CLINICAL CASE – HOW DOES SYPHILIS AFFECT PATIENTS IN THE 21ST CENTURY

INTRODUCTION
Syphilis is a sexual transmited disease, the pathogen being Treponema Pallidum, a gram-negative spirochaete, with human being as the only host. The gateway can be represented by tegumentary or mucoase lesions. The main pathophysiological process triggered by the T. pallidum infection is the obliteration of the terminal arterioles, with inflammation and necrosis (1).
The characteristic psychiatric symptoms for the onset of the disease are affective, psychotic and cognitive. The polymoprhic symptoms can occure in all types and evolutive stages of the infection, with a maximum of intensity, frequency and complexity in progressive general paralysis (2). The final stage of neurosyphilis has severe neurologic symptoms like the impossibility of movement, lose of sphincter control, trophic and vasomotricity dissorders, insomnia and cardio-vascular complications (3).
Treponema pallidum is a pathogen that cannot be grown in vitro, it’s presence can be only confirmed through treponemic tests such as TPHA (Treponema pallidum Haemagglutination Assay), FTA-Abs (Fluorescent Treponemal Antibody – Absorbtion of IgG and IgM) or ELISA (Enzyme-linked Immuno-absorbant Assay) IgG and IgM (4, 5).

OBJECTIVE
In the patient’s case we wanted first to correctly diagnose him and treat him accordingly. In the clinical case article the objective is to share with other clinician our experience in order to help them to save time in similar cases.

METHODS AND MATERIALS
For this clinical case we have used standard tests, medication and other speciality evaluations (dermatology, neurology, infectious disease and psychological evaluation).

CLINICAL CASE
The 40 years old patient had multiple hospital admissions in the psychiatry, neurology and infectious diseases services. From his medical history we should mention that he worked as a technical worker at a monk’s monastery in Greece for 6 years (until 2009).
The history of his disease starts in August 2011 with schizophrenia-like symptoms (delusions, social retreat, bizarre behavior- he beat nails in his brother front door, aggressive behavior and phonophobia). In this context he was diagnosed with schizophrenia and treated with 15mg of olanzapine plus 100 mg of clomipramine daily. His evolution was unfavorable. At the following admisions his diagnostic has suffered various changes.
In September 2011 he was admitted for cognitive deterioration, behavioral changes (unorganized, bizarre and aggressive behavior) and insomnia. The CT scan reveals moderate cortical atrophy. In this context, his medication remains unchanged. His evolution remains stationary.
In April 2012 he is admitted once again for progressive cognitive and amnesic deficit. The CT scan reveals diffuse cortical atrophy at the hippocampi and parahippocampi region, leucoaraiosis and a milimetric lacuna in the right lenticel. The psychological examination reveals a Mini-Mental State Examination – MMSE of 6/30, a personal autonomy of 1/6 and a clock test of 1/10. In this context the patient is diagnosed with early onset – dementia and the antipsychotic treatment is stopped. The patient receives treatment with levodopa and benserazide and minutios neurological evaluation is required.
The patient general health continue to deteriorate with exacerbation of neurological symptoms (generalized rigidity especially) and in Mai 2012 it is admitted in a neurology service. The neurological exam reveals: conscious state but uncooperative patient that is unable to execute complex tasks, bradipsihic, no neck stifness, pyramidal and extrapyramidal hypertonia, Babinski, Noica, Marinescu-Radovici and Hoffman signs were positive bilaterally and bone-tendon reflexes were exacerbated. In this context the MRI reveals the same generalized cortical atrophy that cannot be related with the patient’s age and history. The EEG shows a temporal and symmetric irritative route. Also the TGO and GPT were elevated. The severe dementia diagnostic is maintained and the patient received Cerebrolysin and anxiolytics. In the following weeks the patient shows a light imporvement of his state (MMSE – 12/30; clock test 3/10) and an evaluation at an infectious disease service is recomeneded. The HIV (Human Immunodeficiency Virus) and hepatitic infections are excluded.
In the infectious disease service was also performed a lumbar puncture that showed an increase of IgG for Borrelia in the LCR, moderate elevated proteins and low glucose level. After this episode the patient is send to the psychiatry hospital because his health is deteriorating rapidly (he became mute, refuse the food, presented waxy flexibility and was considered as catatonic). In this context was initiated an antipsychotic treatment with 1,5mg risperidonum daily but with no result.
In December 2012 he is admitted in our service for a catatonic state, with food negativism, waxy flexibility, no visual contact, stereotypic screams and mixed insomnia. The memory, attention and cognition were impossible to be evaluated. The physical exam revealed: cachexia, infected scars due to prolonged immobility and muscular hypertonia. The laboratory tests had showed hypoalbuminemia and anemia that were interpreted in the context of the defficitary alimentation. The high value of the PCR and VSH were put in the context of the inflammation syndrome due to the scar infection. Because of the rapid symptomatologic evolution in the context of the treatment adherence, the ECT was taken into consideration. In order to proceed further we reevaluated the patient from the beginning and we made (among others) the VDRL and TPHA tests that were positive at the qualitative and quantitative evaluation. These results could explain the false positive reaction for Borrelia (cross reaction).
We have contacted a dermatology service for evaluation and treatment. The recommended treatment was dibenzil-aethylendiamindipenicillinum 1,2mil UIx2/weekly for 3 weeks and a sensibility test to penicillin previously. Our patient was tested through Prick method and the test was positive, so he received doxiciclinum clorhidrat 100mgx2/day for 30 days.
In Mai 2013 he was again evaluated and we noticed an improvement (the patient could stand in his chair without support, could rise his left hand, answer simple questions and performing simple tasks.

DISCUSSION
The patient was difficult to diagnose because of the impossibility of the psychiatric interview, of the lack of clinical signs of primary/ secondary syphilis and no record of previous syphilis testing. Moreover, given the manifestations of the various forms and stages of neurosyphilis, the differential diagnostic possibilities are broad.
This case particularity is that the syphilis can determine psychiatric and neurological symptoms that can easily mislead clinicians to other diagnostic or treatment.
Moreover, after establishing the serological diagnosis of syphilis the problem was if the patient symptomatology was in the context of a concomitant catatonic schizophrenia or it was a generalized progressive paralysis due to the tertiary syphilis. For the first diagnostic we had the following symptoms: he refuses the food, he had waxy flexibility, he was catatonic and with hard to established visual contact, stereotypic screams and mixed insomnia (6). But the patient did not respond to previous antipsychotic treatment. The generalized progressive paralysis usually starts with cognitive impairment and with affective symptoms’ like irritability and attention deficit (7). Only in the late phase the powerful dementia symptoms appear and globally and progressively affect the intellectual capacity of the person and destroy its personality (8). In this patient case more symptoms’ of the generalized progressive paralysis due to the tertiary syphilis were found. Moreover, the antibiotic treatment had the objective to stop the disease evolution and to recuperate what was possible due to the fact that the brain damage was present. Despite all that, the patient state has improved, especially the motor verbal and functionality. For further evaluation and treatment the patient will be send to dermatology specialists.
Another comment is that a few decades back, the VDRL and TPHA were routine tests, but nowadays it seems that the screening for HIV or hepatitis are more commonly used. In the current case, the patient was admitted in several hospitals (from 2009 to 2012), he was evaluated by many medical specialties and if the diagnostic and treatment were applied earlier his recovery would have been faster and better.

RESULTS
Our patient’s diagnosis was not suspected at earlier admission and it was difficult because of the unspecific symptomatology and the psychiatric history. Once diagnosed, stage III spirochaetosis was improved by high dose of antibiotics and the patient begun his recovery.

CONCLUSION
The neurosyphilis is a disease that is hard to find nowadays and it can simulate severe psychiatric or neurological affections and confuse clinicians. But the recent experience shows that disease is not extinguished and if is not diagnosed and treated correctly the consequences for the patient can be fatal.. Moreover, for the young psychiatric patients with neuropsychiatric symptoms and with cognitive deterioration this investigation should be made mandatory.

REFERENCES
1.Bajenaru O. Elemente esentiale de neurologie clinica. Bucuresti: Editura Almatea, 2008, 217-219.
2.Chahine LM, Khoriaty RN, Tomford WJ, Hussain MS. The changing face of neurosyphilis. Int J Stroke 2011;6(2): 136-43.
3.Kent ME, Romanelli F. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother 2008; 226–236.
4.Ropper AH, . Brown RH. Adams and Victor’s Principles of Neurology
8th edition. McGraw-Hill Professional Publishing, 2005, 615-618.
5.Mattei PL, Beachkofsky TM, Gilson RT, Wisco OJ. Syphilis: a reemerging infection. Am Fam Physician 2012;86(5): 433-40.
6.Prelipceanu D. Psihiatrie Clinica. Bucuresti: Editura Medicala, 2011, 420-421.
7.Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry,7th edition. Lippincott Williams and Wilkins Publishers, 2000, 308-311.
8.Murray ED, Buttner N, Price BH . Depression and Psychosis in Neurological Practice. Bradley’s Neurology in Clinical Practice: Expert Consult – Online and Print,6th edition. Philadelphia, PA: Elsevier/Saunders, 2012, 101–102.

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