EXPERIENCE & REASON Recurrent Expressive Aphasia as a Presentation of Cat-Scratch Encephalopathy James W. Fox, MDa, Joanna K. Studley, MDb, Daniel M. Cohen, MDc aDepartment of Pediatrics, Division of Emergency Medicine, Children’s Hospital of Akron, Akron, Ohio; bDepartment of Pediatrics, cDivision of Emergency Medicine, Columbus Children’s Hospital, Columbus, Ohio The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT Cat-scratch disease is a common disease, occurring in an estimated 24 000 patients annually in the United States, and is one of the most common causes of chronic lymphadenitis in children. A wide array of neurologic complications occurs as a result of cat-scratch disease. However, there have been no reports of acute-onset, self-resolving, recurrent, expressive aphasia, as we report here in an adolescent boy. In our case, establishing the diagnosis of cat-scratch encephalopathy saved time and resources and afforded the family a benign diagnosis. Cat-scratch encephalopathy must be considered in the differential diagnoses when pediatric patients present with unusual neurologic symptoms. F IRST RECOGNIZED BY Foshay in 19321 and reported by Debre et al2 in 1950, cat-scratch disease (CSD) is an infection that typically results from introduction of a pleomorphic Gram-negative bacillus, Bartonella henselae, into the bloodstream via the scratch or bite of an infected cat, usually of young age. The infection most often occurs in the pediatric age group3; affected individuals exhibit low-grade fever, regional lymphadenopathy, and malaise. Atypical cases of CSD, however, may affect the central nervous system (CNS). This rare presentation (0.17%–2% of cases4) usually manifests as an encephalopathy with sudden-onset seizures or altered consciousness. It is interesting to note that since the first description of CNS involvement in CSD by Stevens5 in 1952, there have been numerous reports in the literature that described a potpourri of neurologic sequelae associated with CSD, including cerebral arteritis6 and Brown-Séquard syndrome.7 Recently, we cared for an adolescent boy whose case of cat-scratch encephalopathy adds to the intriguing list of neurologic presentations of CSD. To our knowledge, an intermittent, expressive aphasia has never been reported in a patient with cat-scratch encephalopathy. In this report, we describe our patient’s presenting symptoms, the differential diagnoses considered, and his clinical course. CASE REPORT A 15-year-old boy with no significant past medical history was evaluated initially at a local community hospital for the complaint of “inability to speak.” Earlier in the e760 FOX et al day, this straight-A student was sent home from school because of nausea and vomiting. Once at home, his parents noticed that he was unable to communicate verbally. He never experienced typical seizure-like activity, became confused, lost consciousness, lost his ability to understand others, or lost the ability to write. At the community hospital, his examination revealed a wellappearing adolescent with an expressive aphasia, mild right facial droop, right-sided weakness (upper greater than lower extremity), and an inability to ambulate. A complete blood count, electrolytes, renal function tests, and computed tomography of his head were unrevealing. As a result, the referring hospital performed magnetic resonance imaging (MRI) of his brain, the results of which were abnormal (Fig 1; initial interpretation: “diffuse white matter periventricular signal abnormality”). A cerebrovascular insult was the physicians’ foremost concern, so aspirin therapy was begun, and he was admitted overnight. Over the course of 6 hours, his symptoms steadily improved and, by morning, had comKey Words: cat-scratch disease, Bartonella henselae, expressive aphasia, encephalopathy, differential diagnosis Abbreviations: CSD, cat-scratch disease; CNS, central nervous system; ED, emergency department www.pediatrics.org/cgi/doi/10.1542/peds.2006-1885 doi:10.1542/peds.2006-1885 Accepted for publication Oct 3, 2006 Address correspondence to James W. Fox, MD, Children’s Hospital of Akron, Division of Emergency Medicine, One Perkins Square, Akron, OH 44308. E-mail: jfox@chmca.org PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2007 by the American Academy of Pediatrics Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015 FIGURE 1 Brain MRI in a patient with cat-scratch encephalopathy. Significant diffuse inflammation in the subcortical white matter is evident in these T2-weighted images, which were obtained during our patient’s initial presentation. pletely resolved. He was discharged later that day on aspirin therapy, with a scheduled follow-up appointment by a pediatric neurologist. Within hours of discharge, the patient had a recurrence of his inability to speak. Subsequent to representing to the referring hospital, he was transferred to the emergency department (ED) of our children’s hospital. Before transfer, intravenous lorazepam was given for “agitation” without noticeable improvement. Our physical examination confirmed findings from the previous day. Specifically, he was a pleasant, cooperative, wellappearing young adult with a pronounced expressive aphasia, right central seventh cranial nerve paresis, right-sided weakness (upper greater than lower extremity), unsteady gait secondary to weakness without cerebellar signs, normal reflexes, no clonus, and extensor Babinski responses bilaterally. In addition, a large (5 ⫻ 3 cm), mildly tender, nonerythematous, nonsuppurative, right axillary lymph node was palpated. A few healing papules and scratches on his chest were also identified. This led to the discovery of the patient’s frequent interactions with his family’s kitten, which often scratched him. Review by a pediatric neuroradiologist of the brain MRI performed by the referring facility revealed the following findings: “symmetric abnormal increased T2weighted signal and decreased diffusion within the white matter of the centrum semiovale bilaterally including involvement of the subcortical U-fibers.” This interpretation made ischemic injury highly unlikely. While in the ED, the patient displayed a remarkable steady recovery on reevaluation. Nevertheless, given the recurrent nature of his impressive symptoms, he was admitted to our hospital for additional evaluation and observation. An extensive inpatient evaluation followed. His workup was negative for metabolic disorders, hypercoagulability, thromboembolism, toxic ingestions, toxin exposures, autoimmune disorders, encephalitis, and evidence of traumatic injury. A pediatric psychiatrist opined that his symptoms were not the result of mental illness. During the boy’s hospitalization, the inpatient service continued the aspirin started by the referring institution. In addition, intravenous steroids were administered because the patient’s brain MRI suggested an acute disseminated encephalomyelitis. The following morning, results of the CSD serum titers sent from the ED were strongly positive (IgM ⬎ 1:32 and IgG ⬎ 1:128). In light of the otherwise negative workup, this finding confirmed the diagnosis of CSD encephalopathy. Per our infectious disease consultant, a 5-day course of azithromycin was instituted. Within hours of hospitalization and recrudescence of his symptoms, the patient made a second complete recovery. He has remained symptom free, without recurrence or need for follow-up with a pediatric neurologist, 5 months after his hospitalization. PEDIATRICS Volume 119, Number 3, March 2007 Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015 e761 DISCUSSION When considering the cause of expressive aphasia in children, physicians commonly consider cerebrovascular ischemia or infarction, partial seizures, cerebral malignancies, traumatic injuries, complex migraines, vasculitic syndromes, and psychiatric illnesses. We have expanded this differential diagnosis by describing a child with cat-scratch encephalopathy who presented primarily with expressive aphasia. In general, CSD is a self-limited, subacute regional lymphadenitis caused by B henselae. Atypical presentations occur in 11% of cases, with encephalopathy among the most common.3 Encephalopathy accounts for 90% of CSD involvement of the CNS and typically manifests as seizure activity (frequently difficult-to-control status epilepticus), headache, coma, and combative behavior.3,4,8–13 Other reported CNS complications include cerebral arteritis, peripheral and central facial nerve paralysis, Brown-Séquard syndrome, neuroretinitis, hemiparesis, cerebellar ataxia, and movement disorders.6– 8,14–17 In 1991, a report by Carithers3 of 61 patients with encephalopathy attributable to CSD suggested that complete recovery was the rule. Although it is now recognized that persistent neurologic morbidity does occur,6,8,11,18–21 this is, fortunately, a rare occurrence. The mechanism by which cat-scratch encephalopathy occurs is not known. Previous authors have suggested direct invasion of the CNS, release of neurotoxin, and an immune-mediated vasculitis.8,22,23 It is surprising that although a bacterium is the etiologic agent of this encephalopathy, the seizures and coma that typically develop abruptly resolve completely over the course of days without antimicrobial therapy. Cat-scratch encephalopathy rarely presents without a change in mental status (seizure, coma, combative behavior), and aphasia as a symptom of cat-scratch encephalopathy has only been reported twice before in the literature.6,24 The first case involved a 25-year-old woman with CSD who was hospitalized after a seizure. After 4 days of treatment, she became lucid enough to speak and, at that time, demonstrated both a receptive and expressive aphasia. In contrast to our patient, aphasia was not her presenting symptom. The other case involved a 7-year-old girl who presented with an expressive aphasia and acute right hemiplegia, similar to our case. This patient demonstrated a protracted course, as her aphasia lasted nearly 2 months and her right hemiplegia was still present after 5 months of follow-up. Therefore, ours is the first report of cat-scratch encephalopathy presenting with an expressive aphasia of very short duration (hours). Another rare occurrence in our patient was the recurrent nature of his symptoms. Only twice before in the literature was a recurrent encephalopathy attributable to CSD described.25,26 One patient was a 14-year-old girl who experienced 2 qualitatively different seizures 3 e762 FOX et al weeks apart. In addition, she continued to suffer from persistent speech and language difficulty 10 weeks after discharge. The other case that demonstrated an element of recurrence involved a 17-year-old girl who was admitted twice, 4 days apart, for generalized seizures that were qualitatively the same. She experienced complete resolution of her symptoms between convulsions and, again, after her second seizure. Our patient represents the first report of a case of CSD with recurrence of the same neurologic abnormality separated by complete resolution within a 24-hour time frame. It is possible that our patient’s neurologic symptoms were a manifestation of nonconvulsive partial status epilepticus. There are several reports in the literature of aphasia representing the predominant symptom (often with right-sided motor deficits, as in our patient) of nonconvulsive partial status epilepticus.27–34 It is interesting to note that partial seizures remain a potential cause of our patient’s aphasia despite his lack of response to intravenous lorazepam. In the setting of cat-scratch encephalopathy, seizures are notoriously difficult to control with antiepileptic medications. Furthermore, reports on aphasic status epilepticus have demonstrated this same difficulty.28,30–32 Abnormalities shown by MRI, electroencephalography, and single-photon emission computed tomography typically localize to the left frontotemporal region in patients with aphasic status epilepticus.27–31,34 Although it is difficult to localize the focus of our patient’s symptoms from a neuroanatomic perspective because of the diffuse, bilateral abnormalities seen on his MRI, the suspect frontotemporal region was certainly involved. It is notable that results of polymerase chain reaction testing of the cerebrospinal fluid for B henselae were negative in our patient. This is consistent with previous reports of patients with cat-scratch encephalopathy whose cerebrospinal fluid tested negative for B henselae by polymerase chain reaction.16,19,20 During his hospitalization, the patient was treated with intravenous corticosteroids because his brain MRI suggested diffuse cerebral inflammation. Although it is unlikely that this treatment resulted in the prompt disappearance of his symptoms, literature does exist that supports the use of corticosteroids for cat-scratch encephalopathy.35 In addition, his therapy included a course of azithromycin. Although the efficacy of antimicrobial therapy for CSD, and even more so for catscratch encephalopathy, is controversial, in light of this atypical presentation and the presence of large lymphadenitis, the use of azithromycin was felt to be of potential benefit and of limited to no harm for this patient. CONCLUSIONS This case adds to the expanding literature on atypical neurologic complications of CSD. Our report confirms the prediction made by Marra in 199536: “Recent ad- Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015 vances in identification of [B henselae] will lead to recognition of more neurologic complications.” It is important to note that this case emphasizes the need to inquire about cat exposure when children present with unusual neurologic symptoms. Furthermore, when a clinician is confronted with a child with expressive aphasia, catscratch encephalopathy should be considered. REFERENCES 1. Greer WER, Keefer CS. Cat-scratch fever: a disease entity. N Engl J Med. 1951;244:545–548 2. Debre R, Lamy M, Jamment ML, Costil L, Mozziconacci P. Cat scratch disease [in French]. Sem Hop. 1950;26:1895–1904 3. Carithers HA. Cat-scratch disease: an overview based on a study of 1,200 patients. Am J Dis Child. 1985;139:1124 –1133 4. Carithers HA, Margileth AM. Cat-scratch disease: acute encephalopathy and other neurologic manifestations. Am J Dis Child. 1991;145:98 –101 5. De-Long X, Zeng W, Yong-jian S. Cat-scratch disease encephalopathy. Chin Med J (Engl). 1994;107:104 –106 6. Selby G, Walker GL. Cerebral arteritis in cat-scratch disease. Neurology. 1979;29:1413–1418 7. Pickerill RG, Milder JE. Transverse myelitis associated with cat-scratch disease in an adult. JAMA. 1981;246:2840 –2841 8. Lewis DW, Tucker SH. Central nervous system involvement in cat scratch disease. Pediatrics. 1986;77:714 –721 9. Harvey RA, Misselbeck WJA, Uphold RE. Cat-scratch disease: an unusual cause of combative behavior. Am J Emerg Med. 1991;9:52–53 10. Tsao CY. Generalized tonic-clonic status epilepticus in a child with cat-scratch disease and encephalopathy. Clin Electroencephalogr. 1992;23:65– 67 11. Hahn JS, Sum JM, Lee KP. Unusual MRI findings after status epilepticus due to cat-scratch disease. Pediatr Neurol. 1994;10: 255–258 12. Hachimi-Idrissi S, Goossens A, Pierard D, Frankx J, Corne L. Severe encephalopathy in a child: an uncommon cause. Eur J Emerg Med. 1998;5:461– 463 13. Easley RB, Cooperstock MS, Tobias JD. Cat-scratch disease causing status epilepticus in children. South Med J. 1999;92: 73–76 14. Steiner MM, Vuckovitch D, Hadawi SA. Cat-scratch disease with encephalopathy. J Pediatr. 1963;62:514 –520 15. Hindle J, Pearce JMS. Cerebellar encephalopathy in cat scratch disease. J Neurol Neurosurg Psychiatry. 1987;50:936 16. Walter RS, Eppes SC. Cat scratch disease presenting with peripheral facial nerve paralysis. Pediatrics. 1998;101(5). Available at: www.pediatrics.org/cgi/content/full/101/5/e13 17. Rocha JL, Pellegrino LN, Riella LV, Martins LT. Acute hemi- plegia associated with cat-scratch disease. Braz J Infect Dis. 2004;8:263–266 18. Chan L, Reilly KM, Snyder HS. An unusual presentation of cat scratch encephalitis. J Emerg Med. 1995;13:769 –772 19. Anbu AT. Basal ganglia involvement in a child with cat-scratch disease. Pediatr Infect Dis J. 2003;22:931–933 20. Puligheddu M, Giagheddu A, Genugu F, Giagheddu M, Marrosu F. Epilepsia partialis continua in cat scratch disease [published correction appears in Seizure. 2006;15:357]. Seizure. 2004;13:191–195 21. Revol A, Vighetto A, Jouvet A, Aimard G, Trillet M. Encephalitis in cat scratch disease with persistent dementia. J Neurol Neurosurg Psychiatry. 1992;55:133–135 22. Adal KA, Cockerell CJ, Petri WA Jr. Cat scratch disease bacillary angiomatosis, and other infections due to Rochalimaea. N Engl J Med. 1994;330:1509 –1515 23. Hadley S, Albrecht MA, Tarsy D. Cat-scratch encephalopathy: a cause of status epilepticus and coma in a young healthy adult. Neurology. 1995;45:196 24. Pollen RH. Cat-scratch encephalitis. Neurology. 1968;18: 1031–1033 25. Noyola DE, Holder DL, Fishman MA, Edwards MS. Recurrent encephalopathy in cat-scratch disease. Pediatr Infect Dis J. 1999; 18:567–568 26. Lyon LW. Neurologic manifestations of cat-scratch disease: report of a case and review of the literature. Arch Neurol. 1971;25:23–27 27. Hamilton GN, Matthews T. Aphasia: the sole manifestation of focal status epilepticus. Neurology. 1979;29:745–748 28. Dinner DS, Lueders H, Lederman R, Gretter TE. Aphasic status epilepticus: a case report. Neurology. 1981;31:888 – 890 29. Wells CR, Labar DR, Solomon GE. Aphasia as the sole manifestation of simple partial status epilepticus. Epilepsia. 1992;33: 84 – 87 30. Kirshner HS, Hughes T, Fakhoury T, Abou-Khalil B. Aphasia secondary to partial status epilepticus of the basal temporal language area. Neurology. 1995;45:1616 –1618 31. Primavera A, Gianelli MV, Bandini F. Aphasic status epilepticus in multiple sclerosis. Eur Neurol. 1996;36:374 –377 32. Grimes DA, Guberman A. De novo aphasic status epilepticus. Epilepsia. 1997;38:945–949 33. DeToledo JC, Minagar A, Lowe MR. Persisting aphasia as the sole manifestation of partial status epilepticus. Clin Neurol Neurosurg. 2000;102:144 –148 34. Hasegawa T, Shiga Y, Narikawa K, et al. Periodic episodes of aphasia as an unusual manifestation of partial status epilepticus. J Clin Neurosci. 2005;12:820 – 822 35. Weston KD, Tran T, Kimmel KN, Maria BL. Possible role of high-dose corticosteroids in the treatment of cat-scratch disease encephalopathy. J Child Neurol. 2001;16:762–763 36. Marra CM. Neurologic complications of Bartonella henselae infection. Curr Opin Neurol. 1995;8:164 –169 PEDIATRICS Volume 119, Number 3, March 2007 Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015 e763 Recurrent Expressive Aphasia as a Presentation of Cat-Scratch Encephalopathy James W. Fox, Joanna K. Studley and Daniel M. Cohen Pediatrics 2007;119;e760 DOI: 10.1542/peds.2006-1885 Updated Information & Services including high resolution figures, can be found at: http://pediatrics.aappublications.org/content/119/3/e760.full.h tml References This article cites 35 articles, 10 of which can be accessed free at: http://pediatrics.aappublications.org/content/119/3/e760.full.h tml#ref-list-1 Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Infectious Diseases http://pediatrics.aappublications.org/cgi/collection/infectious_ diseases_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://pediatrics.aappublications.org/site/misc/Permissions.xht ml Reprints Information about ordering reprints can be found online: http://pediatrics.aappublications.org/site/misc/reprints.xhtml PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015 Recurrent Expressive Aphasia as a Presentation of Cat-Scratch Encephalopathy James W. Fox, Joanna K. Studley and Daniel M. Cohen Pediatrics 2007;119;e760 DOI: 10.1542/peds.2006-1885 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/119/3/e760.full.html PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from pediatrics.aappublications.org at University of Bristol Library on March 20, 2015