Tabes Dorsalis; Ectatic Basilar Artery
Patient #1 presented with an all too familiar challenge that neurologists meet in their practice; that is, absent or inadequate past records, a poor capacity to describe his illness, and/or withholding of medical history due to "feeling it was not important to the current problems" or from embarrassment. With the increasing emphasis on cost-containment and managed care, the shotgun approach of the past is no longer acceptable and many tests that were previously considered routine are being omitted. The interpretation of the clinical picture and selective ordering of appropriate tests are critical.
In this case, the positive serologies pointed to the need for further questioning of the patient's denial of any problem with syphilis. He then stated that he had syphilis as a teenager but was unclear whether he was treated with penicillin at that time. However, he stated that at age 30, when he was applying for a new job, he was found to have a positive "syphilis" test and was given a course of treatment. He does not know the dosages or duration of the therapy.
The increasing "numbness" in the legs was most likely due to the marked proprioceptive defects secondary to dorsal root ganglia compromise. With the elevated CSF protein, IgG synthesis rate, and Q-albumin reflecting an alteration in the blood brain barrier, a normal B12 level, and abnormal serologies, a diagnosis of tabes dorsalis due to neurosyphilis best explained his clinical findings. The CSF VDRL was negative, but in tabes dorsalis it is variably reactive and tends to be normal in late, persistent, and burned out cases. This diagnosis could also explain the autonomic dysfunction (impotency), absent reflexes, and many of the eye findings, such as the disciform macular scar in the right eye, the irregular tonic pupils, and the ptosis.
The bilateral 6th nerve palsies, ptosis, and abnormalities of the brainstem and somatosensory evoked potentials could also be explained by compression of the brainstem from the ectatic basilar artery seen on MRI. However, this could not explain the majority of his symptomatology or his history of recent progression. (comparison with older films from three years prior did not show any change).
He will be treated with penicillin (see suggested regimens in the review that follows). The goal of therapy is to arrest progression of neurological disease. Progression of symptoms despite therapy usually prompts an additional course(s) of treatment.
Tabes Dorsalis is a late meningoradiculitis caused by treponema pallidum, the causative organism of syphilis. It was first described by Guillaume Duchenne in 1885 and is also known as Duchenne's disease. In 1892 Erb described it as "progressive locomotor ataxia".
The incidence of tabes dorsalis, along with other forms of neurosyphilis, has declined considerably since the introduction of antibiotic therapy. In a study of admissions to a psychiatric hospital, the frequency of first admission because of neurosyphilis declined considerably from 5.9/100,000 in 1942 to 0.1/100,000 in 1965. The rise in incidence of sexually transmitted diseases and HIV has been accompanied by a resurgence in the incidence of neurosyphilis. Along with the increase in incidence there has, however, been a shift in the clinical manifestations. The incidence of meningeal and vascular forms has increased while parenchymal forms have become rare. In a series of 457 patients with neurosyphilis studied by Merrit et al in 1946, 45 patients had tabes dorsalis while 23 patients had meningovascular syphilis. In a recent study of 26 patients studied by Burke et al in 1985, however, only five met criteria for tabes dorsalis while 64 had meningovascular forms of syphilis.
The organism enters via the abraded skin or mucous membranes and finds its way into the lymphatic system and blood vessels within hours of entry. Within 1-6 weeks a chancre develops at the site of entry and local lymphadenopathy develops (primary syphilis). Systemic dissemination occurs 6-12 weeks after the lesion develops and manifests itself as a generalized rash and lymphadenopathy (secondary syphilis). This is followed by a latent stage. Finally after a period of two or more years tertiary syphilis develops and is manifested by CNS and cardiovascular symptoms. The symptoms can be due to an obliterative vasculitis (gummas, CNS vasculitis) or direct parenchymal invasion (tabes dorsalis).
In the early stages, a lymphocytic and mononuclear infiltrate is seen in the meninges. These inflammatory reactions may involve the cranial nerves and can cause degeneration of the axons. When the inflammation involves small meningeal vessels, proliferation of the endothelial lining occurs, resulting in vascular compromise and infarction of brain and spinal cord tissue. Similar findings are seen in tabes dorsalis where the inflammation of meninges and blood vessels is followed by degeneration of the posterior roots and posterior fiber columns of the spinal cord and, sometimes changes are seen in the cranial nerves. This explains the multiple symptoms seen in this disease.
The pathological hallmark of the disease is inflammation of the meninges and the nerve roots. The lower spinal cord roots are most commonly involved. There is atrophy and loss of myelinated fibers in the posterior columns, secondary to root pathology. In late untreated cases the inflammation spreads to the anterior roots and atrophy may then be seen in the distribution of the affected roots.
The disease is sometimes called progressive locomotor ataxia. The varied clinical features represent the extent of involvement of the brain, cranial nerves and spinal cord. The initial symptoms consist of diplopia due to paralysis of the 3rd, 4th, or 6th cranial nerves, irregular pupils, paresthesia and hyperesthesia. Pupillary abnormalities are present in 90% of patients. The characteristic pupillary abnormality, which is seen 50 percent of the time, is the Argyll-Robertson pupil in which there is loss of direct and consensual light reflexes, but the accommodation light reflex is preserved. Ptosis and poor facial tone can develop as a result of cranial neuritis and produces the tabetic facies. Patients may also complain of lightning pains mainly in the extremities although no part of the body is spared. Visceral crisis is sometimes seen and patients may complain of abdominal, rectal, and laryngeal pain. Because of involvement of the dorsal root ganglia and posterior columns there is loss of vibratory and position sense in the legs. Analgesia may be seen over the breasts, medial sides of the forearms, lateral aspects of the legs, and perianal regions (Hitzig lines). As the condition progresses, difficulties in coordination and balance develop. These are worse in the dark but are also present when the patient has good visual input. The syndrome is also characterized by the loss of reflexes in the legs, sphincter dysfunction, and sexual dysfunction. The loss of sensation which occurs in the legs may lead to Charcot joints.
The serum RPR is usually reactive at a dilution of less than or equal to 1:16, but it may be negative late in the disease. The serum MHA-TP is always positive; a negative result essentially excludes the diagnosis of tabes dorsalis. In the early stages, the CSF VDRL is abnormal and the WBC count is elevated; most of the cells are mononuclear. In later, burned out cases the VDRL may normalize and the cell count may be normal. The CSF protein is usually elevated to more than 100 mg/dl in active disease, but slowly returns towards normal as the disease "burns out".
Benzathine Penicillin G does not provide therapeutic levels of the drug in the CSF, although three doses each of 2.4 million units at weekly intervals together with probenecid seems to arrest disease in nearly all cases. The Centers for Disease Control (CDC) of the United States Department of Health and Human Services recommends IV Penicillin G, 24 million units daily for 10-14 days. The alternative regimen proposed by the CDC is procaine penicillin 1.2 million units intramuscularly daily for 14 days. After a course of treatment, quantitative blood serology is determined at three month intervals and usually shows a decline in titer. The CSF is examined at 6 and 12 months. If not normal, CSF is re-examined at two years. After three years, if the patient has improved and is clinically stable, and if the CSF and serological tests are normal, neurological and CSF examinations are discontinued. Retreatment is recommended with high doses of IV Penicillin G under the following circumstances if:
The degree of recovery depends on the extent of the disease at the time of starting treatment, but is usually minimal. The principal benefit of therapy is to arrest further progression of the disease. Tabes dorsalis is seldom fatal. Ataxia or blindness may be incapacitating and an atonic bladder may lead to severe recurrent urinary tract infections.
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