Tabes Dorsalis Case File

Tabes Dorsalis Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 30

A 58-year-old man is referred for evaluation of severe lancinating pain in the legs and loss of balance over a period of 3 years. He has recently developed impotence, and his grandchildren have started to tease him about how his eyes are looking droopy. He reports that his balance is worse in the dark or when he closes his eyes. He has a history of gastroesophageal reflux disease and migraine headaches. He is only taking over-the-counter famotidine (Pepcid) and a multivitamin each day. He has been married for 35 years and is a retired structural engineer. He has not been exposed to toxins and does not smoke or drink alcohol. The only other pertinent information is that he served as a natural disaster relief volunteer overseas before getting married and contracted a “venereal disease.” He thinks he contracted syphilis and received oral antibiotics. The neurologic examination reveals a Mini-Mental State Examination (MMSE) score of 30/30 with intact cranial nerves except for Argyll Robertson pupils and ptosis bilaterally. His strength is normal; however, he has impaired proprioception in the toes with diminished temperature sensation in the legs. Additionally, he has loss of pinprick sensation in a glove-and-stocking distribution. A Romberg sign is present. Cerebellar examination is normal; however, his deep tendon reflexes are diminished (1+/2) in the legs. His gait is wide-based with marked ataxia.

▶ What is the most likely diagnosis?

▶ What is the next step to confirm diagnosis?

▶ What is the treatment plan?

ANSWERS TO CASE 30:

Tabes Dorsalis                                                    

Summary: A 58-year-old man with a history of syphilis more than 20 years ago, gastroesophageal reflux disease, and migraine headaches presents with a 3-year history of lancinating pain in the legs, loss of balance, and recent impotence and ptosis. His examination is notable for cranial nerve impairment with Argyll Robertson pupils and ptosis. Other findings include impaired posterior column function with loss of proprioception in the feet and impaired lateral spinothalamic tract function (loss of temperature and pinprick). His deep tendon reflexes are diminished in the legs, and he has a sensory ataxia. The Romberg test is positive.

• Most likely diagnosis: Tabes dorsalis (spinal form of syphilis).
• Next diagnostic step: Lumbar puncture for Venereal Disease Research Laboratory (VDRL).
• Next therapeutic step: High-dose intravenous aqueous penicillin G at a dose of 2 to 4 million units every 4 hours for 10 to 14 days. If there is a penicillin allergy, doxycycline at a dose of 200 mg twice a day for 28 days and ceftriaxone at a dose of 2 g intravenously per day for 14 days should be administered.

ANALYSIS

Objectives

1. Be familiar with the clinical presentation of tabes dorsalis and other neurologic syndromes caused by syphilis.
2. Know how to diagnose tabes dorsalis and differentiate it from other late forms of neurosyphilis.
3. Know how to treat tabes dorsalis.

Considerations

The presentation of an individual with a history of syphilis who presents with neurologic symptoms should alert the clinician to possible neurosyphilis. Other etiologies need to be excluded, as other sexually transmitted diseases such as human immunodeficiency virus (HIV) or hepatitis B or C can cause similar neurologic symptoms. Lancinating pain with associated sensory ataxia, cranial nerve abnormalities, and impotence or bowel and bladder dysfunction is a classic presentation for tabes dorsalis. In this case, tabes dorsalis is the most likely diagnosis; however, to diagnose it, confirmation from laboratory studies must be obtained. The most common serologic studies requested are a rapid plasma reagin (RPR) assay or VDRL test. These are quite sensitive for primary and secondary syphilis but are less sensitive for neurosyphilis. A negative RPR does not exclude neurosyphilis. Importantly, the RPR assay can frequently have a false-positive result. If these tests are positive, proceed in confirming the diagnosis with cerebrospinal fluid (CSF). The following indicates the typical CSF findings in neurosyphilis:

• Elevated CSF protein (up to 200 mg/dL)
• Lymphocytic pleocytosis less than 400/μL
• CSF VDRL positivity in most individuals
• Elevated immunoglobulin G (IgG) synthesis

If, however, the RPR or VDRL studies are negative and neurosyphilis is still clinically suspected, serum studies for Treponema pallidum–specific antibodies should be performed. These include fluorescent treponemal antibody absorption (FTA-ABS) test, T. pallidum hemagglutination (TPHA) test, or microhemagglutination assay–T. pallidum (MHA-TP). These studies are much more expensive than the reaginic assays but are much more sensitive for neurosyphilis. In fact, if these studies are nonreactive, neurosyphilis is excluded.

Detection of T. pallidum by polymerase chain reaction in the CSF is quite low. Importantly, the serologic studies cannot distinguish between syphilis, pinta, and yaws (nonvenereal treponemal endemic diseases) due to cross-reactivity. HIV or hepatitis B and C can present with very similar symptoms of sensory ataxia, cranial mononeuropathies, and pain. A distinguishing feature between these infections and neurosyphilis is the type of pain. Classic lancinating pain is seen with neurosyphilis, whereas a burning-type pain is associated with the others. Nevertheless, laboratory studies are the only way to distinguish these conditions definitively.

APPROACH TO:

Tabes Dorsalis                                            

DEFINITIONS

ARGYLL ROBERTSON PUPILS: Small pupils that constrict when focusing but fail to constrict when exposed to bright light (accommodate but do not react).

ELECTROMYOGRAPH (EMG)/NERVE CONDUCTION STUDIES: An electrophysiologic examination that evaluates the integrity of the peripheral nerve and evaluates various electrical muscle properties, allowing the clinician to determine the presence of either a muscle or nerve disorder. This test is primarily useful in evaluating the peripheral nervous system.

H REFLEX: The H reflex is the electrical equivalent to a monosynaptic stretch reflex. It often reflects pathology along the afferent and efferent fibers and/or the dorsal root ganglion.

LANCINATING PAIN: A sensation of piercing, stabbing, or cutting.

PTOSIS: Droopiness of the eyelids.

ROMBERG SIGN: Falling over when a person is standing with eyes closed, feet together, and hands in the outstretched position.

CLINICAL APPROACH

Neurosyphilis is an infection of the nervous system by the spirochete T. pallidum, the organism responsible for syphilis. It is estimated that up to 10% of patients with primary syphilis who have not received treatment will develop neurosyphilis. In the HIV population, the percentage is higher. Risk factors for syphilis include drug consumption, sexual habits, and social background. It is well recognized that HIV patients with syphilis are at increased risk for developing neurosyphilis and may do so earlier than HIV-negative individuals. Importantly, syphilis is a risk factor for acquiring HIV. Neurosyphilis is twice as common in men as it is in women.

T. pallidum can first be detected clinically approximately 3 weeks after infection by the presence of a primary lesion on the skin or mucous membranes (primary syphilis). Secondary syphilis results from a second bacteremic stage with generalized mucocutaneous lesions. Although neurosyphilis (tertiary syphilis) may not present until many years after a primary infection, T. pallidum enters the central nervous system (CNS) at the same time individuals develop primary and secondary syphilis. Pathogenic changes consist of endarteritis of terminal arterioles with resultant inflammatory and necrotic changes. In the CNS, T. pallidum causes meningeal inflammation, arteritis of small- and medium-sized vessels with subsequent fibrotic occlusion, and eventually direct neuronal damage.

The clinical features of neurosyphilis are dependent on the time period after infection (Table 30–1). Hyporeflexia is the most common finding on clinical examination, with up to 50% of patients with neurosyphilis having this finding. Other clinical findings include sensory impairment (48%), pupillary changes (43%) including Argyll Robertson pupils, cranial neuropathy (36%), dementia or psychiatric symptoms (35%), and a positive Romberg test (24%). The Argyll Robertson pupil is almost pathognomonic for neural syphilis. Tabes dorsalis is caused by the syphilitic involvement of the posterior spinal cord, leading to intermittent pain of the arms and legs, ataxia and gait disturbance as a result of loss of position sense, and impaired vibratory and position sense.

CSF, cerebrospinal fluid.

The diagnosis of neurosyphilis is made on clinical grounds and confirmed by CSF serology (RPR or VDRL). Usually the CSF protein and cell count are abnormal. The differential diagnosis of neurosyphilis is based on clinical features. For example, the differential for gummatous neurosyphilis consists of the differential diagnosis for space-occupying lesions (metastatic brain tumors, primary brain tumors, etc). Meningovascular syphilis presenting like a stroke merits the differential diagnosis of cerebral vascular accident (vasculitis, hemorrhage, etc). Three disorders should be considered in the differential diagnosis of tabes dorsales: subacute combined degeneration from vitamin B12 deficiency, multiple sclerosis, and Lyme disease. Other less common diagnoses in the differential include sarcoidosis, herpes zoster, and diffuse metastatic disease. The finding of an Argyll Robertson

pupil is highly suggestive of tabes dorsalis but can also be seen with multiple sclerosis, diabetes mellitus, sarcoidosis, Lyme disease, and Wernicke encephalopathy. Tabes dorsalis is a slow and progressive disease that causes demyelination in the posterior columns and inflammatory changes in the posterior roots of the spinal cord. Nerve conduction studies can show impaired sensory nerve conduction studies with normal motor nerve conductions. EMG is normal, but absent H reflexes are common due to the damage of the dorsal root ganglion. Abnormalities in motor nerve conduction studies should raise doubt as to the diagnosis of tabes dorsalis.

The treatment of neurosyphilis consists of high-dose intravenous aqueous penicillin G at a dose of 2 to 4 million units every 4 hours for 10 to 14 days. If there is a penicillin allergy, doxycycline at a dose of 200 mg twice a day for 28 days and ceftriaxone at a dose of 2 g intravenously per day for 14 days should be administered. Although there are alternative regimens that have been tried in treating patients with neurosyphilis, these have not been found to be as effective as the use of aqueous penicillin G. Use of intramuscular procaine penicillin at a dose of 2.4 million units intramuscularly every day plus oral probenecid for 10 to 14 days has been tried in those individuals who cannot receive intravenous preparations. This has typically been combined with intramuscular benzathine penicillin G at a

dose of 2.4 million units weekly for 3 weeks. If treatment fails to improve symptoms (for early neurosyphilis) or there is continued progression of symptoms (late neurosyphilis), re-treatment should be considered. CSF studies should be reexamined after the completion of therapy for a drop in white blood cell count, protein, and IgG synthesis.

COMPREHENSION QUESTIONS

30.1 A neurologist performs an examination on a 19-year-old man and diagnoses him with an Argyll Robertson pupil. Which of the following statements is most likely to be accurate?

A. The pupil likely constricts to light.

B. The patient may have multiple sclerosis.

C. The pupils fail to constrict when focusing up close.

D. The patient is diagnosed with subacute combined degeneration.

30.2 All of the following are true regarding neurosyphilis except:

A. T. pallidum infects the CNS at the time of the primary infection.

B. HIV-positive individuals are at increased risk for developing neurosyphilis.

C. Tabes dorsalis occurs 10 years after initial infection.

D. Stroke-like symptoms may occur any time after infection.

E. General paresis may present as a psychiatric illness.

30.3 The differential diagnosis of tabes dorsalis consists of all of the following except:

A. Toxoplasmosis

B. Lyme disease

C. Sarcoidosis

D. Multiple sclerosis

E. Subacute combined degeneration

30.4 A 30-year-old man who abuses intravenous (IV) drugs presents to your office complaining of left-sided weakness for the past 6 weeks. His examination is notable for Argyll Robertson pupils, hyporeflexia in the legs, and left hemiparesis. He is healthy otherwise except for having developed syphilis while serving in the military at age 27. His last HIV test was 18 months ago. Which of the following is most accurate?

A. He does not have neurosyphilis, as the time period from primary infection to development of symptoms is too short.

B. He has definite tabes dorsalis and requires magnetic resonance imaging (MRI) of the spine and CSF analysis.

C. He has neurosyphilis, and should be written up in a medical journal as a novel case presenting after a short incubation time following primary infection.

D. He has possible neurosyphlis, so an HIV test and RPR should be obtained and if they are positive, treatment with IV aqueous penicillin G should be started.

ANSWERS

30.1 B. Argyll Robertson pupils mean accommodation but no light reflex. It is seen with multiple sclerosis. Subacute combined degeneration has not been reported to cause Argyll Robertson pupils.

30.2 D. Stroke-like symptoms occur 5 to 7 years after the initial infection in

individuals who are HIV negative.

30.3 A. Toxoplasmosis usually presents with symptoms suggesting an intracranial mass lesion.

30.4 D. Based on the history of IV drug abuse and now neurological symptoms of neurosyphiliis, this patient likely is HIV infected. HIV-positive individuals are known to develop signs and symptoms of neurosyphilis much earlier than individuals who are HIV-negative. His presentation is not novel and merits treatment as soon as possible. Although patients with tabes dorsalis may have an Argyll Robertson pupil, they present with lancinating pain and not hemiparesis; thus, an MRI of the brain is indicated.

    CLINICAL PEARLS    

▶ Tabes dorsalis classically presents with lancinating pain, sensory deficits, ataxia, and hyporeflexia. ▶ HIV-positive individuals can present with neurosyphilis at a much earlier time than HIV-negative individuals. ▶ The treatment of choice for neurosyphilis remains intravenous aqueous penicillin G. Alternative treatments consisting of intramuscular doses of penicillin have not been found to be as effective. ▶ Individuals who present with neurologic symptoms and have a history of syphilis should be considered to have neurosyphilis until proven otherwise. ▶ There are various different forms of neurosyphilis including asymptomatic, meningovascular, tabes dorsalis, and general paresis. ▶ Syphilitic aseptic meningitis occurs as a chronic infection and can involve headaches, cognitive changes, and cranial nerve abnormalities.

REFERENCES

Clinical Effectiveness Group. National guideline for the management of late syphilis: Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect. 1999;75(suppl 1):S34-S37. 

Dacso CC, Bortz DL. Significance of the Argyll Robertson pupil in clinical medicine. Am J Med. 1989;86(2):199-202. 

Dorland’s Illustrated Medical Dictionary. 27th ed. Philadelphia, PA: WB Saunders; 1988. 

Golden MR, Marra CM, Holmes KK. Update on syphilis: resurgence of an old problem. JAMA. 2003;290(11):1510-1514. 

Marra CM. Update on neurosyphilis. Curr Infect Dis Rep. 2009;11(2):127-134. 

Stevenson J, Heath M. Syphilis and HIV infection: an update. Dermatol Clin. 2006;24(4):497-507.

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