome. A total of 8 cases were retrospectively analyzed. To our knowledge, this is the first radiological investigation of SESA
CASE SERIES We reviewed all cases reported previously with at least one MRI study, as well as 4 patients diagnosed in our center. All subjects met the following criteria: 1) inclusion of patients with clinical and EEG findings compatible with SESA syndrome, having an available description of their MRI study and; 2) exclusion of patients with other key pathologic conditions, like tumors, observed on their neuroimaging studies.
Author Manuscript
We reviewed a total of 10 patients, 4 from our center (3 of them published in previous papers [3-5]) and 6 from other centers [6-10].
Author Manuscript
The initial proposal by Niedermeyer et al. (1981) considered that the clinical picture described in patients with SESA did not fit any of the known neurological complications of chronic alcoholism. Following this definition, we decided to exclude 2 cases from the previous literature that were not characteristic for SESA syndrome, and had included patients with other neurological processes. We have taken this choice in order to reach a more pure group of patients with SESA in this review: i) The patient described by Bugnicourt et al. [8] had a right hemispheric stroke involving a large vascular territory on the side of PLDs. The resultant encephalomalacia would be highly epileptogenic, a very common cause of focal seizures in adults. The presence of PLDs and resolution of Todd’s paralysis would be completely in line with a focal seizure related to an old infarct. Hence, it would be incorrect to diagnose SESA if we assume the initial proposal by Niedermeyer et al. (1981); ii) The patient 1 described by Choi et al. [10] had hippocampal sclerosis, a potential highly epileptogenic lesion, on the same side as PLDs, so to say that this patient had SESA and not mesial temporal lobe epilepsy would be a misdiagnosis in our opinion. In Table 1 the main clinical features and MRI findings of the series of 8 patients are summarized.
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RESULTS All patients had a previous history of chronic alcohol abuse, and were admitted to the Emergency Unit presenting with a confused state and with motor neurological deficits. Six patients were men and two women with a mean age of 60.3 years (54-69). Two patients had generalized tonic-clonic seizures (GTCSs), 3 secondarily GTCSs and 3 simple partial motor seizures (SPMSs). After clinical and EEG evaluation, 4 subjects were diagnosed with focal NCSE. Other symptoms included Wernicke aphasia, hemianopsia, and fever. An EEG revealed PLDs in all patients (Fig. 1).
Author Manuscript
Initial MRI studies revealed cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion in 6 patients. In 5 patients, the affected region included the temporal lobe. The areas of abnormal signal correlated with the origin of the PLDs on the EEG for all 6 cases. (Fig. 2, Fig. 3). Hyperperfusion of the region was observed in 3 of the 6 patients (1 patient had increased distal flow on the MRA, and the other 2 had a SPECT revealing hyperperfusion). The other 3 patients did not have a SPECT or MRA to confirm this fact. Atrophy was present in 62.5% of the patients. Among them, 2 patients showed a temporal predominance, while in 3 patients the atrophy was diffuse or not specified. Chronic microvascular ischemic changes were described in half of the patients. Other isolated findings included: hydrocephalus, Chiari I malformation, and choroid fissure cyst. Follow-up MRI was performed in 50% of the patients, all showing a resolution of the hyperintense lesions (Fig. 4), but developing focal atrophic changes in 75%. Residual T2 hyperintensities were seen in one case in the right temporal lobe and in the splenium of corpus callosum.
Author Manuscript Author Manuscript
Illustrative clinical case (Patient 1 in table 1, Fig. 3, Fig. 4): A 69-year-old man with a history of alcohol abuse and Child class C cirrhosis was admitted to the Emergency Department due to a secondarily GTCS with postictal somnolence and left hemiparesis. Elevated liver enzymes were the only abnormality in the laboratory tests. He underwent stroke protocol imaging (nonenhanced brain CT, CT-perfusion, CT-angio) which demonstrated diffuse atrophy and chronic microvascular ischemic changes, without areas of acute ischemia or abnormality of the main intracranial arteries. A video-EEG showed PLDs in the right temporal region. MRI performed 2 days later revealed atrophy of the left medial temporal lobe and chronic microvascular ischemic changes. The right hippocampus appeared enlarged, with high intensity signal on FLAIR and restricted-diffusion. T2 hyperintensity and restricted diffusion were also present in the right insula, right parietal and cingulate cortex, and right posteromedial thalamus. Antiepileptic treatment with levetiracetam was started, and the patient experienced a gradual neurological recovery, remaining seizure-free at discharge.
DISCUSSION Accurate diagnosis and delineation of acute neurological disorders in patients with chronic ethanol intoxication may be challenging. Alcohol abuse is associated with various entities that cause abnormalities apparent on imaging, such as Wernicke encephalopathy,
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Marchiafava-Bignami disease, osmotic demyelination syndromes, hepatic encephalopathy, alcohol withdrawal syndrome [11], or SESA syndrome. All of these conditions usually present with confusion. Seizures are especially characteristic in Marchiafava-Bignami disease, alcohol withdrawal, and SESA syndrome. From a neuroimaging viewpoint, Wernicke encephalopathy usually affects the medial thalami, mamillary bodies, tectal plate, and periaqueductal gray matter, in a symmetric fashion [12]. The corpus callosum is predominantly affected in Marchiafava-Bignami disease [13]. Osmotic demyelination syndrome is known for central pontine changes (although symmetric signal changes can be seen in other brain areas) [14]. MRI during alcohol withdrawal depicts cytotoxic edema during the acute and subacute phases and significant volume loss in the temporal regions [11].
Author Manuscript Author Manuscript
Early reports on SESA neuroimaging only noted presence of diffuse cerebral atrophy [6, 7]. In 2008, Bugnicourt et al. [8] first described a single case with transient MRI abnormalities resembling those of status epilepticus: focal cortical hyperintensities on T2 and FLAIR sequences, with restricted diffusion and leptomeningeal enhancement. In 2014, Choi et al. presented two patients with SESA syndrome. The brain MRI demonstrated restricted diffusion, increased T2 signal, and hyperperfusion, in the presumed seizure focus and nearby regions of the cerebral hemispheres, similar to posterior reversible encephalopathy syndrome (PRES), raising the possibility of a pathophysiologic relation between the two entities [10]. However, some doubts on the accurate diagnosis of SESA syndrome may arise in these cases. In the case described by Bugnicort et al. (2008), MRI revealed an old ischemic stroke in the territory of the right posterior cerebral artery. In the cases described by Choi et al. (2014) atypical radiological features (hippocampal sclerosis in patient 1) and infrequent clinical findings (enduring aphasia and right hemiplegia in patient 2) were observed. These facts can question a correct diagnosis of SESA syndrome. Our imaging findings are the following: transient cortical-subcortical T2-hyperintense and diffusion restricted areas, in patients with focal status epilepticus and a characteristic EEG. The regions affected the most are the temporal lobe, especially the hippocampus. They all correlated to the PLDs in the EEG. When a follow-up MRI after some months was obtained, the hyperintensities resolved, and a specific atrophy of the medial temporal lobe was observed. This agrees with what has been published before, as we show in Table 1. Atrophy (affecting the temporal lobe predominantly) and chronic microvascular ischemic changes are invariably present. It has been hypothesized that those patients who develop SESA syndrome frequently have pre-existing cerebral lesions which, under some circumstances such as alcohol withdrawal, metabolic disturbances or both, became highly epileptogenic originating PLDs and recurrent focal seizures (simple and complex partial) [15, 16].
Author Manuscript
Our results can be fit within the neuroimaging features in status epilepticus, which typically include T2 hyperintensity in gray matter and/or subcortical white matter with mild mass effect and restricted diffusion acutely, besides a marked hyperemia on side of epileptic focus [17, 18]. T2 and FLAIR hyperintensity plus low ADC values represent cytotoxic edema of the epileptic region, in addition to a probable alteration of the blood brain barrier and increased permeability.
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Thus, these neuroimaging findings are not specific and could be found in seizures associated with other conditions such as Marchiafava-Bignami disease or alcohol withdrawal. However, other characteristic features like an abnormal signal or necrosis of the corpus callosum could lead to the diagnosis of Marchiafava-Bignami disease.
Author Manuscript
In the proposed updated diagnostic criteria for SESA syndrome according to FernándezTorre and Kaplan (2014), chronic multifocal vascular pathology would be an imaging criterion. They also mentioned that watershed-type infarctions are common. Predominantly temporal atrophy and status-like images could be included [3]. Thus, our findings further strengthens the assumption that SESA represents an underlying focal NCSE. Based on the follow-up MRI, one could also presume that SESA syndrome is not a “transient” disorder as thought, but there could be long-term sequelae in terms of temporal atrophy as pointed out in our study. This chronicity is also strongly supported by the existence of episodes of recurrence following medication withdrawal and/or alcohol consumption. We are aware of the limitations of our study: the total number of patients analyzed is small as we decided to include only patients with MRI due to its higher sensitivity, and the acute imaging approach in most of the published cases is CT. In addition, follow-up MRI to ensure the transitory nature of the changes was not available in 50% of the patients. Another important limitation of our study is that MRIs have been done at various centers with different machines, with varying degrees of radiological expertise, different sequences and criteria to reporting presence of specific lobar atrophy. Moreover, quantitative studies were not obtained.
CONCLUSIONS Author Manuscript
SESA syndrome should be included among the alcohol-related encephalopathies that present acute confusional state, PLDs on the EEG, transient neurologic deficits and, convulsive and nonconvulsive seizures. Its radiological features include transient cortical-subcortical T2hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.
References
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1. Niedermeyer E, Freund G, Krumholz A, et al. Subacute encephalopathy with seizures in alcoholics: a clinical-electroencephalographic study. Clin Electroencephalograph. 1981; 12:113–29. 2. Freund G, Niedermeyer E. Subacute encephalopathy with seizures in alcoholics. Electroencephalogr Clin Neurophysiol. 1981; 51:53P–54P. Abstract. 3. Fernández-Torre JL, Kaplan PW. Subacute encephalopathy with seizures in alcoholics (SESA syndrome) revisited. Seizure. 2014; 23:393–6. [PubMed: 24618220] 4. Fernández-Torre JL, Agirre Z, Martínez-Martínez M, et al. Subacute encephalopathy with seizures in alcoholics (SESA syndrome): report of an unusual case. Clin EEG Neurosci. 2006; 37:215–8. [PubMed: 16929707] 5. Fernández-Torre JL, Hernández-Hernández JL, Jiménez-Bonilla J, et al. Complex partial status epilepticus is an unrecognised feature in SESA syndrome: new insights into its pathophysiology. Epileptic Disord. 2007; 9:134–9. [PubMed: 17525021] 6. Otto FG, Kozian R. Subacute encephalopathy with epileptic seizures in alcoholism (SESA): case report. Clin Electroencephalogr. 2001; 32:184–5. [PubMed: 11682811]
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7. Mani J, Sitajayalaksmi S, Borgohain E, Mohandas S. Subacute encephalopathy with seizures in alcoholics. Seizure. 2003; 12:126–9. [PubMed: 12566238] 8. Bugnicourt JM, Bonnaire B, Picard C. Multiple reversible MRI abnormalities associated with SESA syndrome. Seizure. 2008; 17:727–30. [PubMed: 18439845] 9. LaRoche SM, Shivdat-Nanhoe R. Subacute encephalopathy and seizures in alcoholics (SESA) presenting with non-convulsive status epilepticus. Seizure. 2011; 20:505–8. [PubMed: 21459625] 10. Choi JY, Kwon J, Bae EK. A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome. J Clin Neurosci. 2014; 21:1649–52. [PubMed: 24768152] 11. Zuccoli G, Siddiqui N, Cravo I. Neuroimaging findings in alcohol-related encephalopathies. AJR Am J Roentgenol. 2010; 195:1378–84. [PubMed: 21098198] 12. Zuccoli G, Santa Cruz D, Bertolini M. MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics. AJNR Am J Neuroradiol. 2009; 30:171–6. [PubMed: 18945789] 13. Arbelaez A, Pajon A, Castillo M. Acute Marchiafava-Bignami disease: MR findings in two patients. AJNR Am J Neuroradiol. 2003; 24:1955–7. [PubMed: 14625216] 14. Ho VB, Fitz CR, Yoder CC, et al. Resolving MR features in osmotic myelinolysis (central pontine and extrapontine myelinolysis). AJNR Am J Neuroradiol. 1993; 14:163–7. [PubMed: 8427080] 15. Chu NS. Periodic lateralized epileptiform discharges with preexisting focal brain lesions. Role of alcohol withdrawal and anoxic encephalopathy. Arch Neurol. 1980; 37:551–4. [PubMed: 6774701] 16. Fernández-Torre JL, Aguirre-Arrizubieta Z, Pola FC, et al. SESA syndrome: a subtype of localisation-related non-convulsive status epilepticus? Letter to the Editor. Seizure. 2009; 18:306– 7. [PubMed: 19110446] 17. Kim JA, Chung JI, Yoon PH. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. AJNR Am J Neuroradiol. 2001; 22:1149–60. [PubMed: 11415912] 18. Hauf M1, Slotboom J, Nirkko A. Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT. AJNR Am J Neuroradiol. 2009; 30:693–8. [PubMed: 19213823]
Author Manuscript
ABBREVIATIONS SESA
Subacute encephalopathy with seizures in alcoholics
EEG
Electroencephalography
NCSE
nonconvulsive status epilepticus
PLDs
Periodic lateralized discharges
MRI
Magnetic Resonance Imaging
SE
Status epilepticus
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Highlights ➢
SESA syndrome should be included among the alcohol-related encephalopathies
➢
It presents with acute confusional state, PLDs, transient neurologic deficits and seizures
➢
MRI features include temporal atrophy, chronic vascular lesions and findings similar to SE
➢
SESA represent not a “transient” disorder, but can lead to sequelae on serial imaging
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Fig. 1.
EEG shows periodic lateralized discharges (PLDs) (black arrows) involving the right temporal lobe. Low filter: 0.5 Hz; High filter: 35 Hz; Notch filter: 50Hz. Vertical bar: 100 μV; horizontal bar: 1 second.
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Fig. 2.
Coronal FLAIR images from the 4 patients with SESA syndrome registered in our hospital showing the distribution of the signal alterations. A: Right insula and medial temporal lobe hyperintensities. Temporal atrophy. Hydrocephalus. B: Right insula and hippocampus hyperintensities. Diffuse atrophy. C: Left frontoinsular region and cingulate cortex hyperintensities. D: Right enlarged hippocampus and posteromedial thalamus hyperintensities. White matter chronic ischemic changes.
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Author Manuscript Author Manuscript Fig. 3.
Author Manuscript
Illustrative case in the acute setting. Axial DWI images shows restricted diffusion on right hippocampus (left), right parietal cortex, cingulate gyrus and posteromedial thalamus (right).
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Fig. 4.
Illustrative case. Coronal T2-weighted images shows a hyperintense and hypertrophic right hippocampus (left) in the acute setting. In the follow-up MRI performed 2 months later (right), the signal abnormalities are solved, and the right medial temporal lobe shows atrophic changes.
Author Manuscript Seizure. Author manuscript; available in PMC 2017 August 25.
Author Manuscript 58 M
65 M
55 M
66 M
55 M
61 F
Fernández-Torre et al. [4]
Fernández-Torre et al. [5]
Otto et al. [6]
Mani et al. [7]
LaRoche et al. [9]
69 M
Patient 1 of this paper
Fernández-Torre et al. [3]
Age Sex
Seizure. Author manuscript; available in PMC 2017 August 25. R hemiparesis
Confusion
R hemiparesis
SPMSs
Confusion
GTCSs
Wernicke aphasia
Confusion
L hemisphere PLDs
L parieto-occipital PLDs
L fronto-centro-temporal PLDs
Focal NCSE
SPMSs, secondarily GTCSs R hemiparesis.
L frontal and parasagittal PLDs.
Focal NCSE
R temporal PLDs
Focal NCSE
R temporal PLDs
R temporal PLDs
Confusion.
L homonymous hemianopsia.
L hemiparesis.
GTCS
Fever.
L hemiparesis.
SPMSs
Confusion.
L hemiparesis.
Secondarily GTCSs.
Clinical features
EEG
Author Manuscript
Patient
L frontal, parietal and temporal cortical T2 hyperintensities with restricted diffusion.
Cortical atrophy.
Chronic white matter changes.
Cortical and subcortical atrophy.
L frontoinsular T2 hyperintensities with restricted diffusion. Cortical thickening.
Chronic white matter changes.
R hemisphere hyperperfusion, especially in temporal lobe.
R hippocampus and insular T2 hyperintensities.
Atrophy. Chronic white matter changes.
Hydrocephalus. Chiari I
Atrophy (temporal). R hippocampus and amygdale T2/FLAIR hyperintensities. R temporal hyperperfusion (SPECT).
R hippocampus, insula, parietal and cingulated cortex, and posteromedial thalamus: T2 hyperintensity with restricted diffusion.
Atrophy (L medial temporal lobe). Chronic white matter changes.
Brain MRI
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Clinical, EEG and imaging features.
Improvement of the prior T2, FLAIR and DWI hyperintensities.
-
-
-
R temporal and splenium of corpus callosum T2 hyperintensities.
R temporal atrophy, especially hippocampal.
-
Resolution of the T2 hyperintensities.
R hippocampal atrophy.
Follow-up MRI
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Table 1 Drake-Pérez et al. Page 12
Secondarily GTCS
L parieto-occipital PLDs + rythmic delta activities
Focal NCSE
SMPSs
L middle cerebral artery hyperperfusion.
L medial temporal, parietal and occipital T2/ FLAIR/DWI/ADC hyperintensities.
Brain MRI
Normal MRA.
Decreased high signal intensity and atrophic changes of the previous lesions.
Follow-up MRI
presumptive complex partial status epilepticus.
*
CPS. Complex partial seizure; EEG = Electroencephalography; F = Female; GTCS: generalized tonic-clonic seizure; L = Left, M = Male, MRA = Magnetic resonance angiography; PLDs = Periodic lateralized discharges; R = Right; RPCA = Right posterior cerebral artery; SPMS: simple partial motor seizure;
Patient (2) [10]
54 F
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Choi J et al.
EEG
Author Manuscript Clinical features
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Age Sex
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Patient
Drake-Pérez et al. Page 13
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Seizure. Author manuscript; available in PMC 2017 August 25. Published in final edited form as: Seizure. 2016 August ; 40: 102–107. doi:10.1016/j.seizure.2016.06.009.
Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome) Marta Drake-Péreza, Enrique Marco de Lucasa,b, John Lyoc, and José L. FernándezTorreb,d,e aDepartment
of Radiology, Marqués de Valdecilla University Hospital, Santander, Cantabria,
Spain
Author Manuscript
bBiomedical
Research Institute (IDIVAL), Santander, Spain
cDepartment
of Neuroradiology, Memorial Sloan Kettering Cancer Center, New York, New York,
USA dDepartment
of Clinical Neurophysiology, Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain
eDepartment
of Physiology and Pharmacology, University of Cantabria (UNICAN), Santander, Cantabria, Spain
Abstract Author Manuscript
Purpose—To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). Methods—We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. Results—Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%.
Author Manuscript
Conclusions—SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.
*
Corresponding author: Marta Drake Pérez. Department of Radiology. Marqués de Valdecilla University Hospital. Avda. Valdecilla, s/n. 39008 Santander. Cantabria. SPAIN. Tel: +34 942202520; [email protected]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Drake-Pérez et al.
Page 2
Author Manuscript
INTRODUCTION The diagnosis of acute neurological disorders occurring in patients with a history of alcohol abuse may be challenging. An unusual picture of subacute encephalopathy with seizures (SESA syndrome) in chronic alcoholics was initially characterized by Niedermeyer et al. [1] and Freund and Niedermeyer [2] in 1981. SESA syndrome represents a distinct subtype of localization-related non-convulsive status epilepticus (NCSE) in which recurrent complex partial seizures occur in alcoholic adult individuals, with transient neurologic deficits, interictal periodic lateralized discharges (PLDs) on the electroencephalography (EEG), and chronic multifocal vascular cerebral pathology [3]. This syndrome can be precipitated by alcohol abuse or alcohol withdrawal, and chronic treatment with antiepileptic drugs is necessary because recurrences are frequent. Only a few cases have been reported, with the reports mainly focusing on clinical and electroencephalographic features.
Author Manuscript
The aim of this clinical report is to better characterize the full spectrum of neuroimaging findings in SESA syndrome. A total of 8 cases were retrospectively analyzed. To our knowledge, this is the first radiological investigation of SESA
CASE SERIES We reviewed all cases reported previously with at least one MRI study, as well as 4 patients diagnosed in our center. All subjects met the following criteria: 1) inclusion of patients with clinical and EEG findings compatible with SESA syndrome, having an available description of their MRI study and; 2) exclusion of patients with other key pathologic conditions, like tumors, observed on their neuroimaging studies.
Author Manuscript
We reviewed a total of 10 patients, 4 from our center (3 of them published in previous papers [3-5]) and 6 from other centers [6-10].
Author Manuscript
The initial proposal by Niedermeyer et al. (1981) considered that the clinical picture described in patients with SESA did not fit any of the known neurological complications of chronic alcoholism. Following this definition, we decided to exclude 2 cases from the previous literature that were not characteristic for SESA syndrome, and had included patients with other neurological processes. We have taken this choice in order to reach a more pure group of patients with SESA in this review: i) The patient described by Bugnicourt et al. [8] had a right hemispheric stroke involving a large vascular territory on the side of PLDs. The resultant encephalomalacia would be highly epileptogenic, a very common cause of focal seizures in adults. The presence of PLDs and resolution of Todd’s paralysis would be completely in line with a focal seizure related to an old infarct. Hence, it would be incorrect to diagnose SESA if we assume the initial proposal by Niedermeyer et al. (1981); ii) The patient 1 described by Choi et al. [10] had hippocampal sclerosis, a potential highly epileptogenic lesion, on the same side as PLDs, so to say that this patient had SESA and not mesial temporal lobe epilepsy would be a misdiagnosis in our opinion. In Table 1 the main clinical features and MRI findings of the series of 8 patients are summarized.
Seizure. Author manuscript; available in PMC 2017 August 25.
Drake-Pérez et al.
Page 3
Author Manuscript
RESULTS All patients had a previous history of chronic alcohol abuse, and were admitted to the Emergency Unit presenting with a confused state and with motor neurological deficits. Six patients were men and two women with a mean age of 60.3 years (54-69). Two patients had generalized tonic-clonic seizures (GTCSs), 3 secondarily GTCSs and 3 simple partial motor seizures (SPMSs). After clinical and EEG evaluation, 4 subjects were diagnosed with focal NCSE. Other symptoms included Wernicke aphasia, hemianopsia, and fever. An EEG revealed PLDs in all patients (Fig. 1).
Author Manuscript
Initial MRI studies revealed cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion in 6 patients. In 5 patients, the affected region included the temporal lobe. The areas of abnormal signal correlated with the origin of the PLDs on the EEG for all 6 cases. (Fig. 2, Fig. 3). Hyperperfusion of the region was observed in 3 of the 6 patients (1 patient had increased distal flow on the MRA, and the other 2 had a SPECT revealing hyperperfusion). The other 3 patients did not have a SPECT or MRA to confirm this fact. Atrophy was present in 62.5% of the patients. Among them, 2 patients showed a temporal predominance, while in 3 patients the atrophy was diffuse or not specified. Chronic microvascular ischemic changes were described in half of the patients. Other isolated findings included: hydrocephalus, Chiari I malformation, and choroid fissure cyst. Follow-up MRI was performed in 50% of the patients, all showing a resolution of the hyperintense lesions (Fig. 4), but developing focal atrophic changes in 75%. Residual T2 hyperintensities were seen in one case in the right temporal lobe and in the splenium of corpus callosum.
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Illustrative clinical case (Patient 1 in table 1, Fig. 3, Fig. 4): A 69-year-old man with a history of alcohol abuse and Child class C cirrhosis was admitted to the Emergency Department due to a secondarily GTCS with postictal somnolence and left hemiparesis. Elevated liver enzymes were the only abnormality in the laboratory tests. He underwent stroke protocol imaging (nonenhanced brain CT, CT-perfusion, CT-angio) which demonstrated diffuse atrophy and chronic microvascular ischemic changes, without areas of acute ischemia or abnormality of the main intracranial arteries. A video-EEG showed PLDs in the right temporal region. MRI performed 2 days later revealed atrophy of the left medial temporal lobe and chronic microvascular ischemic changes. The right hippocampus appeared enlarged, with high intensity signal on FLAIR and restricted-diffusion. T2 hyperintensity and restricted diffusion were also present in the right insula, right parietal and cingulate cortex, and right posteromedial thalamus. Antiepileptic treatment with levetiracetam was started, and the patient experienced a gradual neurological recovery, remaining seizure-free at discharge.
DISCUSSION Accurate diagnosis and delineation of acute neurological disorders in patients with chronic ethanol intoxication may be challenging. Alcohol abuse is associated with various entities that cause abnormalities apparent on imaging, such as Wernicke encephalopathy,
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Marchiafava-Bignami disease, osmotic demyelination syndromes, hepatic encephalopathy, alcohol withdrawal syndrome [11], or SESA syndrome. All of these conditions usually present with confusion. Seizures are especially characteristic in Marchiafava-Bignami disease, alcohol withdrawal, and SESA syndrome. From a neuroimaging viewpoint, Wernicke encephalopathy usually affects the medial thalami, mamillary bodies, tectal plate, and periaqueductal gray matter, in a symmetric fashion [12]. The corpus callosum is predominantly affected in Marchiafava-Bignami disease [13]. Osmotic demyelination syndrome is known for central pontine changes (although symmetric signal changes can be seen in other brain areas) [14]. MRI during alcohol withdrawal depicts cytotoxic edema during the acute and subacute phases and significant volume loss in the temporal regions [11].
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Early reports on SESA neuroimaging only noted presence of diffuse cerebral atrophy [6, 7]. In 2008, Bugnicourt et al. [8] first described a single case with transient MRI abnormalities resembling those of status epilepticus: focal cortical hyperintensities on T2 and FLAIR sequences, with restricted diffusion and leptomeningeal enhancement. In 2014, Choi et al. presented two patients with SESA syndrome. The brain MRI demonstrated restricted diffusion, increased T2 signal, and hyperperfusion, in the presumed seizure focus and nearby regions of the cerebral hemispheres, similar to posterior reversible encephalopathy syndrome (PRES), raising the possibility of a pathophysiologic relation between the two entities [10]. However, some doubts on the accurate diagnosis of SESA syndrome may arise in these cases. In the case described by Bugnicort et al. (2008), MRI revealed an old ischemic stroke in the territory of the right posterior cerebral artery. In the cases described by Choi et al. (2014) atypical radiological features (hippocampal sclerosis in patient 1) and infrequent clinical findings (enduring aphasia and right hemiplegia in patient 2) were observed. These facts can question a correct diagnosis of SESA syndrome. Our imaging findings are the following: transient cortical-subcortical T2-hyperintense and diffusion restricted areas, in patients with focal status epilepticus and a characteristic EEG. The regions affected the most are the temporal lobe, especially the hippocampus. They all correlated to the PLDs in the EEG. When a follow-up MRI after some months was obtained, the hyperintensities resolved, and a specific atrophy of the medial temporal lobe was observed. This agrees with what has been published before, as we show in Table 1. Atrophy (affecting the temporal lobe predominantly) and chronic microvascular ischemic changes are invariably present. It has been hypothesized that those patients who develop SESA syndrome frequently have pre-existing cerebral lesions which, under some circumstances such as alcohol withdrawal, metabolic disturbances or both, became highly epileptogenic originating PLDs and recurrent focal seizures (simple and complex partial) [15, 16].
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Our results can be fit within the neuroimaging features in status epilepticus, which typically include T2 hyperintensity in gray matter and/or subcortical white matter with mild mass effect and restricted diffusion acutely, besides a marked hyperemia on side of epileptic focus [17, 18]. T2 and FLAIR hyperintensity plus low ADC values represent cytotoxic edema of the epileptic region, in addition to a probable alteration of the blood brain barrier and increased permeability.
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Thus, these neuroimaging findings are not specific and could be found in seizures associated with other conditions such as Marchiafava-Bignami disease or alcohol withdrawal. However, other characteristic features like an abnormal signal or necrosis of the corpus callosum could lead to the diagnosis of Marchiafava-Bignami disease.
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In the proposed updated diagnostic criteria for SESA syndrome according to FernándezTorre and Kaplan (2014), chronic multifocal vascular pathology would be an imaging criterion. They also mentioned that watershed-type infarctions are common. Predominantly temporal atrophy and status-like images could be included [3]. Thus, our findings further strengthens the assumption that SESA represents an underlying focal NCSE. Based on the follow-up MRI, one could also presume that SESA syndrome is not a “transient” disorder as thought, but there could be long-term sequelae in terms of temporal atrophy as pointed out in our study. This chronicity is also strongly supported by the existence of episodes of recurrence following medication withdrawal and/or alcohol consumption. We are aware of the limitations of our study: the total number of patients analyzed is small as we decided to include only patients with MRI due to its higher sensitivity, and the acute imaging approach in most of the published cases is CT. In addition, follow-up MRI to ensure the transitory nature of the changes was not available in 50% of the patients. Another important limitation of our study is that MRIs have been done at various centers with different machines, with varying degrees of radiological expertise, different sequences and criteria to reporting presence of specific lobar atrophy. Moreover, quantitative studies were not obtained.
CONCLUSIONS Author Manuscript
SESA syndrome should be included among the alcohol-related encephalopathies that present acute confusional state, PLDs on the EEG, transient neurologic deficits and, convulsive and nonconvulsive seizures. Its radiological features include transient cortical-subcortical T2hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.
References
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1. Niedermeyer E, Freund G, Krumholz A, et al. Subacute encephalopathy with seizures in alcoholics: a clinical-electroencephalographic study. Clin Electroencephalograph. 1981; 12:113–29. 2. Freund G, Niedermeyer E. Subacute encephalopathy with seizures in alcoholics. Electroencephalogr Clin Neurophysiol. 1981; 51:53P–54P. Abstract. 3. Fernández-Torre JL, Kaplan PW. Subacute encephalopathy with seizures in alcoholics (SESA syndrome) revisited. Seizure. 2014; 23:393–6. [PubMed: 24618220] 4. Fernández-Torre JL, Agirre Z, Martínez-Martínez M, et al. Subacute encephalopathy with seizures in alcoholics (SESA syndrome): report of an unusual case. Clin EEG Neurosci. 2006; 37:215–8. [PubMed: 16929707] 5. Fernández-Torre JL, Hernández-Hernández JL, Jiménez-Bonilla J, et al. Complex partial status epilepticus is an unrecognised feature in SESA syndrome: new insights into its pathophysiology. Epileptic Disord. 2007; 9:134–9. [PubMed: 17525021] 6. Otto FG, Kozian R. Subacute encephalopathy with epileptic seizures in alcoholism (SESA): case report. Clin Electroencephalogr. 2001; 32:184–5. [PubMed: 11682811]
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7. Mani J, Sitajayalaksmi S, Borgohain E, Mohandas S. Subacute encephalopathy with seizures in alcoholics. Seizure. 2003; 12:126–9. [PubMed: 12566238] 8. Bugnicourt JM, Bonnaire B, Picard C. Multiple reversible MRI abnormalities associated with SESA syndrome. Seizure. 2008; 17:727–30. [PubMed: 18439845] 9. LaRoche SM, Shivdat-Nanhoe R. Subacute encephalopathy and seizures in alcoholics (SESA) presenting with non-convulsive status epilepticus. Seizure. 2011; 20:505–8. [PubMed: 21459625] 10. Choi JY, Kwon J, Bae EK. A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome. J Clin Neurosci. 2014; 21:1649–52. [PubMed: 24768152] 11. Zuccoli G, Siddiqui N, Cravo I. Neuroimaging findings in alcohol-related encephalopathies. AJR Am J Roentgenol. 2010; 195:1378–84. [PubMed: 21098198] 12. Zuccoli G, Santa Cruz D, Bertolini M. MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics. AJNR Am J Neuroradiol. 2009; 30:171–6. [PubMed: 18945789] 13. Arbelaez A, Pajon A, Castillo M. Acute Marchiafava-Bignami disease: MR findings in two patients. AJNR Am J Neuroradiol. 2003; 24:1955–7. [PubMed: 14625216] 14. Ho VB, Fitz CR, Yoder CC, et al. Resolving MR features in osmotic myelinolysis (central pontine and extrapontine myelinolysis). AJNR Am J Neuroradiol. 1993; 14:163–7. [PubMed: 8427080] 15. Chu NS. Periodic lateralized epileptiform discharges with preexisting focal brain lesions. Role of alcohol withdrawal and anoxic encephalopathy. Arch Neurol. 1980; 37:551–4. [PubMed: 6774701] 16. Fernández-Torre JL, Aguirre-Arrizubieta Z, Pola FC, et al. SESA syndrome: a subtype of localisation-related non-convulsive status epilepticus? Letter to the Editor. Seizure. 2009; 18:306– 7. [PubMed: 19110446] 17. Kim JA, Chung JI, Yoon PH. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. AJNR Am J Neuroradiol. 2001; 22:1149–60. [PubMed: 11415912] 18. Hauf M1, Slotboom J, Nirkko A. Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT. AJNR Am J Neuroradiol. 2009; 30:693–8. [PubMed: 19213823]
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ABBREVIATIONS SESA
Subacute encephalopathy with seizures in alcoholics
EEG
Electroencephalography
NCSE
nonconvulsive status epilepticus
PLDs
Periodic lateralized discharges
MRI
Magnetic Resonance Imaging
SE
Status epilepticus
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Highlights ➢
SESA syndrome should be included among the alcohol-related encephalopathies
➢
It presents with acute confusional state, PLDs, transient neurologic deficits and seizures
➢
MRI features include temporal atrophy, chronic vascular lesions and findings similar to SE
➢
SESA represent not a “transient” disorder, but can lead to sequelae on serial imaging
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Fig. 1.
EEG shows periodic lateralized discharges (PLDs) (black arrows) involving the right temporal lobe. Low filter: 0.5 Hz; High filter: 35 Hz; Notch filter: 50Hz. Vertical bar: 100 μV; horizontal bar: 1 second.
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Fig. 2.
Coronal FLAIR images from the 4 patients with SESA syndrome registered in our hospital showing the distribution of the signal alterations. A: Right insula and medial temporal lobe hyperintensities. Temporal atrophy. Hydrocephalus. B: Right insula and hippocampus hyperintensities. Diffuse atrophy. C: Left frontoinsular region and cingulate cortex hyperintensities. D: Right enlarged hippocampus and posteromedial thalamus hyperintensities. White matter chronic ischemic changes.
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Illustrative case in the acute setting. Axial DWI images shows restricted diffusion on right hippocampus (left), right parietal cortex, cingulate gyrus and posteromedial thalamus (right).
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Fig. 4.
Illustrative case. Coronal T2-weighted images shows a hyperintense and hypertrophic right hippocampus (left) in the acute setting. In the follow-up MRI performed 2 months later (right), the signal abnormalities are solved, and the right medial temporal lobe shows atrophic changes.
Author Manuscript Seizure. Author manuscript; available in PMC 2017 August 25.
Author Manuscript 58 M
65 M
55 M
66 M
55 M
61 F
Fernández-Torre et al. [4]
Fernández-Torre et al. [5]
Otto et al. [6]
Mani et al. [7]
LaRoche et al. [9]
69 M
Patient 1 of this paper
Fernández-Torre et al. [3]
Age Sex
Seizure. Author manuscript; available in PMC 2017 August 25. R hemiparesis
Confusion
R hemiparesis
SPMSs
Confusion
GTCSs
Wernicke aphasia
Confusion
L hemisphere PLDs
L parieto-occipital PLDs
L fronto-centro-temporal PLDs
Focal NCSE
SPMSs, secondarily GTCSs R hemiparesis.
L frontal and parasagittal PLDs.
Focal NCSE
R temporal PLDs
Focal NCSE
R temporal PLDs
R temporal PLDs
Confusion.
L homonymous hemianopsia.
L hemiparesis.
GTCS
Fever.
L hemiparesis.
SPMSs
Confusion.
L hemiparesis.
Secondarily GTCSs.
Clinical features
EEG
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Patient
L frontal, parietal and temporal cortical T2 hyperintensities with restricted diffusion.
Cortical atrophy.
Chronic white matter changes.
Cortical and subcortical atrophy.
L frontoinsular T2 hyperintensities with restricted diffusion. Cortical thickening.
Chronic white matter changes.
R hemisphere hyperperfusion, especially in temporal lobe.
R hippocampus and insular T2 hyperintensities.
Atrophy. Chronic white matter changes.
Hydrocephalus. Chiari I
Atrophy (temporal). R hippocampus and amygdale T2/FLAIR hyperintensities. R temporal hyperperfusion (SPECT).
R hippocampus, insula, parietal and cingulated cortex, and posteromedial thalamus: T2 hyperintensity with restricted diffusion.
Atrophy (L medial temporal lobe). Chronic white matter changes.
Brain MRI
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Clinical, EEG and imaging features.
Improvement of the prior T2, FLAIR and DWI hyperintensities.
-
-
-
R temporal and splenium of corpus callosum T2 hyperintensities.
R temporal atrophy, especially hippocampal.
-
Resolution of the T2 hyperintensities.
R hippocampal atrophy.
Follow-up MRI
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Table 1 Drake-Pérez et al. Page 12
Secondarily GTCS
L parieto-occipital PLDs + rythmic delta activities
Focal NCSE
SMPSs
L middle cerebral artery hyperperfusion.
L medial temporal, parietal and occipital T2/ FLAIR/DWI/ADC hyperintensities.
Brain MRI
Normal MRA.
Decreased high signal intensity and atrophic changes of the previous lesions.
Follow-up MRI
presumptive complex partial status epilepticus.
*
CPS. Complex partial seizure; EEG = Electroencephalography; F = Female; GTCS: generalized tonic-clonic seizure; L = Left, M = Male, MRA = Magnetic resonance angiography; PLDs = Periodic lateralized discharges; R = Right; RPCA = Right posterior cerebral artery; SPMS: simple partial motor seizure;
Patient (2) [10]
54 F
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Choi J et al.
EEG
Author Manuscript Clinical features
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Age Sex
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Patient
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