Neurosyphilis

This ppt contains a detailed description, pathogenesis, clinical feature, diagnostic approaches and treatment to a case of neurosyphilis

1. Neurosyphilis Dr. Tareq Esteak Resident(Neurology, Phase B) National Institute of Neurosciences and Hospital

2. Q.1.What is the diagnosis? Q.2.Where are the probable lesions? Q.3.What are the expected examination findings considering his complaints?

3. Introduction Infection of nervous system by T.pallidum The incidence has reduced drastically, since the introduction of penicillin However, in more recent years, the number of reported cases of early syphilis has increased, both in non-immunocompromised and compromises The organism usually invades the CNS within 3 to 18 months of inoculation. The initial event of meningitis, which occurs in approximately 25% of all cases If the nervous system is not involved by the end of the 2 nd year, there is only 5% that the patient will develop neurosyphilis as a result of the original infection. At the end of 5 years, that likelihood falls to 1%.

4. Asymptomatic Neurosyphilis From a clinical point of view, asymptomatic neurosyphilis is perhaps the most important form As, if a dequately treated, the symptomatic varieties would be prevented in most instances In this condition, there are no symptoms I n rare cases, Argyll Robertson pupils may be found The diagnosis is based entirely on the CSF findings

5. Meningeal Syphilis M ay occur at any time after infection Usually occurs within the first 2 years. The patient is afebrile, unlike the case in tuberculous meningitis. M ost common symptoms are headache, stiff neck, cranial-nerve palsies,confuion Occasionally, signs of increased intracranial pressure may present as well The CSF always has a lymphocytic reaction , With adequate treatment, the prognosis is good. The symptoms usually disappear within days to weeks

6. Meningovascular Syphilis T he most common form of neurosyphilis. U sually occurs 6 to 7 years after first inoculation, but may occur anytime . In the past, strokes associated with 10 % of cases , which is now around 35 %. P athogenesis - inflammation and fibrosis of meninges ;small arteries ( Heubner arteritis ) I nfarctions occur in the medium- and small-caliber lenticulostriate branches Common site: Internal capsule, Basal ganglia, periventricular region A dequate treatment will prevent further vascular episodes. If repeated strokes occur despite adequate therapy, consider the possibility of non-syphilitic vascular disease of the brain.

7. Meningovascular syphilis DWI: Diffusion restriction left basal ganglia region MRA: Narrowing and irregularities in M1 segment of Left MCA https://doi.org/10.7861/clinmed.2019-0368

8. Paretic Neurosyphilis Usually occurs 15-20 years after the primary infection Once a major cause of various forms of mental illness, progressive dementia Often associated with paretic symptoms Hence called General Paresis of insane/ Dementia Paralytica The clinical picture in its fully developed form includes progressive dementia, dysarthria, myoclonic jerks, action tremor, seizures, hyperreflexia, Babinski signs, and Argyll Robertson pupils However, a greater importance attaches to diagnosis at an earlier stage

9. Cont. The insidious onset of dementia and disorders of speaking and writing can be early manifestation (mimics FTD) As the deterioration continues into the paralytic stage, intellectual function progressively declines, and aphasias, agnosias , and apraxias intrude themselves All these disabilities lead eventually to a bedridden state; hence the term paretic . Dilution and mania, such symptoms are late features along with paresis. P sychiatric syndromes that can be differentiated by cognitive decline, neurologic signs, and CSF findings

10. High signal intensity in both mesial temporal regions and hyper intense rim shaped lesion attached with the falx in the left frontal lobe .The temporal horns of the lateral ventricle are dilated due to atrophy of the mesial temporal regions. There is also generalized atrophy of brain ( Paretic Neurosyphilis) FLAIR T2 T1

11. Mnemonics

12. Tabes Dorsalis U sually develops 15 to 20 years after the onset of the infection. The major symptoms are - Sharp, radicular pains, absent tendon reflexes U rinary incontinence(overflow incontinence) Impaired vibratory and position sense in feet and legs, sensory ataxia and a Romberg sign. Power, by contrast, is fully retained in most cases. P erforating foot ulcers , and Charcot joints are characteristic complications of the tabes In most cases now seen, the CSF is normal when the patient is first examined (so-called burned-out tabes ).

13. Pathophysiology

14. Comparison of other dorsal column lesion

15. Tabes Dorsalis T2WI : hyperintensity along the dorsal column in thoracic segment T2WI : hyperintensity along dorsal part of spinal cord

16. spinal meningovascular syphilis T2WI demonstrates increase signal intensities signal from T1-T3  T2-weighted MRI , axial section demonstrates high signal intensities in anterior two third of the cord

17. syphilitic meningomyelitis T1WC+: shows multiple nodular foci of enhancement throughout the thoracic cord T2WI: diffuse T2 hyperintensity throughout the thoracic cord, slight irregularities corresponds to foci of enhancements

18. Syphilitic tabo -paresis Tabes dorsalis + general paresis of insane Absent knee, ankle jerk with bilateral planatar Extensor

19. Argyll Robertson pupil (ARB) Commonly seen in neurosyphilis Light-near dissociation(Light-reflex impaired; Accommodation- intact) Bilateral involvement miotic , irregular pupil Bilateral constricted pupil – absence of supranuclear lesion to the visceral oculomotor nuclei Light reflex impaired –lesion in dorsal midbrain/pre- tectal neuclei

20. Accomodation reflex Light reflex

21. Syphilitic Optic Atrophy P rogressive blindness in one eye and then involving the other Pathophysiology- Peri-optic meningitis ,occasionally vasculitis may cause it. Occur within months of the primary infection or as a later manifestation. C onstriction of the visual fields, but scotomata may occur in rare cases. The prognosis is poor if severe and bilateral. If only one eye is badly affected, sight in the other eye can usually be saved. CSF is almost invariably abnormal, In exceptional cases, visual impairment may progress, even after the CSF becomes negative.

22. Syphilitic Nerve Deafness and Vestibulopathy V ertigo, with or without hearing loss Some of the characteristics of vestibular neurosyphilis are identical to those of Meniere disease. T here is seldom a history of clear primary syphilitic infection. The pathology, mainly endarteritis in the cochlea and labyrinths, So, syphilis serology should be tested in patients with cryptic vestibular dysfunction

23. Gumma N on-caseating granuloma resulting from the tertiary stage of  syphilis   but can occur in early stages as well. Cerebral syphilitic gumma is very rare and can only be histo logically confirmed following surgery caused by a reaction to spirochaete bacteria in the tissue

24. Gumma of neurosyphilis T1C+: A dural -based, peripheral enhancement of the lesion T2wI: A dural -based, peripherally hyperintense and centrally hypointense lesion located lateral to the left frontal lobe

25. Investigation CBC with ESR S. Creatinine S. electrolyte LFT RFT U.R/E CXR P/A view S. VDRL S. TPHA FTA-abs( Flurocent treponemal ab absorbtion ) MRI of brain & spinal cord with contrast CSF study

26. CSF The CSF is a sensitive indicator of the presence of active neurosyphilis. The CSF findings are consist of Protein: raised, from 40 - 200 mg/dL; Glucose: normal Cell: pleocytosis more common in early , up to 100 cells/mm3,mostly lymphocytes (May be normal patients with HIV and those with leukopenia); an increase IgG index usually with oligoclonal banding; VDRL/RPR Treponemal test-TPHA/FTA-abs

27. Peeling, R., Mabey, D., Kamb , M.  et al.  Syphilis.  Nat Rev Dis Primers   3,  17073 (2017). https://doi.org/10.1038/nrdp.2017.73

28. Types of Neurosyphilis Asymptomatic Neurosyphilis Symptometic Neurosyphilis Meningeal Syphilis Meningovascular Syphilis Paretic Neurosyphilis Spinal Syphilis Syphilitic Optic Atrophy Argyll Robertson pupil Syphilitic Nerve Deafness and Vestibulopathy

29. Treatment If Allergic to penicillin Ceftriaxone 2g/day IV for 10-14 days

30. Cont. Caution The Jarisch-Herxheimer reaction, Special situation If co-infection with HIV, longer treatment and surveillance for relapse Symptomatic therapy Radicular pains may respond to gabapentin or carbamazepine Atropine; phenothiazine derivatives are said to be useful in the treatment of visceral crises. Neuropathic (Charcot) joints require bracing or fusion

31. Follow up

32. A persistent weakly positive serologic (VDRL) test after the cells and protein levels have returned to normal does not constitute an indication for additional treatment.

33. Site Clinical Features Meninges Meningitis (acute or chronic) , CN palsy(2,6,7,8) Blood vessels Heubner arteritic stroke, Brain Dementia paralytica’ /general paralysis of insane Dementia + spastic paraparesis(cortical degeneration) Neuropsychiatric symptoms(dilutions of grandeur) Gumma /mass lesion : seizure , tremors, Ataxia Spinal cord Tabes Dorsalis: Degeneration of dorsal column + dorsal roots + dorsal root ganglia sensory ataxia, radicular pain, areflexia ,bladders symptoms syphilitic meningomyelitis : spastic paraparesis spinal meningovascular syphilis : anterior spinal artery syndrome Eyes Optic atrophy (peri-optic meningitis) Argyll Robertson pupil( pretectal lesion) Others Neuropathic joint/ Charcot joint, Deafness and Vestibulopathy

34. Q.1.What is the diagnosis? Q.2.Where are the probable lesions? Q.3.What are the expected examination findings considering his complaints?

35. Thank you