504756 research-article2013
EEGXXX10.1177/1550059413504756Venhovens et alClinical EEG and Neuroscience
Article
Ischemic Stroke as a Complication of Varicella Zoster Encephalitis: A Case Report With Detailed EEG Discussion
Clinical EEG and Neuroscience 2014, Vol. 45(4) 310–314 © EEG and Clinical Neuroscience Society (ECNS) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059413504756 eeg.sagepub.com
Jeroen Venhovens1, Bianca Stelten1, Bart F. E. Feyen2, Gert van Dijk1, and Jan Meulstee1
Abstract A 72-year-old man with varicella zoster virus (VZV) encephalitis complicated by an ischemic stroke in the right internal capsule, possibly due to secondary small-vessel vasculopathy, is described in this case report. The focus of this article is on the electroencephalogram (EEG) description of varicella zoster encephalitis and secondary vasculopathy because EEG descriptions are scarce in the literature and detailed descriptions are lacking. In this patient’s EEG, right temporal theta waves were found in combination with a mild slowing of the background rhythm to 7.5 to 8 Hz in the acute stage with an amplitude asymmetry (right temporal lobe amplitudes were significantly higher compared with the left side). The theta waves were thought to originate from the ischemic lacunar stroke, the slowing of the background rhythm from early encephalitis, and the amplitude asymmetry was presumed to be of physiologic origin. A follow-up EEG 6 days after initiation of treatment with acyclovir showed a normal symmetrical background rhythm of 8 to 8.5 Hz, wherein the theta waves were significantly reduced in abundance, and the amplitude asymmetry was unchanged. In conclusion, the EEG may localize focal abnormalities possibly due to cortical or lacunar ischemia, which could be explained by early small and/or large vessel vasculopathy in patients with suspected VZV encephalitis. Keywords viral encephalitis, varicella zoster virus (VZV), ischemic stroke, vasculopathy, electroencephalography (EEG) Received May 13, 2013; revised August 8, 2013; accepted August 16, 2013.
Introduction Acute viral infections of the central nervous system are rare and can present with a variety of neurological syndromes. Of these syndromes, acute aseptic meningitis and viral encephalitis are most common. However, the clinical syndrome is not always obvious and can present as a continuous spectrum with overlapping features of aseptic meningitis, encephalitis, myelitis, and sometimes acute cerebellar ataxia.1 Viral encephalitis has an estimated prevalence of 1.4 to 2.2 per 100,000 cases; however, the majority of the viral central nervous system infections are self-limiting, and acute aseptic meningitis is 10 times more common.1 Neurological sequelae after the acute infection are a major problem, with a high impact on the quality of life. Viral encephalitis is suspected when a patient has a febrile disease accompanied by neurological signs and symptoms, such as headache, confusion, or epileptic seizures. The neurological abnormalities can be divided into 4 classes: (a) cognitive dysfunction, (b) behavioral changes, c) focal neurological abnormalities, and (d) seizures.2 After the diagnosis is suspected it can be confirmed by neuroimaging and a lumbar puncture (ie, cerebrospinal fluid [CSF] biochemistry, serology and microbiological analysis by polymerase chain reaction of the neurotropic viruses).
In this case report, we describe a patient with VZV encephalitis complicated with a lacunar ischemic stroke of the right internal capsule possibly due to secondary small vessel vasculopathy.
Case Report A 72-year-old man was referred to the emergency department of Canisius-Wilhelmina hospital by his family doctor. His medical history included a coronary artery bypass graft and aortic valve replacement (biovalve) 2 years ago, gout, legionella pneumonia, and recurrent herpes zoster. The patient did not have any risk factors for stroke except for his cardiac medical 1
Canisius Wilhelmina Hospital, Nijmegen, Netherlands Department of Neurosurgery, Antwerp University Hospital, Antwerp, Belgium 2
Corresponding Author: Jeroen Venhovens, Department of Neurology and Clinical Neurophysiology, Canisius-Wilhelmina hospital, Weg door Jonkerbos 100, PO Box 9015, Nijmegen, 6500 GS, Netherlands. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com
311
Venhovens et al history and advanced age. The patient used acetylsalicylic acid for prophylaxis due to his biovalve replacement. His wife noted discrete progressive cognitive abnormalities (ie, fluctuating disorientation in time and place), bradyphrenia, and behavioral changes (ie, progressive emotional lability) for 4 weeks, with fast progression for 3 days. He developed a left-sided facial paresis in combination with a discrete paresis of the left arm 1 day prior to the visit to the emergency department. The patient’s wife noted that he just recently recovered from an ophthalmic herpes zoster on the right side 6 weeks ago, which was treated with oral acyclovir for 1 week by the family doctor. This reactivation of VZV however, was complicated by a keratitis of the right eye, which was treated with acyclovir eyecream by the ophthalmologist. Besides the left-sided facial paresis, bradyphrenia, latent paresis of the left arm, and a subjective difficulty retrieving some words, no other neurological abnormalities could be detected by neurological examination. Neuropsychiatric evaluation was normal except for the bradyphrenia (ie, normal attention and higher cognitive functions). Blood analysis in the emergency department was normal (ie, normal white blood cell count, C-reactive protein, electrolytes, glucose, and kidney function). Cerebral computed tomography, ordered because of the focal neurological findings, showed no abnormalities (Figure 1D). Primary analysis of the CSF showed an elevated white blood cell count (11 × 106/L), slight elevation of the protein count (0.80 g/L), elevated lactate (2.6 mmol/L), normal glucose levels (CSF 4.0 mmol/L, serum 6.5 mmol/L), and a normal opening pressure of 13 cm H2O. EEG showed mild diffuse symmetrical slowing of the background rhythm to 7.5 to 8 Hz, with irregular right temporal theta waves (frequency of 4-6 Hz). The amplitude of the background rhythm was asymmetrical, with significantly higher amplitudes at the right temporal and occipital lobes (right temporal 15-30 µV, left temporal 10-15 µV, right occipital 15-20 µV, and left occipital 10-15 µV). The abnormalities suggested a deep subcortical focal abnormality in the right temporal lobe because these theta waves were not seen in the left temporal lobe (Figure 2A). Spectral analysis of the background rhythm showed no asymmetries of the mu- and alpha-background rhythms. However, the homologous F4-C4 derivation showed a small peak in the theta range (5.5 Hz), which could not be found in the F3-C3 derivations. This is in concordance with the qualitative EEG conclusion. The patient was admitted to the neurology ward with the tentative diagnosis of VZV encephalitis for treatment with intravenous acyclovir (10 mg/kg every 8 hours) for 10 days. Microbiological results of the serum and CSF, available 3 days after admission, showed a positive polymerase chain reaction for VZV in the CSF. Magnetic resonance imaging of the brain, 3 days after admission, showed a lacunar ischemic stroke of the right internal capsule on the T2 sequence and diffusion series (Figure 1A-C). EEG, repeated 6 days after initiation of treatment with acyclovir, showed normal symmetrical background pattern of 8 to 8.5 Hz, the amplitude asymmetry, however, persisted and the right temporal theta waves were significantly
Figure 1. (A and B) An ischemic lacunar stroke of the right internal capsule 3 days after admission characterized by a diffusion deficit with a high signal on the diffusion-weighted imaging (DWI; B) and a low signal on the apparent diffusion coefficient (ADC; A). (C) The T2-weighted imaging with a high signal at the place of the ischemic stroke. (D) The admission cerebral computed tomography scan with no evident signs of ischemia or other abnormalities besides mild generalized atrophy, which can be considered normal for the patient’s age.
reduced in abundance and had almost completely disappeared (Figure 2B). Spectral analysis still showed no asymmetries of the mu- or alpha-background rhythm, and the theta peak seen in the homologous F4-C4 derivation had completely disappeared. During the hospital stay, the patient slowly improved with respect to the behavioral abnormalities and bradyphrenia, though the latent paresis of the left arm and left-sided facial paresis did not significantly improve in the following 5 months.
Discussion This patient developed a varicells zoster encephalitis as a complication of a VZV infection in the area of the ophthalmic branch of the trigeminal nerve on the right side. The varicella zoster encephalitis was probably complicated by a secondary small-vessel vasculopathy causing an ischemic stroke in the internal capsule. There is also a possibility that the ischemic stroke could be a coincidence because of the patient’s risk factors (biovalve, previous cardiac atherosclerotic disease, and advanced age). However, the fact that (a) the cerebral magnetic resonance imaging scan showed evidence of acute ischemia (high signal on the diffusion-weighted imaging and low signal on the apparent diffusion coefficient) in the absence of other
312
Clinical EEG and Neuroscience 45(4)
Figure 2. EEG recording A was performed in the emergency department and EEG recording B was performed 6 days later. Refer to the text for description of both EEGs. The arrows point to irregular right temporal theta waves. High-pass filter 0, 100 Hz; low-pass filter 60 Hz; notch-filtered, bipolar montage, sensitivity 5 µV/mm, speed 30 mm/s.
vascular lesions, (b) there is a temporal relationship of the clinical signs of the cerebral varicella infection and the ischemic stroke, and (c) varicella encephalitis is a major risk factor for ischemic stroke due to vasculopathy, make an underlying atherosclerotic etiology for the stroke less likely
than a secondary varicella virus–induced vasculopathy. A small-vessel vasculopathy is more likely in this patient than a large-vessel vasculopathy because (a) the location of the lacunar stroke is in the right anterior choroideal branch, which is per definition considered a small vessel and (b) the erythrocyte
313
Venhovens et al sedimentation rate is normal (4 mm/h); it would be expected to be higher in large-vessel vasculopathy. A concomitant largevessel vasculopathy, however, cannot be excluded but seems unlikely (a cerebral magnetic resonance angiography or cerebral digital subtraction angiography was not performed because of the lack of clinical suspicion). VZV–induced cerebral vasculopathies are a well-known and serious complication that can lead to ischemic stroke, aneurysm, carotid dissection, subarachnoid, or intracerebral haemorrhage1. The clinical outcome of patients with a secondary vasculopathy due to an infectious origin are unfavorable and often result in severe neurological deficits or death.3,4 In an original article by Katchanov et al,3 8 adult patients with an infectious nonatherosclerotic cerebral vasculopathy were studied (2 patients with a varicella-induced cerebral vasculopathy). The outcome of the patients with an infectious vasculopathy was highly unfavorable with 1 dead, 2 locked-in syndromes, and 5 patients with severe neurological deficits (of the varicella-induced vasculopathies, 1 patient had a locked-in syndrome and 1 left the intensive care unit with severe neurological deficits). The patient in this case report, however, left the hospital with only relatively minor neurological deficits (Modified Rankin Scale 2). The preferred treatment of viral encephalopathy is intravenous acyclovir 10 mg/kg thrice daily (every 8 hours) for 10 to 14 days. The duration of treatment for immuno-suppressed patients is 21 days according to the European Federation of Neurological Societies guidelines.2 Early diagnosis and treatment of viral encephalopathy is very important because the mortality rate is reduced from 70% in untreated patients to 20% to 30% in early treated patients.2 There are very few case reports or series describing EEG patterns in patients with VZV encephalitis. A small case series of 20 VZV encephalopathy patients (10 patients had EEG examinations) described EEG abnormalities in 6 patients.5 The majority had intermittent diffuse slowing with focal accentuation (mostly temporal) or focal slowing (mostly temporal) of the background rhythm. In our patient, the background rhythm was slowed diffusely to 7.5 to 8 Hz, the background amplitude was asymmetrical, whereby the amplitude especially in the right temporal lobe was significantly higher in comparison with the left temporal lobe (right temporal 15-30 µV and left temporal 10-15 µV), and the right temporal lobe showed irregular theta activity (4-6 Hz) throughout the recording in an awake patient. The EEG 6 days after initiation of treatment showed a mild improvement of the symmetrical background rhythm to 8 to 8.5 Hz, the amplitude asymmetry was unchanged, and the right temporal theta waves had almost disappeared (Figure 2A and B). Additional spectral analysis of the mu- and alpha-background rhythms showed no asymmetries in power or frequency; however, the first analysis showed a 5.5 Hz theta peak of the homologous F4-C4 derivation, which was not found at the homologous F3-C3 derivation and which had completely disappeared in the second analysis. The origin of the theta waves is thought to be the deep subcortical lacunar
ischemic stroke of the internal capsule on the right side. The mild slowing of the background rhythm was thought to be caused by early encephalopathy, however, could also be explained by the lacunar ischemic stroke. An EEG study by Petty et al6 of 55 patients with a lacunar stroke showed that 29 (53%) had EEG abnormalities, of which 13 had diffuse generalized slowing, 6 had focal slowing, and 10 had generalized plus focal slowing. Of the abnormal EEGs, 13 of the 29 patients had ipsilateral slowing and 9 of the 29 had contralateral slowing. None of the study EEGs contained epileptiform activity in the form of spikes and spike-and-slow-wave discharges or voltage asymmetries. The EEGs in the patients with lacunar infarctions in the internal capsule (4 patients) were abnormal in 2 . In another study by Kappelle et al,7 10 of the 12 patients with lacunar infarctions showed EEG abnormalities (after visual and quantitative EEG analysis). These abnormalities were compromised by asymmetries in the mu- and/or alpha-background rhythm. The amplitude asymmetry of the background rhythm (the amplitude on the dominant left side is less than 50% compared with the amplitude on the subdominant right side) is thought to be of physiologic origin and represents neither the encephalopathy nor the ischemic stroke. This hypothesis is supported by the lack of mu- or alpha-background asymmetries, and the observation that the background amplitude asymmetry does not exceed the 50%. In conclusion, the EEG may localize focal abnormalities possibly due to cortical or lacunar ischemia, which could be explained by an early small and/or large vessel vasculopathy in patients with suspected VZV encephalitis. Authors’ Note Jeroen Venhovens and Bianca Stelten had an equal contribution in writing this article.
Acknowledgments The authors thank J. ten Cate and H. Lentjes, clinical neurophysiological technicians, for their support and for performing the EEGs.
Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Studahl M, Lindquist L, Eriksson B, et al. Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management. Drugs. 2013;73:131-158. 2. Steiner I, Budka H, Chaudhuri A, et al. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010;17:999-1009. 3. Katchanov J, Siebert E, Klingebiel R, Endres M. Infectious vasculopathy of intracranial large- and medium-sized vessels
314 in neurological intensive care unit: a clinico-radiological study. Neurocrit Care. 2010;12:369-374. 4. Gilden D, Cohrs R, Mahalingam R, Nagel M. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenisis, and treatment. Lancet Neurol. 2009;8:731740. 5. Pollak L, Dovrat S, Book M, Mendelson E, Weinberger M., Varicella zoster vs. herpes simplex meningoencephalitis in
Clinical EEG and Neuroscience 45(4) the PCR era. A single center study. J Neurol Sci. 2012;314:2936. 6. Petty G, Labar D, Fisch B, Pedley T, Mohr J, Khandji VaricellaA. Electroencephalography in lacunar infarction. J Neurol Sci. 1995;134:47-50. 7. Kappelle L, Huffelen van A, Gijn van J. Is the EEG really normal in lacunar stroke? J Neurol Neurosurg Psychiatry. 1990;53: 63-66.
EEGXXX10.1177/1550059413504756Venhovens et alClinical EEG and Neuroscience
Article
Ischemic Stroke as a Complication of Varicella Zoster Encephalitis: A Case Report With Detailed EEG Discussion
Clinical EEG and Neuroscience 2014, Vol. 45(4) 310–314 © EEG and Clinical Neuroscience Society (ECNS) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059413504756 eeg.sagepub.com
Jeroen Venhovens1, Bianca Stelten1, Bart F. E. Feyen2, Gert van Dijk1, and Jan Meulstee1
Abstract A 72-year-old man with varicella zoster virus (VZV) encephalitis complicated by an ischemic stroke in the right internal capsule, possibly due to secondary small-vessel vasculopathy, is described in this case report. The focus of this article is on the electroencephalogram (EEG) description of varicella zoster encephalitis and secondary vasculopathy because EEG descriptions are scarce in the literature and detailed descriptions are lacking. In this patient’s EEG, right temporal theta waves were found in combination with a mild slowing of the background rhythm to 7.5 to 8 Hz in the acute stage with an amplitude asymmetry (right temporal lobe amplitudes were significantly higher compared with the left side). The theta waves were thought to originate from the ischemic lacunar stroke, the slowing of the background rhythm from early encephalitis, and the amplitude asymmetry was presumed to be of physiologic origin. A follow-up EEG 6 days after initiation of treatment with acyclovir showed a normal symmetrical background rhythm of 8 to 8.5 Hz, wherein the theta waves were significantly reduced in abundance, and the amplitude asymmetry was unchanged. In conclusion, the EEG may localize focal abnormalities possibly due to cortical or lacunar ischemia, which could be explained by early small and/or large vessel vasculopathy in patients with suspected VZV encephalitis. Keywords viral encephalitis, varicella zoster virus (VZV), ischemic stroke, vasculopathy, electroencephalography (EEG) Received May 13, 2013; revised August 8, 2013; accepted August 16, 2013.
Introduction Acute viral infections of the central nervous system are rare and can present with a variety of neurological syndromes. Of these syndromes, acute aseptic meningitis and viral encephalitis are most common. However, the clinical syndrome is not always obvious and can present as a continuous spectrum with overlapping features of aseptic meningitis, encephalitis, myelitis, and sometimes acute cerebellar ataxia.1 Viral encephalitis has an estimated prevalence of 1.4 to 2.2 per 100,000 cases; however, the majority of the viral central nervous system infections are self-limiting, and acute aseptic meningitis is 10 times more common.1 Neurological sequelae after the acute infection are a major problem, with a high impact on the quality of life. Viral encephalitis is suspected when a patient has a febrile disease accompanied by neurological signs and symptoms, such as headache, confusion, or epileptic seizures. The neurological abnormalities can be divided into 4 classes: (a) cognitive dysfunction, (b) behavioral changes, c) focal neurological abnormalities, and (d) seizures.2 After the diagnosis is suspected it can be confirmed by neuroimaging and a lumbar puncture (ie, cerebrospinal fluid [CSF] biochemistry, serology and microbiological analysis by polymerase chain reaction of the neurotropic viruses).
In this case report, we describe a patient with VZV encephalitis complicated with a lacunar ischemic stroke of the right internal capsule possibly due to secondary small vessel vasculopathy.
Case Report A 72-year-old man was referred to the emergency department of Canisius-Wilhelmina hospital by his family doctor. His medical history included a coronary artery bypass graft and aortic valve replacement (biovalve) 2 years ago, gout, legionella pneumonia, and recurrent herpes zoster. The patient did not have any risk factors for stroke except for his cardiac medical 1
Canisius Wilhelmina Hospital, Nijmegen, Netherlands Department of Neurosurgery, Antwerp University Hospital, Antwerp, Belgium 2
Corresponding Author: Jeroen Venhovens, Department of Neurology and Clinical Neurophysiology, Canisius-Wilhelmina hospital, Weg door Jonkerbos 100, PO Box 9015, Nijmegen, 6500 GS, Netherlands. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com
311
Venhovens et al history and advanced age. The patient used acetylsalicylic acid for prophylaxis due to his biovalve replacement. His wife noted discrete progressive cognitive abnormalities (ie, fluctuating disorientation in time and place), bradyphrenia, and behavioral changes (ie, progressive emotional lability) for 4 weeks, with fast progression for 3 days. He developed a left-sided facial paresis in combination with a discrete paresis of the left arm 1 day prior to the visit to the emergency department. The patient’s wife noted that he just recently recovered from an ophthalmic herpes zoster on the right side 6 weeks ago, which was treated with oral acyclovir for 1 week by the family doctor. This reactivation of VZV however, was complicated by a keratitis of the right eye, which was treated with acyclovir eyecream by the ophthalmologist. Besides the left-sided facial paresis, bradyphrenia, latent paresis of the left arm, and a subjective difficulty retrieving some words, no other neurological abnormalities could be detected by neurological examination. Neuropsychiatric evaluation was normal except for the bradyphrenia (ie, normal attention and higher cognitive functions). Blood analysis in the emergency department was normal (ie, normal white blood cell count, C-reactive protein, electrolytes, glucose, and kidney function). Cerebral computed tomography, ordered because of the focal neurological findings, showed no abnormalities (Figure 1D). Primary analysis of the CSF showed an elevated white blood cell count (11 × 106/L), slight elevation of the protein count (0.80 g/L), elevated lactate (2.6 mmol/L), normal glucose levels (CSF 4.0 mmol/L, serum 6.5 mmol/L), and a normal opening pressure of 13 cm H2O. EEG showed mild diffuse symmetrical slowing of the background rhythm to 7.5 to 8 Hz, with irregular right temporal theta waves (frequency of 4-6 Hz). The amplitude of the background rhythm was asymmetrical, with significantly higher amplitudes at the right temporal and occipital lobes (right temporal 15-30 µV, left temporal 10-15 µV, right occipital 15-20 µV, and left occipital 10-15 µV). The abnormalities suggested a deep subcortical focal abnormality in the right temporal lobe because these theta waves were not seen in the left temporal lobe (Figure 2A). Spectral analysis of the background rhythm showed no asymmetries of the mu- and alpha-background rhythms. However, the homologous F4-C4 derivation showed a small peak in the theta range (5.5 Hz), which could not be found in the F3-C3 derivations. This is in concordance with the qualitative EEG conclusion. The patient was admitted to the neurology ward with the tentative diagnosis of VZV encephalitis for treatment with intravenous acyclovir (10 mg/kg every 8 hours) for 10 days. Microbiological results of the serum and CSF, available 3 days after admission, showed a positive polymerase chain reaction for VZV in the CSF. Magnetic resonance imaging of the brain, 3 days after admission, showed a lacunar ischemic stroke of the right internal capsule on the T2 sequence and diffusion series (Figure 1A-C). EEG, repeated 6 days after initiation of treatment with acyclovir, showed normal symmetrical background pattern of 8 to 8.5 Hz, the amplitude asymmetry, however, persisted and the right temporal theta waves were significantly
Figure 1. (A and B) An ischemic lacunar stroke of the right internal capsule 3 days after admission characterized by a diffusion deficit with a high signal on the diffusion-weighted imaging (DWI; B) and a low signal on the apparent diffusion coefficient (ADC; A). (C) The T2-weighted imaging with a high signal at the place of the ischemic stroke. (D) The admission cerebral computed tomography scan with no evident signs of ischemia or other abnormalities besides mild generalized atrophy, which can be considered normal for the patient’s age.
reduced in abundance and had almost completely disappeared (Figure 2B). Spectral analysis still showed no asymmetries of the mu- or alpha-background rhythm, and the theta peak seen in the homologous F4-C4 derivation had completely disappeared. During the hospital stay, the patient slowly improved with respect to the behavioral abnormalities and bradyphrenia, though the latent paresis of the left arm and left-sided facial paresis did not significantly improve in the following 5 months.
Discussion This patient developed a varicells zoster encephalitis as a complication of a VZV infection in the area of the ophthalmic branch of the trigeminal nerve on the right side. The varicella zoster encephalitis was probably complicated by a secondary small-vessel vasculopathy causing an ischemic stroke in the internal capsule. There is also a possibility that the ischemic stroke could be a coincidence because of the patient’s risk factors (biovalve, previous cardiac atherosclerotic disease, and advanced age). However, the fact that (a) the cerebral magnetic resonance imaging scan showed evidence of acute ischemia (high signal on the diffusion-weighted imaging and low signal on the apparent diffusion coefficient) in the absence of other
312
Clinical EEG and Neuroscience 45(4)
Figure 2. EEG recording A was performed in the emergency department and EEG recording B was performed 6 days later. Refer to the text for description of both EEGs. The arrows point to irregular right temporal theta waves. High-pass filter 0, 100 Hz; low-pass filter 60 Hz; notch-filtered, bipolar montage, sensitivity 5 µV/mm, speed 30 mm/s.
vascular lesions, (b) there is a temporal relationship of the clinical signs of the cerebral varicella infection and the ischemic stroke, and (c) varicella encephalitis is a major risk factor for ischemic stroke due to vasculopathy, make an underlying atherosclerotic etiology for the stroke less likely
than a secondary varicella virus–induced vasculopathy. A small-vessel vasculopathy is more likely in this patient than a large-vessel vasculopathy because (a) the location of the lacunar stroke is in the right anterior choroideal branch, which is per definition considered a small vessel and (b) the erythrocyte
313
Venhovens et al sedimentation rate is normal (4 mm/h); it would be expected to be higher in large-vessel vasculopathy. A concomitant largevessel vasculopathy, however, cannot be excluded but seems unlikely (a cerebral magnetic resonance angiography or cerebral digital subtraction angiography was not performed because of the lack of clinical suspicion). VZV–induced cerebral vasculopathies are a well-known and serious complication that can lead to ischemic stroke, aneurysm, carotid dissection, subarachnoid, or intracerebral haemorrhage1. The clinical outcome of patients with a secondary vasculopathy due to an infectious origin are unfavorable and often result in severe neurological deficits or death.3,4 In an original article by Katchanov et al,3 8 adult patients with an infectious nonatherosclerotic cerebral vasculopathy were studied (2 patients with a varicella-induced cerebral vasculopathy). The outcome of the patients with an infectious vasculopathy was highly unfavorable with 1 dead, 2 locked-in syndromes, and 5 patients with severe neurological deficits (of the varicella-induced vasculopathies, 1 patient had a locked-in syndrome and 1 left the intensive care unit with severe neurological deficits). The patient in this case report, however, left the hospital with only relatively minor neurological deficits (Modified Rankin Scale 2). The preferred treatment of viral encephalopathy is intravenous acyclovir 10 mg/kg thrice daily (every 8 hours) for 10 to 14 days. The duration of treatment for immuno-suppressed patients is 21 days according to the European Federation of Neurological Societies guidelines.2 Early diagnosis and treatment of viral encephalopathy is very important because the mortality rate is reduced from 70% in untreated patients to 20% to 30% in early treated patients.2 There are very few case reports or series describing EEG patterns in patients with VZV encephalitis. A small case series of 20 VZV encephalopathy patients (10 patients had EEG examinations) described EEG abnormalities in 6 patients.5 The majority had intermittent diffuse slowing with focal accentuation (mostly temporal) or focal slowing (mostly temporal) of the background rhythm. In our patient, the background rhythm was slowed diffusely to 7.5 to 8 Hz, the background amplitude was asymmetrical, whereby the amplitude especially in the right temporal lobe was significantly higher in comparison with the left temporal lobe (right temporal 15-30 µV and left temporal 10-15 µV), and the right temporal lobe showed irregular theta activity (4-6 Hz) throughout the recording in an awake patient. The EEG 6 days after initiation of treatment showed a mild improvement of the symmetrical background rhythm to 8 to 8.5 Hz, the amplitude asymmetry was unchanged, and the right temporal theta waves had almost disappeared (Figure 2A and B). Additional spectral analysis of the mu- and alpha-background rhythms showed no asymmetries in power or frequency; however, the first analysis showed a 5.5 Hz theta peak of the homologous F4-C4 derivation, which was not found at the homologous F3-C3 derivation and which had completely disappeared in the second analysis. The origin of the theta waves is thought to be the deep subcortical lacunar
ischemic stroke of the internal capsule on the right side. The mild slowing of the background rhythm was thought to be caused by early encephalopathy, however, could also be explained by the lacunar ischemic stroke. An EEG study by Petty et al6 of 55 patients with a lacunar stroke showed that 29 (53%) had EEG abnormalities, of which 13 had diffuse generalized slowing, 6 had focal slowing, and 10 had generalized plus focal slowing. Of the abnormal EEGs, 13 of the 29 patients had ipsilateral slowing and 9 of the 29 had contralateral slowing. None of the study EEGs contained epileptiform activity in the form of spikes and spike-and-slow-wave discharges or voltage asymmetries. The EEGs in the patients with lacunar infarctions in the internal capsule (4 patients) were abnormal in 2 . In another study by Kappelle et al,7 10 of the 12 patients with lacunar infarctions showed EEG abnormalities (after visual and quantitative EEG analysis). These abnormalities were compromised by asymmetries in the mu- and/or alpha-background rhythm. The amplitude asymmetry of the background rhythm (the amplitude on the dominant left side is less than 50% compared with the amplitude on the subdominant right side) is thought to be of physiologic origin and represents neither the encephalopathy nor the ischemic stroke. This hypothesis is supported by the lack of mu- or alpha-background asymmetries, and the observation that the background amplitude asymmetry does not exceed the 50%. In conclusion, the EEG may localize focal abnormalities possibly due to cortical or lacunar ischemia, which could be explained by an early small and/or large vessel vasculopathy in patients with suspected VZV encephalitis. Authors’ Note Jeroen Venhovens and Bianca Stelten had an equal contribution in writing this article.
Acknowledgments The authors thank J. ten Cate and H. Lentjes, clinical neurophysiological technicians, for their support and for performing the EEGs.
Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Studahl M, Lindquist L, Eriksson B, et al. Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management. Drugs. 2013;73:131-158. 2. Steiner I, Budka H, Chaudhuri A, et al. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010;17:999-1009. 3. Katchanov J, Siebert E, Klingebiel R, Endres M. Infectious vasculopathy of intracranial large- and medium-sized vessels
314 in neurological intensive care unit: a clinico-radiological study. Neurocrit Care. 2010;12:369-374. 4. Gilden D, Cohrs R, Mahalingam R, Nagel M. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenisis, and treatment. Lancet Neurol. 2009;8:731740. 5. Pollak L, Dovrat S, Book M, Mendelson E, Weinberger M., Varicella zoster vs. herpes simplex meningoencephalitis in
Clinical EEG and Neuroscience 45(4) the PCR era. A single center study. J Neurol Sci. 2012;314:2936. 6. Petty G, Labar D, Fisch B, Pedley T, Mohr J, Khandji VaricellaA. Electroencephalography in lacunar infarction. J Neurol Sci. 1995;134:47-50. 7. Kappelle L, Huffelen van A, Gijn van J. Is the EEG really normal in lacunar stroke? J Neurol Neurosurg Psychiatry. 1990;53: 63-66.
