NEURO SYPHILIS

📌A sexually transmitted disease

📌Agent-Tryponema pallidum

📌Synonyms-Lues venera/Great pox/French disease/Polish disease/German disease/Christian disease/Spanish disease/Castilian disease/Nepolitan disease

📌Named after-Syphilus(a shepherd) in the poem “Syphilis sive morbus gallicus” by Girolamo Fracastro(Italian)

📌SYPHILIS-THE GREAT IMITATOR

📌  Sexual Contact-1/3rd of the individuals will get  infected)

📌Neurosyphilis prevalence-5-10%

📌Neurosyphilis can occur at any stage of syphilis
But historically its considered as a part of tertiary syphilis
Within hours of tryponemal infection,it reaches the CNS
A healthy body usually can clear this neuroinvasion
Sometimes body fails in this attempt (especially in immuno compromised patients like AIDS) ,thus developing neurosyphilis

📌Epidemiology:-

-Incidence is low since the antibiotic era

-Reported more in males

📌NEUROSYPHILIS-GENERAL CLASSIFICATION

1)Asymptomatic Neurosyphilis
2)Syphilis of the brain
3)Syphilis of the spinal cord

🔍ASYMPTOMATIC NEUROSYPHILIS

It means:-
Neurological symptoms/signs-ABSENT
CSF changes-PRESENT

📌4 TESTS IN CSF FOR NEUROSYPHILIS
1)Cell count
2)Total protein
3)Reagin test
4)Lange’s colloidal gold curve-Obselete now

📌COLLECTION OF CSF-By lumbar puncture

📌CELL COUNT IN CSF:-
Normal count is  0 to 4 cells/mm³
5 or more lymphocytes /mm³ may be the 1st indicator of CNS involvement

📌TOTAL PROTEIN  IN CSF:-
Normal amount of protein in CSF is 20 to 40mg/100mL
Estimation of IgG and IgM also helps

📌REAGIN TESTS:-
Complement fixation and flocculation tests
But it can be false positive if syphilis patient develop meningitis due to other causes

📌LANGE’S COLLOIDAL-GOLD TEST:-
Reported as graphs/series of numerals
Classifies abnormal readings into zone 1(paretic curve),mid zone or zone 2(Luetic curve) and 3rd zone(Meningitic curve) zone

🔍SYPHILIS OF THE BRAIN

📌CLASSIFICATION
1)Meningeal involvement
2)Vascular involvement
3)Parenchymatous involvement
4)Gumma

1)MENINGEAL INVOLVEMENT     (SYPHILITIC MENINGITIS)

📍Pathology:-
*Perivascular infiltration, mainly in pia &arachnoid- small lymphocytes and plasma cells
*Perivascular cuffing
*Fibroblastic proliferation later
*Subependymal gliosis

📍Symptoms:-
*Headache
*Nausea
*Vomiting
*Neck stiffness

📍Signs:-
*If meninges over the vertex affected & spreads to underlying cortex,it can cause convulsions,aphasia,mono/hemiplegia, mental confusion and papilledema
*If meninges over base of the brain are affected,cranialnerves will get
compressed,thereby resulting in cranial nerve palsies(CN 3,6,7,8 ususally)
*Leptomeningitis and  blockade of CSF circulation
*Hydrocephalus&papilledema
*Subependymal gliosis interrupts fibres of tracts carrying light reflex,thereby resulting in ARP

📍CSF:-Type I/II

📍Differential diagnoses:-

Tuberculous&Meningococcal meningitis

 Brain tumor/abscesses

Osteomyelitis of skull with extradural abscess

Other causes of papilloedema/raised ICT/epilepsy/CN palsies,mental diseases

2)VASCULAR INVOLVEMENT

📍Pathology:-
*Vascular thrombosis & Intimal shrinkage
*CNS infarcts
*Most commonly in branches of Middle cerebral artery

📍Symptoms:-

*Prodromal headaches,giddiness
*Mental disturbances
*Onset of main attack is sudden
*Transient muscle weakness
*Paresthesias
*Motor paralysis
*Convulsions

📍Signs:-
*MCA thrombosis-C/L hemiplegia&hemianesthesia,aphasia
*ACA thrombosis-C/L hemiplegia,sensory loss of legs, cognitive &personality changes
*PCA thrombosis-C/L homonymous hemianopia,sensory loss
*PICA thrombosis-Wallenburg syndrome
*Basilar artey thrombosis-Weber s/d,Benedikt s/d
*Pontine vessel thrombosis-Millard Gubler syndrome

📍CSF:-Type I but may be absent in upto 40%

📍Differential diagnoses:

*Cerebral thrombosis due to other causes,mainly atheroma
*Meningovascular syphilis-both meninges and vascular structures affected

3)PARENCHYMATOUS INVOLVEMENT
(GENERAL PARALYSIS OF INSANE/DEMENTA PARALYTICA)

📍Pathology:-

*Dura thickened,adherent to skull vault
*Weight of brain reduced due to cortical atrophy (more anteriorily)
*Sulci flattened

*Firm to touch due to gliosis

*Pia mater firmly adherent to surface
*Dilated ventricles
*Subependymal gliosis mainly in floor of 4th ventricle

*Typical perivascular inflammatory reaction in meninges

*Degenerative changes in parenchyma,ganglion cells,myelin sheaths
*Lymphocytes&plasma cells infiltrate cortex
*Increased glial tissue
*Proliferation and hypertrophy of histiocytes(Contain iron, pathognomonic)
*Tryponema pallidum identifiable with special stains in 50%

📍SYMPTOMS:-

*It develops only 10 or more years after the infection
*Often short in stature and heavy physique
*Patient may be the last to be aware of that he has a disease;Usually 1st recognised by family members/collegues

*Progression of symptoms is decribed as:-

a) Period of onset
b)Period of full development
c)Period of decline

a)Period of onset:-

✅Insidious onset-irritable,looses concentration,memory reduces,personality changes ,deteriorated behaviour, insomnia,defective judgement,emotional lability, confusion, disorientation, petit mal

✅Sudden onset-"congestive attack"(convulsions, aphasia, confusions, mono/hemiplegia). Usually its transient;only few hours or days
Sudden onset-"brain storm"(fully developed psychosis,following a convulsion/bout of drinking).May then improve but relapses

b)Period of full development:-

Psychosis due to irrepairable&considerable damage to cortex
Forms of psychosis-deteriorated demented type(Most common),Manic/paranoid type,grandiose type

c)Period of decline:-
Dementia is the main issue
Conspicuous mental&physical deterioration
Emasciated,bed ridden

✅Terminal stages-convulsions,status epilepticus
Usually within 5 years of GPI,untreated patients will die

Signs:-
-Pupils-ARP(Taboparesis),Sometimes large pupils with absent light reflex and accomodation
-Other eye signs-3rd CN palsy,optic atrophy,hemianopia
-Dysarthria & slurring of speech
-Impairment of handwriting(Illegibility,omits letters)
-Face-Relaxed,empty expression,lip tremor,tremor of tongue on protrusion (Trombone tremor-can be a very early sign)
-Mild spastic paraplegia
-Increased kneejerk & ankle jerk
-Loss of abdominal reflex
-Extensor plantar reflex

LISSAUER’S TYPE OF GPI-Hemiparesis+convulsions+aphasia
Sensory system-normal

📌Causes of death in neurosyphilis:-

1)Intercurrent infections(pneumonia,renal infections)

2)Respiratory failure(due to convulsions)

📍CSF:-Type III usually;occasionally I/II.

📍DDs:-Meningeal/vascular neurosyphilis,Psychoneurosis, Schizophrenia,Manic depressive psychosis,Cerebral atherosclerosis,Alzheimer’s disease,Huntington’s
chorea,Pick’s dementia,Carcinomatosis,Cerebral tumors/abscesses

4)GUMMA OF BRAIN

*Very rare
*Most common sites-Meninges, vertex,base of brain
*Size increase🡪invade &compress brain parenchyma
*Symptoms-as any other space occupying lesions (headache,nausea,vomiting,convulsions,vision problems)
*Signs-as any other case of raised Intracranial tension(papilledema,cranial nerve palsies,hemiplegia)

📍EEG-Evidence of localised’ tumor’

📍CSF-Type I/II

📍Differential diagnoses -Brain tumor,other types of Neurosyphilis

🔍SYPHILIS OF THE SPINAL CORD

📌CLASSIFICATION

1)Meningeal involvement
2)Vascular involvement
3)Parenchymatous involvement
4)Gumma

1)MENINGEAL INVOLVEMENT (MENINGOMYELITIS)

📍Pathology:-
*Similar to that of brain meningeal involvement
*Likely to spread to pyramidal&other motor tracts
*Spinal nerves affected🡪LMN lesions

📍Based on area affected:-
a).Dorso-lumbar meningitis involving mainly pyramidal tracts
(Erb’s syphilitic spastic paraplegia)
b).Cervical meningitis involving spinal nerve roots&spinal tracts
(Syphilitic hypertrophic cervical pachymeningitis)
c).Combination of 1&2(Syphilitic amyotrophy)

📍SYMPTOMS & SIGNS:-

****Erb’s syphilitic spastic paraplegia-Gradual onset,progressive
stiffness of legs,drags his feet on walking,Irritable bladder with
frequent micturition,hypertonic leg muscles,Increased reflexes,
extensor plantar response

****Syphilitic hypertrophic cervical pachymeningitis-Gradual
onset,headache,bulbar CN palsies,Horner’s syndrome,flaccidity,
wasting,LMN palsy,sensory loss below the level of lesion

****Syphilitic amyotrophy-Gradual onset,LMN palsies,affected
muscles are initially painful

📍CSF:-Type I/II

📍DDs:-

Vascular neurosyphilis,Gumma of spinal cord
Disseminated sclerosis
Spinal tumor,Cervical disc lesion
Motor neuron disease

2)VASCULAR INVOLVEMENT

📍Pathology:-
*Vascular thrombosis🡪Infarction
*The single Anterior spinal artery supplies the whole central area of spinal cord.So,if its thrombosed, sudden onset, dramatic symptoms
*MC level of thrombosis-Thoracic/Lumbar

📍Symptoms & signs:-

*ASA thrombosis:-
Sudden onset
Leg paralysis
Urinary&fecal incontinence
Loss of pain&temperature below the level of lesion
1st,Spinal shock stage(reflexes lost,muscle atonia)
Then spasticity,reflexes increase,Mass reflex
Finally,paraplegia in flexion&trophic ulcers

*PSA thrombosis:-Unlikely to be diagnosed during life

📍CSF:-Type I/Normal

📍DDs:-

Meningomyelitis,Gumma,Transverse myelitis,tumorof spinal cord

3)PARENCHYMATOUS INVOLVEMENT
(TABES DORSALIS/LOCOMOTOR ATAXIA)

📍Pathology:-
Macroscopy-Shrunken posterior columns of spinal cord
Microscopy-Lymphocytes & plasma cells initially,  later on, reduced nerve fibres in posterior nerve root destroyed(esp.lower thoracic&lumbosacral),sensory nerve
ganglia affected

📍SYMPTOMS OF TABES DORSALIS:-

*Usually 10-20 yrs after the onset of disease( or even later)
*Lightning pain-legs (Most commonly), sudden, brief, intermittent, stabbing pain, may have a specific trigger, may be so severe to make him even think of suicide
*Ataxia-unsteadiness in dark
*Paresthesia-Muscle cramps like rheumatism, Feels like walking on cotton wool/snow, girdle sensation around abdomen
*Bladder disturbances-occur early, unaware of full bladder, slow to start , inadequate stream, residual urine. So UTI can happen frequently
*Bowel symptoms-Constipation
*Crises-Gastric/Abdominal crisis, Laryngeal crisis, Rectal crisis ,Vesical/Renal crisis
*Impotence-Early in the course when sacral roots affected
*Visual failure-Blindness due to progressive optic atrophy

📍SIGNS OF TABES DORSALIS:-

*General appearance-Thin,Tabetic facies(flabby facialmuscles,moderate ptosis, wrinkling of brow from compensatory overaction of frontalis)
*Pupillary changes-In 90%,Small pin point ARP pupils with irregular outline,Will not dilate with mydriatics/painful stimuli; Irregular, pale, atrophic iris

*Douglas Argyll Robertson-Scottish Ophthalmologist described ARP as a specific finding of tabes dorsalis in mid 1860s

*Areflexia &Atonia-Lower limbs(MC),Absent tendon reflexes,Cremasteric reflex& Arm reflexes lost occasionally, Abdominal reflex lost later, Flexor plantar
reflex also lost

*Ataxia-Begins in Lower limbs,Romberg test+ve,no proprioception,Tabetic gait, 

*Finger-nose test for upper limbs should be done

*Sensory changes:-
Surface sensation-pinprick, light touch; Lost either over Hitzig’s zones or in the stocking areas of LL

*Other sensations lost-deep pain,testicular sensations,vibration sense mainly in sacrum&lower limbs,position sense in toes

*Trophic changes:-

Charcot’s arthropathy
Loss/impairment of pain in joints.So severe degenerative changes especially if traumatised
Mostly affects-Knee joint
1 side of joint rapidly destroyed🡪Angulation,Deformity

*Xray-destruction,erosion,osteophytes,gross sclerosis of boneends
*Flail joint,Gross crepitus

*Mal perforans

*Primary optic atrophy-In 15 to 20%,Earliest sign is contraction of visual fields,gradual diminution of vision begins in 1 eye,progress to a certain point,then begins in the other eye,becomes blind in 3 to 8yrs if untreated

📍Ophthalmoscopy:
Bluish white disc with normal/blurred disc margins, later becomes funnel shaped with central depression due to atrophy of central fibres, attenuated vessels

📍Atonic bladder-Loss of sensation .So when bladder fills, there will be no
detrusor reflex; demonstrated by cystometrogram

📍CN palsies-CN 3,4,6,8,ptosis

📍Chemoreceptor reflex

📍Postural hypotension

📍CSF:-Type II(Normal in 11%)

📍DDs:-Meningomyelitis,Chronic polyneuritis due to vitamin deficiency/  alcoholism/ lead poisoning/DM/ diphtheria, Frederich’s ataxia,SACD,Disseminated sclerosis,Adies pupil syndrome

4)GUMMA OF SPINAL CORD

📍Very rare
Most common site-Meninges
Size increase🡪invade &compress spinal cord

📍Symptoms-Gradual onset ,spastic paraplegia with sensory level below a specific level, trophic ulcers

📍CSF-Type I/II;high protein level( loculation syndrome of
Froin)

📍Other tests-Queckenstedt’s test,Xray myelography

📍DDs-Spinal tumor,other forms of spinal syphilis

📌FEW  MISCELLANEOUS  ENTITIES

📍TABOPARESIS
In the same patient,  of both brain &spinal cord are affected
So , features of both present

📍HIV and NEUROSYPHILIS
🔔Early onset of Neurosyphilis

🔔May occur within 2 years of diagnosis

🔔Atypical and severe presentations

🔔CSF cell count of more than 20 is significant

🔔“Neurorelapse”-May not be cured even after adequate therapy

🔔Maximum risk-CD4 less than 350,RPR titre more than 1:32

📍BABINSKI SYNDROME:-

Co- existence of neurosyphilis and cardiovascular syphilis

📌TREATMENT  OF  NEUROSYPHILIS

📍Evolution of Rx of Neurosyphilis

1)Pyrotherapy

*Rationale-artificially induce fever to kill tryponemes

*Agents used-hot water, warm air, Turpentine ,tuberculine, Hg, samonella typhi

2)Malaria therapy

*Rationale-malaria induce fever paroxysms.It treats neurosyphilis

*Malaria can then be cured by Quinine

*By Julius Wagner Jauregg(1917)
He received Nobel prize for this Rx method

3)Other agents used-Neoarsphenamine,Bismuth etc

4)SINCE1943 ,PENICILLIN IS THE TREATMENT OF
SYPHILIS INCLUDING NEUROSYPHILIS

MANAGEMENT OF NEUROSYPHILIS(CDC-2015)

*Recommended regime:-
Aqueous crystalline Penicillin G 18-24 million units per day ,administered as 3-4 million units iv every 4 hours or continuous infusion for 10-14 days

*Alternative regimes:-
-Procaine Penicillin G 2.4 million units IM once daily ,for 10-14 days
-Probenecid 500mg orally 4 times a day,for 10-14 days
-Benzathine Penicillin 2.4million units im once per week for upto 3weeks 

📍All neurosyphilis patients must be tested for HIV

📍When to retreat the patient?
a)CSF cell count not decreased after 6 months of Rx
b)CSF cell count or protein is not normal after 2 years

📍If Penicillin allergy??
*Ceftriaxone 2g daily im/iv for 10-14 days(limited evidence)
*Penicillin desensitization

📍Pregnant patients with neurosyphilis-Penicillin

📍Follow up of a neurosyphilis case:-

Every 6mths until CSF cell count is normal(CSF proteins& VDRL takes much more time to become normal)

📍Dattner Thomas Concept(1942)-The cure of a neurosyphilis patient is assured if all his spinal fluid tests become and remain negative

📍Risk of life threatening Jarisch-Herxheimer reaction is high in neurosyphilis- Some advice oral Prednisolone 30-60 mg daily for 3 days.May begin Penicillin,24 hours after the 1st dose

📍As per the CDC , indications of CSF VDRL:-
1)Neurologic or ophthalmic symptoms/signs
2)Evidence of active tertiary syphilis(aortitis/gumma/iritis)
3)Who has Rx failure as defined by serological titre response
4)Who is HIV+ve ,with late latent syphilis or syphilis of unknownduration
5)If sustained(>2weeks) 4-fold increase or more in titre
6)Initially high titre(1:32 or more)fails to decline atleast 4-fold
within 12-24months of therapy

📍CSF VDRL-Highly specific but not very sensitive (upto 50% false negativity).So
a negative CSF VDRL does not rule out Neurosyphilis

📍CSF Tryponemal tests are more sensitive but less specifi

📌CONCLUSION

📍Neurosyphilis is now an uncommon,but serious presentation of the great imitator disease

📍Must be thought about this entity in, early strokes,HIV patients,mental disturbances in young adults and patients with pupillary abnormalities

📍The treatment of Neurosyphilis is Penicillin