The Neurology of Neurosyphilis - Research Paper Example

 The Neurology of Neurosyphilis Introduction Concentration on the acquired immunodeficiency syndrome (AIDS) has led to a diminished focus on sexually transmitted diseases like syphilis and its consequences. Lack of timely recognition and diagnosis of syphilis can result in the progression of disease into its tertiary stages, with consequences like neurosyphilis and its mortality and cognitive impairment dimensions (Schiff & Lindberg, 2002). The spirochete Treponema Pallidum is responsible for the chronic infection of syphilis. The usual route of infection is through sexual contact. Syphilis can also be transmitted vertically in an infected pregnant woman through the placenta onto the fetus, which is termed as congenital syphilis (Schiff & Lindberg, 2002). In the United States of America, estimates from health records show that the prevalence of syphilis was over 36,000 in 2006, and that the prevalence had increased by 11.8% in comparison to 2005, with a gender bias towards the male population (Center for Disease Control and Prevention, 2010). Syphilis Infection and Potential Progression Once infection has occurred it takes between 10 days to 90 days for the appearance of the first symptom. In an infected individual the symptom of infection is usually the presence of a single sore that is called a chancre. It is also possible that individual presents with several chancres. The chancre is can be seen as a firm, round, small, and painless sore, which is present at the site of the pathogen entering the body. It can be seen for a time period of three weeks to six weeks after which it disappears even without treatment. The problem is that in the absence of appropriate treatment the infection progresses silently to its second stage (Center for Disease Control and Prevention, 2010). The secondary stage of the infection occurs in almost 25% of infected individuals that have not received appropriate treatment. The secondary stage of the infection can appear months after the initial infection (Schiff & Lindberg, 2002). Rashes on the skin and lesions of the mucous membrane are the characteristic features of the secondary stage of the infection, which appear on one or more parts of the body. Normally there is no itching associated with the rashes that can be usually seen as rough, red, or reddish brown spots on the palms of the hands and bottom of the feet. These rashes may occur in other parts of the body. There is also the possibility of fever, swollen lymph glands, sore throat, hair loss, headaches, loss of weight, pain in the muscles, and a feeling of tiredness during the secondary phase of the infection. Just as in the case of the primary stage of the infection, the symptoms of the secondary stage can disappear in the absence of appropriate treatment, but the infection can progress into the tertiary stage or latent stage of the infection (Center for Disease Control and Prevention, 2010). Tertiary syphilis or the latent stage of the infection starts at the time of the disappearance of the primary or secondary symptoms of the infection. It is also called the hidden stage of the disease, as the infection continues in the individual without showing any signs or symptoms. This hidden stage of the infection can last for anywhere between 10 years to 20 years. Tertiary syphilis can occur in nearly 15% of the individuals, who have not received appropriate treatment during the earlier stages of the infection (Center for Disease Control and Prevention, 2010). Tertiary syphilis is a slowly progressive inflammatory disease, and it finally presents as neurosyphilis, or cardiovascular syphilis, or gummatous syphilis (Schiff & Lindberg, 2002). Development of Neurosyphilis Among the differential of neuropsychiatric conditions, neurosyphilis was a common presentation in earlier times. It is believed that in the fifteenth century, explorers to the Americas and the Caribbean contracted the infection, and spread it to the rest of the world (Lair & Naidech, 2004). The actual incidence of neurosyphilis still lacks clarity. It is generally believed that four per cent to ten per cent of patients infected with syphilis are likely to develop neurosyphils, as Treponema Pallidum, the causative pathogen invades the central nervous system (CNS) at an early stage after the initial infection. The lack of appropriate treatment of the infection at any stage of the disease heightens the risk for the development of neurosyphilis. The recent HIV infection epidemic has had its influence on the increased incidence of neurosyphilis, as the risk for contracting neurosyphilis is enhanced in HIV infected patients (Lynn, Newton & Rae-Grant, 2004). Lair & Naidech, 2004, p.1333, define definitive neurosyphilis as “as a positive CSF VDRL test (specific, but only about 50% sensitive), while probable neurosyphilis means CSF leukocytosis or elevated protein in the context of syphilis exposure without a better explanation.” Table – 1 below gives the neurological features of neurosyphilis. Table – 1 The Neurological Features of Neurosyphilis Asymptomatic Meningitis Based fully on Cerebro-spinal fluid (CSF) findings Meningeal Disease Headache, stiff neck, cranial nerve palsies, no fever, and raised intracranial pressure. Parenchymal Disease Meningovascular Tabes Dorsalis, Tabetic Neurosyphilis General Paralysis /Paresis, Dementia Paralytica Syphilitic Optic Atrophy Spinal Syphilis other than Tabes Syphilitic Nerve Deafness Cerebrovascular events that cause hemiplegia, aphasia, visual disturbances, and sensory loss Sensory (locomotive) ataxia, absence of lower limb tendon reflexes, lightening pains in the legs, Charcot joints, urinary incontinence, Argyll Robertson pupils, ptosis, ophthalmoplegia, optic atrophy, and degeneration of the posterior columns of the spinal cord Dementia, myoclonus, seizures, hyperreflexia, and Argyll Robertson pupils Frequently coexists with Tabes Dorsalis Meningomyclitis, and meningovascular disease Gummatous Disease May mimic mass lesions Osteitis of Skull and Spine (Adapted from Larner et al, 2011) The initial stages of the neurological manifestation of the early form of tertiary syphilis are through pure meningeal or meningovascular disease that appear after a 5 year to 10 year period of latency from the time of the initial infection, or in the parenchymal forms of the disease that make their appearance after 10 years to 30 years from the time of the primary infection. Neurosyphilis spreads across all stages of the disease. The different forms of the disease meningeal, meningovascular and parenchymal syndromes need to be viewed from the perspective of being a continuum of the disease, instead of disparate disorders. The fundamental pathological events as a result of meningeal invasion, obliterative endarteritis, and parenchymal invasion are clinically expressed through syphilitic meningitis, meningovascular syphilis, general paresis, and tabes. This is particularly true in the modern era with widespread antibiotic use, whereby neurosyphilis manifests not as a single classic syndrome, but as a mixed, subtle, or incomplete disease. The various neurological complications of tertiary syphilis are also seen in HIV/AIDS disease, which is likely to speed up the onset and progression of neurosyphilis (Verma & Solbrig, 2004). The earliest typical form of neurosyphilis to manifest is syphilitic meningitis, which quite often is asymptomatic. However, rare complications from acute syphilitic meningitis can occur in the form of hydrocephalus, myelitis, or lumbosacral radiculitis. Normally syphilitic meningitis raises its head after four to seven years from the time of the primary infection. Additionally, due to the possible occurrence of stroke and involvement of the large and small cerebral blood vessels in the disease, headache, vertigo, insomnia, and psychiatric or personality disorders are associated with the disease (Verma & Solbrig, 2004). The encephalitic form of neurosyphilis general paresis usually manifests as progressive dementia, with it starting anywhere between 15 years to 20 years from the time of the primary infection. The patient could present with any of the following symptoms or signs of delusional or apathetic states of dysarthria, myoclonus, intention tremor, seizures, hyper-reflexia, and Argyll Robertson pupils, which is small and irregular pupils that do not constrict to light, but with accommodation. The manifestations of the encephalitic form of neurosyphilis can be recalled through association with the short form of paresis, which stands for personality, affect, reflexes, eye, sensorium, intellect, and speech (Verma & Solbrig, 2004). The spinal form of neurosyphilis, namely Tabes dorsalis manifests itself almost 15 to 20 years from the time of the primary infection. Characteristic symptoms or signs associates with Tabes dorsalis are lightening pain, autonomic dysfunction, and sensory ataxia. The affected individuals demonstrate normal strength, but have no reflexes in the legs, a positive Romberg sign that is seen with reduced proprioception. In more than 90% of the individuals with Tabes dorsalis abnormal pupils are seen, and in nearly 50% of the affected individuals Argyll Robertson pupils are present. There are other features that are associated with Tabes dorsalis that includes optic atrophy, ophthalmoplegia, ptosis, gastric or other visceral events (pharyngeal, laryngeal, genitourinary, intestinal, and rectal), impotence, fecal incontinence, pain, and loss of temperature that causes changes, like Charcot’s joints and perforating foot ulcers (Verma & Solbrig, 2004). Inflammatory syphilitic diseases of the eye are uveitis, chorioretinitis, and vasculitis. Any of these diseases may be seen along with syphilitic meningitis, though they may appear at the secondary stage of the disease. Optic atrophy can develop after a time lapse of months or years, and be present along with any of the other forms of neurosyphilis, with particular emphasis on tabes. The degeneration of the optic nerve is usually observed to start peripherally, and then extend towards the center of the optic nerve. This causes progressive constriction of the field of vision that is accompanied by preserved acuity. Syphilis otitis is a rare occurrence with neurosyphilis, but when it occurs it is characterized by unexplained loss of hearing ability or vestibular abnormalities, with a positive picture of treponemal serology (Verma & Solbrig, 2004). In the vertical transmission of syphilis, children may be born with the congenital disease that presents as serous nasal discharge, rash, condylomas, hepatosplenomegaly, or osteochondritis. In the absence of appropriate treatment at this stage the classical signs of the disease are demonstrated through Hutchinson’s teeth, saddle nose, interstitial keratitis, saber shins, mental retardation, hearing loss, and hydrocephalus (Verma & Solbrig, 2004). Diagnosis of Neurosyphilis In the case of the early stage of the disease treponemal and non-treponemal serologic tests are the recommended diagnostic means. However, in the case of neurosyphilis mere treponemal and non-treponemal serological tests are insufficient, and need to be accompanied by CSF examination for the disease. Quite often eye diseases are demonstrated by patients with Neurosyphilis, and so LP is recommended. Recommendations from the Center for Disease Control and Prevention (CDC) include the use of CSF for all individuals with syphilis who demonstrate symptoms or signs of neurological or ophthalmic progression of the disease, or show symptoms and signs of the active tertiary stage of the disease, or have failed treatment of the disease. Furthermore, since there is close association of the disease with HIV/AIDS, the CDC also recommends CSF tests with LP in the case of all individuals having HIV infection with latent syphilis or latent syphilis of unknown duration prior to initiating treatment procedures (Verma & Solbrig, 2004). The diagnosis of neurosyphilis rests on the legs of clinical findings, CSF findings, and serology. CSF examination showing mononuclear pleocytosis and high levels of protein support a diagnosis of neurosyphilis. A more specific diagnostic test for neurosyphilis is CSF-VDRL. However, it is more sensitive to meningovascular syphilis and general paresis, than in the cases of asymptomatic neurosyphilis and tabes. There is the possibility of false-positive findings with CSF-VDRL in the event of blood contamination of CSF, which can happen in the case of traumatic LP. Though serum VDRL may show negative findings with 25% of patients with late neurosyphilis, specific treponemal tests remain active. In the case of individuals with tabes, there is the possibility of the CSF showing less pronounced inflammatory changes, as is seen in the other forms of neurosyphilis (Verma & Solbrig, 2004). Treatment of Neurosyphilis and Response Penicillin still remains the only proven antibiotic for the treatment of neurosyphilis. The recommended treatment regimen for neurosyphilis is aqueous crystalline penicillin G, 18-24 million units IV on a daily basis, in divided doses of three to four million units, every four hours, for a period of 10 to 14 days. The alternate treatment regimen for neurosyphilis is procaine penicillin 2.4 million units IM with probenecid 500 mg four times a day, over a period of 10 to 14 days. In the case of infants and children the recommended treatment regimen consists of aqueous crystalline penicillin G, 200,000 to 300,000 units/kg/day IV, which is to be administered in the form of 50,000 units/kg every four to six hours for a period of 10 days. In patients with earlier confirmed allergy to penicillin, the recommendation is for skin testing and desensitization, given that penicillin is the only active antibiotic against the infecting pathogen. No other antibiotic or alternative treatment is recommended for neurosyphilis (Lynn, Newton & Rae-Grant, 2004). The response to treatment of neurosyphilis is varied, with it depending on how long the disease has persisted in the individual and the neurological damage that has already occurred. In the case of meningovascular syphilis symptoms and signs that persist even after six months of the treatment, in all probability will remain. In the general paresis form of the disease early treatment can lead to improvement of the cognitive and psychiatric disease, or at least arrest progression of the disease in a minimum of 50% of the patients. In the tabes form of the disease residual symptoms will continue even after the CSF demonstrates normalization. These residual symptoms will have to be treated symptomatically. The symptomatic treatment includes treatment for joint deformities with the assistance of orthotics, visceral crises with atropine, and anticonvulsants or amitriptyline for pain. Progression of pretreatment loss of vision and extensive perioptic meningeal infiltrate can be arrested through treatment. The thumb rule is that damage that has occurred prior to the initiation of treatment cannot be rectified, and only further progression of the disease is arrested through the treatment of neurosyphilis. In the case of vertical transmission from mother to fetus, appropriate treatment of the disease prior to the sixteenth week of gestation will prevent the new born from having the disease (Verma & Solbrig, 2004). Conclusion Infection from the spirochete Treponema Pallidum causes the development of syphilis in the human body. The problem with the disease is that the primary infection disappears even without treatment, though the pathogen remains in the human body. The secondary stage of the disease then appears, and again can go away without treatment. This latent stage of the disease that can extend over many years can return in some of the patients with harmful consequences. Neurosyphilis is one such possible reemergence of the disease from its latent stage. In any case the development of neurosyphilis or the other consequences is essentially from the lack of appropriate treatment during the earlier stages of the disease. Though neurosyphilis presents in many forms like meningeal, meningovascular and parenchymal syndromes, they are not separate disorders, but a continuation of the same disease. Neurosyphilis is diagnosed with the assistance of clinical findings, CSF findings, and serology. The only antibiotic active against Treponema Pallidum is penicillin, and it remains the only recommended treatment for neurosyphilis. However, damage that has occurred prior to initiation of the treatment cannot be reversed and only progression of the disease halted. The rule in the treatment of neurosyphilis is to prevent its occurrence by appropriate treatment of the primary infection, or at least at the secondary stage. In the event neurosyphilis develops due to lack of appropriate treatment earlier, then early diagnosis and treatment is essential to prevent damage occurring due to neurosyphilis. Literary References Center for Disease Control and Prevention. (2010). Syphilis – CDC Fact Sheet. Retrieved February 21, 2012, from Web Site: http://www.cdc.gov/std/syphilis/stdfact-syphilis.htm. Lair, L. & Naidech, A. M. (2004). Modern neuropsychiatric presentation of neurosyphilis. Neurology, 63(7), 1331-1333. Larner, A. J., Coles, A. J., Scolding, N. J. & Barker, R. A. (2011). A – Z of Neurology Practice: A Guide to Clinical Neurology, Second Edition, London: Springer Verlag, Lynn, J. D., Newton, H. B. & Rae-Grant, A. D. (2004). The 5-Minute Neurology Consult. Philadelphia, PA: Lippincott, Williams & Wilkins. Schiff, E. & Lindberg, M. (2002). Neurosyphilis. Southern Medical Journal, 95(9), Retrieved February 21, 2012, from Web Site: http://www.medscape.com/viewarticle/442908. Verma, A. & Solbrig. (2004). Bacterial Infections. In Walter G. Bradley, Robert B. Daroff, Gerald M. Fenichel & Joseph Jankovic (Eds.), Neurology in Clinical Practice, Volume – II, Fourth Edition (pp.1475-1514). Philadelphia, PA: Butterworth Heinemann. Read More