NEUROLOGY/CASE REPORT
Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia Arseny A. Sokolov, MD*; Reto Lienhard, MSc; Renaud Du Pasquier, MD; Véronique Erard, MD *Corresponding Author. E-mail: [email protected].
Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered. To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution. [Ann Emerg Med. 2015;66:60-64.] 0196-0644/$-see front matter Copyright © 2015 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2015.01.011
INTRODUCTION Lyme disease is a spirochetosis transmitted by tick bites and represents the major arthropod-borne infection in North America and Europe,1-3 with a prevalence of approximately 1 to 1,000 people.2 Nervous system affection occurs in up to 15% of patients3-5 who present with lymphocytic meningitis, various cranial neuropathies, painful radiculitis, neuropathy, and, rarely, encephalomyelitis.5,6 Lyme neuroborreliosis is usually subacute, whereas acute disease onset is considered uncommon. Here, we report suddenonset neuroborreliosis with focal neurologic signs mimicking other neurologic conditions, thus representing a diagnostic challenge in the emergency department (ED). CASE REPORT The morning after a party at a discotheque, a 16-year-old female patient living in the Swiss plateau presented with acute onset of severe headache and confusion, witnessed by her family. Clinical evaluation conducted at a primary care emergency center (in Switzerland, this is similar to an urgent-care center) yielded right-sided face and arm weakness, and language deficits. For evaluation before possible thrombolysis, the patient was transferred by helicopter. Hemiparesis resolved during the helicopter flight. Clinical Findings On arrival, 3 hours after symptom onset, the patient exhibited reduced spontaneous speech production with 60 Annals of Emergency Medicine
phonologic paraphasia, echolalia, and impaired execution of orders, along with substantial fluctuations and interexaminer differences. Agitation, confusion and aggressiveness were also retained. There was no meningismus. Neither motor nor sensory deficits were retained, although cooperation was limited. Reflexes and the rest of neurologic examination were normal. Medical history was remarkable only for recently diagnosed gluten intolerance. No regular medication except oral contraception was noted. Diagnostic Considerations The language deficits with reduced speech production and comprehension but preserved repetition were compatible with transcortical sensory aphasia. Although right-sided face and arm weakness could not be confirmed, both language and motor symptoms pointed to focal left parietotemporal affection, with ischemic stroke and nonconvulsive status epilepticus to be excluded first. Although thrombolytic treatment in pediatric stroke is an evolving area, the patient would have been within the European 4.5-hour window in which thrombolysis has been effective in adults.7 Cerebral venous sinus thrombosis may also present with headache and focal neurologic symptoms.8 Other diagnostic considerations included Todd’s paralysis and central nervous system autoimmune inflammation or infection. In addition, drug intoxication or a psychogenic origin were considered; Volume 66, no. 1 : July 2015
Sokolov et al
Acute Lyme Neuroborreliosis
Figure 1. Cerebral CT perfusion findings showing diffuse brain hyperperfusion, with a relative perfusion deficit in the deep left frontal white matter and the left parietotemporal junction, as illustrated by A, regional cerebral blood volume, B, regional cerebral blood flow, C, mean transit time, and D, mismatch between mean transit time and cerebral blood volume. White arrow indicates left temporal area of relative hypoperfusion corresponding to focal EEG slowing (B). Magnetic resonance diffusion (E) and T2-weighted diffusion (F) do not show corresponding structural brain lesions. CT, Computed tomography; EEG, electroencephalography.
however, the patient had been accompanied for at least 16 hours before admission, without drug use or signs of seizure activity witnessed. ED Evaluation Given a pending indication for thrombolysis, contrastenhanced brain computed tomography (CT) with arterial and venous angiographies was conducted immediately after clinical examination and was not suggestive of brain lesion, hemorrhagic stroke, vasculitis, or cerebral venous sinus thrombosis. However, cerebral CT revealed diffuse brain hyperperfusion with relatively insufficient patchy perfusion (Figure 1), mainly in the left temporoparietal junction, compatible with the patient’s symptoms. Diffuse hyperperfusion may be related to inflammation or epileptic activity. In the absence of a thrombus on angiography and given the CT perfusion findings, suspicion of ischemia was considered low and thrombolysis was not indicated. Nonconvulsive status epilepticus was excluded by electroencephalography (EEG) showing fluctuating Volume 66, no. 1 : July 2015
moderate diffuse encephalopathy with frontal intermittent rhythmic delta activity and pronounced nonepileptic left parietotemporal slowing (Figure 2), matching CT perfusion and clinical findings. Extensive toxicologic screening results were negative. Given unexplained organic brain dysfunction, lumbar puncture was performed, but the procedure was substantially delayed because of the patient’s agitation. In addition to infection, autoimmune encephalitis had to be considered in the context of absence of clinical or biological signs of inflammation, age, sex, and the acute neuropsychiatric symptoms.9 Cerebrospinal fluid analysis showed elevated leucocyte levels (74/mm3), with 45% neutrophils, protein at 335 mg/dL (normal 15 to 45 dL), and lactate at 4.8 mmol/L (normal 1.2 to 2.0 mmol/L). Cerebrospinal fluid glucose level was diminished, at 17% of serum glucose level (0.8 versus 4.8 mmol/L). Thus, despite relatively low leucocyte count and unremarkable Gram’s staining results, bacterial meningitis was suspected. The patient received intravenous antibacterial and antiviral agents (ceftriaxone, amoxicillin/ Annals of Emergency Medicine 61
Acute Lyme Neuroborreliosis
Sokolov et al
Figure 2. A, Diagnostic pathway in the ED and during the early hospital course. B, EEG at admission indicates diffuse encephalopathy with bilateral frontal intermittent rhythmic delta activity (highlighted in orange) and more pronounced left temporal slowing without epileptic activity (highlighted in green). EEG recorded on 23 electrodes according to the 20/10 international system, presented in monopolar (average) display. CCT, Cranial computed tomography; LP, kumbar puncture; MRI, magnetic resonance imaging.
clavulanate, and acyclovir). Substantial improvement was observed immediately after treatment initiation. Hospital Course and Further Evaluation The next morning, brain magnetic resonance imaging (MRI), including arterial and venous angiography, excluded left-sided parietotemporal ischemia, cerebral venous sinus thrombosis, and vessel abnormalities suggestive of vasculitis (Figure 1). It revealed a pineal cyst and right frontal developmental venous anomaly. Meanwhile, symptoms had completely resolved, except for circumstantial amnesia. Initial microbiological evaluation results were negative, and a detailed testing was performed. 62 Annals of Emergency Medicine
The blood immunoassay results for Borrelia burgdorferi Immunoglobulin G (IgG; RIDASCREEN; R-Biopharm, Darmstadt, Germany), Immunoglobulin M (IgM; IDEIA; Oxoid, Hampshire, UK), and Immunoglobulin (Ig; C6 Lyme ELISA; Immunetics, Boston, MA) were positive. Isoelectrofocalization revealed intrathecal production of IgG (cerebrospinal fluid oligoclonal bands). The capture tests for B burgdorferi IgM and IgG in cerebrospinal fluid and serum (IDEIA; Oxoid) yielded a highly significant intrathecal antibody index of 7.1 (normal
Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia Arseny A. Sokolov, MD*; Reto Lienhard, MSc; Renaud Du Pasquier, MD; Véronique Erard, MD *Corresponding Author. E-mail: [email protected].
Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered. To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution. [Ann Emerg Med. 2015;66:60-64.] 0196-0644/$-see front matter Copyright © 2015 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2015.01.011
INTRODUCTION Lyme disease is a spirochetosis transmitted by tick bites and represents the major arthropod-borne infection in North America and Europe,1-3 with a prevalence of approximately 1 to 1,000 people.2 Nervous system affection occurs in up to 15% of patients3-5 who present with lymphocytic meningitis, various cranial neuropathies, painful radiculitis, neuropathy, and, rarely, encephalomyelitis.5,6 Lyme neuroborreliosis is usually subacute, whereas acute disease onset is considered uncommon. Here, we report suddenonset neuroborreliosis with focal neurologic signs mimicking other neurologic conditions, thus representing a diagnostic challenge in the emergency department (ED). CASE REPORT The morning after a party at a discotheque, a 16-year-old female patient living in the Swiss plateau presented with acute onset of severe headache and confusion, witnessed by her family. Clinical evaluation conducted at a primary care emergency center (in Switzerland, this is similar to an urgent-care center) yielded right-sided face and arm weakness, and language deficits. For evaluation before possible thrombolysis, the patient was transferred by helicopter. Hemiparesis resolved during the helicopter flight. Clinical Findings On arrival, 3 hours after symptom onset, the patient exhibited reduced spontaneous speech production with 60 Annals of Emergency Medicine
phonologic paraphasia, echolalia, and impaired execution of orders, along with substantial fluctuations and interexaminer differences. Agitation, confusion and aggressiveness were also retained. There was no meningismus. Neither motor nor sensory deficits were retained, although cooperation was limited. Reflexes and the rest of neurologic examination were normal. Medical history was remarkable only for recently diagnosed gluten intolerance. No regular medication except oral contraception was noted. Diagnostic Considerations The language deficits with reduced speech production and comprehension but preserved repetition were compatible with transcortical sensory aphasia. Although right-sided face and arm weakness could not be confirmed, both language and motor symptoms pointed to focal left parietotemporal affection, with ischemic stroke and nonconvulsive status epilepticus to be excluded first. Although thrombolytic treatment in pediatric stroke is an evolving area, the patient would have been within the European 4.5-hour window in which thrombolysis has been effective in adults.7 Cerebral venous sinus thrombosis may also present with headache and focal neurologic symptoms.8 Other diagnostic considerations included Todd’s paralysis and central nervous system autoimmune inflammation or infection. In addition, drug intoxication or a psychogenic origin were considered; Volume 66, no. 1 : July 2015
Sokolov et al
Acute Lyme Neuroborreliosis
Figure 1. Cerebral CT perfusion findings showing diffuse brain hyperperfusion, with a relative perfusion deficit in the deep left frontal white matter and the left parietotemporal junction, as illustrated by A, regional cerebral blood volume, B, regional cerebral blood flow, C, mean transit time, and D, mismatch between mean transit time and cerebral blood volume. White arrow indicates left temporal area of relative hypoperfusion corresponding to focal EEG slowing (B). Magnetic resonance diffusion (E) and T2-weighted diffusion (F) do not show corresponding structural brain lesions. CT, Computed tomography; EEG, electroencephalography.
however, the patient had been accompanied for at least 16 hours before admission, without drug use or signs of seizure activity witnessed. ED Evaluation Given a pending indication for thrombolysis, contrastenhanced brain computed tomography (CT) with arterial and venous angiographies was conducted immediately after clinical examination and was not suggestive of brain lesion, hemorrhagic stroke, vasculitis, or cerebral venous sinus thrombosis. However, cerebral CT revealed diffuse brain hyperperfusion with relatively insufficient patchy perfusion (Figure 1), mainly in the left temporoparietal junction, compatible with the patient’s symptoms. Diffuse hyperperfusion may be related to inflammation or epileptic activity. In the absence of a thrombus on angiography and given the CT perfusion findings, suspicion of ischemia was considered low and thrombolysis was not indicated. Nonconvulsive status epilepticus was excluded by electroencephalography (EEG) showing fluctuating Volume 66, no. 1 : July 2015
moderate diffuse encephalopathy with frontal intermittent rhythmic delta activity and pronounced nonepileptic left parietotemporal slowing (Figure 2), matching CT perfusion and clinical findings. Extensive toxicologic screening results were negative. Given unexplained organic brain dysfunction, lumbar puncture was performed, but the procedure was substantially delayed because of the patient’s agitation. In addition to infection, autoimmune encephalitis had to be considered in the context of absence of clinical or biological signs of inflammation, age, sex, and the acute neuropsychiatric symptoms.9 Cerebrospinal fluid analysis showed elevated leucocyte levels (74/mm3), with 45% neutrophils, protein at 335 mg/dL (normal 15 to 45 dL), and lactate at 4.8 mmol/L (normal 1.2 to 2.0 mmol/L). Cerebrospinal fluid glucose level was diminished, at 17% of serum glucose level (0.8 versus 4.8 mmol/L). Thus, despite relatively low leucocyte count and unremarkable Gram’s staining results, bacterial meningitis was suspected. The patient received intravenous antibacterial and antiviral agents (ceftriaxone, amoxicillin/ Annals of Emergency Medicine 61
Acute Lyme Neuroborreliosis
Sokolov et al
Figure 2. A, Diagnostic pathway in the ED and during the early hospital course. B, EEG at admission indicates diffuse encephalopathy with bilateral frontal intermittent rhythmic delta activity (highlighted in orange) and more pronounced left temporal slowing without epileptic activity (highlighted in green). EEG recorded on 23 electrodes according to the 20/10 international system, presented in monopolar (average) display. CCT, Cranial computed tomography; LP, kumbar puncture; MRI, magnetic resonance imaging.
clavulanate, and acyclovir). Substantial improvement was observed immediately after treatment initiation. Hospital Course and Further Evaluation The next morning, brain magnetic resonance imaging (MRI), including arterial and venous angiography, excluded left-sided parietotemporal ischemia, cerebral venous sinus thrombosis, and vessel abnormalities suggestive of vasculitis (Figure 1). It revealed a pineal cyst and right frontal developmental venous anomaly. Meanwhile, symptoms had completely resolved, except for circumstantial amnesia. Initial microbiological evaluation results were negative, and a detailed testing was performed. 62 Annals of Emergency Medicine
The blood immunoassay results for Borrelia burgdorferi Immunoglobulin G (IgG; RIDASCREEN; R-Biopharm, Darmstadt, Germany), Immunoglobulin M (IgM; IDEIA; Oxoid, Hampshire, UK), and Immunoglobulin (Ig; C6 Lyme ELISA; Immunetics, Boston, MA) were positive. Isoelectrofocalization revealed intrathecal production of IgG (cerebrospinal fluid oligoclonal bands). The capture tests for B burgdorferi IgM and IgG in cerebrospinal fluid and serum (IDEIA; Oxoid) yielded a highly significant intrathecal antibody index of 7.1 (normal
