Neurosyphilis is the infection of the central nervous system by Treponema pallidum, the bacterium that causes the sexually transmitted infection syphilis. In the era of modern antibiotics, the majority of neurosyphilis cases have been reported in HIV-infected patients.

Neurosyphilis may present a variety of symptoms that depend on the affected structure of the central nervous system. While early neurosyphilis is often asymptomatic, meningitis is the most common neurological presentation of the early stage. Late neurosyphilis typically involves the brain and spinal cord parenchyma, manifesting as tabes dorsalis and general paresis. Tertiary syphilis can involve several different organ systems, though neurosyphilis may occur at any stage of infection.

Clinical history, a physical neurological examination, and a lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis are crucial for diagnosing neurosyphilis. There is no single laboratory test to confirm the diagnosis of neurosyphilis in all cases. A positive CSF-VDRL test in the presence of neurological symptoms is sufficient for a diagnosis, but additional tests may be needed in certain instances.

Standard treatment is an infusion of intravenous penicillin G for 10 to 14 days. Patients with neurosyphilis should also be evaluated for HIV, and their sexual partners should be properly evaluated by a medical professional.

While the stages of syphilis are categorized as primary, secondary, latent, and tertiary, neurosyphilis is typically categorized into early, intermediate, and late stages. Neurosyphilis may occur any time after initial infection.

Early neurosyphilis often has no clinical symptoms. Meningitis is the most-common neurological presentation in early syphilis, typically arising within one year of initial infection. Symptoms of syphilitic meningitis are similar to other forms of meningitis, including headache, neck stiffness, photophobia, confusion, nausea, and vomiting. Meningeal inflammation may also affect the cranial nerves, most commonly the facial nerve, presenting as facial paralysis. Cerebral gummas, which are caused by granulomatous destruction of the brain from syphilis, can also cause symptoms of meningitis.

Meningovascular syphilis is often in the intermediate stage of neurosyphilis, typically presenting 5 to 12 years after infection. It is due to inflammation of the blood vessels supplying the central nervous system, resulting in the death of brain tissue called ischemia. It may present as stroke or spinal cord injury. Signs and symptoms vary with the blood vessel that is affected. The middle cerebral artery is most often affected, causing a variety of symptoms including weakness, sensory loss, eye deviation, and hemineglect syndrome.

Parenchymal syphilis occurs in the late stage of neurosyphilis, with average presentation occurring 15 to 25 years after initial infection. This stage of the disease is generally in the form of tabes dorsalis or general paresis. Tabes dorsalis, also called locomotor ataxia, describes a constellation of symptoms resulting from a degenerative process of the posterior columns of the spinal cord. Symptoms include pain, ataxic wide-based gait, paresthesias, bowel or bladder incontinence, loss of position and vibratory sense, acute episodic gastrointestinal pain, Charcot joints, and reduced reflexes. The Argyll Robertson pupil, which is a condition where the pupils do not constrict to bright light but constrict when focusing on a near object (accommodation reflex), is another feature that may be present.