Tabes Dorsalis

Etiology

Treponemes are thin, spirally coiled helical spirochete bacteria. T pallidum subspecies pallidum, pertenue, and endemicum cause venereal syphilis, yaws, and endemic syphilis, respectively. T carateum causes pinta. Humans are the only natural hosts of T pallidum.  

Epidemiology

Determining the actual incidence of neurosyphilis, including tabes dorsalis, remains challenging despite the rising rates of primary and secondary syphilis worldwide. Recent data reveal a 28.6% increase in the number of primary and secondary syphilis cases from 2020 to 2021. Current estimates indicate a prevalence of 16.2 cases per 100,000 for syphilis.[4]

Nearly 75% of primary and secondary syphilis cases occur in men between the ages of 25 and 34, predominantly attributed to the increasing cases among men who have sex with men (MSM).[5][6] Associated risk factors in MSM include methamphetamine use and having acquired recent sexual partners via social media.[7][8] A high rate of HIV coinfection exists in MSM who have syphilis. The incidence of HIV coinfection for MSM, men who exclusively have sex with women, and women are 45%, 7%, and 4%, respectively.[9][10][11] Since 2012, the incidence of syphilis in women has increased by 700%. Experts feel this increase is likely due to the rise in drug use. As a result of increasing cases in women, the number of cases of congenital syphilis is also increasing.

Globally, approximately 25% to 35% of syphilis cases progress to late neurosyphilis, with approximately one-third of these cases developing into tabes dorsalis. Experts suggest approximately 1.5% to 9% of patients with syphilis will develop tabes dorsalis.[12] In the United States, Black patients experience a significantly higher incidence of syphilis compared to their White counterparts.[6][13] On a global scale, the highest incidence of syphilis is observed in lower-income regions of Africa and Southeast Asia.[14]

Pathophysiology

Early Infection

T pallidum invades the body through direct contact with an infected lesion during sexual activity, by crossing the placenta, or, rarely, by blood transfusions and solid organ transplantation.[15][16] Infection may occur at any site of inoculation, including kissing or touching a person who has active lesions on the lips, mouth, breasts, or genitals.

Once the bacteria enter the host's body, they evade the immune system and cause the initial lesion or chancre. Concurrently, some organisms disseminate into regional lymph nodes.[15] Initially, the immune system infiltrates the chancre with polymorphonuclear leukocytes, later replaced by T lymphocytes. Studies reveal that fluids isolated from the lesions contain CD4+ and CD8+ T cells, activated monocytes, macrophages, and dendritic cells. The body also develops a humoral immune response, developing antibodies clinicians can detect early in the disease course. Essentially, the immune system controls the local disease while allowing the dissemination of spirochetes, leading to the potential development of secondary and tertiary syphilis if patients remain untreated.

Late Infection

Cellular immunity likely controls syphilis and contributes to late syphilis. Late syphilis is characterized by a prolonged latent period, with researchers suggesting that waning immunity with aging or a hypersensitive host with partial immunity reacting to treponemes may underlie its pathophysiology. Gummas, or late benign syphilis, are characterized pathologically by the presence of granulomas, supporting the idea of a cellular hypersensitivity reaction.

Neurosyphilis

Neurosyphilis occurs when T pallidum invades the CNS, which likely occurs soon after infection. However, CNS infection does not always result in a persistent infection. Some patients may clear the infection entirely, while others may clear it after a transient meningitis. Those who do not clear the infection completely are at risk for symptomatic neurosyphilis. 

The pathogenesis of tabes dorsalis involves an inflammatory response against the treponeme, characterized by perivascular infiltrates of lymphocytes, histiocytes, plasma cells, macrophages, T-helper cells, and the development of gummas or caseous necrosis in granulomata.

Cytokines released from these inflammatory cells cause additional cellular damage, promoting neuronal degradation. Direct treponemal invasion of large myelinated nerves may also lead to their degeneration and promote the development of neuropathy. Some studies demonstrate that T pallidum disrupts iron metabolism and homeostasis by forming reactive oxidative agents, contributing to neuronal cellular damage.[17]

The net result of these processes is neurodegeneration with demyelination of the sensory nerve fibers in the dorsal roots and posterior columns of the spinal cord, ultimately resulting in the characteristic symptoms of ataxic gait and sharp, stabbing pain, often with paresthesias and other signs of nerve root compression.[18][19] Spinal cord atrophy may also occur and indicate a poorer prognosis.[18][20][21][22] Given the high rate of HIV coinfection with neurosyphilis in the United States, clinical suspicion of neurosyphilis must remain high in patients with HIV who develop neurological, visual, or otologic signs or symptoms.[11] 

Histopathology

Histologic examination reveals demyelination and subsequent degeneration of dorsal root neurons. The affected dorsal column appears pale white, resulting from atrophy and corresponding pallor due to the loss of dorsal root axons and myelin sheaths.[20] 

Perivascular infiltration primarily comprises CD4+ and CD8+ T lymphocytes, macrophages, and plasma cells, accompanied by the obliteration of small vessels. Gummas, characterized by nodules of central caseous necrosis encircled by inflammation displaying a granulomatous appearance, may manifest throughout the CNS.[23][24] Although the infecting organisms are generally not visible in most cases of spinal cord lesions, their presence may still be detectable through 16S ribosomal deoxyribonucleic acid (rDNA) sequencing for T pallidum.[25][26][27]

History and Physical

Clinical suspicion is crucial for diagnosing neurosyphilis. A previous history of a primary syphilitic lesion, the presence of ophthalmic or otological symptoms, or HIV infection can lead to clinical suspicion of syphilis. The stages of syphilis, based on clinical findings and timing, are not always clinically apparent.[15][28]

Stages of the Disease

The classification of syphilis distinguishes between early and late stages, with further delineation within these categories.

Early-stage disease: This is distinguished as primary, secondary, and early latent syphilis.

• Primary syphilis: Primary syphilis manifests as a single, painless chancre at the site of inoculation, accompanied by regional lymphadenopathy. The average time from infection to the appearance of the chancre is 21 days, with a range of 3 to 90 days.

• Secondary syphilis: Secondary syphilis occurs in approximately 25% of patients, presenting as a systemic illness within a few months of infection. Symptoms include a rash, which may be diffuse or affect the palms and soles, along with fever, malaise, pharyngitis, hepatitis, condyloma lata, and alopecia.

• Early latent syphilis: Patients in this stage are asymptomatic, but serologic tests reveal infection. Early latent infection occurs within 1 year of T pallidum infection by definition. 

Late-stage disease: This is distinguished as tertiary and late latent syphilis.

Between 25% and 40% of untreated patients will develop late-stage disease. Symptoms can manifest anywhere from 1 to 30 years following the initial infection. Affected patients may not have experienced symptomatic primary or secondary syphilis, making the diagnosis challenging.

• Tertiary syphilis: Patients exhibit symptomatic manifestations involving the cardiovascular system or gummatous disease.[28]

• Late latent syphilis: Serologic testing indicates infection, but the patient is asymptomatic. Late latent infection occurs more than 1 year following the initial infection.

Neurosyphilis: This is distinguished as early and late latent neurosyphilis.

• Early neurosyphilis: Many exposures resolve spontaneously in individuals with intact immune systems. Nearly 40% of patients experience asymptomatic neurological involvement.[3] Affected patients may present with asymptomatic and symptomatic meningitis or, less commonly, meningovascular disease such as stroke. Some patients may present with vision or hearing loss without concomitant meningitis. In patients with HIV infection, the presence of photophobia, vision loss, or diminished hearing, along with gait incoordination, increases the likelihood of neurosyphilis.[3][29]

• Late neurosyphilis: Most commonly presents as general paresis or tabes dorsalis. General paresis is a progressive dementing illness initially characterized by forgetfulness and personality changes, which progressively worsen to severe dementia. Symptoms typically develop 10 to 25 years following the initial infection but may appear as early as 2 years after infection. Less frequently, affected patients can present with depression, mania, or psychosis. Additional associated symptoms include dysarthria, hypotonia of the face and limbs, intention tremors of the face, tongue, and hands, and abnormal reflexes. Pupillary abnormalities may be present but are more likely associated with tabes dorsalis.[30][31][32][33] 

Presently, early neurosyphilis is more prevalent than its late counterpart and is especially common among individuals with concurrent HIV infection. Tabes dorsalis has an average latent period of 20 years between primary infection and the onset of symptoms, making having a high index of suspicion necessary.[1][3][30][31] Symptoms of tabes dorsalis include ongoing loss of pain sensation, peripheral reflexes, impairment of vibration and position senses, paresthesias, and progressive ataxia.[1][34][1] In addition, patients experience intermittent bouts of acute, severe stabbing pain, primarily in the back, abdomen, or legs.[1] The pain may only last a few minutes or persist for days.[1] These painful crises may occur spontaneously, triggered by cold exposure, stress, or without any identifiable stimulus. Visceral crises may lead to recurrent episodes of severe epigastric pain accompanied by gastric symptoms, including nausea and vomiting. Urinary retention with overflow incontinence and impotence may also occur in the early stages of the disease.

Physical Examination

Abnormalities of the pupil are a hallmark finding on physical examination in patients with tabes dorsalis. An Argyll Robertson pupil accounts for nearly 50% of these abnormalities. This type of pupil is small and irregular and fails to constrict in response to light, but it constricts briskly to near targets. Its dilation response to mydriatics is imperfect, and it does not dilate in response to painful stimuli.[35] Please see StatPearls' companion resource, "Argyll Robertson Pupil," for more detailed information.

Other examination findings include decreased lower extremity deep tendon reflexes, diminished pain sensation, sensory ataxia, and a positive Romberg test, with proprioceptive deficits affecting nearly 60% of patients.[10] The absence of normal proprioception leads to a distinct wide-based, purposeful, unsteady gait, where the patient's feet "slap" or "stomp" the ground. These findings indicate severe dorsal column dysfunction or peripheral nerve disease. Patients can mitigate this effect by watching their feet while walking. Deficiencies in vibrational and tactile sensation may also be evident. Additionally, manifestations such as optic atrophy and progressive joint degeneration may be observed.[10] Late stages demonstrate severe spastic paraparesis and autonomic neurogenic dysfunction.[36] 

Charcot joints, most commonly affecting the knees and hips, may also be present.[37] Charcot spine, or spinal neuroarthropathy, characterizes the rare but progressive deterioration of bone, cartilage, intervertebral discs, and ligaments in the spine due to prolonged sensory loss and lack of proprioception.[38] While historically associated mainly with tabes dorsalis, it has more recently been linked to spinal cord injuries accompanied by sensory and proprioceptive deficits.[39][38][40][41] Common symptoms and signs include vertebral destruction, pain, paresthesias, weakness, decreased sensation, spasticity, diminished deep tendon reflexes, autonomic dysfunction, and spinal instability leading to deformity, typically kyphosis.[25][39][42][43][44][45][46][47]

Sensory loss disrupts normal protective muscle contractions, resulting in recurrent spinal microtrauma and localized inflammatory effusions. Traumatic microfractures contribute to bone and cartilage fragments to the effusions, exacerbating inflammation, forming calluses, narrowing intervertebral disc spaces, damaging ligaments, and possibly leading to paraspinal masses.[25][39][38][42][43][48] Progression may result in compression fractures, vertebral destruction, kyphosis, or nerve root compression with associated neurological symptoms.[39][43][44][45][46] 

Evaluation

Establishing the diagnosis of tabes dorsalis can be challenging for clinicians. Factors such as clinical presentation, examination findings, laboratory data, history of concurrent HIV infection, and sometimes imaging studies must be carefully considered.[3] As T pallidum cannot be cultured in a standard medium, serology and cerebrospinal fluid (CSF) examinations serve as the primary methods for evaluating late-stage syphilis, and they can effectively confirm the diagnosis of late neurosyphilis.[3][15][49][50] Additionally, sensory evoked potentials from the tibial nerve may exhibit delays depending on the pathological involvement of the dorsal roots. However, nerve conduction testing typically remains normal, as motor neurological activity is generally unaffected.[51]

Serological Testing  

Serologic testing is crucial in providing a presumptive diagnosis of syphilis. These tests are categorized into nontreponemal and treponemal-specific tests. It's important not to rely solely on one type of test because of the possibility of false-positive results, especially with nontreponemal tests. Additionally, false-negative results can occur, especially in patients with advanced immunosuppression or during the early stages of the disease, as serological testing depends on a humoral immune response. 

Nontreponemal assays: Nontreponemal assays detect antibodies against lipoidal antigens and are semi-quantitative. The amount of antibodies present generally reflects the infection's activity. Over time, they tend to become nonreactive and also indicate a response to treatment. Positive nontreponemal tests are reported by labs as a titer of antibody. For instance, a titer of 1:32 signifies the detection of antibodies in serum diluted 32-fold. These tests can be conducted on blood, serum, or CSF and include the following:

• Rapid plasma reagin (RPR)
• Venereal Disease Research Laboratory (VDRL)
• Toluidine Red Unheated Serum Test (TRUST) [52]

Treponemal antibody tests: Treponemal antibody tests detect antibodies directed against specific treponemal antigens and are more specific than nontreponemal assays. They are qualitative and only indicate reactive or nonreactive results. Most infected patients remain positive for life, and these tests are not useful for disease tracking. However, some patients may become negative within 2 to 3 years if treated early during the primary syphilis stage. Treponemal assays include:

• Fluorescent treponemal antibody absorption (FTA-ABS)
• Microhemagglutination test for antibodies to T pallidum (MHA-TP)
• T pallidum particle agglutination assay (TPPA)
• T pallidum enzyme immunoassay (TP-EIA)
• Chemiluminescence immunoassay (CIA)

Serologic testing should include both nontreponemal and treponemal tests, with confirmatory testing recommended due to the potential for false-positive results. CSF evaluation becomes necessary when neurosyphilis is suspected. Interpretation of serologic testing depends on the clinical disease presence, prior syphilis history, and the individual's immune status. Clinicians typically confirm a new syphilis infection with positive results from both nontreponemal and treponemal tests, particularly in individuals without a history of prior syphilis.

In patients with a history of treated syphilis, a positive nontreponemal test may indicate a new infection, a response to treatment, or treatment failure. Patients with positive nontreponemal and negative treponemal test results are typically considered false-positive. Those with recent high-risk exposures should undergo repeat testing. False-positive nontreponemal test results can be due to pregnancy, acute infection, recent immunization, or autoimmune conditions. Conversely, a positive treponemal and negative nontreponemal test may indicate previously treated syphilis or early or late-stage syphilis. Negative nontreponemal test results in patients with symptoms of early syphilis may be false-negative due to the timing of testing or prozone effects, where high antibody levels interfere with the clumping of antigen-antibody complexes. Asymptomatic patients with serologic evidence of infection are diagnosed with latent syphilis, classified as early latent if acquired within 12 months and late latent otherwise.

Patients With an Unknown Syphilis History

For patients with an unknown syphilis history, the initial step in diagnosing neurosyphilis involves confirming the presence of T pallidum infection. While nontreponemal tests tend to be positive in early neurosyphilis, they may yield nonreactive results in late-stage neurosyphilis. Therefore, to evaluate suspected cases of tabes dorsalis, it is crucial to perform treponemal antibody tests.

Patients With a Known History of Syphilis

In patients with a known history of syphilis, a lumbar puncture becomes necessary when presenting with neurological, otological, or ocular symptoms. Similarly, clinicians should also consider this procedure for individuals showing similar symptoms suggestive of syphilis-related conditions, particularly if their syphilis history is unclear. According to the United States Centers for Disease Control (CDC) recommendations, patients with a known syphilis history require a lumbar puncture to assess the potential presence of symptomatic or asymptomatic neurosyphilis if they exhibit neurologic or ophthalmic signs or symptoms during any syphilis stage, show evidence of active tertiary syphilis affecting other body parts, or experience treatment failure across any syphilis stage.[3][53]

Some experts advocate for performing a lumbar puncture in all patients diagnosed with syphilis and concomitant HIV infection. Individuals with a CD4+ T-cell count of 350 cells/µL or less, an RPR titer of greater than or equal to 1:32, detectable plasma HIV ribonucleic acid, or those who are not receiving antiretroviral therapy are notably at higher risk of asymptomatic neurosyphilis. Historical data from the pre-antibiotic era demonstrate improved patient outcomes with the detection of asymptomatic neurosyphilis. However, there is a lack of data from the antibiotic era to directly address this concern. European guidelines recommend lumbar puncture for HIV-positive individuals with syphilis who exhibit the mentioned risks, as treatment with penicillin at higher doses for longer durations than used for primary and secondary syphilis may retard or prevent the development of clinically debilitating neurosyphilis later.[3][11] Also, symptoms associated with late neurosyphilis are less amenable to reversal.

Cerebrospinal Fluid Findings in Tabes Dorsalis

The CSF findings associated with neurosyphilis include the following:

• Increased protein concentration, ranging from 45 to 75 mg/dL
• CSF pleocytosis exceeding 20 WBCs/µL
• Positive VDRL
• T pallidum hemagglutination (TPHA) titer greater than 1:320 [54][55] 

A reactive CSF-VDRL test confirms the diagnosis of neurosyphilis. However, a nonreactive result does not definitively rule out the diagnosis.[3] Notably, a false-positive result can occur if the CSF is grossly bloody and the serum nontreponemal test titer is high. Recent studies have demonstrated that the sensitivity of CSF-VDRL ranges from 67% to 72%.[56][57] While CSF RPR testing is generally avoided due to its lower sensitivity compared to VDRL, in regions where VDRL is unavailable, RPR may be considered necessary.[3]

Clinicians order a CSF–FTA-ABS or CSF-TPPA if the CSF-VDRL is nonreactive. Although less specific than a CSF-VDRL, the CSF–FTA-ABS or CSF TP-PA tests are more sensitive, and if negative, neurosyphilis is highly unlikely. For patients who have a lymphocytic CSF pleocytosis and a nonreactive CSF-VDRL, a nonreactive CSF–FTA-ABS test excludes the diagnosis of asymptomatic neurosyphilis in most instances. Researchers have investigated nested polymerase chain reaction (nPCR) testing of the CSF in the diagnosis of neurosyphilis. One such study reported a sensitivity of 42.5% and a specificity of 97% for nPCR.[58] 

CSF pleocytosis and elevated CSF protein concentrations are indicative of neurosyphilis. Conversely, a normal CSF white blood cell count and protein concentration would make a diagnosis of late neurosyphilis and tabes dorsalis highly unlikely.[25] A CSF pleocytosis and elevated protein concentration can be used to confirm the diagnosis in patients with a negative CSF-VDRL if no HIV infection is present, as HIV infection can cause pleocytosis and an elevation in CSF protein concentration.[59][60] Patients with HIV who are taking antiretroviral agents and have CD4 counts ≤200 cells/µL or an undetectable plasma HIV RNA viral load reduce the risk of pleocytosis caused by HIV by 70% to 96%. In these patients, neurosyphilis is more likely the cause of pleocytosis than HIV infection.

Recent studies demonstrate the role of testing levels of C-X-C motif chemokine ligand 13 (CXCL 13), a B cell chemokine, in distinguishing between CSF pleocytosis due to syphilis and CSF pleocytosis due to HIV. This test is not currently widely available. The value of CXCL 13 increases in HIV-infected patients with tabes dorsalis.[53]

Imaging 

Abnormal magnetic resonance imaging (MRI) findings associated with tabes dorsalis are infrequent. However, when present, they can include swelling and high signal intensity enhancement in the affected spinal cord segment after gadolinium administration, known as the "flip-flop" sign. Peripheral band-like enhancement suggests focal inflammation of the spinal cord compatible with tabes dorsalis.[20][49][60][61][62][63] Additionally, strong, intense longitudinal signaling along the dorsal spinal columns and spinal cord atrophy may also be observed, indicating a poorer prognosis.[18][20][21][22] Diagnosing the Charcot spine is challenging due to its rarity, nonspecific symptoms, and delayed onset long after the initial infection. Clinical indicators include identifying spinal regions displaying neurological impairment and excessive mobility, particularly in the thoracolumbar and lumbosacral junctions. The lumbosacral spine is frequently affected, and symptoms may persist post-antibiotic treatment. While serological testing can confirm the diagnosis, initial symptoms are often nonspecific, potentially causing diagnostic delays.[25][39] MRI and computed tomography (CT) imaging are instrumental in diagnosing the Charcot spine, especially if they reveal gas inside the disc space caused by a vacuum effect from excessive motion. This finding is highly suggestive of the diagnosis but is subtle and may be challenging to visualize.[39][64] 

Treatment / Management

According to the CDC, penicillin stands as the preferred treatment for all stages of neurosyphilis, including tabes dorsalis. Aqueous crystalline penicillin G is the formulation of choice for tabes dorsalis and late neurosyphilis. Clinicians treat ocular or otologic syphilis as neurosyphilis. Patients should undergo HIV screening before initiating treatment. The treatment regimen for neurosyphilis is aqueous penicillin G 3 to 4 million units intravenously (IV) every 4 hours or 18 to 24 million units continuous IV infusion daily for 10 to 14 days. Because the duration of this regimen for neurosyphilis is shorter than the regimens used for other forms of late syphilis, some experts recommend a one-time dose of 2.4 million units of benzathine penicillin G intramuscularly (IM) after completing IV therapy. Insufficient evidence exists to support this practice, and further studies are necessary. Currently, alternatives to IV therapy do not exist. Previously, procaine penicillin G 2.4 million U/d IM combined with probenecid 500 mg orally 4 times per day for 10 to 14 days was an acceptable option, but procaine penicillin is no longer available. 

The CSF-VDRL results may be negative in as many as 70% of patients with neurosyphilis, making the diagnosis of neurosyphilis uncertain. Experts recommend treating with IV penicillin G if the patient has a compatible clinical syndrome, risk factors for syphilis, reactive blood serology for syphilis, and a CSF pleocytosis, even if the CSF-VDRL is not reactive. If signs and symptoms persist, along with clinical assessment of interval serologies and CSF testing, further courses of penicillin may be warranted. The chance of relapse is particularly high in patients with HIV. Treatment of early neurosyphilis arrests the disease and halts symptom progression, possibly preventing the development of tabes dorsalis, and may also result in symptom improvement. However, treatment of late neurosyphilis and tabes dorsalis may only limit disease progression without necessarily improving existing symptoms.

Patients With Penicillin Allergy

Patients with a penicillin allergy should undergo skin testing for confirmation, as penicillin is the preferred antibiotic therapy.[65][66][67] Nearly 90% of patients with a reported penicillin allergy do not have a true allergy.[66][67][68] Patients with a confirmed penicillin allergy should undergo evaluation by an allergist to determine if they can be desensitized or rechallenged with penicillin.[67][68] (A1)

If penicillin desensitization is impossible, the CDC recommends ceftriaxone 1 to 2 g/d IM or IV for 10 to 14 days.[69][70][71][72][73] Cross-reactivity between penicillin and ceftriaxone is possible but rare. Patients can undergo skin testing in select cases.[74] A study reported the successful use of ceftriaxone and dexamethasone as a good alternative after aqueous penicillin G treatment failure in a patient with tabes dorsalis.[60] Patients who are unable to be desensitized to penicillin and are unable to tolerate cephalosporins can use doxycycline 200 mg twice daily for 21 to 28 days. This regimen has limited clinical data supporting its use, and clinicians should reserve it for extreme cases. (B2)

The Jarisch-Herxheimer reaction (JHR) is an acute, self-limiting febrile response that typically occurs within the first 24 hours following treatment for spirochetal infections such as syphilis. Occurring in approximately 10% to 35% of cases, most commonly after treating early syphilis, the symptoms generally resolve within 12 to 24 hours, and patients can use nonsteroidal anti-inflammatory medications to help with the symptoms.[75] Symptoms include fever and systemic manifestations such as headache, myalgias, rigors, diaphoresis, hypotension, and worsening of rash. Rarely, it can lead to meningitis, respiratory distress, renal or hepatic dysfunction, mental status changes, stroke, seizures, and uterine contractions in pregnancy. The exact mechanism remains unclear, but accelerated phagocytosis by white blood cells, followed by the release of various inflammatory substances from killed organisms, is likely.[75] No preventative measures exist, and patients should be aware of this possible reaction. 

Additional treatments are symptomatic and depend on the clinical signs and symptoms. Analgesics such as opiates and valproate may be helpful for severe pain crises. Physical or occupational therapy can help prevent muscle wasting and weakness. Sexual partners must be fully educated about the condition and provided with preventive drug therapy.

Posttreatment Surveillance

Following treatment, patients should undergo a neurologic examination and lumbar puncture at 3 and 6 months, followed by repeat evaluations at 6-month intervals until the CSF white blood cell count is normal and the CSF-VDRL is nonreactive.[3] Successful treatment is marked by a decline in the CSF white blood cell count within 6 months, with complete resolution of all CSF abnormalities within 2 years after treatment. Retreatment is necessary if the patient experiences any increase in the CSF white blood cell count, a 4-fold increase in CSF-VDRL titer, or if the CSF white blood cell count does not decrease within 6 months, or if all CSF abnormalities do not resolve within 2 years. CSF abnormalities may normalize slower in patients with HIV infection.

Charcot Spine 

Treatment for the Charcot spine involves addressing individual symptoms, such as autonomic dysreflexia, and performing spinal fusion surgery to stabilize the spine and alleviate nerve root compression.[39][76][77][78] Surgical interventions for the Charcot spine are complex and involve reconstructing, stabilizing, realigning, and fusing the spine.[79] Due to the spine's high mobility and weakened vertebrae, particularly in the lumbosacral region where shear forces are significant, nearly 75% of patients require at least a surgical revision to achieve a successful fusion.[79] Complications may necessitate additional surgeries in up to 40% of patients.[80] A recent surgical approach involving triple rod stabilization of the lumbosacral spine with tricortical laminovertebral screws has shown promise in 3 patients with extensive spinal neuroarthropathy, yielding good results without the need for revisions.[79] However, further research is needed to evaluate the long-term efficacy of this technique.(B2)

Individuals who are unable or opt not to undergo surgery may utilize conservative measures such as braces and bed rest.[39] Some researchers have suggested bisphosphonate therapy based on its use in managing Charcot foot neuropathy, although current studies yield conflicting results.[39][81][82][83][84](A1)

Differential Diagnosis

Conditions primarily affecting the spinal cord, especially involving the dorsal columns, often present similar symptoms. A comprehensive evaluation is necessary to ensure an accurate diagnosis and prompt initiation of treatment. The differential diagnoses include:

• Hereditary and other demyelinating disorders
• Hereditary spastic paraplegia
• Amyotrophic lateral sclerosis
• Spinal muscular atrophy
• Friedreich ataxia
• Adrenomyeloneuropathy [85]

• Miscellaneous spinal cord myelopathy
• Vitamin B12 deficiency
• Copper deficiency
• Nitrous oxide and heroin intoxication
• Lathyrism, an incurable neurological disorder resulting from excessive consumption of grass peas, which clinically manifests as paralysis of lower limbs
• Excessive zinc intake [86][87]

• Non-syphilitic Argyll Robertson pupil
• An ophthalmological consult is recommended when diagnosing tabes dorsalis in the presence of pupillary abnormalities. Other diseases that may cause an Argyll Robertson pupil include diabetes and multiple sclerosis. Holmes-Adie syndrome, Lyme disease, and sarcoidosis may present with a tonic pupil and confound the proper diagnosis of tabes dorsalis.[35]

• Additional differential diagnoses
• Postinfectious demyelination
• Vascular disease myelopathy due to diminished perfusion and infarction
• Spinal tumor-induced myelopathy [88][89][90]

Distinguishing features of hereditary and other demyelinating disorders include progressive neurodegeneration, demyelination, muscle atrophy and weakness, ataxia, paraplegia, and sensory loss. Associations with diabetes, cerebellar disease, scoliosis, and the absence of primary and secondary syphilitic lesions, along with negative nontreponemal and treponemal test results, help exclude tabes dorsalis. MRI of the brain and spinal cord is necessary for a correct diagnosis.[85] 

Vitamin B12 deficiency leads to subacute combined degeneration of the dorsal and lateral columns of the spinal cord. When accompanied by megaloblastic anemia, hemogram, and nontreponemal and treponemal tests help differentiate it from tabes dorsalis. Copper deficiency myelopathy also involves the posterior column of the spinal cord, resembling tabes dorsalis. Other toxins, such as nitrous oxide and heroin, produce posterior and lateral column myelopathy. MRI findings can assist in distinguishing these myelopathies from tabes dorsalis.

Prognosis

The prognosis of tabes dorsalis is generally good after proper treatment, especially if diagnosed early, but if left untreated, can lead to paralysis, dementia, and blindness. Existing nerve damage cannot be reversed. 

Complications

General Complications of Syphilis 

• Aortitis and aortic aneurysm
• Dementia
• Stroke
• Membranous glomerulonephritis
• Paroxysmal cold hemoglobinemia
• Disfigurement by gummas
• Hearing loss
• Renal failure

Complications Associated with Tabes Dorsalis

• Joint degeneration resulting in deformities or Charcot joints
• Periarticular pathological fractures
• Dementia
• Paralysis
• Blindness
• Postural hypotension
• Charcot spine