A 53 year-old man with HIV (CD4 51/10%) presents with progressive confusion and weakness over two months. He had previously been employed and able to perform all activities of daily living. He is not on anti-retroviral therapy. He denies alcohol or illicit drug use and is not sexually active.
On physical exam, he is afebrile. He is oriented only to person and place, scoring a 21 on MMSE. He has 4/5 strength in all extremities and decreased deep tendon reflexes. Fine touch, vibratory and temperature sensation are intact. He is unable to stand without assistance. There is no dysdiadokinesia and heel-to-shin are intact bilaterally.
Significant laboratory findings included normal WBC, B12 and TSH. MRI showed moderate to severe periventricular and subcortical white matter changes, but no masses or lesions. CSF studies were significant for elevated protein and 17 WBCs with 92% PMNs. CSF Cryptococcal antigen, HSV PCR and JC PCR were negative. Serum EBV and CMV PCR were negative. Serum RPR was reactive (1:8), EIA confirmed. CSF RPR was reactive (1:4).
He was diagnosed with neurosyphilis and treated with penicillin G 3,000,000 units IV every 4 hours for a total of 14 days. He was discharged to inpatient rehab with improvement in his mental status.
Neurosyphilis is an infection of the central nervous system by the Treponema pallidum. Syphilis can be categorized into primary, secondary, latent and late stages, which includes neurosyphilis. Early neurosyphilis includes asymptomatic neurosyphilis and symptomatic meningitis. Late neurosyphilis includes general paresis and tabes dorsalis. Symptoms of general paresis include forgetfulness, personality change, deficits in judgment and progression to dementia. Tabes dorsalis is disease of the posterior columns of the spinal cord and the dorsal roots. Symptoms include sensory ataxia and lancinating pains.
Lumbar puncture is recommended in all patients with known syphilis disease presenting with neurological symptoms. CDC recommends a lumbar puncture in all HIV infected patients with late/latent syphilis or syphilis of unknown duration. HIV patients with a CD4 count < 350 are considered at particular risk of developing neurosyphilis, even in the absence of symptoms. Unfortunately, diagnosing neurosyphilis in HIV patients can be complicated by HIV itself. A reactive CSF-VDRL confirms the diagnosis of neurosyphilis. While highly specific, the sensitivity ranges from 30-70%, therefore the diagnosis is not excluded by a negative test. Elevated CSF protein or WBC is consistent with neurosyphilis. However, CSF protein may also be elevated secondary to the HIV infection. In HIV patients with a non-reactive CSF-VDRL, CSF WBC between 6 and 20 and CD4 less than 200, it is recommended to treat for neurosyphilis.
Treatment of neurosyphilis is penicillin G IV every 4 hours for a total of 14 days. Patients must be monitored with lumbar puncture three to six months after treatment and every six months thereafter until CSF WBC is normal and CSF-VDRL is non-reactive. Additionally, a fourfold decline in RPR titers is considered successful treatment.
Dementia is a common complaint among hospitalized patients. It is important to consider reversible causes, including neurosyphilis. Though rare this day in age, when properly diagnosed, neurosyphilis can be easily treated and symptoms of dementia can improve.
To cite this abstract:Abrams-Downey A, Purpura L. General Paralysis of the Insane. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 429. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/general-paralysis-of-the-insane/. Accessed April 10, 2020.