Neurosyphilis: Considerations for a Psychiatrist

« Psychiatry

Mark A. Ritchie, MD

Louisiana State University School of Medicine



Joseph A. Perdigao, MA

Louisiana State University School of MedicineCorrespondence to:



Mark A. Ritchie, MD

Louisiana State University School of Medicine

Department of Psychiatry

1542 Tulane Avenue

New Orleans, Louisiana 70112-2822

(504) 568-3427, FAX (504) 568-8647

While penicillin has virtually eliminated the dramatic presentations of parenchymatous neurosyphilis, HIV, inadequate antibiotic treatment for syphilis, and the rising incidence of early syphilis among the young and urban poor, have increased the frequency of subtle, atypical and often monosymptomatic presentations of neurosyphilis. These presentations are increasingly missed as psychiatric patients receive fewer physical exams and laboratory work-ups, physicians are less experienced at diagnosing neurosyphilis, and non-physicians and non-psychiatrists care for the mentally ill. Neurologic symptoms and risks for sexually transmitted disease often signal the presence of neurosyphilis, but the disease can present with psychiatric symptoms alone, psychiatric symptoms that can mimic any other psychiatric illness. In this review of literature, the authors suggest criteria for screening and stress that a specific treponemal test should be used because of their higher sensitivity. Treatment should consist of penicillin plus psychotropics for any psychiatric symptoms secondary to or concurrent with neurosyphilis. Pathogenesis, staging, clinical presentations, and special considerations for HIV coinfection are discussed.

Keywords: Neurosyphilis, screening, psychiatry

The incidence of neurosyphilis, the potentially devastating infection of the central nervous system by the spirochete Treponema pallidum, is rising in spite of widely available curative treatment (Center for Disease Control, 1992; Flores, 1995). Prior to the advent of penicillin in the 1940s, the dramatic presentations of parenchymatous neurosyphilis accounted for 20% of all admissions to psychiatric hospitals. Today, while cases of tertiary syphilis still occur, subtle psychiatric symptoms secondary to earlier stages of infection are much more common. As physical exams on the mentally ill are performed less often, laboratory screening is limited by managed care, and physicians are less experienced at diagnosing neurosyphilis, the rises in primary and secondary syphilis of the past twenty years will continue to translate into an increased incidence of neurosyphilis. Currently few labs use dark field examination for early syphilis, and the most commonly used serologic tests, the RPR and VDRL, are only 72-77% sensitive for neurosyphilis. With its complex and often elusive pathogenesis, neurosyphilis remains a cause of psychiatric disease.

Medical historians accept that syphilis originated in the multinational, multiethnic mercenary army of Charles VIII of France during his invasion of Italy in 1494. Neurosyphilis, unlike the psychiatric diseases of antiquity like melancholia and schizophrenia, was unknown before the last quarter of the 18th century. During the 19th century "madness," particularly neurosyphilis, was on the rise. It was known as the "disease of the century." Typically a young man would have sex with a prostitute and later experience a sore on his penis or swollen inguinal lymph nodes. This primary syphilis resolved while the spirochetes would remain in the bloodstream. Within a year they would have invaded the meninges while remaining clinically silent. For many years our young man would walk around symptom-free. If the immune system could not overcome the disease, the individual might become symptomatic ten to fifteen years later. Perhaps the aging man became unable to pronounce some kinds of phrases. Or, less commonly, the early meningitis might have produced more frankly psychiatric symptoms such as grandiosity characteristic of mania. As the illness advanced it primarily affected the spinal cord causing tabes dorsalis (or locomotor ataxia), a wasting of the posterior part of the spinal cord. Tabes would cause lancinating pains to the abdomen and high-stepping gait called "walking on cotton." If the disease affected mainly the brain, psychiatric symptoms would predominate, followed by dementia and paralysis known as general paresis of the insane (G.P.I.), dementia paralytica, or progressive paralysis. A disease primarily of middle-aged men, this was the kind most commonly encountered in the end-stages in asylums; middle class patients were more likely to seek relief at a spa, a resort-like treatment facility. Both tabes dorsalis and general paresis were invariably fatal (Shorter,1997).

In 1822, Antoine-Laurent Bayle, a French physician, attributed the psychiatric symptoms of neurosyphilis to a chronic inflammation of the meninges, and thus made him the first to discover a psychiatric disease with definite organicity. He established that as the underlying disease progressed, the symptoms worsened as well (Muller, 1965). In the 1840s, potassium iodide was introduced and proved effective in the latter stages of the disease. An epidemic of venereal disease spread across Europe and North America in the 19th century with neurosyphilis lagging by ten to fifteen years, the interval between the original infection and the appearance of psychiatric symptoms. There was a reported 5 to 20% lifetime risk for syphilis in the population at that time, (Austin, 1992) and about 6% of those would go on to develop neurosyphilis (Clark et al, 1964). By the mid-nineteenth century, advanced neurosyphilis was treated in public asylums and private clinics. The enormous rise in frequency of neurosyphilis explains the flood of patients into these institutions, where paretics and tabetics constituted a large portion of the asylum population. Not all of the afflicted were admitted to institutions. Some died at home out of shame, others in spas or by suicide with morphine (Flores, 1995).

In 1905 two Germans, F.R. Schaudinn and P.E. Hoffman, discovered the causative organism which they named Spirochaeta pallida, since changed to Treponema pallidum. In 1906-7 the Wasserman test was developed to show the presence of the disease even when latent. The Berlin physician Paul Ehrlich in 1910 announced that "Salvarsan," a combination of arsenic and an organic substance, blocked the development of primary and secondary syphilis (Shorter, 1997). In 1943 John Mahoney, a physician in the U.S. Public Health Service and Head of the Venereal Disease Research Center on Staten Island, proved that penicillin was highly effective against primary syphilis (Mahoney, et al, 1984). At this juncture Psychiatry lost the treatment of syphilis to the physicians. After 1958 there was a marked decline in incidence. However in the 1960s changes in sexual freedom probably contributed to a rise in the number of cases. Perhaps more important than the successful pharmacologic treatment of syphilis have been the social measures against it. The Swedes in particular have successfully tackled this very difficult problem via model legislation involving the provision of information to the population and voluntary anonymous testing of persons at risk. All infected individuals must be reported and registered, but provisions of full names is not required. Contact tracing must be performed and testing is obligatory for contacts which may be done with the assistance of the police. Infected persons who deliberately expose others to risk may be condemned to isolation for an unrestricted time (Cronberg, 1993).

Early syphilis includes primary, secondary, and latent syphilis. Primary syphilis is the painless, solitary chancre that occurs three to four weeks after infection. One-tenth to one-fourth of patients with primary syphilis can show CSF abnormalities, most commonly a positive VDRL but also pleocytosis and hyperglobulinemia (Moore, 1928). Patients may have an asymptomatic primary infection or have no recollection of the primary chancre and thus do not receive treatment. Virtually all patients with untreated primary syphilis advance to secondary syphilis within weeks to months. Symptoms of secondary syphilis are varied and include fever, lymphadenopathy, palmar and plantar rash, and the pathognomonic condyloma lata mucocutaneous lesions. Patients can also have a symptomatic aseptic neurosyphilis showing cranial nerve palsies and neuro-opthalmologic findings. Early latent syphilis occurs in the first two years after infection when serologic markers have resolved. Patients are asymptomatic and can be reliably diagnosed only through specific treponemal tests. Patients with early latent syphilis frequently relapse to secondary syphilis and present with the characteristic mucocutaneous lesions. Late latent syphilis occurs, by conventional definition, two years after the initial infection. One-third of the untreated patients with late latent syphilis progress to tertiary, or late, syphilis, many years after the initial infection, while other patients remain asymptomatic indefinitely (Clark et al, 1964). Early Syphilis can manifest as meningeal and meningovascular syphilis(see Table 1) and has become increasingly common as number of immunocompromised patients rise (Flores, 1995). Tertiary, or late syphilis, manifests as cardiovascular, dermatologic, visceral, and neurologic disease.

About one-third of all patients with untreated syphilis progress to tertiary disease. Tertiary disease is twice as common in men as women, and two to three times more common in whites than blacks. African-Americans are more likely to develop cardiovascular than neurologic disease (Merritt, et al, 1946). Explanations for different rates in different groups, including gender and race, have eluded researchers. Some have proposed the emergence of a neurotropic strain of the spirochete to explain its appearance in the early 18th century, three hundred years after the appearance of syphilis (Hare, 1959).

TABLE 1: CLINICAL PRESENTATIONS OF NEUROSYPHILIS (%) Type: Pre-antibiotic Era (Merritt, et al, 1946) PCN era (Hotson, 1981) Asymptomatic 31 37 Tabes 30 3 Paresis 12 8 Vascular 10 12 Meningeal 6 - Taboparetic 3 - Optic Neuritis/Neuro-ophthalmologic 3 17 Spinal Cord Involvement/Myelopathy 3 3 Seizures 1 18 Other 1 3

Why some neurosyphilitic patients progress and others remain asymptomatic has remained a mystery. Investigators have documented the progression of paretic symptoms after treponemocidal levels of antibiotics have been reached in the central nervous system, but have not been able to explain why this occurs. What is clear is that syphilis is acquired primarily through sexual contact, and as such, its incidence can be dramatically reduced by the use of condoms. Transmission can also occur transplacentally and through nonsexual human contact. Clinical Presentations of Neurosyphilis CNS invasion by T. pallidum can occur at any stage of syphilis (Hook, 1989), though clinically apparent disease often takes years to develop. Up to forty percent of syphilitics show CNS involvement (Hahn, et al, 1946), and one study estimated four to nine percent of the cases of untreated syphilitics develop symptomatic neurosyphilis (Moore, et al, 1930). Asymptomatic patients are often discovered in routine screenings for syphilis or in work-ups for other diseases. Symptomatic neurosyphilis is more likely to occur with longer duration of illness, and most likely to present in white males. Symptomatic neurosyphilis can occur at any stage of infection (Scheck, et al, 1994), and accounts for about one percent of all patients admitted to short term psychiatric facilities in some studies (Roberts, et al, 1992).

Meningeal Syphilis is the first clinically evident presentation of CNS involvement. It typically occurs two months to two years after the initial infection by T. pallidum. Symptoms include headache, confusion, stiff neck, and vomiting. Patients are afebrile and invariably have CSF abnormalities. Progression to Meningovascular Syphilis occurs five to ten years after the initial infection, but can occur much earlier. Patients present with focal neurologic findings secondary to multiple small infarcts due to an endarteritis that produces hypertrophy of the intimal layer of the vasculature and fibroblastic proliferation (Gabay, et al 1983; Lishman, 1987). CT and SPECT show multiple cortical infarcts (Ortego, et al, 1995). Symptoms include hemiparesis, hemianopsia, aphasia and a confusional state and are often preceded by a prodromal phase of mood change. The onset of symptoms can be abrupt but preceded by premonitory symptoms of headache, dizziness, insomnia, memory loss and mood disturbances that can last weeks to months. Psychiatric symptoms including personality and behavioral change, and slowing of mentation and speech may present similarly (Merritt, et al 1946; Holmes et al, 1984) to paresis.

The diagnosis of meningovascular neurosyphilis should be considered in young patients presenting with symptoms of a cerebrovascular accident. The differential diagnosis of meningovascular syphilis includes lacunar strokes secondary to hypertension, atherosclerotic vascular disease, cerebral emboli and cerebral vasculitis (Swartz, 1990). Meningovascular syphilis is still relatively common.(see Table 1).

Parenchymatous Neurosyphilis, including Tabes, meaning wasting, and Paresis, from the Greek word meaning 'relaxation,' occurs ten to twenty years after the initial infection. It has become rare in the post-antibiotic era but anecdotal reports still make note of its existence (Giles, 1980; Hoffman, 1982; Fitchtner, et al, 1991). Patients may also present with taboparesis, a combined form of the two (Lishman, 1987).

Paresis involves the general deterioration of mental and physical capabilities. Symptoms typically begin ten to fifteen years after the initial infection and include memory loss, impaired concentration and ability to learn, irritability, mania, depression, and psychosis. Its insidious onset can mimic any neurologic or psychiatric illness. Neurologic symptoms include a lack of facial expression, or paralyzed facies, tremors of the lips, tongue, facial muscles, and fingers, and impaired handwriting and speech (Swartz, 1990). Late psychiatric symptoms are predominated by a dementia indistinguishable from other forms of dementia, including impaired judgment, confusion and lack of insight (Dawson-Butterworth, et al, 1970).

Late neurologic symptoms include pupillary abnormalities, hypotonia, seizures, and involvement in cranial nerves II, III, VI, VII and VIII (Simon, 1985). The differential diagnosis includes organic brain syndromes of any etiology, including cerebral tumor, subdural hematoma, Alzheimer's Disease, multiple sclerosis, senile dementia, and chronic alcoholism. Pupillary change, focal neurologic symptoms, and EEG or CT abnormality (Godt, et al, 1979; Ganti, et al, 1981) should raise suspicion for paresis (Schwartz, 1990).

Confirming a diagnosis of paresis can be accomplished through laboratory testing(see Table 1). Though treatable, it has a poor prognosis for recovery of function because of diffuse neuronal loss (Merritt, et al, 1946). Paresis most commonly occurs in the fourth through sixth decades of life (Dewhurst, 1969). Tabes, occurring 15-25 years after infection, has the longest latency period and is exceedingly rare in the post-Antibiotic era(see Table 2). Symptoms begin with sensory loss and progress to lightning pains secondary to atrophy and fibrosis of muscle nerve roots, wasting, Argyll Robertson pupils, a positive Romberg sign, and diminished deep tendon reflexes. Ataxia predominates the later symptoms (Scheck, et al, 1994). Lower extremity pain secondary to tabes is described as shooting, in contrast to pain secondary to pain due to diabetic and other peripheral neuropathies, which is often described as burning (Swartz, 1990).

The diagnosis of neurosyphilis on laboratory data alone is difficult, if not impossible. Patients may have abnormal CSF values without neurosyphilis and conversely, neurosyphilis without abnormal CSF findings. Diagnosis requires using several tests in addition to clinical findings. Laboratory tests for syphilis include non-treponemal and specific treponemal tests. Specific treponemal tests include fluorescent treponemal antibody absorption (FTA) and Treponema pallidum hemagluttinin (TPHA). FTA involves incubating a patient's serum on a slide coated with dead T.p., then adding fluorescent tagged antibodies to human antibodies.

TPHA, also referred to as Microhemagglutination for Treponema pallidum(MHA-TP), uses sheep erythrocytes coated with T.p. antigens that agglutinate in the presence of serum exposed to T.p. Specific tests have a sensitivity between 97% and 100%, but remain positive even after successful treatment. Thus FTA or TPHA can be used alone as an effective screening test to rule out neurosyphilis. Retrospective studies have shown that ten percent of patients with a positive serum TPHA have CNS involvement (Roberts, et al, 1992). CSF-FTA may not be useful because of the high number of false positives (Simon, 1985).

Non-treponemal tests include the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR), which are less sensitive than FTA and TPHA. VDRL uses an antigen composed of cardiolipin, cholesterol, and lecithin that is cross reactive with T.p. antigens to precipitate antibodies to T.p. The RPR is a similar test that uses carbon particles as the antigen, and since its introduction in 1976, has largely replaced the VDRL. Non-treponemal CSF exam remains the best method for confirming a diagnosis of neurosyphilis. Non-treponemal tests are, however, unsuitable for screening of neurosyphilis because their sensitivity is between thirty and seventy percent in latent and late syphilis and because twenty-five percent of patients with latent syphilis may revert to negative VDRL within two years (Hart, 1986). Dementia is due to late disease and thus a non-treponemal test is more likely to be falsely negative. Additionally, prior antibiotic treatment for other infections can eliminate serologic VDRL markers while leaving CNS treponemal involvement intact (Dijkstra, 1983). Though some of the historically low sensitivity of non-treponemal tests may reflect the erroneous over-diagnosis of "seronegative neurosyphilis," specific treponemal tests should be used preferentially for screening (Flores, 1995). Non-treponemal CSF exam is the diagnostic test of choice in follow-up. Rising titers, as indicated by an increase in the dilutional number, may signify continued disease (Roberts, 1995). Patients with a non-reactive CSF-VDRL who present with other signs of neurosyphilis, including atypical neurologic or psychiatric symptoms, a prior history of Syphilis, and a positive specific serum test, warrant an expanded work-up (Vartdal, et al, 1982). An intrathecal Treponema pallidum antibody (ITPA) index has been used for increased specificity (Gachnait, et al, 1981). CSF polymerase chain reaction (PCR) is an expensive test that does not provide additional benefit in diagnosing neurosyphilis (Marra, et al, 1996).

TABLE 2: SENSITIVITY OF SERUM TESTS FOR SYPHILIS BY STAGE (%) (Jaffe, et al, 1990) Test Name Primary Secondary Latent Tertiary VDRL 72 100 73 77 FTA 91 100 97 100 MHA/TPHA 69 100 98 100

Controversy has surrounded the issue of routine screening for neurosyphilis in patients presenting with new onset neurologic or psychiatric symptoms. Several studies have argued that routine screening is an important part of work-ups for new onset psychosis, mania, depression, and dementia (Wijesurendra, et al, 1992; Roberts, et al, 1992; Mlisana, et al, 1992; Bell, 1959) while others have argued that the cost of screening outweighs the rare cases of neurosyphilis that are discovered (Banks, 1968).

One study presented seventeen patients with neurosyphilis, of which only six were diagnosed correctly at initial presentation. The remaining eleven patients were referred to nine different departments before the correct diagnosis of neurosyphilis was made (Luxon et al, 1979). Numerous anecdotal reports present cases of misdiagnosis of neurosyphilis and the resulting increase in cost and morbidity (Allen, et al, 1983; Sivakumar, et al, 1992; Hoffman, 1981). As the mentally ill are increasingly cared for by non-physicians and non-psychiatrists, at peripheral or community care centers, and in managed care institutions, physical exams and laboratory work-ups are performed much less frequently (Hoffman, 1981). The incidence of syphilis and neurosyphilis are rising as subtle neurologic findings on physical exam and serologic markers are missed or overlooked. Patients with a history of psychiatric illness have an increased incidence of sexually transmitted disease and are more likely to be misdiagnosed than are non-psychiatric patients. The physical complaints of psychiatric patients are often neglected, as other medical care-givers label their presentations as purely "psychiatric" (Leeman, 1975). In addition, psychiatric patients are often unaware of or unable to communicate their medical illnesses (Hall, et al, 1982). As a result, greater than forty percent of patients presenting to psychiatric clinics have underlying medical illness, and between ten and twenty percent of these have a medical illness contributing to their symptomatology (Koranyi, 1979).

As clinical presentations of neurosyphilis have changed in the last fifty years, the demographics of the disease have changed as well (Hutchinson, et al, 1991; Hamill, et al, 1989). Sub-therapeutic antibiotic therapy has arrested a large number of cases in latent disease and virtually eliminated parenchymal neurosyphilis in the elderly. In contrast, the rise in intravenous drug abuse, oral contraceptives and promiscuity among youths have contributed to the rise of syphilis in younger patients. The incidence of early syphilis is also rising dramatically in urban centers, in adolescent and adult females, and in populations with high rates of social disruption (Rolfs, et al, 1990). Syphilis, like other sexually transmitted diseases, is increasing in inner-city minority populations(Anonymous, 1988). One study found that the prevalence of syphilis was increased in women in urban centers who had not sought prenatal care, and inferred that patients like them, with little knowledge of sexually transmitted disease, less access to health care, and young age, had a higher chance of contracting syphilis and other sexually transmitted diseases (Mlisana, et al, 1992).

Homosexual males, though still at increased risk, have modified their sexual practices in response to the AIDS threat, and thus have contracted fewer cases of syphilis. Though the incidence of neurosyphilis is changing among different groups, risk factors remain the same as for other sexually transmitted diseases. Drug usage, active male homosexuality, unprotected sex, and prostitution are all contributing to the rise in early syphilis and thus the increased incidence of neurosyphilis. Factors that should raise suspicion include a negative family history of mental illness (Gomez, et al, 1984), risk factors for sexually transmitted disease, neurologic symptoms and an organic component to the mental status exam. A history of syphilis, either treated or untreated, HIV, and pre-existing mental illness (Kalichman, et al, 1994; Coverdale, 1995; Kelly, et al, 1995) are the most important risk factors in the development of neurosyphilis.

What is clear is that any patient presenting with neurologic or psychiatric symptoms and risk factors for sexually transmitted diseases should be screened for neurosyphilis (Farshy, et al, 1986). Patients with severe and chronic mental illness, including schizophrenia, bipolar disorder, dementia and psychotic depression should alert the clinician to the possibility of neurosyphilis because of their risks for sexually transmitted disease. Cournos, et al., 1994 and Kalichman, et al., 1994 have documented the alarming frequency of high-risk sexual activity in the chronically mentally ill population, often in the context of drug or alcohol use.56,60 One set of screening guidelines is that of O'Neil and McCaffrey, who recommend selective screening for syphilis based on risks and clinical presentations. (SeeTable 3)61 Psychiatric history and a history of poor medical care should also be considered in testing psychiatric patients for neurosyphilis. As serum FTA is nearly 100% sensitive in all stages of the disease and costs the provider between $7-19, it is thus the screening test of choice. If positive, a lumbar puncture for CSF cell count and VDRL should be performed (Roberts, et al, 1992). A diagnosis of neurosyphilis is made if there is CSF pleocytosis (> 5 cells/mm3) and a positive CSF-VDRL or neurologic symptoms with a negative CSF-VDRL. Additionally, family members and sexual contacts of a patient with neurosyphilis should receive serologic screening (Rundell, et al, 1995).

TABLE 3 : CRITERIA FOR SELECTIVE SCREENING FOR NEUROSYPHILIS 1. New Onset Dementia 2. Patients with an organic component to the mental status exam. 3. High risk groups (prostitutes, homosexual males, h/o syphilis or other STD, HIV, etc). 4. Neurologic findings on physical exam 5. Patients with atypical illness who are not responding to treatment. 6. Member of a medically under-served group 7. Serious and persistent mental illness 8. History of risk taking while in a psychotic or manic episode 9. New onset partial seizures of unknown etiology 10. History of drug or alcohol abuse in a psychiatric patient

The presentation of psychiatric symptoms due to neurosyphilis is often identical to psychiatric presentations secondary to any other etiology, and neurosyphilis can present as any psychiatric symptom.

Unlike the striking clinical presentations of parenchymatous neurosyphilis that were common prior to antibiotic therapy, presentations have become subtle and atypical. Dementia, depression and grandiosity are currently the most common psychiatric presentations. Auditory hallucinations listed as the most common psychotic symptom in an article publishe in 1905 (Craig, 1905). One study implicated neurosyphilis as the causative agent in three of 268 cases of schizophrenia (Johnstone, et al, 1987). With the high prevalence of psychiatric disease in the general population and the relatively low incidence of neurosyphilis, it is likely that a significant number of psychiatric patients also have neurosyphilis contributing in varying amounts to their condition. Neurosyphilis can alter the course of pre-existing psychiatric illness. Frequency of psychotic episodes in schizophrenics can increase, response to treatment can decrease, and organic involvement can cloud consciousness (Sivakumar, et al, 1992). Psychosomatic presentations of neurosyphilis must also be considered. Subtle findings on physical exam or vague complaints in a patient's history when accompanied by histrionic, grandiose, or irritable personality change are easily misdiagnosed as somatoform disorders (Rundell, et al, 1995). Neurosyphilis has also been misdiagnosed as chronic alcoholism. Paretic alcoholics were misdiagnosed with Korsakoff's psychosis or dementia (Lishman, 1987). Even before the use of antibiotics, psychiatric presentations were changing. In the late 19th and early 20th centuries, well before the advent of penicillin, dementia replaced grandiosity as the most common psychiatric presentation of neurosyphilis.

Hare suggests that the Upper Classes were more likely to experience delusions of wealth and grandeur, and since its spread to the population at large, dementia and depression have become the most common psychiatric manifestations (Hare, 1959).

Neurologic symptoms in a new onset illness should raise the possibility of neurosyphilis. Neurosyphilis often presents with both psychiatric and neurologic symptoms. Common symptoms include decreased tendon reflexes (76% with reflex change, 67% with absent ankle jerk, 5% with Babinski sign), seizures, and neuro-opthalmologic findings (45% with pupillary abnormality, 12% with chorioretinitis/retinary pigmentosa, and 5% with optic atrophy). Thirty-four percent have a sensory abnormality (Hooshmand, et al, 1972). Transient neurologic symptoms including aphasias, parasthesias, sensory deficits, headaches, ataxia, or symptoms of cerebrovascular events should raise suspicion of neurosyphilis. Adults with new onset partial seizures of unknown etiology, whether remaining focal or with secondary generalization, should be screened for neurosyphilis (Hotson, 1981). It is also possible that neurosyphilis can increase susceptibility to other neurologic diseases (Wilner, et al, 1968).

Standard treatment of neurosyphilis is aqueous penicillin G. Alternative regimens of Amoxicillin and Ceftriaxone have been used successfully but their efficacy has not been documented in large scale studies (Tramont, 1976; Mohr, et al, 1976). HIV positive patients may need higher doses of PCN and additional follow-up. The Jarisch-Herxheimer reaction of fever and aggravation of syphilitic symptoms, including exacerbation of psychosis and development of seizures, can follow the initiation of therapy (Hahn, et al, 1958). It occurs more commonly in early Syphilis but can occur in 2% of paretics who undergo treatment. The reaction, thought to be caused by the release of products from dead spirochetes, can affect long term outcome in parenchymal infection, particularly when in the optic and auditory nerves (Idsoe, et al, 1976). Tabetic sensory complaints secondary to fibrosis and atrophy of dorsal roots and posterior columns may fail to resolve with penicillin therapy. Lightning pains can be treated with carbamazepine (Ekborn, 1972).

Psychiatric symptoms due to neurosyphilis should be addressed in the same manner as the psychiatric illnesses they mimic. Certain caution should be observed in that patients with neurosyphilis may be more susceptible to the side effects of psychotropics. Cannon and Sperry reported the case of a patient with neuroleptic malignant syndrome and suggested that neurosyphilis acted as a cofactor in the initiation of the reaction.

Electroconvulsive therapy (ECT) may be contra-indicated because the temporary disruption of the blood brain barrier that it causes may allow an increased involvement of the parenchyma by spirochetes (Dewhurst, 1969), but reports have been inconclusive (Dewhurst, 1969). Another report suggested that ECT was effective in the treatment of a patient refractory to medical treatment (Weaver, et al, 1982). Physical and occupational therapy, as well as psychotherapy, may be beneficial in re-integrating a patient back into his normal life (Cannon, et al, 1992). Response to therapy occurs more rapidly with shorter duration of both infection and neurologic disease (Brown, et al, 1985). Successful treatment is defined as a normalization of CSF cell count in six months and a fourfold drop in CSF-VDRL titers. Diligent follow-up is needed in patients with neurosyphilis.

One study showed that at least 31% of patients who had been treated for paresis showed progression of neurologic disease after ten years (Bordon, et al, 1985). Other reports have presented treatment failures in spite of recommended dosages of penicillin therapy (Dijkstra, 1983; Tramont, 1976; Gimenez-Roldan, et al, 1979). Patients should receive lumbar punctures every six months for two years. CSF-VDRL remains the best diagnostic test to monitor recurrence of the disease. IV PCN is the drug of choice in treatment failures, and though no guidelines have been made, higher dosages are needed for cases resistant to treatment (Mohr, et al, 1976). In a five year follow-up of patients with neurosyphilis, 50% of patients showed resolution of disorientation, convulsions, tremors, incontinence, euphoria and depression, while only 25% of patients showed resolution in delusions, hallucinations, and impaired memory, judgment, speech, and calculations. Mild or early cases predictably have a greater chance in showing resolution of symptoms. Patients with active disease, as evidenced by CSF pleocytosis, were more likely to respond to treatment than were patients with static pathology without CSF pleocytosis (Lishman, 1987). Men are more likely to be confused after ten to fifteen years, while women are more often dysarthric and depressed (Dawson-Butterworth, et al, 1970).

Several recent studies have shown the existence of high coinfection rates between syphilis and HIV (Hutchinson, et al, 1991; Bordon, et al, 1985; Quinn, et al, 1990, Musher, et al, 1990; Katz, et al, 1989; Dowell, et al, 1992; Lukehart, et al, 1988; Schofer, 1996; Katz, et al, 1993), and subsequent alterations in the natural course of neurosyphilis. It has been suggested that a specific relationship between HIV and neurosyphilis exists (Johns, et al, 1987; Tramont, 1987; Spence, et al, 1987,; Hook, 1989). One study of 4863 STD patients revealed 24% of those with syphilis to be HIV positive compared to 3.5% of those without syphilis (Quin, et al, 1990). Another study showed that 44% of neurosyphilis patients had AIDS. Coinfection patients are more likely to be younger and present with more CSF abnormalities, syphilitic meningitis, ophthalmologic findings and a larger variety of neurosyphilis (Katz, et al, 1989). Half of HIV positive asymptomatic patients with serologic markers for syphilis may have neurosyphilis (Dowell, et al, 1992), in contrast to 10% of HIV negative patients. A patient with HIV, serologic markers for syphilis and CSF pleocytosis should be diagnosed with neurosyphilis even in the absence of symptoms or CSF-VDRL reactivity (Musher, et al, 1990). Presentation of HIV and syphilis coinfection is even more likely to be atypical than other presentations of neurosyphilis (Radolf, et al, 1988). HIV causes treatment failures and relapses after treatment. It also causes early neurosyphilis to occur frequently, especially after conventional penicillin therapy (Musher, et al, 1990). Patients with HIV need more aggressive work-ups, treatment and follow-up for neurosyphilis.

Neurosyphilis has not become a disease relegated to historical interest. One study attributed 1.3% of the admissions to a short-term psychiatric unit to neurosyphilis (Roberts, et al, 1992), while a much higher incidence of asymptomatic neurosyphilis in psychiatric patients exists. The dramatic presentations of tabes and paresis have been replaced by subtle, atypical findings that are more likely to be missed as clinicians are less experienced in diagnosing the disease, managed care facilities limit the availability of routine testing, and non-MDs care for the mentally ill. Syphilis remains the "great imitator," only now our ability to accurately diagnose patients is markedly compromised. Patients presenting with risk factors for sexually transmitted disease and subtle neurologic or psychiatric symptoms should receive a serologic screening with a specific treponemal test, and if positive, lumbar puncture for CSF-VDRL and cell count. Though the likelihood of discovering new cases of neurosyphilis through routine screening is statistically small, the clinical significance of a twenty dollar test cannot be overstated because of the disease's response to treatment and potentially devastating outcome if not addressed. Patients with HIV and syphilis coinfection warrant aggressive work-ups and treatment. All patients should be followed-up with lumbar punctures every six months for two years. Perhaps because of the dramatic drop in the incidence of neurosyphilis since the advent of penicillin, fewer researchers have focused on the disease than other organic diseases causing psychiatric illness. Researchers have been unable to explain how neurosyphilis, like HIV, can cause such a wide-spectrum of seemingly unpredictable clinical presentations. There exists the possibility that a new epidemic of syphilis could translate into large numbers of patients with potentially devastating CNS infection. This risk is particularly high in the chronically mentally ill. Research on the treatment of psychiatric symptoms independent of penicillin therapy is lacking. Neurosyphilis has played a profound role in the development of psychiatry as the first psychiatric disease for which an organic etiology was found. Today, as neuropsychiatrists are grappling with the complex presentations and reemergence of the disease as new diagnostic modalities and mind-brain paradigms emerge, psychiatrists are challenged with diagnosing neurosyphilis with only subtle clinical findings in their new found roles as "primary care" physicians and serving as consultants on neurosyphilis patients treated by other physicians.

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Neurosyphilis: Considerations for a Psychiatrist

« Psychiatry

Mark A. Ritchie, MD

Louisiana State University School of Medicine



Joseph A. Perdigao, MA

Louisiana State University School of Medicine

Correspondence to:



Mark A. Ritchie, MD

Louisiana State University School of Medicine

Department of Psychiatry

1542 Tulane Avenue

New Orleans, Louisiana 70112-2822

(504) 568-3427, FAX (504) 568-8647



Copyright Priory Lodge Education 1998-9

First Published 6th June 1998

Version 1.0

Last Amended 03/28/99