CASE REPORT
Electroconvulsive Therapy Treatment in a Patient With Neurosyphilis and Psychotic Disorder Case Report and Literature Review
Jan Pecenak, MD, PhD, Peter Janik, MD, PhD, Barbora Vaseckova, MD, and Kristina Trebulova, MD Abstract: Syphilis is an infectious disease caused by Treponema pallidum that presents clinically in different ways. Over recent years, an upsurge of new cases of syphilis has been reported, often in combination with human immunodeficiency virus infection. The clinical picture is changing because of the widespread use of antibiotics, and psychiatric manifestations may be the main reason why patients seek medical help. In most cases, treatment with penicillin and psychotropic medication is effective. Electroconvulsive therapy (ECT) is rarely used for the psychiatric manifestations of neurosyphilis: we identified only 19 cases in the literature. We report here on a 40-year-old man newly diagnosed with neurosyphilis during hospitalization for a psychotic state with depression and also review the literature. He was treated with 2 courses of penicillin and several antipsychotics. The ECTwas indicated because he failed to respond well to antipsychotic treatment and developed a high risk of dangerous behavior. A series of 8 sessions of ECT rapidly relieved the psychotic symptoms. Key Words: electroconvulsive therapy, neurosyphilis, psychosis, syphilis (J ECT 2015;31: 268–270)
S
yphilis had spread rapidly throughout Europe in the 15th century. The pathogen responsible, Treponema pallidum, was identified in 1905, and in 1910, the first serological test was introduced (Wasserman reaction). A more specific T. pallidum immobilization test was introduced in 1949.1 The availability of antibiotics and a long period with decreasing incidence turned syphilis into a “forgotten disease,”2 but an upsurge has recently been reported from different countries, often associated with human immunodeficiency virus infection.3,4 Slovakia is among the countries where the incidence of syphilis decreased over the past years,5 and the widespread use of antibiotics has shifted attention to cases which present with atypical signs and symptoms, as illustrated in this case report.
METHODS We used the search terms syphilis, neurosyphilis, neurolues, psychosis, psychiatric, electroconvulsive, and electro shocks in different combinations using Boolean ‘AND’ and ‘OR’ phrases to search in Medline for published reports without any restriction on the year of publication. We also searched in Embase, Science Direct, Ebsco, and Google Scholar. Relevant publications were also subsequently identified from references in the publications identified. The case report of patient with psychosis and neurosyphilis confirmed by positive serology and in cerebrospinal fluid (CSF) treated with electroconvulsive therapy (ECT) is described. From the Department of Psychiatry, Faculty of Medicine Comenius University, University Hospital, Bratislava, Slovakia. Received for publication November 21, 2014; accepted December 15, 2014. Reprints: Peter Janik, MD, PhD, Department of Psychiatry, Mickiewiczova 13 813 69 Bratislava, Slovakia (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000217
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CASE REPORT A 40-year-old man with no psychiatric history was admitted. His wife reported gradual personality changes over the past 3 years and had started showing signs of egotism and ignorance. In the week before admission, he had developed feelings of persecution and guilt, stopped eating, and did not seem to be fully oriented. The night before admission, he wandered around the city all night, which was quite out of character. He had no history of head injuries, unconsciousness, or epileptic seizures, and had never taken illegal psychoactive drugs. He was fully oriented on admission, and psychomotor inhibition, reduced affective expression, depressive mood, feelings of guilt, feelings of persecution, and auditory hallucinations were documented. He stated that he had unprotected extramarital sexual contact many years before. A depressive episode with psychotic features was diagnosed and treatment with quetiapine 200 mg/day was started. The blood count, biochemical variables, thyroid gland hormones, urine, and erythrocyte sedimentation rate were all normal. Computed tomography of the brain was normal, and low voltage occipital α rhythm and flat β activity were found in the electroencephalogram. A routine laboratory test for syphilis realized on the second day after admission showed rapid plasma reagin test positive for syphilis, as was the T. pallidum hemagglutination assay (titer 1:20480). The patient underwent dermatological and neurological assessment, and a lumbar puncture and more specific serological tests for Treponema infection were recommended. The patient had positive results for the following: the reactive venereal disease research laboratory test, fluorescent treponemal antibody absorption test (FTA-abs) for immunoglobulin (Ig)G, enzyme-linked immunoabsorbent assay-IgG, and the T. pallidum hemagglutination assay test in serum and CSF. The results from CSF showed a disrupted blood-brain barrier and intrathecal oligoclonal IgG synthesis with increased levels of IgG, IgG index, albumin, total protein, and mononucleotides. Latent syphilis was therefore diagnosed by the dermatologist and 24 million units of benzyl penicillin per day were given intravenously for 28 days. Quetiapine was titrated up to 600 mg/day combined with clonazepam 1.5 mg/day to control the psychotic symptoms. The depressive and psychotic symptoms resolved after adding aripiprazole titrated up to 30 mg/day, and the patient was discharged on the 51st day of hospitalization with a diagnosis of organic delusional disorder (F06.2 according International Classification of Diseases, 10th Revision). Seven months later, he was readmitted after he had attacked his wife and son. They reported that he had stopped the antipsychotic medication 2 weeks before. On admission, he was catatonic and had delusions of guilt and persecution, and severe anxiety and agitation. Repeated laboratory tests showed persistent positive serological and CSF findings for syphilis. The dermatologist diagnosed seroresistant syphilis and a second course of 30 million units of benzyl penicillin intravenously per day was given for 28 days. He tested negative for human immunodeficiency virus, hepatitis B, and hepatitis C. Magnetic resonance imaging of the brain was normal. During hospitalization, he was started on amisulpride up to 600 mg/day and clonazepam 3 mg/day, and he Journal of ECT • Volume 31, Number 4, December 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 4, December 2015
also received haloperidol injections several times for purposeless aggressive outburst. The catatonic symptoms resolved, but severe depressive syndrome with psychotic signs persisted. The medication was changed to quetiapine 500 mg/day in combination with mirtazapine 45 mg/day. His symptoms improved, and he was discharged on the 57th day of hospitalization. He was readmitted after 1 month. He was found by the police after standing motionless for several hours producing incomprehensible sounds. On admission, he had hallucinations (coenesthetic, olfactory, and verbal-acoustic) and pronounced bizarre hypochondriac and paranoid delusions (not having a stomach, any viscera, veins, feelings of rotting from inside). In addition, massive anxiety and periods of agitation and aggressive behavior alternating with ambivalence and perplexity were present. Treatment with haloperidol titrated up to 9 mg/day combined with clonazepam 4.5 mg/day was started. Haloperidol intramuscular treatment and physical restraint were needed because of agitation and aggressive outbursts. The violent behavior subsided, and amisulpride titrated up to 800 mg/day was given instead of haloperidol. Hallucinations, delusions, and catatonic features with mutism were still present. He refused to eat or drink because he thought that the food would fall into his abdomen because he had no stomach. Because of the inadequate response to treatment, it was decided to use ECT. The ECT was given under anesthesia with atropine, thiopenthal, and succinylcholine, using a Spectrum 4000Q device (Mecta Corporation, Lake Oswego, OR) with bitemporal placement of electrodes with the following settings: pulse width, 1 ms; frequency, 30 Hz; stimulus duration, 6 seconds; and current, 800 mA. After 8 ECT sessions, the psychotic and catatonic signs had disappeared, and the patient's mood changed to euthymic with restored affective expression. He started to interact with other patients and participated in ergotherapy at a day care center. He was discharged from hospitalization on the 83rd day. According to his psychiatrist, 2 years after discharge, he is on antipsychotic treatment with no psychotic or affective symptoms and no decline in cognitive functions.
Literature Review and Discussion This case report raises questions about the problem of diagnosing neurosyphilis in patients who presents with only psychiatric symptoms and the indication for ECT in such patients. Neurosyphilis is classified as a symptomatic, late syphilitic disorder. These disorders, which also include cardiovascular and gummatous forms, are sometimes named tertiary syphilis.6 Studies from the preantibiotic era—mainly results from the “Oslo Study”7—showed that tertiary syphilis develops in about one third of untreated patients involving different systems with the corresponding symptoms.8 Neurosyphilis is defined by the presence of ocular, auricular, meningovascular, and parenchymatous symptoms (general paresis, tabes dorsalis), or is considered to be latent (or asymptomatic) when only laboratory CSF findings are positive.9 The psychiatric presentation of neurosyphilis can vary so widely, as described in the preantibiotic era and in a recent review, that it has been called a “chameleon” in terms of the range of clinical signs and symptoms.7,10,11 When seen nowadays, neurosyphilis usually presents with atypical symptoms because of the widespread use of antibiotics.12 Our patient had a broad spectrum of affective symptoms, and signs of psychotic disintegration with dangerous, violent behavior, and catatonic symptoms were identified even without domination of cognitive symptoms. Development of personality changes followed by acute psychotic symptoms together with positive laboratory findings in serum and CSF are sufficient to indicate a link between an infectious process and clinically evident psychopathological condition. This complies with guidelines from the USA Centers for Disease
ECT for Neurosyphilis and Psychotic Disorder
Control and Prevention3 which list “acute or chronic altered mental status” among the criteria for symptomatic neurosyphilis. The atypical presentation of the psychosis with a combined affective, schizophrenia-like and catatonic syndrome and the emergence of the psychosis at an age where the incidence of the first presentation of psychotic episode is usually low13 also support an etiological connection. The psychotic symptoms continued despite 2 courses of very intensive intravenous treatment with penicillin. Other patients with neurosyphilis and chronic psychopathological symptoms have reacted positively to treatment with antibiotics alone.14 The conceptual problems of an organic-functional dichotomy in the field of psychiatry have not been solved or adequately classified, as thoroughly discussed in a recent review of psychotic symptoms in patients with neurosyphilis.11 The treatment of syphilis has been documented from medieval times15 but the revolutionary breakthrough in the treatment was the introduction of fever (malaria) therapy which caused fever paroxysms. Julius Wagner-Jauregg was awarded the Nobel Prize in 192716,17 for this discovery. Nowadays, penicillin, or other antibiotics in the case of allergy to penicillin, is the first-line therapy.9 Convulsive therapy was invented and introduced into medicine by Ladislas Meduna in 1934 using camphor and cardiazol18 and later in 1938 Ugo Cerletti and Lucio Bini used electric stimuli for induction of convulsions.19 The ECTwas used in patients with neurosyphilis soon after. In 1943, Heilbrunn and Feldman20 described 5 patients treated with “electric shock” applied after sixteen months post-malaria therapy. All patients had persistent psychotic symptoms. Serious adverse effects associated with the treatment were interpreted as due to the syphilitic brain that constituted a place of least resistance prone to react negatively to any exogenous noxae. Tomlinson21 reported convulsive treatment in 18 patients with syphilitic meningoencephalitis; 13 of them received insulin, 3 electric shocks, and 2 patients a combination of both. Vilanova and De Moragas22 published a case report on a patient who developed tabes dorsalis with severe neurological symptoms, despite 5 years of treatment for syphilis with arsenic, bismuth, mercury, and penicillin. The decision to give palliative treatment with ECT was made, and as early as after 2 of 5 ECT sessions improvements in pain, incontinence, and ataxia were observed, with progressive improvement during 1 month of follow-up after the end of ECT. Another report from the same country at a similar time23 illustrates the negative approach to the use of ECT in neurosyphilis. The author criticizes treatment with ECT during a previous hospital stay in a psychiatric department in a patient with neurosyphilis as it might have aggravated pathological changes in the brain caused by Treponema infection with negative neurological consequences. Dawson-Butterworth and Heathcote24 identified 43 patients with neurosyphilis (general paresis of the insane) among 1845 hospitalized persons in a large psychiatric hospital. Six patients received ECT during the hospitalization for uncontrollable mania with an adequate calming effect. Weaver and Remick25 reported the case of a 67-year-old man who developed personality changes over several years and was subsequently hospitalized for signs of dementia with behavioral problems and confusion. After syphilis was diagnosed, and he was treated with penicillin, he developed signs of depression and psychotic symptoms. The psychotic symptoms did not respond adequately to haloperidol titrated up to 50 mg/day, but a series of 13 ECT sessions substantially improved the symptoms with long-term positive effects. The case we describe is a rare report of a psychiatric syndrome associated with neurosyphilis treated with ECT. The most recent publication by Weaver and Remick25 is from 1982. We have found reports on only 19 patients with neurosyphilis treated with ECT at all. Reports on such cases may be so infrequent
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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because therapy with antibiotics and modern psychopharmacological drugs is effective, or because of the absence of guidelines and recommendations for the treatment of severe psychiatric complication of neurosyphilis.26 Although ECT is considered to be a life-saving intervention27 in some patients, the most common indication is poor response to other treatments. Indeed, this was also the case in our patient, whose severe psychotic symptoms were not adequately controlled by antipsychotics. The importance of routine laboratory tests for Treponema infections in newly admitted patients to psychiatric wards is underlined by our case. The cost-effectiveness of doing so has been questioned28 and problems with sensitivity and specificity have also been suggested.29 According to European guidelines,9 patients with signs of uveitis, otitis with deafness, or meningitis, suspected to have neurosyphilis should be routinely tested for syphilis. The routine screening for syphilis provided in our department contributed to arriving at the correct diagnosis in a patient who presented with an atypical clinical picture.
CONCLUSIONS The ECT was indicated in a patient with neurosyphilis and psychosis who responded inadequately to psychopharmacological agents and developed the risk of autoaggression and heteroaggression. Although the infection was controlled by intensive treatment with penicillin, neurosyphilis was still associated with severe psychotic symptoms. Treatment with ECT showed to be more effective than the treatment with antipsychotics, and the patient remained stable for a long period. This case also highlights the importance of screening for Treponema infection in patients who present with atypical psychiatric syndromes, even without typical neurological findings. ACKNOWLEDGMENTS Language revision of the text was done by A. Reeves of ASCRIBE, Wiesbaden, Germany.
8. Singh AE, Romanowski B. Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. Clin Microbiol Rev. 1999;12: 187–209. 9. French P, Gomberg M, Janier M, et al. IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS. 2009;20: 300–309. 10. Friedrich F, Geusau A, Friedrich ME, et al. The chameleon of psychiatry—psychiatric manifestations of neurosyphilis. Psychiatr Prax. 2012;39:7–13. 11. Friedrich F, Aigner M, Fearns N, et al. Psychosis in neurosyphilis—clinical aspects and implications. Psychopathology. 2014;47:3–9. 12. Mitsonis CH, Kararizou E, Dimopoulos N, et al. Incidence and clinical presentation of neurosyphilis: a retrospective study of 81 cases. Int J Neurosci. 2008;118:1251–1257. 13. Kirkbride JB, Fearon P, Morgan C, et al. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry. 2006;63:250–258. 14. Kararizou E, Mitsonis C, Dimopoulos N, et al. Psychosis or simply a new manifestation of neurosyphilis? J Int Med Res. 2006;34:335–337. 15. Abraham JJ. Some account of the history of the treatment of syphilis. Br J Vener Dis. 1948;24:153–161. 16. Karamanou M, Liappas I, Antoniou C, et al. Julius Wagner-Jauregg (1857-1940): introducing fever therapy in the treatment of neurosyphilis. Psychiatriki [serial online]. 2013;24:208–212. Available from: PubMed. Accessed August 29, 2014. 17. JuliusWagner-Jauregg—Facts [NobelMedia AB 2014]. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1927/ wagner-jauregg-facts.html. Accessed November 5, 2014. 18. Fink M. Meduna and the origins of convulsive therapy. Am J Psychiatry. 1984;141:1034–1041. 19. Fink M. Convulsive therapy: a review of the first 55 years. J Affect Disord. 2001;63:1–15. 20. Heilbrunn G, Feldman P. Electric shock treatment in general paresis. Am J Psychiatry. 1943;99:702–705. 21. Tomlinson PJ. Insulin and electric therapy in general paresis. Psychiatr Q. 1944;18:413–421.
REFERENCES 1. Tampa M, Sarbu I, Matei C, et al. Brief history of syphilis. J Med Life. 2014;7:4–10. 2. Burnett A, Omar HA. Syphilis: a forgotten sexually transmitted disease? Front Public Health [serial online]. 2014;2:15. Available from: PubMed. Accessed September 16, 2014. 3. Centers for Disease Control and Prevention (CDC). Notes from the field: repeat syphilis infection and HIV coinfection among men who have sex with men-Baltimore, Maryland, 2010-2011. MMWR Morb Mortal Wkly Rep. 2013;62:649–650. 4. Chen XS, Yin YP, Wang QQ, et al. Historical perspective of syphilis in the past 60 years in China: eliminated, forgotten, on the return. Chin Med J (Engl). 2013;126:2774–2779. 5. European Centre for Disease Prevention and Control. Sexually transmitted infections in Europe 2011. September 2013. Available at: www.ecdc. europa.eu. Accessed eptember 16, 2014. 6. Kingston M, French P, Goh B, et al. UK National Guidelines on the Management of Syphilis 2008. Int J STD AIDS. 2008;19:729–740. 7. Clark EG, Danbolt N. The Oslo study of the natural history of untreated syphilis; an epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material; a review and appraisal. J Chronic Dis. 1955;2:311–344.
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22. Vilanova X, De Moragas JM. El electroshok como tratamiento paliativo de la sintomatologia de la tabes; aportacion casuistica. Article in Spanish. [Electroshock as a palliative symptomatic therapy of tabes; report of cases]. Actas Dermosifiliogr. 1953;44:583–585. 23. Gonzalez Guija A. Un caso de lues cerebri (vascularitis) influenciado por alcohol y electrochoque. Article in Spanish. [Case of cerebral lues (vascularitis) influenced by alcohol and electroshock]. Rev Clin Esp. 1955;58:362–364. 24. Dawson-Butterworth K, Heathcote PR. Review of hospitalized cases of general paralysis of the insane. Br J Vener Dis. 1970;46:295–302. 25. Weaver G, Remick R. Electroconvulsive treatment of depression associated with neurosyphilis. J Clin Psychiatry. 1982;43:468–469. 26. Sanchez FM, Zisselman MH. Treatment of psychiatric symptoms associated with neurosyphilis. Psychosomatics. 2007;48:440–445. 27. Moksnes KM. Electroconvulsive therapy without consent. Tidsskr Nor Laegeforen. 2013;133:2047–2050. 28. Arce-Cordon R, Perez-Rodriguez MM, Baca-Baldomero E, et al. Routine laboratory screening among newly admitted psychiatric patients: is it worthwhile? Psychiatr Serv. 2007;58:1602–1605. 29. Wöhrl S, Geusau A. Neurosyphilis is unlikely in patients with late latent syphilis and a negative blood VDRL-test. Acta Derm Venereol. 2006;86: 335–339.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Electroconvulsive Therapy Treatment in a Patient With Neurosyphilis and Psychotic Disorder Case Report and Literature Review
Jan Pecenak, MD, PhD, Peter Janik, MD, PhD, Barbora Vaseckova, MD, and Kristina Trebulova, MD Abstract: Syphilis is an infectious disease caused by Treponema pallidum that presents clinically in different ways. Over recent years, an upsurge of new cases of syphilis has been reported, often in combination with human immunodeficiency virus infection. The clinical picture is changing because of the widespread use of antibiotics, and psychiatric manifestations may be the main reason why patients seek medical help. In most cases, treatment with penicillin and psychotropic medication is effective. Electroconvulsive therapy (ECT) is rarely used for the psychiatric manifestations of neurosyphilis: we identified only 19 cases in the literature. We report here on a 40-year-old man newly diagnosed with neurosyphilis during hospitalization for a psychotic state with depression and also review the literature. He was treated with 2 courses of penicillin and several antipsychotics. The ECTwas indicated because he failed to respond well to antipsychotic treatment and developed a high risk of dangerous behavior. A series of 8 sessions of ECT rapidly relieved the psychotic symptoms. Key Words: electroconvulsive therapy, neurosyphilis, psychosis, syphilis (J ECT 2015;31: 268–270)
S
yphilis had spread rapidly throughout Europe in the 15th century. The pathogen responsible, Treponema pallidum, was identified in 1905, and in 1910, the first serological test was introduced (Wasserman reaction). A more specific T. pallidum immobilization test was introduced in 1949.1 The availability of antibiotics and a long period with decreasing incidence turned syphilis into a “forgotten disease,”2 but an upsurge has recently been reported from different countries, often associated with human immunodeficiency virus infection.3,4 Slovakia is among the countries where the incidence of syphilis decreased over the past years,5 and the widespread use of antibiotics has shifted attention to cases which present with atypical signs and symptoms, as illustrated in this case report.
METHODS We used the search terms syphilis, neurosyphilis, neurolues, psychosis, psychiatric, electroconvulsive, and electro shocks in different combinations using Boolean ‘AND’ and ‘OR’ phrases to search in Medline for published reports without any restriction on the year of publication. We also searched in Embase, Science Direct, Ebsco, and Google Scholar. Relevant publications were also subsequently identified from references in the publications identified. The case report of patient with psychosis and neurosyphilis confirmed by positive serology and in cerebrospinal fluid (CSF) treated with electroconvulsive therapy (ECT) is described. From the Department of Psychiatry, Faculty of Medicine Comenius University, University Hospital, Bratislava, Slovakia. Received for publication November 21, 2014; accepted December 15, 2014. Reprints: Peter Janik, MD, PhD, Department of Psychiatry, Mickiewiczova 13 813 69 Bratislava, Slovakia (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000217
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CASE REPORT A 40-year-old man with no psychiatric history was admitted. His wife reported gradual personality changes over the past 3 years and had started showing signs of egotism and ignorance. In the week before admission, he had developed feelings of persecution and guilt, stopped eating, and did not seem to be fully oriented. The night before admission, he wandered around the city all night, which was quite out of character. He had no history of head injuries, unconsciousness, or epileptic seizures, and had never taken illegal psychoactive drugs. He was fully oriented on admission, and psychomotor inhibition, reduced affective expression, depressive mood, feelings of guilt, feelings of persecution, and auditory hallucinations were documented. He stated that he had unprotected extramarital sexual contact many years before. A depressive episode with psychotic features was diagnosed and treatment with quetiapine 200 mg/day was started. The blood count, biochemical variables, thyroid gland hormones, urine, and erythrocyte sedimentation rate were all normal. Computed tomography of the brain was normal, and low voltage occipital α rhythm and flat β activity were found in the electroencephalogram. A routine laboratory test for syphilis realized on the second day after admission showed rapid plasma reagin test positive for syphilis, as was the T. pallidum hemagglutination assay (titer 1:20480). The patient underwent dermatological and neurological assessment, and a lumbar puncture and more specific serological tests for Treponema infection were recommended. The patient had positive results for the following: the reactive venereal disease research laboratory test, fluorescent treponemal antibody absorption test (FTA-abs) for immunoglobulin (Ig)G, enzyme-linked immunoabsorbent assay-IgG, and the T. pallidum hemagglutination assay test in serum and CSF. The results from CSF showed a disrupted blood-brain barrier and intrathecal oligoclonal IgG synthesis with increased levels of IgG, IgG index, albumin, total protein, and mononucleotides. Latent syphilis was therefore diagnosed by the dermatologist and 24 million units of benzyl penicillin per day were given intravenously for 28 days. Quetiapine was titrated up to 600 mg/day combined with clonazepam 1.5 mg/day to control the psychotic symptoms. The depressive and psychotic symptoms resolved after adding aripiprazole titrated up to 30 mg/day, and the patient was discharged on the 51st day of hospitalization with a diagnosis of organic delusional disorder (F06.2 according International Classification of Diseases, 10th Revision). Seven months later, he was readmitted after he had attacked his wife and son. They reported that he had stopped the antipsychotic medication 2 weeks before. On admission, he was catatonic and had delusions of guilt and persecution, and severe anxiety and agitation. Repeated laboratory tests showed persistent positive serological and CSF findings for syphilis. The dermatologist diagnosed seroresistant syphilis and a second course of 30 million units of benzyl penicillin intravenously per day was given for 28 days. He tested negative for human immunodeficiency virus, hepatitis B, and hepatitis C. Magnetic resonance imaging of the brain was normal. During hospitalization, he was started on amisulpride up to 600 mg/day and clonazepam 3 mg/day, and he Journal of ECT • Volume 31, Number 4, December 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 4, December 2015
also received haloperidol injections several times for purposeless aggressive outburst. The catatonic symptoms resolved, but severe depressive syndrome with psychotic signs persisted. The medication was changed to quetiapine 500 mg/day in combination with mirtazapine 45 mg/day. His symptoms improved, and he was discharged on the 57th day of hospitalization. He was readmitted after 1 month. He was found by the police after standing motionless for several hours producing incomprehensible sounds. On admission, he had hallucinations (coenesthetic, olfactory, and verbal-acoustic) and pronounced bizarre hypochondriac and paranoid delusions (not having a stomach, any viscera, veins, feelings of rotting from inside). In addition, massive anxiety and periods of agitation and aggressive behavior alternating with ambivalence and perplexity were present. Treatment with haloperidol titrated up to 9 mg/day combined with clonazepam 4.5 mg/day was started. Haloperidol intramuscular treatment and physical restraint were needed because of agitation and aggressive outbursts. The violent behavior subsided, and amisulpride titrated up to 800 mg/day was given instead of haloperidol. Hallucinations, delusions, and catatonic features with mutism were still present. He refused to eat or drink because he thought that the food would fall into his abdomen because he had no stomach. Because of the inadequate response to treatment, it was decided to use ECT. The ECT was given under anesthesia with atropine, thiopenthal, and succinylcholine, using a Spectrum 4000Q device (Mecta Corporation, Lake Oswego, OR) with bitemporal placement of electrodes with the following settings: pulse width, 1 ms; frequency, 30 Hz; stimulus duration, 6 seconds; and current, 800 mA. After 8 ECT sessions, the psychotic and catatonic signs had disappeared, and the patient's mood changed to euthymic with restored affective expression. He started to interact with other patients and participated in ergotherapy at a day care center. He was discharged from hospitalization on the 83rd day. According to his psychiatrist, 2 years after discharge, he is on antipsychotic treatment with no psychotic or affective symptoms and no decline in cognitive functions.
Literature Review and Discussion This case report raises questions about the problem of diagnosing neurosyphilis in patients who presents with only psychiatric symptoms and the indication for ECT in such patients. Neurosyphilis is classified as a symptomatic, late syphilitic disorder. These disorders, which also include cardiovascular and gummatous forms, are sometimes named tertiary syphilis.6 Studies from the preantibiotic era—mainly results from the “Oslo Study”7—showed that tertiary syphilis develops in about one third of untreated patients involving different systems with the corresponding symptoms.8 Neurosyphilis is defined by the presence of ocular, auricular, meningovascular, and parenchymatous symptoms (general paresis, tabes dorsalis), or is considered to be latent (or asymptomatic) when only laboratory CSF findings are positive.9 The psychiatric presentation of neurosyphilis can vary so widely, as described in the preantibiotic era and in a recent review, that it has been called a “chameleon” in terms of the range of clinical signs and symptoms.7,10,11 When seen nowadays, neurosyphilis usually presents with atypical symptoms because of the widespread use of antibiotics.12 Our patient had a broad spectrum of affective symptoms, and signs of psychotic disintegration with dangerous, violent behavior, and catatonic symptoms were identified even without domination of cognitive symptoms. Development of personality changes followed by acute psychotic symptoms together with positive laboratory findings in serum and CSF are sufficient to indicate a link between an infectious process and clinically evident psychopathological condition. This complies with guidelines from the USA Centers for Disease
ECT for Neurosyphilis and Psychotic Disorder
Control and Prevention3 which list “acute or chronic altered mental status” among the criteria for symptomatic neurosyphilis. The atypical presentation of the psychosis with a combined affective, schizophrenia-like and catatonic syndrome and the emergence of the psychosis at an age where the incidence of the first presentation of psychotic episode is usually low13 also support an etiological connection. The psychotic symptoms continued despite 2 courses of very intensive intravenous treatment with penicillin. Other patients with neurosyphilis and chronic psychopathological symptoms have reacted positively to treatment with antibiotics alone.14 The conceptual problems of an organic-functional dichotomy in the field of psychiatry have not been solved or adequately classified, as thoroughly discussed in a recent review of psychotic symptoms in patients with neurosyphilis.11 The treatment of syphilis has been documented from medieval times15 but the revolutionary breakthrough in the treatment was the introduction of fever (malaria) therapy which caused fever paroxysms. Julius Wagner-Jauregg was awarded the Nobel Prize in 192716,17 for this discovery. Nowadays, penicillin, or other antibiotics in the case of allergy to penicillin, is the first-line therapy.9 Convulsive therapy was invented and introduced into medicine by Ladislas Meduna in 1934 using camphor and cardiazol18 and later in 1938 Ugo Cerletti and Lucio Bini used electric stimuli for induction of convulsions.19 The ECTwas used in patients with neurosyphilis soon after. In 1943, Heilbrunn and Feldman20 described 5 patients treated with “electric shock” applied after sixteen months post-malaria therapy. All patients had persistent psychotic symptoms. Serious adverse effects associated with the treatment were interpreted as due to the syphilitic brain that constituted a place of least resistance prone to react negatively to any exogenous noxae. Tomlinson21 reported convulsive treatment in 18 patients with syphilitic meningoencephalitis; 13 of them received insulin, 3 electric shocks, and 2 patients a combination of both. Vilanova and De Moragas22 published a case report on a patient who developed tabes dorsalis with severe neurological symptoms, despite 5 years of treatment for syphilis with arsenic, bismuth, mercury, and penicillin. The decision to give palliative treatment with ECT was made, and as early as after 2 of 5 ECT sessions improvements in pain, incontinence, and ataxia were observed, with progressive improvement during 1 month of follow-up after the end of ECT. Another report from the same country at a similar time23 illustrates the negative approach to the use of ECT in neurosyphilis. The author criticizes treatment with ECT during a previous hospital stay in a psychiatric department in a patient with neurosyphilis as it might have aggravated pathological changes in the brain caused by Treponema infection with negative neurological consequences. Dawson-Butterworth and Heathcote24 identified 43 patients with neurosyphilis (general paresis of the insane) among 1845 hospitalized persons in a large psychiatric hospital. Six patients received ECT during the hospitalization for uncontrollable mania with an adequate calming effect. Weaver and Remick25 reported the case of a 67-year-old man who developed personality changes over several years and was subsequently hospitalized for signs of dementia with behavioral problems and confusion. After syphilis was diagnosed, and he was treated with penicillin, he developed signs of depression and psychotic symptoms. The psychotic symptoms did not respond adequately to haloperidol titrated up to 50 mg/day, but a series of 13 ECT sessions substantially improved the symptoms with long-term positive effects. The case we describe is a rare report of a psychiatric syndrome associated with neurosyphilis treated with ECT. The most recent publication by Weaver and Remick25 is from 1982. We have found reports on only 19 patients with neurosyphilis treated with ECT at all. Reports on such cases may be so infrequent
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
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Journal of ECT • Volume 31, Number 4, December 2015
Pecenak et al
because therapy with antibiotics and modern psychopharmacological drugs is effective, or because of the absence of guidelines and recommendations for the treatment of severe psychiatric complication of neurosyphilis.26 Although ECT is considered to be a life-saving intervention27 in some patients, the most common indication is poor response to other treatments. Indeed, this was also the case in our patient, whose severe psychotic symptoms were not adequately controlled by antipsychotics. The importance of routine laboratory tests for Treponema infections in newly admitted patients to psychiatric wards is underlined by our case. The cost-effectiveness of doing so has been questioned28 and problems with sensitivity and specificity have also been suggested.29 According to European guidelines,9 patients with signs of uveitis, otitis with deafness, or meningitis, suspected to have neurosyphilis should be routinely tested for syphilis. The routine screening for syphilis provided in our department contributed to arriving at the correct diagnosis in a patient who presented with an atypical clinical picture.
CONCLUSIONS The ECT was indicated in a patient with neurosyphilis and psychosis who responded inadequately to psychopharmacological agents and developed the risk of autoaggression and heteroaggression. Although the infection was controlled by intensive treatment with penicillin, neurosyphilis was still associated with severe psychotic symptoms. Treatment with ECT showed to be more effective than the treatment with antipsychotics, and the patient remained stable for a long period. This case also highlights the importance of screening for Treponema infection in patients who present with atypical psychiatric syndromes, even without typical neurological findings. ACKNOWLEDGMENTS Language revision of the text was done by A. Reeves of ASCRIBE, Wiesbaden, Germany.
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
