Acute syphilitic meningitis

Acute syphilitic meningitis was relatively rare even before antibiotics became available, accounting for 6% of all cases of neurosyphilis.


Signs and symptoms


The incubation period in the majority of patients with syphilitic meningitis is less than 1 year. In about one-quarter of these patients, meningitis is the first clinical manifestation of syphilis. A small percentage of patients still have a secondary rash at the time of meningitis. The clinical presentations of acute syphilitic meningitis may be divided into several patterns, but these categories overlap extensively. The principle neurologic manifestations include cranial nerve palsies (seen in 40% of cases) and signs of increased intracranial pressure. The involvement of multiple cranial nerves, particularly the third, sixth, seventh, and eighth, is consistent wit an extensive basilar meningitis. Sensorineural deafness occurs in about 20% of patients, commonly in association with other cranial nerve palsies. Deafness is often preceded by tinnitus and may develop rapidly, for example, over 1 to 2 weeks. The hearing loss primarily involves higher frequencies  vestibular involvement is uncommon. Involvement of the eighth cranial nerve may be an isolated finding, and the CSF may be entirely normal. Thus, early acquired syphilis is a cause of potentially reversible, rapidly progressive, or sudden sensorineural deafness and must be considered in diagnosis, even in the absence of clinical findings of secondary syphilis or of overt lymphocytic meningitis.

Acute syphilitic meningitis was relatively common in patients who received inadequate doses of antisyphilitic therapy. Ehrlich documented this association and called the condition neuro recurrence  In the 1990s, this same constellation of symptoms and signs was noted in HIV-infected patients, especially after penicillin treatment, leading to the concept that such disease occurred after treatment of immunologically normal hosts with inadequate antimicrobials or treatment immunocompromised hosts with ordinarily excellent antibiotics.

Acute syphilitic hydrocephalus was seen in one-third of the cases of syphilitic meningitis. Symptoms usually develop 3-7 months after primary infection, but they can appear as many as 6 years later. The principal symptoms and signs are those of increased intracranial pressure; fever is only low-grade or may be absent.


Laboratory findings


The CSF changes include elevated pressure, mononuclear pleocytosis of 10-200 cells per cubic millimeter (but occasionally as high as 1000-2000 cells per cubic millimeter), elevated protein concentration (up to 200mg/dL), elevated globulin level, and a modest reduction in glucose in 45% of cases. The VDRL test on CSF is reactive in most but not all cases. Patients with isolated involvement of the eighth cranial nerve are likely to have normal CSF with a nonreactive VDRL test.


Pathologic changes


The inflammatory process involves not only the meninges but also the ependyma (granular ependymitis.) The meningeal infiltrate consists of lymphocytes and plasma cells located particularly in perivascular spaces. Progressive inflammatory changes produce an endarteritis, which may result in thrombosis, vascular occlusion, and cerebral infarction. The process underlies the focal cerebral signs (aphasia and hemiplegia) and seizures that occur in some patients with acute syphilitic meningitis. Acute syphilitic hydrocephalus develops as a result of obstruction, by organizing exudate, of CSF flow either from the posterior to middle cranial fossa (communicating hydrocephalus) or from the fourth ventricle (obstructive hydrocephalus). Cranial nerve abnormalities result from compression by basilar exudate and fibrous organization or as a consequence of increased intracranial pressure.


Diagnosis and differential diagnosis


Diagnosis of acute syphilitic meningitis is based on the clinical picture of aseptic meningitis, and reactive blood and CSF serology. A history of a recent chancre or secondary rash or the presence of generalized lymphadenopathy may suggest the diagnosis, but meningitis may be the first clinical manifestation of syphilitic infection, especially in HIV-infected patients.

Differential diagnosis includes the various causes of a lymphocytic meningitis, including enteroviruses, HSV, HIV, other spirochetes, mycobacteria, fungi, drug reactions, malignancy, and autoimmune disease. Syphilis is likely to be accompanied by reactive serology, which does not, a priori, exclude any other diagnosis. Each of these other conditions may have some unique epidemiologic, clinical, and laboratory features pointing to the correct diagnosis. Acute syphilitic hydrocephalus may suggest the diagnosis of brain tumor, and the presence of low-grade fever and signs of increased intracranial pressure might raise the question of brain abscess.

The clinical features, particularly the distinctive skin lesion, and epidemiology of Lyme disease serve to distinguish it from secondary syphilis. When Lyme disease occurs in the absence of extra meningeal findings, the distinction between the two processes becomes more difficult. The sera and CSF of patients with the neurologic involvement of Lyme disease have been said to be nonreactive in nontreponemal tests. However, 11% of patients with Lyme disease have a reactive fluorescent treponemal antibody (FTA) test after absorption (ABS) with nonvirulent treponemes (FTA-ABS). Furthermore, patients with syphilis show serologic reactivity with Borrelia burgdorferi: five of 18 patients with various stages (primary, secondary, latent, and late) of syphilis had positive ELISA tests for Lyme disease, and 11 had positive FTA tests. Utilizing the clinical and epidemiologic features of the two diseases as well as VDRL reactivity and B. burgdorferi antibody testing of serum and CSF, distinction between the two spirochetal diseases usually can be made. Western blots may help to resolve serological ambiguity.

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