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Neurosyphilis.



ABSTRACT

We describe the case of a young woman with a rapid deterioration in her cognitive status and physical functioning. An extensive laboratory and radiologic evaluation confirmed the diagnosis of neurosyphilis neurosyphilis /neu·ro·syph·i·lis/ (-sif´il-is) syphilis of the central nervous system.

neu·ro·syph·i·lis
n.
. Despite the reemergence of syphilis with the acquired immunodeficiency syndrome acquired immunodeficiency syndrome, see AIDS.  (AIDS) epidemic, neurosyphulis is often neglected in the differential diagnosis of patients with aseptic meningitis and mental status changes who are negative for the human immunodeficiency virus human immunodeficiency virus
n.
HIV.


Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans.
 (HIV). The high mortality rate associated with delay in recognition, diagnosis, and treatment of neurosyphilis obligates its inclusion in the differential of young patients with cognitive decline.

**********

SYPHILIS is a chronic infection caused by the spirochete spirochete

Any of an order (Spirochaetales) of spiral-shaped bacteria. Some are serious pathogens for humans, causing such diseases as syphilis, yaws, and relapsing fever. Spirochetes are gram-negative (see gram stain) and motile.
 Treponema pallidum. Most commonly acquired through sexual contact, syphilis is also transmitted vertically through the placenta to the fetus, resulting in congenital syphilis. (1) The introduction of penicillin decreased the incidence of syphilis to a low of 4 cases per 100,000 population in the 1950s. (2) Through the mid1980s, bisexual and homosexual men comprised almost 50% of cases. Despite a decrease in cases in the homosexual population, by 1990 the overall incidence had increased, with 50,233 newly reported cases of primary and secondary syphilis. The increase was due to new cases identified in heterosexual, urban, African American men and women. (3,4) Syphilis has also reemerged in the urban HIV-positive population. (5) A total of 6,657 (2.2 per 100,000 population) cases were reported in 1999, which is the lowest number reported since 1941. Sixty-five percent of cases occurred in the southern United States The Southern United States—commonly referred to as the American South, Dixie, or simply the South—constitutes a large distinctive region in the southeastern and south-central United States. . The peak incidence of primary syphilis now occurs in people between the ages of 15 and 34 years. The male:female ratio has increased from 1.1:1 in 1994 to 1.5:1 in 1999; the male:female ratio of patients identified as Hispanic is 2.9:1. (6)

Primary syphilis presents as a painless chancre chancre: see syphilis.
chancre

Primary sore or ulcer at the site of entry of a pathogen; specifically, the typical skin lesion of primary infectious syphilis. In women it is often internal and may go unnoticed.
, which heals within 2 to 3 weeks. Secondary syphilis presents in 25% of untreated patients within weeks to months of primary infection. Common findings of secondary syphilis include rash of the palms and soles, fever, lymphadenopathy and central nervous system (CNS) changes. Forty percent of patients with secondary syphilis have CNS symptoms of visual disturbances, hearing loss, tinnitus, and facial weakness. (7) After a latency period, 25% of untreated patients have late (tertiary) syphilis. Tertiary syphilis presents from 1 to 30 years after primary infection. (8) This disease is slowly progressive and inflammatory and presents as neurosyphilis, cardiovascular syphilis, or gummatous gum·ma  
n. pl. gum·mas or gum·ma·ta
A small rubbery granuloma that has a necrotic center and is enclosed by an inflamed fibrous capsule. It is characteristic of an advanced stage of syphilis.
 syphilis. We present a case of neurosyphilis is a previously healthy, HIV-negative patient.

CASE REPORT

A 48-year-old Hispanic woman presented with complaints of fatigue and forgetfulness. She was vague in describing her symptoms. Her medical history was significant only for previous treatment for Trichomonas vaginalis, tubal ligation, and atypical squamous cells of unknown significance on Papanicolaou smear. Family history was unremarkable. She was taking no medications and denied use of alcohol, tobacco, or illegal substances. She was divorced and living with her stepdaughter and boyfriend of 4 years. She reported only two sexual partners since her divorce 10 years earlier. Initial outpatient evaluation led to a presumptive diagnosis of depression. She was given paroxetine paroxetine /par·ox·e·tine/ (pah-rok´se-ten) a selective serotonin uptake inhibitor used as the hydrochloride salt to treat depression and obsessive-compulsive, panic, and social anxiety disorders. , but she continued to decline. Her family reported that the patient would put clean clothing in the laundry; fabricate stories about nonexistent visitors, and claim that her husband was the devil. The patient had a bilateral facial droop, left arm weakness, and left leg weakness; she began to stumble and fall. She lost her job as a clerk. C omputed tomography (CT) showed slight prominence of the lateral and third ventricles and the temporal horns (Fig 1). Magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures.  (MRI) showed mild hydrocephalus hydrocephalus (hī'drəsĕf`ələs), also known as water on the brain, developmental (congenital) or acquired condition in which there is an abnormal accumulation of body fluids within the skull.  but no parenchymal lesions.

After the MRI, her mental status rapidly deteriorated. She became incontinent of urine and stopped eating. The patient had expressed no complaints of headache, vision difficulties, hearing loss, tinnitus, paresthesias Paresthesias
A prickly, tingling sensation.

Mentioned in: Autoimmune Disorders
, pain, stiff neck, myalgias, arthralgias, or other symptoms. She became unresponsive to verbal and tactile stimuli and was admitted to the hospital.

On admission, her temperature was 99.6[degrees]F, radial pulse rate was 110/min, respiratory rate was 18/min, and blood pressure was 140/80 mm Hg. Initial examination showed a nonverbal, minimally responsive woman with clonic spasms of the upper and lower extremities four times per minute. She would respond to a loud voice or sternal sternal /ster·nal/ (ster´n'l) of or relating to the sternum.

ster·nal
adj.
Of, relating to, or occurring near the sternum.



sternal

pertaining to the sternum.
 rub but would not follow commands. She was thin but not cachectic cachectic /ca·chec·tic/ (kah-kek´tik) pertaining to or characterized by cachexia.

ca·chec·tic
adj.
Affected by or relating to cachexia.
. Her pupils were 1.5 mm and minimally reactive to light. She had bilateral clonus clonus /clo·nus/ (klo´nus)
1. alternate involuntary muscular contraction and relaxation in rapid succession.

2.
, was hyperreflexic, and had bilateral down-going toes on Babinski test. The remainder of the examination was unremarkable.

Initial laboratory studies were remarkable for a normal leukocyte count and differential, a mild anemia with a low mean cell volume, and normal chemistry profile, transaminase transaminase /trans·am·i·nase/ (-am´i-nas) aminotransferase.

trans·am·i·nase
n.
See aminotransferase.
 levels, coagulation coagulation (kōăg'ylā`shən), the collecting into a mass of minute particles of a solid dispersed throughout a liquid (a sol), usually followed by the precipitation or  parameters, thyroid-stimulating hormone level, pancreatic tests, [B.sub.12] level, and folate level. Urine toxicology screen was negative for cocaine, narcotics, benzodiazepines Benzodiazepines Definition

Benzodiazepines are medicines that help relieve nervousness, tension, and other symptoms by slowing the central nervous system.
Purpose

Benzodiazepines are a type of antianxiety drugs.
, barbiturates Barbiturates Definition

Barbiturates are medicines that act on the central nervous system and cause drowsiness and can control seizures.
Purpose
, and cannabis. Serum alcohol level was undetectable. Chest radiograph and electrocardiogram were normal. Hepatitis B and hepatitis C serologies, Lyme Western blot, serum cryptococcal anti-bodies, enterovirus enterovirus /en·tero·vi·rus/ (en´ter-o-vi?rus) any virus of the genus Enterovirus. enterovi´ral
Enterovirus /En·tero·vi·rus/ (en´ter-o-vi?rus 
 polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is , antinuclear antibodies, test for rheumatoid arthritis, cysticercosis cysticercosis /cys·ti·cer·co·sis/ (sis?ti-ser-ko´sis) infection with cysticerci. In humans, infection with the larval forms of Taenia solium.

cys·ti·cer·co·sis
n.
 antibodies, angiotensin converting enzyme Noun 1. angiotensin converting enzyme - proteolytic enzyme that converts angiotensin I into angiotensin II
angiotensin-converting enzyme, ACE

peptidase, protease, proteinase, proteolytic enzyme - any enzyme that catalyzes the splitting of proteins into
, and HIV tests were all negative. An electroencephalogram electroencephalogram /elec·tro·en·ceph·a·lo·gram/ (EEG) (-en-sef´ah-lo-gram?) a recording of the potentials on the skull generated by currents emanating spontaneously from nerve cells in the brain, with fluctuations in potential seen as  showed left-sided slowing with no seizure activity. On lumbar puncture, the cerebrospinal fluid (CSF) glucose level was 66 mg/dL, protein level was 87 mg/dL; 80 white blood cells White blood cells
A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system.

Mentioned in: Abscess Incision & Drainage, Bone Marrow Transplantation, Complement Deficiencies
 (69% reactive lymphocytes) and no red blood cells Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.

Mentioned in: Bone Marrow Transplantation

red blood cells 
 or bacteria were seen. India ink staining was negative for cryptococcus Cryptococcus /Cryp·to·coc·cus/ (-kok´us) a genus of yeastlike fungi, including C. neofor´mans, the cause of cryptococcosis in humans.cryptococ´cal

Cryp·to·coc·cus
n.
. Stain for acid-fast bacilli (AFB) was negative. She was initially started given intravenous ceftriaxone and acyclovir.

The next day, the serum and CSF returned with a reactive rapid plasma reagin Rapid Plasma Reagin (RPR) refers to a type of test that looks for non-specific antibodies in the blood of the patient that may indicate that the organism (Treponema pallidum) that causes syphilis is present.  (RPR), and penicillin was started. Acyclovir was discontinued when the herpes simplex polymerase chain reaction was reported negative. Cultures of the blood and CSF for bacteria, fungi, and AFB were negative, and CSF cytology was negative. Fluorescent treponemal trep·o·ne·mal
adj.
Relating to Treponema.
 antibodies (VIA) were present in both the serum and CSF. A gallium scan and CT of the chest were normal.

The patient's clonic clonic /clon·ic/ (klon´ik) pertaining to or of the nature of clonus.

clon·ic
adj.
Of the nature of clonus, marked by contraction and relaxation of muscle.
 temors responded to divalproex. She slowly improved in functional status and cognitive abilities over the next 20 days. She showed improved muscle strength after 1 week of therapy. She became oriented to person and could follow simple commands. Her cognitive status continued to wax and wane, with occasional visual hallucinations and violent outbursts. Repeated CT showed decreased prominence of the lateral and third ventricles. Lumbar puncture showed CSF protein of 126 mg/dL and WBC count of 165 cells (94% lymphocytes and 6% monocytes monocytes,
n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence.
). Cultures and repeat cytology were again negative. Magnetic resonance imaging showed normal ventricles but extensive parenchymal abnormalities with increased signal in the medial portion of the temporal lobes involving the hippocampal gyri gyri /gy·ri/ (ji´ri) plural of gyrus.  (Fig 2). There was also increased signal in the medial portions of the frontal lobes, in the left thalamus thalamus (thăl`əməs), mass of nerve cells centrally located in the brain just below the cerebrum and resembling a large egg in size and shape. , and in the bilateral insular cortices cor·ti·ces  
n.
A plural of cortex.
.

By the 20th day of treatment, she had regained continence of urine and was in dependent in walking, grooming, and bathing. She was conversant, pleasant, and organized in her thoughts. She had no clonic motions after stopping the divalproex. She was alert and oriented but continued to show deficits in short-term memory. A lumbar puncture on the 21st day of treatment showed CSF protein level of 57 mg/dL and only 9 WBCs (8 lymphocytes and 1 monocyte monocyte /mono·cyte/ (mon´o-sit) a mononuclear, phagocytic leukocyte, 13µ to 25µ in diameter, with an ovoid or kidney-shaped nucleus, and azurophilic cytoplasmic granules. ). The patient was discharged home after a 21-day course of intravenous penicillin.

DISCUSSION

The patient presented with progressive and accelerating decline in mental status. Her initial lumbar puncture was consistent with aseptic meningitis. The differential diagnoses for aseptic meningitis in this setting are summarized in the Table. Seventy-five percent of cases of aseptic meningitis are due to enteroviruses Enteroviruses
Viruses which live in the gastrointestinal tract. Coxsackie viruses, viruses that cause hand-foot-mouth disease, are an enterovirus.

Mentioned in: Hand-Foot-and-Mouth Disease
 (echoviruses echoviruses (ECHO virus),
n.pl an enteric pathogen associated with fever and mild respiratory disease; sometimes may produce an aseptic meningitis.
). Noninfectious causes of aseptic meningitis, including medications, malignancies, and inflammatory or autoimmune diseases, always need to be considered. (9) In this patient, drug and toxic causes were eliminated by careful history from multiple sources and by toxicology screening. The CSF was not consistent with tuberculosis (CSF glucose is usually depressed in tuberculous meningitis), and stains and cultures were negative. Tests eliminated other infectious causes for her symptoms during her hospitalization.

The serum and CSF RPRs and FTA were reactive in our patient. Serum RPR and FTA have a specificity of 97% to 99%; RPR sensitivity is 71 % and FTA sensitivity is 96%. Cerebrospinal fluid RPR is insensitive, positive in only 30% of late syphilis cases, so a positive CSF RPR is considered diagnostic. (10) The combination of a reactive serum and CSF PTA is 94% specific and 87% sensitive. (11) False-positive rates decrease dramatically when combining the RPR test with the FTA to confirm the diagnosis. False-positive tests can occur when there is a strong immunologic stimulus present. Conditions producing false-positive results include Lyme disease, rheumatoid arthritis, malignancies, AIDS, and certain drugs. (12) These confounding causes must be considered and eliminated. False-negative syphilis tests occur in patients with HIV infection. (13) Dark-field examination technique cannot be done without an identifiable lesion from which to isolate the spirochete.

Impairments of memory and intellect due to involvement of the frontal and temporal lobes occur early in neurosyphilis. (14) Common MRI findings in neurosyphilis patients with general paresis (personality [paranoia, carelessness in appearance]; affect [labile labile /la·bile/ (la´bil)
1. gliding; moving from point to point over the surface; unstable; fluctuating.

2. chemically unstable.


la·bile
adj.
1.
]; reflexes [hyperactive]; eye [Argyll Robertson pupils]; sensorium sensorium /sen·so·ri·um/ (sen-sor´e-um)
1. a sensory nerve center.

2. the state of an individual as regards consciousness or mental awareness.


sen·so·ri·um
n. pl.
 [hallucinations, illusions, delusions]; intellect [decreased recent memory, judgment, insight]; and speech [slurred]) include dilated ventricles and either increased signal or atrophy of the medial temporal lobes. (15,16) Frontal cortical atrophy and disseminated frontal high signal lesions are also seen. (17) Magnetic resonance imaging that shows cerebral atrophy indicates a poor prognosis. These patients frequently maintain deficits in social functioning, personality changes and generalized dementia. (15) Our patient's MRI showed no evidence of atrophy but did show enhancement in the temporal and frontal regions. These lesions are consistent with neurosyphilis.

The patient's cognitive decline is consistent with parenchymatous neurosyphilis. Central nervous system pathologic findings of neurosyphilis include meningovascular neurosyphilis and parenchymatous neurosyphilis. Meningovascular neurosyphilis occurs 5 to 10 years after initial infection and produces classic findings ranging from progressive neurologic deficits to aphasias and seizures. Parenchymatous neurosyphilis develops 10 to 20 years after initial infection and includes tabes dorsalis and general paresis. Early paresis includes subtle deterioration of cognition with poor concentration, irritability, and loss of higher cortical functions. Associated psychiatric symptoms include depression and psychosis.

This patient likely contracted syphilis from her husband or shortly after her divorce 10 years before hospitalization. Her lack of previous treatment with penicillin is an important item in her history, since many people may be inadvertently treated for syphilis while receiving penicillin for an upper respiratory tract infection upper respiratory tract infection URI Infectious disease A nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx, the prototypic URI is the common cold; flu/influenza is a systemic illness involving the URT  or other common illness. Despite lack of history of primary or secondary syphilis, this patient showed symptoms of parenchymatous neurosyphilis and paresis. Asymptomatic syphilis occurs in 8% to 40% of infected patients. (7,18) Since 1993, cases of late syphilis have outnumbered reported cases of primary and secondary syphilis. By 1999, 2.5 cases of late or late-latent syphilis were reported for each case of primary or secondary syphilis. (6) Although the patient denied any memory of a chancre or symptoms of secondary syphilis, on admission she had depression, illusions, hallucinations, carelessness, hyperreflexia, and loss of judgment, all of which are consistent with paresis.

The Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  recommendations for the treatment of neurosyphilis include 18 to 24 million IU of intravenous penicillin each day for 10 to 14 days. (19)

Penicillin's profound impact on this disease is shown by a 60-fold decrease in admissions for neurosyphilis to US mental hospitals. Admissions declined from 5.9 cases per 100,000 population in 1942 to 0.1 cases per 100,000 in 1965. (20) Penicillin treatment for primary and secondary syphilis is curative. In 1986, Fiumara (21) reported on 588 patients with primary syphilis and 623 patients with secondary syphilis. Penicillin treatment resulted in all becoming seronegative seronegative /se·ro·neg·a·tive/ (-neg´ah-tiv) showing negative results on serological examination; showing a lack of antibody.

se·ro·neg·a·tive
adj.
 within 2 years. The World Health Organization (WHO) reported in 1972 that of 1,030 patients treated with 2.4 to 4.0 million IU of penicillin, 93% to 100% achieved serologic nonreactivity. (22) In a 1956 study, 756 patients with asymptomatic neurosyphilis were treated with penicillin and followed up for 7 years. Symptomatic neurosyphilis developed in 3.3% of these patients; most had only subtle neurologic changes and none had true paresis.(23) The WHO summarized 24 studies encompassing almost 7,000 patients treated for neurosyphilis. Methodolo gic differences made trial comparisons difficult. Persistent reactivity was found in the majority of trials. Side effects to penicillin were rare and usually not severe. Irreversible brain damage often occurred before treatment and sometimes progressed even after therapy for neurosyphilis. (24)

Penicillin treatment has potential adverse reactions. Treatment has been known to precipitate the Jarisch-Herxheimer reaction, particularly in patients with early syphilis. This reaction is an inflammatory response to the destruction of treponemes. (25) It occurs within hours of treatment and subsides within 24 hours. The symptoms of Jarisch-Herxheimer, reaction are fever, headache, hypotension, and myalgias. The reaction occurs in up to 95% of treated cases of primary syphilis but is rare in treated late syphilis. (26) Penicillin can also produce an allergic reaction and anaphylactic shock. In 1965, the Department of Health, Education, and Welfare (now the Department of I-Health and Human Services) reported the frequency of penicillin allergy in patients treated for gonorrhea or syphilis to be 0.67%; only 0.015% had anaphylaxis.(27) No deaths were observed. In 1987, approximately 10% of adults in the United States reported an allergy to penicillin. (28)

Our patient received the maximum penicillin dosage recommended for treatment. Unresponsive on admission, this 48-year-old woman became alert and oriented with marked improvement in neurologic status in less than 3 weeks. Her CSF studies also improved during treatment. Clinical improvement correlates with decreased CSF pleocytosis pleocytosis /pleo·cy·to·sis/ (ple?o-si-to´sis) presence of a greater than normal number of cells in cerebrospinal fluid.

ple·o·cy·to·sis
n.
.(29) The CDC guidelines state that CSF leukocyte count should decrease within 6 months after therapy. Protein levels are expected to drop at a slower rate and normalize within 2 years. Although CSF RPR titers decrease, it may be years before they become nonreactive.(13)

All patients with secondary syphilis or syphilis of more than 1 year should be evaluated for neurosyphilis. Patients should be monitored closely for signs and symptoms of recurrence. Sexual contacts of patients need be identified and evaluated. Our patient continues to be followed up in the outpatient setting and remains neurologiclaly stable.

CONCLUSIONS

Neurosyphilis remains a disease of contemporary society. This disease may mimic other diseases and be difficult to recognize and to diagnose. The differential diagnosis of any patient presenting with aseptic meningitis needs to include late syphilis. A complete history and physical examination complemented by appropriate testing are essential. With appropriate antibiotic therapy, primary and secondary syphilis are curable. Patients with early neurosyphilis may respond better to therapy than those with a late presentation of the disease; thus, early diagnosis remains important for a good clinical outcome.
TABLE.

Causes of Aseptic Menigitis


Infectious causes
  Viruses             Enterovirus (poliovirus,
                      coxsackievirus, echovirus),
                      herpes simplex, types 1 and 2,
                      varicella-zoster virus,
                      adenovirus, Epstein-Barr virus,
                      lymphocytic choriomeningitis
                      virus, human immunodeficiency
                      virus
  Bacteria            Partially treated bacterial
                      meningitis, endocarditis,
                      parameningeal infection,
                      Mycoplasma pneuomniae,
                      Mycobacterium tuberculosis,
                      Ehrlichiosis, Borrelia
                      burgdorferi, Treponema pallidum,
                      Brucella
  Fungi               Cryptococcus neoformans,
                      Histoplasma capsulatum,
                      Coccidioides immitis, Blastomyces
                      dermatitidis
  Parasites           Toxoplasma gondii, Toxoplasma
                      solium

Noninfectious causes
  Drugs               Nonsteroidal anti-inflamatory
                      drugs,
                      trimethoprim-sulfamethoxazole,
                      OKT3, intravenous immunoglobulin,
                      isoniazid intrathecal methotrexate
                      and cytosine arabinoside,
                      postvaccination
  Systemic diseases   Sarcoidosis, leptomeningeal
                      cancer, posttransplantation
                      lymphoproliferative disorder,
                      sytemic lupus erythematosis,
                      Wegener's granulomatosis, central
                      nervous system vasculitis,
                      Behcet's syndrome
  Other               Arachnoiditis, migraine,
                      postinfectious syndromes


References

(1.) Kampmeier RH: Essentials of Syphilology. Philadelphia, JB Lippincott Co, 3rd Ed, 1943

(2.) Kilmarx PH, Louis ME: The evolving epidemiology of syphilis. Am J public Health 1995; 8:1053-1054

(3.) Summary of Notifiable Diseases, United States, 1997. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg,  Morb Mortal Wkly Rep 1998: 46:60-61

(4.) Summary of Notifiable Diseases, United States. MMWR Morb Mortal Wkly Rep 1997; 46:42

(5.) Musher DM: Syphilis, neurosyphilis, penicillin and AIDS. J. Infect Dis 1991; 163:1201-1206

(6.) Division of STD Prevention: Sexually Transmitted Disease sexually transmitted disease (STD) or venereal disease, term for infections acquired mainly through sexual contact. Five diseases were traditionally known as venereal diseases: gonorrhea, syphilis, and the less common granuloma inguinale,  Surveillance 1999. Atlanta, Ga, US Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS
, Centers for Disease Control and Prevention, 2000

(7.) Lukehart S, Hook EW, Baker-Zander SH, et al: Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and therapy. Ann Intern Med 1998; 109:855-862

(8.) Clark EG, Danbolt N: The Oslo study of the natural course of untreated syphilis. Med Clin North Am 1964; 48:613-621

(9.) Pruitt AA: Infections of the central nervous system. Neurol Clin 1998; 16:419-447

(10.) Hook EW, Marra CM: Acquired syphilis in adults. N Engl J Med 1992; 326:1060-1065

(11.) Maclean S, Luger A: Finding syphilis without the Venereal Disease Research Laboratory test The Venereal Disease Research Laboratory test (VDRL) is a nontreponemal serological screening for syphilis, the monitoring of the response to therapy, the detection of CNS involvement, and as an aid in the diagnosis of congenital syphilis. . Sex Transm Dis 1996; 23:392

(12.) Roos K: Neurosyphilis. Semin Neurol 1992; 12:209-212

(13.) Erbelding EJ, Vlahov D, Nelson KE, et al: Syphilis serology in HIV infection: evidence for false negative fluorescent treponemal testing. J Infect Dis 1997; 176:1397-1399

(14.) Denays R, Collier A: A 51-year-old woman with disorientation and amnesia. Lancet 1999; 354:1786

(15.) Kodama K: Relationship between MRI findings and prognosis for patients with general paresis. J Neuropsychiatr Clin Neurosci 2000; 12:246-250

(16.) Russouw HG, Roberts MG, Emsley RA, et al: Psychiatric manifestations and magnetic resonance imaging in HIV-negative patients. Biol Psychiatry 1997; 41:467-473

(17.) Querol-Pascual MR, Casado-Naranjo I: Diagnostic value of magnetic resonance in neurosyphilis. Neurologia 1993; 8:78-81

(18.) Tramont E: Treponema pallidum. Principles and Practice of Infectious Diseases. Mandell CC, Bennett JE, Palm R, eds. New York, Churchill-Livingstone, 5th Ed, 2000, pp 2474-2489

(19.) Centers for Disease Control and Prevention: 1998 guidelines for treatment of sexually transmitted diseases Sexually transmitted diseases

Infections that are acquired and transmitted by sexual contact. Although virtually any infection may be transmitted during intimate contact, the term sexually transmitted disease is restricted to conditions that are largely
. MMWR Morb Mortal Wkly Rep 1998; 47:1-116

(20.) Scheck DN, Hook E: Neurosyphilis. Infect Dis Clin North Am 1994; 8:769-795

(21.) Fiumara NJ: The treatment of primary and secondary syphilis: the serologic response. J Am Acad Dermatol 1986; 14:487-491

(22.) Idsoe O, Guthe T, Wilcox RR: Penicillin in the treatment of syphilis, the experience of three decades. Bull World Health Org 1972; 47(suppl):1-68

(23.) Hahn RD, Webster B, Weickhardt G, et al: Penicillin treatment of asymptomatic central nervous system syphilis II. results of therapy as measured by laboratory findings. Arch Dermatol 1956; 174:367-377

(24.) Wilner E, Brody JA: Prognosis of general paresis after treatment. Lancet 1968; 2:1370-1371

(25.) Johnson RA, White M: Syphilis in the 1990s: cutaneuous and neurologic manifestations. Semin Nearol 1992; 12:287-298

(26.) Wilcox RR A Textbook of Venereal Diseases and Treponematoses. London, Heinemann Medical Books, 2nd Ed, 1964

(27.) VD Fact Sheet 1965. Washington, DC, US Department of Health, Education and Welfare, 22nd rev, 1965, Public Health Service Publication 341

(28.) Centers for Disease Control and Prevention: Primary and secondary syphilis--United States, 1997. MMWR Morb Mortal Wkly Rep 1998; 47:493-497

(29.) Currie JN, Coppeto JR, Lessell S: Chronic syphilitic syph·i·lit·ic
adj.
Of, relating to, or affected with syphilis.

n.
A person with syphilis.
 meningitis resulting in superior orbital fissure superior orbital fissure
n.
A cleft between the greater and the lesser wing of the sphenoid, through which pass the oculomotor and trochlear nerves, the ophthalmic division of the trigeminal nerve, the abducens nerve, and the ophthalmic veins.
 syndrome and posterior fossa gumma Gumma (gm`mä), prefecture (1990 pop. 1,966,287), 2,446 sq mi (6,335 sq km), central Honshu, Japan. Maebashi is the capital; other important cities are Isezaki, Kiryu, and Takasaki. : a report of two cases followed for 20 years. J Clin Neuroophthalmol 1988; 8:145-155

RELATED ARTICLE: KEY POINTS

* There are 2.2 cases of syphilis per 100,000 population in the United States.

* False-positive rapid plasma reagin test rapid plasma reagin test
n.
Any of a group of serologic tests for syphilis. Also called RPR test.
 can be seen in patients with Lyme disease, rheumatoid arthritis, malignancies, AIDS, and those taking certain drugs.

* Impairments in memory and intellect are seen early in neurosyphilis. Patients may show deficits in social functioning, personality changes, and generalized dementia.

* The diagnosis of neurosyphilis must be considered early and aggressively pursued. Delay in recognition and treatment can result in a poor outcome.

From the Department of Medicine, Hartford Hospital, Hartford, Conn.

Reprint requests to Michael Lindberg, MD, Hartford Hospital, Department of Medicine, 80 Seymour Street, Hartford, CT 06102.
COPYRIGHT 2002 Southern Medical Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Date:Sep 1, 2002
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