552704 research-article2014
EEGXXX10.1177/1550059414552704Clinical EEG and NeuroscienceTakagaki et al
Original Article
Periodic Lateralized Epileptiform Discharges (PLEDs) in Patients With Neurosyphilis and HIV Infection
Clinical EEG and Neuroscience 1–4 © EEG and Clinical Neuroscience Society (ECNS) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059414552704 eeg.sagepub.com
Kentaroh Takagaki1,2, Megan K. Morales3, Daniel Vitantonio1, Frank Berkowitz4, William L. Bell1, Princy N. Kumar3, and Gholam K. Motamedi1
Abstract Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic pattern recorded in the setting of a variety of brain abnormalities. It is best recognized for its association with acute viral encephalitis, stroke, tumor, or latestatus epilepticus. However, there are other conditions that have been recognized as the underlying pathology for PLEDs such as alcohol withdrawal, Creutzfeldt–Jacob disease, anoxic brain injury, and hemiplegic migraine. However, there are only rare case reports of PLEDs in patients with neurosyphilis. Here, we report 2 patients presenting with encephalopathy and seizures with PLEDs, ipsilateral or contralateral to their main brain magnetic resonance imaging abnormalities. Further workup revealed neurosyphilis in both patients, one in association with human immunodeficiency virus (HIV) infection. Given the increasing incidence of neurosyphilis with or without HIV infection, these cases suggest neurosyphilis as a consideration in the differential for patients presenting with PLEDs. Keywords neurosyphilis, periodic lateralized epileptiform discharges (PLEDs), HIV, cerebrospinal fluid Received June 14, 2014; revised August 1, 2014; August 22, 2014; accepted August 29, 2014.
Introduction
Case Report
Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic (EEG) pattern described in 1952 as periodic sharp discharges lateralized to one hemisphere. They are typically seen transiently early in the course of a variety of conditions that result in an acute irritative insult to the cerebral cortex. While PLEDs may be commonly associated with herpes simplex virus (HSV) encephalitis, they are often seen with acute stroke, brain tumors, inflammatory and/or infectious diseases, status epilepticus, anoxic encephalopathy, metabolic derangements such as uncontrolled diabetes, or acute alcohol intoxication.1 Periodic lateralized epileptiform discharges have been rarely reported in association with neurosyphilis.2-5 Here, we report 2 patients presenting with acute/subacute encephalopathy and PLEDs recorded ipsilateral or contralateral to the side of the most pronounced magnetic resonance imaging (MRI) abnormalities, who were found to have late neurosyphilis, one in association with human immunodeficiency virus (HIV) infection. Considering the rise in incidence of neurosyphilis, with or without HIV, these cases emphasize the importance of association between these conditions and this particular EEG pattern even in the absence of lateralizing MRI findings.
Patient 1 A 52-year-old man with history of hepatitis C, prostate cancer, and possible alcohol-related seizures presented with confusion, seizures, and a new onset left hemiparesis for 3 days. After ruling out stroke using brain MRI, based on EEG evidence of right temporal sharp discharges, he was started on intravenous levetiracetam, phenytoin, and lacosamide and was transferred to our center.
1
Department of Neurology, Georgetown University Hospital, Washington, DC, USA 2 Department of Systems Physiology of Learning, Leibniz Institute for Neurobiology, Magdeburg, Germany 3 Department of Medicine, Division of Infectious Disease and Travel Medicine, Georgetown University Hospital, Washington, DC, USA 4 Department of Radiology, Georgetown University Hospital, Washington, DC, USA Corresponding Author: Gholam K. Motamedi, MD, Department of Neurology, PHC 7, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
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Clinical EEG and Neuroscience
Figure 1. Standard 10-second EEG traces recorded using 10-20 electrode system. Patient 1: (A) Periodic lateralized epileptiform discharges (PLEDs) are seen in the right hemisphere, maximal posterior head regions (electrodes O2, T6, C4), with slight reflection over the left posterior quadrant. The EEG background is diffusely slow but more suppressed on the right. (B). Follow-up EEG 17 days later and following treatment shows improvement in background slowing with no PLEDs. Patient 2: (C) Left-sided PLEDs are seen maximally recorded in the medial frontal head regions on a diffusely slow background with superimposed fast discharges (sedative drug effect) that is more pronounced on the right. (D) Follow-up EEG on day-16 shows significant improvement with no PLEDS but occasional delta slow activity more pronounced in the left anterior head regions.
On admission he was unresponsive and agitated despite seizure control and empiric intravenous acyclovir. Video-EEG monitoring showed right hemispheric PLEDs maximally present in the posterior head regions, with intermittent brief suppression periods that persisted until the end of a 6-day monitoring with no ictal events (Figure 1A). Fluid-attenuated inversion recovery (FLAIR) MRI images showed subcortical white matter and gray matter hyperintensity in the anterior portions of both temporal lobes and subcortical white matter hyperintensity in the posteromedial left frontal lobe with no abnormal enhancement (Figure 2A). However, the PLEDs seemed to be associated with the right anterior temporal lesions. Toxicology screen was negative. HIV enzyme-linked immunosorbent assay (ELISA) was positive and was confirmed by Western blot. The patient had a CD4 count of 237 and viral load of 645 copies/mL by polymerase chain reaction (PCR). Serum rapid plasma reagin (RPR) was reactive (titer 1:64), cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL) screen and fluorescent treponemal antibody absorption (FTA-Abs) were also positive. CSF studies showed 119 leukocytes (76% lymphocytes, 8% monocytes, 12% segs), elevated protein (120 mg/dL), low glucose (35 mg/dL), negative HSV 1/2 DNA PCR, varicella-zoster virus (VZV) PCR,
human T-lymphotropic virus(HTLV)-I/-II antibody screen, India ink stain, JC polyoma virus PCR, and cryptococcal antigen screen; CSF culture had no growth. An infectious diseases consultation was obtained and the patient was treated with a 14-day course of intravenous penicillin G. A follow-up EEG on day 17 showed significant improvement with no PLEDs but did show bilateral slowing and intermittent right posterior sharp discharges (Figure 1B). His mental status continued to improve on treatment. He was discharged home on antiretroviral therapy and 2 antiepileptic drugs in stable condition, oriented and able to walk independently, to follow up with a local HIV clinic.
Patient 2 A 66-year-old man with history of hypertension presented with altered mental status after being found down by family the night before. He was incoherent and mumbling with involuntary leg movements and later had a witnessed convulsive seizure in the hospital; he was intubated and started on propofol and levetiracetam and was transferred to our center. On arrival, brain MRI ruled out stroke. Basic CSF studies showed 226 cells (87% lymphocytes, 10% monocytes, 3%
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
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Takagaki et al
Figure 2. (A): Patient 1: Fluid-attenuated inversion recovery (FLAIR) images show subcortical white matter and gray matter hyperintensity in the anterior portions of both temporal lobes and subcortical white matter hyperintensity in the posteromedial left frontal lobe. (B) Patient 2: Precontrast FLAIR image (left) and postcontrast FLAIR image (right) show left frontal leptomeningeal enhancement (arrows).
segs), elevated protein (122 mg/dL), low glucose (52 mg/dL), and negative bacterial or fungal culture. CSF PCR was negative for HSV 1/2, cytomegalovirus, Epstein–Barr virus, and Lyme disease. Test for VZV was not performed. CSF VDRL was reactive (1:8), serum RPR was reactive (1:32), and confirmatory FTA-Abs was also reactive. Rapid HIV and HIV ELISA were negative and HIV RNA was undetectable by PCR. Testing for other sexually transmitted infections revealed IgG antibody to HSV 1 and 2, but no IgM to indicate recent infection. Hepatitis B was negative but PCR probe for gonorrhea/chlamydia was not done. The patient completed a 14-day course of penicillin G for neurosyphilis. On admission, video-EEG monitoring showed diffuse background slowing and 1- to 3-Hz left-sided PLEDs maximally in the mesial frontal head regions (Figure 1C) that persisted for the 8 days of monitoring without any ictal events. Brain MRI
showed left frontal leptomeningeal enhancement correlating with the left anterior PLEDs on EEG (Figure 2B). Following treatment with penicillin G and levetiracetam, an EEG on day 16 showed significant improvement with no PLEDS and occasional slow activity more on the left (Figure 1D). His hospital course was complicated by aspiration pneumonia, acute respiratory distress syndrome, and acute renal failure requiring hemodialysis. Seizures were controlled with valproate. He was discharged home in stable condition on valproate and antihypertensive medications.
Discussion Periodic lateralized epileptiform discharges are usually indicative of a unilateral hemispheric lesion. A review of a large cohort of 96 cases found PLEDs most often recorded in the
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
4
Clinical EEG and Neuroscience
setting of acute stroke, brain tumor, infection, acute hemorrhage, traumatic brain injury, and alcohol withdrawal as well as previously unreported etiologies, that is, posterior reversible encephalopathy syndrome, familial hemiplegic migraine, Creutzfeldt–Jacob disease, and cerebral amyloidosis.1 However, there are only rare reports of PLEDs in patients with neurosyphilis.6 Overall, 70% of patients with PLEDs may experience seizures during the acute phase of illness but 23% to 66% will eventually develop epilepsy.7 Based on hypermetabolism and increased blood flow seen on functional neuroimaging scans, PLEDs are considered within the spectrum of ictal activity. It has been proposed that PLEDs might represent a dynamic hyperexcitable state creating an ictal–interictal continuum, as seen in the hyperexcitable penumbra of ischemic stroke.8 One of our patients was also diagnosed with HIV during this admission. Since the emergence of HIV, there has been a rise in the incidence of neurosyphilis. However, the Centers for Disease Control and Prevention does not recommend CSF examination for HIV-positive patients with positive RPR in the absence of neurological symptoms, although this remains controversial and an RPR titer of >1:32 or CD4 count
EEGXXX10.1177/1550059414552704Clinical EEG and NeuroscienceTakagaki et al
Original Article
Periodic Lateralized Epileptiform Discharges (PLEDs) in Patients With Neurosyphilis and HIV Infection
Clinical EEG and Neuroscience 1–4 © EEG and Clinical Neuroscience Society (ECNS) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059414552704 eeg.sagepub.com
Kentaroh Takagaki1,2, Megan K. Morales3, Daniel Vitantonio1, Frank Berkowitz4, William L. Bell1, Princy N. Kumar3, and Gholam K. Motamedi1
Abstract Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic pattern recorded in the setting of a variety of brain abnormalities. It is best recognized for its association with acute viral encephalitis, stroke, tumor, or latestatus epilepticus. However, there are other conditions that have been recognized as the underlying pathology for PLEDs such as alcohol withdrawal, Creutzfeldt–Jacob disease, anoxic brain injury, and hemiplegic migraine. However, there are only rare case reports of PLEDs in patients with neurosyphilis. Here, we report 2 patients presenting with encephalopathy and seizures with PLEDs, ipsilateral or contralateral to their main brain magnetic resonance imaging abnormalities. Further workup revealed neurosyphilis in both patients, one in association with human immunodeficiency virus (HIV) infection. Given the increasing incidence of neurosyphilis with or without HIV infection, these cases suggest neurosyphilis as a consideration in the differential for patients presenting with PLEDs. Keywords neurosyphilis, periodic lateralized epileptiform discharges (PLEDs), HIV, cerebrospinal fluid Received June 14, 2014; revised August 1, 2014; August 22, 2014; accepted August 29, 2014.
Introduction
Case Report
Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic (EEG) pattern described in 1952 as periodic sharp discharges lateralized to one hemisphere. They are typically seen transiently early in the course of a variety of conditions that result in an acute irritative insult to the cerebral cortex. While PLEDs may be commonly associated with herpes simplex virus (HSV) encephalitis, they are often seen with acute stroke, brain tumors, inflammatory and/or infectious diseases, status epilepticus, anoxic encephalopathy, metabolic derangements such as uncontrolled diabetes, or acute alcohol intoxication.1 Periodic lateralized epileptiform discharges have been rarely reported in association with neurosyphilis.2-5 Here, we report 2 patients presenting with acute/subacute encephalopathy and PLEDs recorded ipsilateral or contralateral to the side of the most pronounced magnetic resonance imaging (MRI) abnormalities, who were found to have late neurosyphilis, one in association with human immunodeficiency virus (HIV) infection. Considering the rise in incidence of neurosyphilis, with or without HIV, these cases emphasize the importance of association between these conditions and this particular EEG pattern even in the absence of lateralizing MRI findings.
Patient 1 A 52-year-old man with history of hepatitis C, prostate cancer, and possible alcohol-related seizures presented with confusion, seizures, and a new onset left hemiparesis for 3 days. After ruling out stroke using brain MRI, based on EEG evidence of right temporal sharp discharges, he was started on intravenous levetiracetam, phenytoin, and lacosamide and was transferred to our center.
1
Department of Neurology, Georgetown University Hospital, Washington, DC, USA 2 Department of Systems Physiology of Learning, Leibniz Institute for Neurobiology, Magdeburg, Germany 3 Department of Medicine, Division of Infectious Disease and Travel Medicine, Georgetown University Hospital, Washington, DC, USA 4 Department of Radiology, Georgetown University Hospital, Washington, DC, USA Corresponding Author: Gholam K. Motamedi, MD, Department of Neurology, PHC 7, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007, USA. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
2
Clinical EEG and Neuroscience
Figure 1. Standard 10-second EEG traces recorded using 10-20 electrode system. Patient 1: (A) Periodic lateralized epileptiform discharges (PLEDs) are seen in the right hemisphere, maximal posterior head regions (electrodes O2, T6, C4), with slight reflection over the left posterior quadrant. The EEG background is diffusely slow but more suppressed on the right. (B). Follow-up EEG 17 days later and following treatment shows improvement in background slowing with no PLEDs. Patient 2: (C) Left-sided PLEDs are seen maximally recorded in the medial frontal head regions on a diffusely slow background with superimposed fast discharges (sedative drug effect) that is more pronounced on the right. (D) Follow-up EEG on day-16 shows significant improvement with no PLEDS but occasional delta slow activity more pronounced in the left anterior head regions.
On admission he was unresponsive and agitated despite seizure control and empiric intravenous acyclovir. Video-EEG monitoring showed right hemispheric PLEDs maximally present in the posterior head regions, with intermittent brief suppression periods that persisted until the end of a 6-day monitoring with no ictal events (Figure 1A). Fluid-attenuated inversion recovery (FLAIR) MRI images showed subcortical white matter and gray matter hyperintensity in the anterior portions of both temporal lobes and subcortical white matter hyperintensity in the posteromedial left frontal lobe with no abnormal enhancement (Figure 2A). However, the PLEDs seemed to be associated with the right anterior temporal lesions. Toxicology screen was negative. HIV enzyme-linked immunosorbent assay (ELISA) was positive and was confirmed by Western blot. The patient had a CD4 count of 237 and viral load of 645 copies/mL by polymerase chain reaction (PCR). Serum rapid plasma reagin (RPR) was reactive (titer 1:64), cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL) screen and fluorescent treponemal antibody absorption (FTA-Abs) were also positive. CSF studies showed 119 leukocytes (76% lymphocytes, 8% monocytes, 12% segs), elevated protein (120 mg/dL), low glucose (35 mg/dL), negative HSV 1/2 DNA PCR, varicella-zoster virus (VZV) PCR,
human T-lymphotropic virus(HTLV)-I/-II antibody screen, India ink stain, JC polyoma virus PCR, and cryptococcal antigen screen; CSF culture had no growth. An infectious diseases consultation was obtained and the patient was treated with a 14-day course of intravenous penicillin G. A follow-up EEG on day 17 showed significant improvement with no PLEDs but did show bilateral slowing and intermittent right posterior sharp discharges (Figure 1B). His mental status continued to improve on treatment. He was discharged home on antiretroviral therapy and 2 antiepileptic drugs in stable condition, oriented and able to walk independently, to follow up with a local HIV clinic.
Patient 2 A 66-year-old man with history of hypertension presented with altered mental status after being found down by family the night before. He was incoherent and mumbling with involuntary leg movements and later had a witnessed convulsive seizure in the hospital; he was intubated and started on propofol and levetiracetam and was transferred to our center. On arrival, brain MRI ruled out stroke. Basic CSF studies showed 226 cells (87% lymphocytes, 10% monocytes, 3%
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
3
Takagaki et al
Figure 2. (A): Patient 1: Fluid-attenuated inversion recovery (FLAIR) images show subcortical white matter and gray matter hyperintensity in the anterior portions of both temporal lobes and subcortical white matter hyperintensity in the posteromedial left frontal lobe. (B) Patient 2: Precontrast FLAIR image (left) and postcontrast FLAIR image (right) show left frontal leptomeningeal enhancement (arrows).
segs), elevated protein (122 mg/dL), low glucose (52 mg/dL), and negative bacterial or fungal culture. CSF PCR was negative for HSV 1/2, cytomegalovirus, Epstein–Barr virus, and Lyme disease. Test for VZV was not performed. CSF VDRL was reactive (1:8), serum RPR was reactive (1:32), and confirmatory FTA-Abs was also reactive. Rapid HIV and HIV ELISA were negative and HIV RNA was undetectable by PCR. Testing for other sexually transmitted infections revealed IgG antibody to HSV 1 and 2, but no IgM to indicate recent infection. Hepatitis B was negative but PCR probe for gonorrhea/chlamydia was not done. The patient completed a 14-day course of penicillin G for neurosyphilis. On admission, video-EEG monitoring showed diffuse background slowing and 1- to 3-Hz left-sided PLEDs maximally in the mesial frontal head regions (Figure 1C) that persisted for the 8 days of monitoring without any ictal events. Brain MRI
showed left frontal leptomeningeal enhancement correlating with the left anterior PLEDs on EEG (Figure 2B). Following treatment with penicillin G and levetiracetam, an EEG on day 16 showed significant improvement with no PLEDS and occasional slow activity more on the left (Figure 1D). His hospital course was complicated by aspiration pneumonia, acute respiratory distress syndrome, and acute renal failure requiring hemodialysis. Seizures were controlled with valproate. He was discharged home in stable condition on valproate and antihypertensive medications.
Discussion Periodic lateralized epileptiform discharges are usually indicative of a unilateral hemispheric lesion. A review of a large cohort of 96 cases found PLEDs most often recorded in the
Downloaded from eeg.sagepub.com at RMIT UNIVERSITY on August 19, 2015
4
Clinical EEG and Neuroscience
setting of acute stroke, brain tumor, infection, acute hemorrhage, traumatic brain injury, and alcohol withdrawal as well as previously unreported etiologies, that is, posterior reversible encephalopathy syndrome, familial hemiplegic migraine, Creutzfeldt–Jacob disease, and cerebral amyloidosis.1 However, there are only rare reports of PLEDs in patients with neurosyphilis.6 Overall, 70% of patients with PLEDs may experience seizures during the acute phase of illness but 23% to 66% will eventually develop epilepsy.7 Based on hypermetabolism and increased blood flow seen on functional neuroimaging scans, PLEDs are considered within the spectrum of ictal activity. It has been proposed that PLEDs might represent a dynamic hyperexcitable state creating an ictal–interictal continuum, as seen in the hyperexcitable penumbra of ischemic stroke.8 One of our patients was also diagnosed with HIV during this admission. Since the emergence of HIV, there has been a rise in the incidence of neurosyphilis. However, the Centers for Disease Control and Prevention does not recommend CSF examination for HIV-positive patients with positive RPR in the absence of neurological symptoms, although this remains controversial and an RPR titer of >1:32 or CD4 count
