American Journal of Emergency Medicine 33 (2015) 742.e1–742.e2
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A hair-raising diagnosis: goose bumps as sign of herpes simplex encephalitis☆,☆☆,★ Abstract Herpes simplex virus (HSV) encephalitis is an infectious disease emergency with potential for significant patient morbidity and mortality. Although lumbar puncture, computed tomography, and magnetic resonance imaging (MRI) remain useful diagnostic modalities in the diagnosis of HSV encephalitis, clinical signs prompting providers to obtain these studies are often nonspecific. The diagnosis requires a high index of suspicion, and the importance of a thorough history and physical examination cannot be overemphasized. We present a case of HSV encephalitis presenting with unilateral piloerection as the sole manifestation on physical examination, a finding that is most likely explained by neuronal excitation in the temporal lobe. In 2004, a published case series addressed the localizing and lateralizing value of piloerection during seizures. The authors concluded that ictal piloerection is predominately seen in patients with temporal lobe seizure foci and does not appear to correlate with laterality [1]. This finding dovetails with the characteristic pattern of temporal and insular lobe edema seen on MRI in patients with HSV encephalitis [2]. The associated focal piloerection seen in our patient is likely attributable to neuronal hyperexcitation of his left or right mesial temporal lobe given the MRI findings. To the best of our knowledge, an association of focal piloerection or focal pilomotor seizure activity with acute HSV encephalitis has not been published. We present a case in which detection of this subtle feature prompted timely brain imaging and ultimately led to the diagnoses and timely treatment of HSV encephalitis. Patients with herpes simplex virus (HSV) encephalitis classically present with fever, headache, and delirium as the predominant symptoms. In addition, focal weakness and seizures are common in patients with HSV. In particular, patients presenting to the emergency department (ED) with unexplained focal neurologic deficits or with new onset seizures should raise concern for a potential central nervous system infection. Although there are no pathognomonic clinical findings associated with HSV, early consideration of the diagnosis is essential for improving outcomes. A 60-year-old man with a medical history of hyperlipidemia presented to the ED with a new onset seizure occurring 1 hour before arrival. The patient related experiencing a headache, nausea, and 1 episode of nonbloody vomiting earlier that morning but denied fever, chills, neck pain, focal or generalized weakness, memory impairment, and speech
☆ Meetings: None. ☆☆ Grant: None. ★ Conflicts of interest: The authors declare they have no conflicts of interest.
0735-6757/© 2014 Elsevier Inc. All rights reserved.
or visual disturbances. He denied rash or recent travel and had no history of prior seizures or head trauma. The patient's blood pressure, heart rate, respiratory rate, temperature, and oxygen saturation were within normal limits. Point-of-care blood glucose level was 116 mg/dL. He was well nourished, conversing appropriately, and was in no apparent distress but tired appearing. Head was without signs of trauma and neck was supple, without rigidity. He conversed normally; was alert; and oriented to person, place, year, and month but not to day. Cranial nerves II-XII were intact; pathologic nystagmus was absent. Pinprick and light touch were normal throughout. Motor strength was 5/5 in all upper and lower extremity muscle groups. Finger-to-nose and heel-to-shin tests were normal bilaterally as was his gait. The only pertinent positive finding on physical examination was piloerection of the left upper extremity. Basic laboratory studies were unremarkable with a normal white blood cell count of 9.7 K/UL (reference range, 4.8-10.8), neutrophils of 53.6% (reference range, 37.9%-70.5%), and sodium level of 139 mmol/L (reference range, 133-146). Head computed tomography was normal. Without a previous history of seizures and the finding of unilateral piloerection of unknown significance, the decision was made to order a magnetic resonance imaging (MRI). Magnetic resonance imaging revealed a nonenhancing flair signal hyperintensity, with restricted diffusion and mass effect in the left mesial temporal lobe and similar changes to a lesser extent on the right (Figure). Findings were concerning for HSV encephalitis. Lumbar puncture was performed, and cerebrospinal fluid (CSF) analysis demonstrated a white blood cell count of 128 cells/UL (reference range, 0-10) with a lymphocyte predominance of 76%. Cerebrospinal fluid glucose was 78 mg/dL (reference range, 40-70), and CSF total protein was 44 mg/dL (reference range, 15-45). No organisms were identified on CSF Gram stain or culture. Empiric intravenous acyclovir therapy was initiated in the ED, and the patient was admitted to the hospital for continued treatment. On day 2, polymerase chain reaction of CSF returned positive for HSV type 2 DNA. The patient had an uneventful hospital course, and follow-up MRI 1 month later showed interval improvement. If untreated, HSV encephalitis is progressive and often results in death within 1 or 2 weeks. Mortality rates have been recorded as high as 70% in untreated patients, and those that survive are often left with severe neurologic deficits [3]. With increasing availability of MRI and polymerase chain reaction, early detection of disease and initiation of acyclovir treatment have substantially reduced the mortality rate in HSV with some studies reporting mortality rates of 6% to 11% in those receiving treatment [4]. Older age, severity of symptoms on presentation, and delay of antiviral treatments are 3 factors known to be associated with a worse prognosis [5,6]. Clinicians can improve patient outcomes
742.e2
J. Brazg, B. Gillett / American Journal of Emergency Medicine 33 (2015) 742.e1–742.e2
subtle feature may prompt future providers to the early diagnosis and treatment of individuals with HSV encephalitis. Herpes simplex encephalitis is diagnostically challenging, yet delay in treatment imparts significant morbidity and mortality. We identify an association of focal piloerection with HSV encephalitis—a finding that may prove useful in the clinical detection of this highstake disease process. Jared Brazg, MD⁎ Brian Gillett, MD Maimonides Medical Center, New York, NY, USA ⁎Corresponding author. Emergency Medicine Maimonides Medical Center, 4802 10th Ave, New York, NY 11219 Tel.: +1 206 4550 642 http://dx.doi.org/10.1016/j.ajem.2014.11.030 References
Figure. Axial fluid-attenuated inversion recovery image shows signal hyperintensity in the left mesial temporal lobe.
with a high index of suspicion and early antiviral treatment. Many studies, however, demonstrate that acyclovir therapy is rarely initiated early in its symptoms in patients ultimately diagnosed with HSV [7]. The patient described in this case report presented with a new onset generalized tonic-clonic seizure before arrival and the subtle physical examination finding of piloerection of the left arm. Classic findings of encephalitis such as fever, persistent headache, bizarre behavior, focal weakness, or marked memory impairment were absent. As discussed above, the associated focal piloerection in our patient is likely a result of neuronal activity in his left or right mesial temporal lobe. In addition, piloerection has been elicited by electrical or pharmacological stimulation at multiple sites in these areas such as the insula, hippocampus, and amygdala [8-11]. The association of focal piloerection or focal pilomotor seizure activity with acute HSV encephalitis is a unique finding, and the detection of this
[1] Loddenkemper T, Kellinghaus C, Gandjour J, Nair DR, Najm IM, Bingaman W, Luders HO. Localizing and lateralizing value of ictal piloerection. J Neurol Neurosurg Psychiatry 2004;75(6):879–83. [2] Wasay M, Mekan SF, Khelaeni B, Saeed Z, Hassan A, Cheema Z, et al. Extra temporal involvement in herpes simplex encephalitis. Eur J Neurol Jun 2005;12(6):475–9. [3] Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch'ien LT, Alford CA. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med 1977;297(6): 289–94. [4] Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res Sep 2006;71(2–3):141–8. [5] McGrath N, Anderson NE, Croxson MC, Powell KF. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 1997; 63:321–6. [6] Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, et al. Vidarabin versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 1986;314:144–9. [7] Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis. Ann Emerg Med 2006 Jan;47(1):100–5 [Epub 2005 Nov 8]. [8] Freeman R, Schachter SC. Autonomic epilepsy. Semin Neurol 1995;15:158–66. [9] Fish DR, Gloor P, Quesney FL, Oliver A. Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Brain 1993;116:397–414. [10] Sato M. Long-lasting hypersensitivity to methamphetamine following amygdaloid kindling in cats: the relationship between limbic epilepsy and the psychotic state. Biol Psychiatry 1983;18:525–36. [11] Kaada BR, Andersen P, Jansen J. Stimulation of the amygdaloid nuclear complex in unanesthetized cats. Neurology 1954;4:48–64.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A hair-raising diagnosis: goose bumps as sign of herpes simplex encephalitis☆,☆☆,★ Abstract Herpes simplex virus (HSV) encephalitis is an infectious disease emergency with potential for significant patient morbidity and mortality. Although lumbar puncture, computed tomography, and magnetic resonance imaging (MRI) remain useful diagnostic modalities in the diagnosis of HSV encephalitis, clinical signs prompting providers to obtain these studies are often nonspecific. The diagnosis requires a high index of suspicion, and the importance of a thorough history and physical examination cannot be overemphasized. We present a case of HSV encephalitis presenting with unilateral piloerection as the sole manifestation on physical examination, a finding that is most likely explained by neuronal excitation in the temporal lobe. In 2004, a published case series addressed the localizing and lateralizing value of piloerection during seizures. The authors concluded that ictal piloerection is predominately seen in patients with temporal lobe seizure foci and does not appear to correlate with laterality [1]. This finding dovetails with the characteristic pattern of temporal and insular lobe edema seen on MRI in patients with HSV encephalitis [2]. The associated focal piloerection seen in our patient is likely attributable to neuronal hyperexcitation of his left or right mesial temporal lobe given the MRI findings. To the best of our knowledge, an association of focal piloerection or focal pilomotor seizure activity with acute HSV encephalitis has not been published. We present a case in which detection of this subtle feature prompted timely brain imaging and ultimately led to the diagnoses and timely treatment of HSV encephalitis. Patients with herpes simplex virus (HSV) encephalitis classically present with fever, headache, and delirium as the predominant symptoms. In addition, focal weakness and seizures are common in patients with HSV. In particular, patients presenting to the emergency department (ED) with unexplained focal neurologic deficits or with new onset seizures should raise concern for a potential central nervous system infection. Although there are no pathognomonic clinical findings associated with HSV, early consideration of the diagnosis is essential for improving outcomes. A 60-year-old man with a medical history of hyperlipidemia presented to the ED with a new onset seizure occurring 1 hour before arrival. The patient related experiencing a headache, nausea, and 1 episode of nonbloody vomiting earlier that morning but denied fever, chills, neck pain, focal or generalized weakness, memory impairment, and speech
☆ Meetings: None. ☆☆ Grant: None. ★ Conflicts of interest: The authors declare they have no conflicts of interest.
0735-6757/© 2014 Elsevier Inc. All rights reserved.
or visual disturbances. He denied rash or recent travel and had no history of prior seizures or head trauma. The patient's blood pressure, heart rate, respiratory rate, temperature, and oxygen saturation were within normal limits. Point-of-care blood glucose level was 116 mg/dL. He was well nourished, conversing appropriately, and was in no apparent distress but tired appearing. Head was without signs of trauma and neck was supple, without rigidity. He conversed normally; was alert; and oriented to person, place, year, and month but not to day. Cranial nerves II-XII were intact; pathologic nystagmus was absent. Pinprick and light touch were normal throughout. Motor strength was 5/5 in all upper and lower extremity muscle groups. Finger-to-nose and heel-to-shin tests were normal bilaterally as was his gait. The only pertinent positive finding on physical examination was piloerection of the left upper extremity. Basic laboratory studies were unremarkable with a normal white blood cell count of 9.7 K/UL (reference range, 4.8-10.8), neutrophils of 53.6% (reference range, 37.9%-70.5%), and sodium level of 139 mmol/L (reference range, 133-146). Head computed tomography was normal. Without a previous history of seizures and the finding of unilateral piloerection of unknown significance, the decision was made to order a magnetic resonance imaging (MRI). Magnetic resonance imaging revealed a nonenhancing flair signal hyperintensity, with restricted diffusion and mass effect in the left mesial temporal lobe and similar changes to a lesser extent on the right (Figure). Findings were concerning for HSV encephalitis. Lumbar puncture was performed, and cerebrospinal fluid (CSF) analysis demonstrated a white blood cell count of 128 cells/UL (reference range, 0-10) with a lymphocyte predominance of 76%. Cerebrospinal fluid glucose was 78 mg/dL (reference range, 40-70), and CSF total protein was 44 mg/dL (reference range, 15-45). No organisms were identified on CSF Gram stain or culture. Empiric intravenous acyclovir therapy was initiated in the ED, and the patient was admitted to the hospital for continued treatment. On day 2, polymerase chain reaction of CSF returned positive for HSV type 2 DNA. The patient had an uneventful hospital course, and follow-up MRI 1 month later showed interval improvement. If untreated, HSV encephalitis is progressive and often results in death within 1 or 2 weeks. Mortality rates have been recorded as high as 70% in untreated patients, and those that survive are often left with severe neurologic deficits [3]. With increasing availability of MRI and polymerase chain reaction, early detection of disease and initiation of acyclovir treatment have substantially reduced the mortality rate in HSV with some studies reporting mortality rates of 6% to 11% in those receiving treatment [4]. Older age, severity of symptoms on presentation, and delay of antiviral treatments are 3 factors known to be associated with a worse prognosis [5,6]. Clinicians can improve patient outcomes
742.e2
J. Brazg, B. Gillett / American Journal of Emergency Medicine 33 (2015) 742.e1–742.e2
subtle feature may prompt future providers to the early diagnosis and treatment of individuals with HSV encephalitis. Herpes simplex encephalitis is diagnostically challenging, yet delay in treatment imparts significant morbidity and mortality. We identify an association of focal piloerection with HSV encephalitis—a finding that may prove useful in the clinical detection of this highstake disease process. Jared Brazg, MD⁎ Brian Gillett, MD Maimonides Medical Center, New York, NY, USA ⁎Corresponding author. Emergency Medicine Maimonides Medical Center, 4802 10th Ave, New York, NY 11219 Tel.: +1 206 4550 642 http://dx.doi.org/10.1016/j.ajem.2014.11.030 References
Figure. Axial fluid-attenuated inversion recovery image shows signal hyperintensity in the left mesial temporal lobe.
with a high index of suspicion and early antiviral treatment. Many studies, however, demonstrate that acyclovir therapy is rarely initiated early in its symptoms in patients ultimately diagnosed with HSV [7]. The patient described in this case report presented with a new onset generalized tonic-clonic seizure before arrival and the subtle physical examination finding of piloerection of the left arm. Classic findings of encephalitis such as fever, persistent headache, bizarre behavior, focal weakness, or marked memory impairment were absent. As discussed above, the associated focal piloerection in our patient is likely a result of neuronal activity in his left or right mesial temporal lobe. In addition, piloerection has been elicited by electrical or pharmacological stimulation at multiple sites in these areas such as the insula, hippocampus, and amygdala [8-11]. The association of focal piloerection or focal pilomotor seizure activity with acute HSV encephalitis is a unique finding, and the detection of this
[1] Loddenkemper T, Kellinghaus C, Gandjour J, Nair DR, Najm IM, Bingaman W, Luders HO. Localizing and lateralizing value of ictal piloerection. J Neurol Neurosurg Psychiatry 2004;75(6):879–83. [2] Wasay M, Mekan SF, Khelaeni B, Saeed Z, Hassan A, Cheema Z, et al. Extra temporal involvement in herpes simplex encephalitis. Eur J Neurol Jun 2005;12(6):475–9. [3] Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch'ien LT, Alford CA. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med 1977;297(6): 289–94. [4] Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res Sep 2006;71(2–3):141–8. [5] McGrath N, Anderson NE, Croxson MC, Powell KF. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 1997; 63:321–6. [6] Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, et al. Vidarabin versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 1986;314:144–9. [7] Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis. Ann Emerg Med 2006 Jan;47(1):100–5 [Epub 2005 Nov 8]. [8] Freeman R, Schachter SC. Autonomic epilepsy. Semin Neurol 1995;15:158–66. [9] Fish DR, Gloor P, Quesney FL, Oliver A. Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Brain 1993;116:397–414. [10] Sato M. Long-lasting hypersensitivity to methamphetamine following amygdaloid kindling in cats: the relationship between limbic epilepsy and the psychotic state. Biol Psychiatry 1983;18:525–36. [11] Kaada BR, Andersen P, Jansen J. Stimulation of the amygdaloid nuclear complex in unanesthetized cats. Neurology 1954;4:48–64.
