Neurosyphilis – features, diagnosis and treatment

 

Involvement of nervous system in syphilis is not very common and because of introduction of Penicillin therapy its incidence has markedly declined but in recent years it incidence has again increased due to spread of HIV.

Neurosyphilis occurs only in a small percentage of cases, it being not more than 10% in those infected with Trepenoma Pallidum. It has been observed that certain strains of spirochaetes possess special affinity for the nervous system. Nervous system is infected primarily through the blood stream and cerebro spinal fluid infection may play a secondary role in its spread.

Secondary neuro syphilis generally occurs within the 2-24 weeks of the primary infection and in only 1-2% cases there is involvement of CNS and it is in the form of slight changes in the CSF.

The symptoms may not be more than slight headache and pains in the body. Rarely an acute form of meningo encephalitis may develop with features of convulsions, ocular palsies, aphasia or hemiplegia.

Though central nervous system involvement in syphilis is continuation of primary infection yet number of cases remain asymptomatic for a number of years. Abnormalities in CSF in such patients are important predictors about developing neurological features.

If CSF remains normal for 2 yeas after infection chances of developing neurosyphilis are less than 5% and if CSF shows no abnormalities (Rise in proteins, Pleocytosis) after 5 years then chances of developing neurosyphilis are probably not more than 1%.

Patients of asymptomatic neurosyphilis if not treated their chances of developing symptomatic neurosyphilis varies from 20% to above in the first 10 years. Risk of developing neurosyphilis is 4 to 5 times more in men than women. There are two major clinical varieties of neurosyphitis.

1. Meningovascular syphilis

2. Parenchymatous syphilis comprising mainly of Tabes Dorsalis and general paralysis of insane.

Meningo vascular form of neurosyphilis (Early tertiary stage) develops at varying time on average 5-10 years while general paresis and tabes dorsalis may develop after 20-30 years.

Meningo vascular syphilis

It may be cerebral or spinal form. In the cerebral form there is involvement of the hemisphere and base of brain. The essential lesion is diffuse inflammation of Pia and arachnoid matter along with vascular and perivascular infimmation.

There is widespread involvement of vessels (proliferation and inflammatory infiltration of the vessel wall) leading to endarteritis obliterans. The lesions may range from cranial pachymeningitis (secondary to osteitis of bones of the skull), gummatous leptomeningitis (thickening of pia and arachnoid mater with gummatous exudate), cerebral endarteritis (proliferation of intima, thinning of media and inflammatory changes in adventita) to gumma (soft rounded greyish vascular mass, varying in size from a few millimetres to centimetres). A cerebral gumma rarely contains spirochaets and there is infiltration with lymphocytes and plasma cells.

Clinical features

Symptoms of meningo vascular type of neurosyphilis develop generally within first five years after primary infection. Syphilitic meningitis is rare and manifests in the form of acute presentation with headache, nausea and features of meningeal irritation.

Signs of raised intracranial tension and cranial nerve palsies develop. CSF examination shows raised protein content with lymphocytic pleocytosis. Wisserman Reaction is positive.

Cranial pachymeningitis gives rise to headache, convulsions and focal neurological defects like paresis of the limbs or Hemiplegia. Syphilitic endarteritis is an important cause of vascular lesions especially in the young.

There are often premonitory symptoms. The middle cerebral artery or its branches and posterior cerebral are commonly involved. Hemiplegia is the common presentation of such cases.

A syphilitic gumma may produce no symptoms if it is small in size. A laige gumma shall produce features of intracranial tumour. A gumma should be suspected if there is any history of contact. CSF exam shall show increase in pressure, rise in proteins, pleocytosis and strongly positive W.R. reaction.

Spinal forms

Here the pathology is the same as that of cerebral form. Spinal pachymeningitis mainly involves the cervical region (Pachymeningitis cervicalis Hypertrophica) where inflammation spreads from syphilitic osteitis involving dura mater which becomes adherant to arachnoid and pia.

In meningo myelitis, there is endarteritis and perivascular inflammation of the vessels of spinal cord (spinal endarteritis). There may be degeneration of myelin sheaths and softening of the cord.

Erb’s syphilitic spinal paralysis is a form of meningo myelitis where there is primarly involvement of pyramidal tracts. Radiculitis may be produced when one or more spinal posterior roots are involved.

Clinical features of spinal form of syphilis

Meningomyelitis gives rise to picture of acute transverse myelitis and is the commonest form of spinal neurosyphilis. There are usually symptoms of pain in back spreading in froat and back. There is parasthesia.

Motor weakness of lower limbs develops over period ranging from few days to several weeks. Initially there is flaccid paraplegia but subsequently spastic paraplegia develops with bladder dysfunction though sensory loss is slight.

In hypertrophic cervical pachymeningitis there are features of compression of cord in the cervical region. There is pain in the neck with root pains radiating down to the upper limbs.

Corresponding weakness and atrophy of muscles supplied by corresponding anterior nerve roots develops. As the disease progresses patient develops spastic paraplegia with sensory loss below the level of lesion.

Erb’s syphilitic spinal paralysis is of gradual onset with spastic paresis of lower limbs. There is predominantly early involvement of bladder but sensory loss is slight.

Spinal endarteritis has same picture as that of myelitis. Symptoms are like that of complete or almost complete transaction of the cord depending on which spinal artery is involved. Onset is always sudden.

If thrombosis of post spinal artery occurs there is involvement of post columns and pyramidal tracts on the same side involving postural sensibility and vibration sense below the level of the lesion.

Radiculitis is due to involvement of posterior roots giving rise to pain in the segmental distribution of nerve. There is hyperalgesia with or without analgesia. Weakness and wasting of muscles develop when anterior roots are affected.

Syphilitic amyotrophy is a rare form of spinal syphilis and resembles amyotrophic lateral sclerosis with wasting of muscles. Pain in the affected region may occur. Wasserman reaction is positive.

Paren chymatous syphilis

It comprises mainly of general paralysis of Insane and Tabes Dorsalis.

General paralysis of insane

It is a late disorder of neurosyphilis and is seen 15-20 years after the initial infection. It generally occurs in men between the age of 40-50 years, males being more liable to suffer as compared to females in the ratio of 4:1. Alcoholism, physical trauma and an inherited neuropathic diathesis are known to predispase to this condition.

Pathologically there is diffuse atrophy of the brain confined to frontal and temporal lobes of the brain. The cells in the cortex show varying degree of degeneration. Demyelination of the fibres of the cortex is invariably present. The meninges

Clinical features of Neurosyphilis

Stage Clinical features

1. Secondary Meningitis

2. Tertiary

(a) Meningovascular

• Cerebral Hemiplegia

Basal meningitis

Pachymeningitis

Gumma

• Spinal Meningomyelitis

Cervical hypertrophic

pachymeningitis

Spinal paralysis

Radiculitis

Syphilitic amyotrophy

(b) Parenchymatons

• General paralysis of insane

* Tabes dorsalis

Show thickening and the wall of ventricles show ependymitis. There is compensatory dilatation of the ventricles. Spirochaetes are detectable in 50% of cases.

Clinical features

Deterioration of higher mental functions is the earliest feature. These patients show loss of memory especially recent, power to concentrate and develop a euphoric Grandiose state.

There are features of lack of social behavior, hallucinations, delusions loss of judgement and dementia. Many patients demonstrate features of depression, agitation and maniacal behavior.

Convulsive attacks occur in about 40-50% of cases and an attack may be followed by a brief period of unconsciousness I hemiparesis. On physical examination there is deterioration of higher mental functions.

Patient may have bilateral pyramidal signs. Tendon reflexes are usually exaggerated with plantars being extensor. Loss of sphincter control may be present at an early stage.

Main physical sign is pupillary abnormalities. Pupils are irregular, contracted and react to light sluggishly. Accommodation reflex is preserved. This is typical Argyll Robertson Pupil. Optic atrophy may be seen in 5-10% of cases. Besides this patient may show progressive motor weakness and widespread tremors. Limbs, lips and tongue may be tremulous. Syphilitic aortitis may be present in some cases.

Diagnosis is based on clinical history and examination. CSF shows increased pressure with increased levels of proteins and excess of cells which are usually mononuclear. Lange’s colloidal gold curve is of paretic type.

The course of the disease is progressive with periods of fluctuations. Early diagnosis and treatment carries good prognosis.

Treatment of Neurosyphilis

Penicillin is the drug of choice. There are two regimens of giving penicillin.

1. Inj. Procaine penicillin 1.2 million units twice a day with probenecid 2 G daily for 2 weeks.

2. Inj. Penicillin 02 million units I/V 4 hry for

2 weeks. Other regimens advocated are Cap amoxycillin 108 hry daily for 15 days along with probenecid. Repeat courses may be required.

In patients sensitive to penicillin, third generation cephalosporins / Tetra cyclines are advocated. Where penicillin allergy is documented, desensitisation may be tried. Earlier on long acting Benzathin Penicillin was advocated in the treatment of neurosyphilis but results have not been satisfactory. Allergic Reactions (Jarisch-Herxhemier) may occur in some with Penicillin. Tabetic pains respond to analgesics and carbamazepine 100 mg thrice a day. Visceral crisis responds to Adrenaline (0.5 ml 1: 1000). Where there is worsening of neurological picture, it is treated with heavy doses of steroids.

Patient may be assessed about treatment after 6 weeks. CSF examination for cells and protein context is done. VDRL test may become negative though TPHAJ FT Abs are not effected.