by Alexander Kurz
Syphilis is a systemic infectious disease caused by the spirochete Treponema pallidum. Involvement of the nervous system may occur at any stage of the infection.
A chronic meningitis is the pathological substrate of all forms of neurosyphilis which include meningovascular syphilis, progressive paralysis, and tabes dorsalis.
Syphilis is transmitted by sexual contact, rarely by sharing venous puncture needles in drug addicts. The percentage of patients with syphilitic CNS infection has been increasing since the advent of the human immunodeficiency virus (HIV) epidemic.
Neurosyphilis, progressive paralysis, lues
Symptoms and course
Psychiatric symptoms may evolve at any time during the development of syphilis. At the early stage non-specific depression and anxiety may occur. Later, common psychiatric symptoms include sleep disturbances, distractibility, irritability, disorientation, confusion as well as delusional or hypochondrical worries. However, spells of elation and confabulation may also be present.
There are three major variants of neurosyphilis. Meningovascular syphilis becomes manifest as a cerebral or spinal vascular syndrome caused by the occlusion of small vessels. Patients show intellectual decline accompanied by confusional states. Agitation or stupor and stroke-like neurological symptoms including hemiplegia, aphasia, or seizures, are also usually present. Meningovascular syphilis occurs 4 – 7 years after the infection. Without treatment it causes small vessel occlusions and persistent neurologic deficits.
With treatment remission of symptoms is usually satisfactory. Parenchymal neurosyphilis may present as progressive paralysis or as tabes dorsalis.
Progressive paralysis is the most important psychiatric complication of neurosyphilis. It usually develops 10 to 15 years after the infection. Clinical features include progressive dementia, which is frequently accompanied by psychotic symptoms, personallity change, dysphoric or elevated mood and striking lapses in social functioning.
The dementia is of a frontal type with prominent apathy, elation, attentional deficits and memory impairment. Salient features are coarse movements, dull facial expression, increased muscle reflexes and pupil abnormalities.
At the late stage seizures may occur. The “classic” megalomanic psychosis was always a rarity. In untreated cases, death usually occurs within 4 – 5 years. Progressive paralysis develops 10 – 20 years after the infection. The condition is rapidly progressive and leads to death after 2 – 5 years.
Penicillin therapy normalises the inflammatory changes in the cerebrospinal fluid and arrests the progression of symptoms. Improvements are seen in 60 % of the patients. Tabes dorsalis is the consequence of an infectious and degenerative destruction of the posterior horn cells and tracts. Classical symptoms are sharp pain in the legs, difficulty emptying the bladder, spinal ataxia and delayed pain recognition. Psychiatric symptoms are rare. More than 90 % of all patients show pupil abnormalities, which in half of the cases presents as a miotic pupil which fails to react to direct light (Argyll Robertson phenomenon). Tabes dorsalis occurs 10 – 20 years after the infection. Progression is slow and may end in a residual state without further worsening. Treatment stops probression and normalises cerebrospinal parameters. Incomplete remission is the most likely outcome.
Causes and risk factors
Syphilis is caused by an infection with the spirochete Treponema pallidum. Neurosyphilis has two major forms: meningovascular syphilis, and parenchmymal neurosyphilis.
Meningovascular syphilis is a small-vessel disease with thickening of the intima, obliterations, and brain infarcts associated with focal neurological deficits which frequently involve the cranial nerves.
In European countries the incidenced of newly identified syphilis fell below 10 per 1.000.000 inhabitants after 1980. The true frequency is not precisely known but is estimated to be 50 per cent higher. With the HIV epidemic the incidence of syphilis increased by 75 % between 1985 and 1990 in the US, but declined afterwards. Of patients with untreated syphilis, 4 to 9 % develop symptoms of neurosyphilis (2 – 3 % meningovascular syphilis, 2 – 5 % progressive paralysis, 1 – 5 % tabes dorsalis).
There are two forms of laboratory tests for syphilis, non-specific and specific for Treponema pallidum. The non-specific Venereal Disease Research Laboratory (VDRL) test has been replaced by the simpler but also non-specific Rapid-Plasma-Reagin (RPR) test. Both tests use cardioloipin antigenes for the identification of antibodies which are generated by the interaction of Treponema pallidum with human antigens. For the diagnosis of neurosyphilis at a late stage these tests are insufficient and must be complemented by tests which are specific for the infectious agent. The Fluorescent Treponemal-Antibody Absorption test (FTA-ABS), the Treponema Pallidum Hemagglutination test (TPHA), and the Microhemagglutination Assay for Treponema Pallidum (MHA-TP) are commonly used. The become positive before the cardiolipin tests and remain so for life, even after successful treatment. The cerebrospinal fluid usually shows typical signs of inflammation including proliferation of lymphocytes and an elevated total protein content.
Care and treatment
Neurosyphilis is treated with high doses of penicillin G over 10 to 14 days intravenuously (6 x 4 mio units per day). Alternatives are Doxycycline (2 x 100 mg per day intravenously for 30 days), and ceftriaxone (1 g per day for 14 days).
- M A Conde-Sendin, J L Hernandes-Fleta, M A Cardanes-Santana, R Amela-Peris. Neurosyphilis: forms of presentation and clinical management. Rev Neurol 35: 380-386, 2002
- G Hart. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 104: 368.376, 1986
- E W Hook, C M Marra. Acquired syphilis in adults. N Engl J Med 326: 1060-1069, 1992
- D Pao, B. T. Goh, J. S. Bingham. Management issues in syphilis. Drugs 62: 1447-1461, 2002
- M C Roberts, R. A. Emsley. Psychiatric manifestations of neurosyphilis. S Afr Med J 82: 335-337, 1992
- R P Simon. Neurosyphilis. Arch Neurol 42: 606-613, 1985
- E C Tramont. Treponema pallidum (Syphilis). In: G L Mandell, J E Bennett, R Dolin (eds) Principles and Practice of Infectious Diseases, 4 Ed. New York: Churchill Livingstone, Vol. 2: 2117-2113, 1995
Last Updated: Friday 09 October 2009