CNS syndromes,pyogenic meningitis Flashcards
(91 cards)
1
Q
Leptomeninges
A
Arachnoid and pia mater
2
Q
Modes of spread of CNS infections
A
- Hematogenous spread
- Direct spread
- Anatomical defect
- Direct intraneural spread
3
Q
Infective syndromes of CNS
A
1. Meningitis: • acute bacterial • acute viral • chronic 2. Encephalitis and encephalopathy: 3. Space occupying lesions: • focal CNS lesions • cystic parasitic diseases 4. Other
4
Q
Types of meningitis
A
Acute meningitis:
progresses rapidly in a few hours. It can be further grouped acute bacterial (or pyogenic) and acute viral meningitis
Chronic meningitis: Progressively worsens over weeks (>4 weeks). This includes bacterial, parasitic, fungal agents and viral agents.
Some of the agents of chronic meningitis have a subacute course that progressively worsens over several days.
5
Q
Host reaction to meningitis
A
The host inflammatory response in meningitis may vary—acute bacterial meningitis - 🔼 neutrophil count in CSF, whereas
both acute viral meningitis and chronic meningitis are predominantly lymphocytic
6
Q
Chronic meningitis types
A
- Chronic persistent meningitis:
In most of the cases, the symptoms are chronic and persistent
2. Chronic recurrent meningitis: Characterized by discrete episodes of illness along with the absence of symptoms with normal CSF parameters between episodes.
Eg., Mollaret’s meningitis, caused by HSV type 2
7
Q
Aseptic meningitis
A
Traditionally used to describe those meningitis, where the infectious etiology is unidentified. This used to include agents other than bacteria such as the agents of acute viral meningitis and chronic meningitis. However in the modern era of sophisticated diagnostic facility (e.g. molecular methods), it is now possible to detect most of these agents
8
Q
Clinical manifestations of meningitis
A
Patients with meningitis present with high-grade fever, 🤮, headache, neck rigidity and certain unique signs: Kernig’s and Brudzinski’s signs
9
Q
Manifestations of encephalitis
A
The common manifestations include altered consciousness, behavioral changes, seizures, focal neurological deficits and sometimes, extrapyramidal signs such as involuntary movements
The cellular infiltrate present in the CSF is typically lymphocytic rather than neutrophilic
10
Q
Agents of encephalitis
A
1. Viruses: • rabies • herpes • arboviruses such as JE & West Nile viruses 2. Parasites: • Toxoplasma gondii • Naegleria fowleri
11
Q
meningoencephalitis
A
Very often, encephalitis is associated with concomitant meningitis; called as meningoencephalitis (e.g. primary amoebic meningoencephalitis, caused by a free-living amoeba called Naegleria fowleri)
12
Q
Brain abscesses
source of infection
A
- Contiguous infection of the adjacent structures such as sinuses, middle ear or mastoids (45%–50%)
2. Hematogenous:
especially in patients with cyanotic congenital heart disease (25%) - Direct inoculation as a result of trauma or surgery (10%)
4. Cryptogenic: In at least 15% of cases, the source of the infection is unknown.
13
Q
Brain abscesses in immunocompetent individuals
A
1. Streptococci: M/C anaerobic, aerobic, and viridans group (e.g. S. anginosis) 2. Anaerobes: Bacteroides fragilis, Fusobacterium 3. Enterobacteriaceae: Proteus, E. coli, Klebsiella 4. Staphylococcus aureus: Usually in post-trauma or post-neurosurgery cases
14
Q
Brain abscesses in immunocompromised hosts
A
- Nocardia
- Toxoplasma gondii
- Aspergillus
- Candida and Cryptococcus
- Taenia solium (neurocysticercosis):
especially in Latin America
6. M. tuberculosis (tuberculoma):
especially in India and East Asia
15
Q
Brain abscesses
clinical features
A
Triad of: 1. 🤒 2. Severe headache (unilateral, on the side of the abscess) 3. Focal neurologic deficit constitute the major manifestations
16
Q
Brain abscess
treatment
A
1. Surgical excision or drainage of the abscess combined with prolonged antibiotics (for 6-8 weeks) remains the treatment of choice
2. Ceftriaxone plus metronidazole is the preferred regimen, if bacterial etiology is suspected
17
Q
Subdural Empyema
A
- Subdural empyema (or abscess) is an intracranial focal collection of purulent material located between the dura mater and the arachnoid
- 95% confined to frontal lobe.
- Source of infection, etiological agents and clinical presentation are similar to that described for brain abscess.
18
Q
Suppurative Intracranial Thrombophlebitis
A
Septic venous thrombosis of cortical veins and sinuses such as cavernous sinus, the lateral sinus, or the superior sagittal sinus.
• Cavernous sinus thrombophlebitis occurs secondary to infection of sinuses (sphenoid and ethmoid sinuses) and oral cavity
• Septic phlebitis of the lateral sinuses is associated with mastoiditis and otitis media
19
Q
Infectious myelitis
A
Inflammation of the spinal cord which can result in disruption of the connection from the brain to the rest of the body, and vice-versa. It may have either infectious or autoimmune etiology.
- Viral myelitis: M/C
e. g. poliovirus - Non-viral: rare
20
Q
Acute encephalitis syndrome (AES)
clinical presentation
A
AES presents with acute-onset of fever and a change in mental status (mental confusion, disorientation, delirium, or coma) and/or new-onset of seizures
• Japanese encephalitis virus (JEV) M/C in India (ranging from 5%-35%)
• The etiology in a large number of AES cases still remains unidentified.
21
Q
Agents of pyogenic meningitis
(overall)
A
- Streptococcus pneumoniae: M/C (~50%)
- Meningococcus (~25%)
- Streptococcus agalactiae(~15%)
- Listeria (~10%)
- Haemophilus influenzae (<10%)
22
Q
Acute bacterial meningitis in neonates
A
- Streptococcus agalactiae (elderly also)
- Gram-negative bacilli such as E coli and Klebsiella
- Listeria monocytogenes (elderly also)
23
Q
Transmission of acute bacterial meningitis
A
Bacteria that cause acute meningitis are transmitted through:
- Droplets M/C
- Close and prolonged contact—kissing, sneezing or coughing on someone, or living in close quarters with an infected person facilitate the spread of the disease.
24
Q
Acute bacterial meningitis
routes of spread
A
- Hematogenous spread:M/C
through the choroid plexus or through other blood vessels
2. Direct spread from an infected site present close to meninges—otitis media, mastoiditis, sinusitis, etc.
3. Anatomical defect in central nervous system (CNS):
surgery, trauma, congenital defects,
25
Neonates have the highest prevalence of meningitis; probably due to
1. Immature immune system,
2. Microbes of mother’s
birth canal (e.g. Listeria or Streptococcus agalactiae)
3. 🔼 permeability of blood brain barrier
26
Predisposing factors of pyogenic meningitis
1. Age: neonates are more susceptible
2. Vaccination status
3. Factors that promote infection at 1° site: respiratory
4. Presence of CSF shunts
5. Breach in BBB
27
Symptoms of pyogenic meningitis
1. 🤒
2. 🤮
3. Intense headache
4. Altered consciousness
5. Occasionally photophobia
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Signs of pyogenic meningitis
1. Nuchal rigidity (“stiff neck”) specific:
neck resists passive flexion
2. Kernig’s sign:
Severe stiffness of the hamstrings ➡️ inability to straighten the leg when the hip is flexed to 90°
3. Brudzinski’s sign: When the neck is passively flexed, results in spontaneous flexion of the hips and knees
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Manifestations of pyogenic meningitis in infants
Pyogenic meningitis in infants may have a slower onset, signs may be nonspecific, and neck stiffness may not be present. Babies usually present with fever, irritability and bulging fontanelle
30
Specimen collection of pyogenic meningitis
CSF is obtained by lumbar puncture under strict aseptic conditions.
It is divided into three sterile containers;
1. cell count
2. biochemical analysis
3. bacteriological examination
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Specimen transport of pyogenic meningitis
CSF should be examined immediately
• When the bacteriological examination (culture) is required, it should never be refrigerated as delicate pathogens such as H. influenzae, pneumococci or meningococci may die
➡️ if a delay is expected, it may be kept in an incubator at 37°C
• However for molecular diagnosis, CSF can be kept inside the freezer
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Specimen collection & transport for suspected meningococcal meningitis
Lumbar puncture. Other useful specimens are nasopharyngeal swabs, pus or scrapings from rashes; carried in transport media (such as Stuart’s medium).
• These specimens are inoculated onto selective media, such as Thayer Martin medium or New York City medium, to suppress the growth of normal flora
33
Cytological and biochemical parameters in CSF of pyogenic meningitis
1. CSF pressure: >180
2. TLC: 100-10,000
3. Neutrophils predominant
4. Glucose <40 mg
Decreased to absent
5. Total proteins:
>45 mg/dL
34
Heaped smear
As the bacterial load in CSF may be very low, to increase the sensitivity, several drops of CSF should be placed at the same spot on the slide, each drop being allowed to air dry before the next is added
Centrifugation can be used
35
Direct antigen test for pyogenic meningitis
1. From CSF:
Latex agglutination test for detection of capsular antigens of agents of meningitis such as S. pneumoniae, S. agalactiae, N. meningitidis, H. influenzae or E. coli
(Antigen detection is more sensitive than CSF microscopy)
2. From urine:
Immunochromatographic test (ICT) is available to detect the C-polysaccharide antigen of S. pneumoniae in urine.
36
Culture of agents of pyogenic meningitis
1. Enriching:
Bacterial load 🔽➡️ a part of the CSF is inoculated into enriched media such as blood culture bottles at the bed side (preferred) or BHI broth in the laboratory
2. Blood culture can be collected in conventional blood culture bottles such as BHI broth/agar or preferably in automated blood cultures
37
Molecular methods for pyogenic meningitis detection
1. Multiplex PCR and multiplex real-time PCR
can be used for simultaneous detection
2. BioFire FilmArray:
• automated nested multiplex PCR
• simultaneously detect 14 common agents of meningitis (both pyogenic and viral) in CSF
• turnaround time of 1 hour
38
Genes targeted for pyogenic meningitis
```
1. Meningococcus:
ctrA (capsule transport gene)
sodC (Cu-Zn superoxide dismutase gene)
2. Pneumococcus:
lytA (autolysin gene)
ply (pneumolysin)
psaA (pneumococcus surface antigen A)
3. H. influenzae: Conserved capsular gene bexA.
```
39
Empirical treatment of pyogenic meningitis
Based on the type of organism suspected and good CSF penetration ability of the agent.
Empirical therapy comprises of:
1. Adult: IV cefotaxime or ceftriaxone and vancomycin
If Listeria is suspected, IV ampicillin can be added
2. For neonates: IV ampicillin plus gentamicin
3. IV dexamethasone is added to the regimen to reduce intra-cranial pressure
40
Pneumococcal meningitis
| basics
```
Streptococcus pneumoniae (or pneumococcus)
M/C
The principle virulence factors:
1. capsular polysaccharide
2. C-carbohydrate antigen
3. pneumolysin
4. autolysin
Mortality rate remains high (~20%), despite antibiotic therapy.
```
41
Risk factors of pneumococcal meningitis
1. Underlying pneumococcal pneumonia (most important)
2. Otitis media
3. Alcoholism
4. Diabetes
5. Splenectomy
6. Complement deficiency
7. Hypogammaglobulinemia
8. Head trauma
42
Meningococcal meningitis
| basics
```
Neisseria meningitidis or meningococcus
Potential to cause large outbreaks
Virulence factors:
1. Capsular polysaccharide:
divided into serogroups
2. Outer membrane proteins
3. LPS and endotoxin
```
43
Serogroups of meningococcus
Group A:
Was leading cause of epidemic meningitis worldwide. With vaccination ➡️ 🔽 considerably
Group B and C are currently the major serogroups
Group B can cause hyperendemic diseases
Group C continues to cause outbreaks
Group X, Y and W are less commonly reported worldwide.
📝 :Group W can cause outbreaks in mass gatherings; has caused the global outbreak in 2000 in Hajj pilgrimage
44
Risk factors that promote colonization for meningococcus
1. Overcrowding and semiclosed communities, such as schools, military and refugee camps
2. Travelers (e.g. Hajj pilgrims)
3. 🚬
4. Recent URTI
45
Risk factors that promote disease in meningococcus
1. Deficiency of terminal complement components (C5–C9)
2. Eculizumab or ravulizumab therapy—a terminal complement inhibitor
3. Hypogammaglobulinemia and hyposplenism.
46
Pathogenesis of meningococcus
Humans are the only natural host for meningococci. M/C source of infection - nasopharyngeal carriers.
Mode of transmission: droplet inhalation
Spread of infection:
1. Hematogenous route:M/C septicemia
2. Direct spread along olfactory nerve through cribriform plate
3. Rarely through conjunctiva
47
```
Neisseria meningitidis (or meningococcus)
clinical manifestations
```
1. Non-blanching rashes: M/C
2. Septicemia: endotoxins
3 Waterhouse–Friderichsen syndrome
4. Pyogenic meningitis: young children
5. Chronic meningococcemia
6. Post meningococcal reactive disease
48
Waterhouse–Friderichsen syndrome
It is a severe form of fulminant meningococcemia, characterized by:
1. Large purpuric rashes (purpura fulminans)
2. Shock
3. DIC
4. Bilateral adrenal hemorrhage
5. Multiorgan failure
49
Chronic meningococcemia
It occurs rarely and is characterized by:
1. Repeated episodes of petechial rashes
2. 🤒
3. Arthritis
4. Splenomegaly
50
Postmeningococcal reactive disease
```
Immune complexes (made up of capsular antigens and their antibodies) develop 4–10 days later, lead to:
1. Rash
2. Arthritis, iritis,
pericarditis, polyserositis
3. 🤒
```
51
Treatment for meningococcal meningitis
1. Drug of choice is third-generation cephalosporins, such as ceftriaxone or cefotaxime, given for 7 days.
(Penicillin can also be given; however, reduced meningococcal sensitivity to penicillin has been reported from few countries)
2. Symptomatic treatment:
such as aggressive fluid resuscitation (for shock) and measures to decrease intracranial pressure should be instituted.
52
Chemoprophylaxis of meningococcal meningitis
Chemoprophylaxis is indicated to the close contacts of primary cases, regardless of their vaccination status.
• Close contacts refers to household contacts and others who are directly exposed to patient’s oral secretions, in the 7 days before symptom onset.
• Ceftriaxone (single dose, IM) is the drug of choice
• Alternatively, rifampicin or ciprofloxacin can be given.
53
Indications for vaccine prophylaxis of meningococcus
(i) contacts of patients during outbreaks,
(ii) splenic dysfunction,
(iii) terminal complement component deficiency
(iv) taking eculizumab therapy,
(v) laboratory staff at risk
(vi) international travellers, including students
54
Capsular vaccine is not available for serogroup B of meningococcus as
Complications?
Capsule of serogroup B (made up of sialic acid) is less immunogenic
It is also encephalitogenic due to expression of similar cross reactive antigens on neural cells
55
Meningococcal vaccine is not given below 3 years because
Similar to pneumococcal vaccine, meningococcal capsular vaccine is also an example of T cell-independent antigen and is poorly immunogenic to children
56
Haemophilus influenzae Meningitis
| basics
• Haemophilus influenzae was previously an important agent of pyogenic meningitis
• Incidence has been dramatically reduced after the start of its effective vaccination.
• Virulence factor:
Capsular polysaccharide is the most important virulence factor, acts by inhibiting phagocytosis
57
Serotypes of Haemophilus influenzae
Hib: Out of the six capsular serotypes, H. influenzaeserotype b (Hib) is the most virulent types; responsible for pneumonia, which subsequently spread by hematogenous route to cause meningitis
58
Hib causes various CNS infections such
| as:
1. Pyogenic meningitis:
mainly in children less than 2 years of age
2. Subdural effusion: It is a common complication following meningitis, characterized by seizures or hemiparesis
📝: Mortality rate is high if untreated. Survivors develop neurologic sequelae, such as partial hearing loss and delayed language development
59
Group B Streptococcal (S. agalactiae) meningitis
Group B Streptococcus major cause of neonatal sepsis and meningitis.
Two types
1. Early-onset:
in 1st week of life and due to transmission from the maternal genital tract during or before birth
2. Late-onset:
from 7-90 days of birth, transmitted by contact with a colonized mother or nurse.
📝: Group B Streptococcus has been reported with increasing frequency in individuals aged >50 years, particularly those with underlying diseases
60
Gram-negative bacilli meningitis
| seen in
1. Individuals with chronic and debilitating diseases such as diabetes, cirrhosis, or alcoholism
2. Chronic UTI
3. 2° to neurosurgical procedures and head trauma with CSF rhinorrhea or otorrhea.
61
Examples of agents causing Gram-negative bacilli meningitis
1. Escherichia coli and Klebsiella M/C cause of pyogenic meningitis in neonates
2. Pseudomonas can cause meningitis in post-op or post-traumatic patients (head trauma with CSF rhinorrhea or otorrhea)
3. Acinetobacter is associated with post-neurosurgical meningitis
4. Elizabethkingia meningosepticum can cause meningitis in neonates
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Listeria monocytogenes
| basics
Listeriosis is caused by Listeria monocytogenes, which is a food-borne pathogen that can cause serious infections, particularly in neonates, 🤰 and elderly
Ubiquitous saprophyte and known to cause epizootic disease in birds and animals
Can survive refrigeration (4°C), ➡️ commonly found in stored foods
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Transmission and Risk factors of listeriosis
Mode of transmission: M/C through contaminated food followed by vertical transmission (mother to fetus)
1. Common food sources include contaminated coleslaw, milk, soft cheeses, and several types of “ready-to-eat” foods
2. Listeriosis is common among extremes of age,🤰 and immunocompromised
3. Proton pump inhibitors 🔼 risk by 🔽 the gastric acid mediated killing of Listeria
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Listeriosis
| pathogenesis
1. Intracellular survival: After entry into the intestinal epithelium, it survives inside the host cell, mainly due to lysis of phagosome by forming pores (mediated by listeriolysin O)
2. Then it causes host cell actin polymerization, which helps the bacterium to reach near the cell membrane
3. Finally, it migrates to the adjacent epithelial cells/macrophages by direct cell-to-cell spread, mediated by listeriopods
65
Clinical manifestations of listeriosis
Most of the human infections are caused due to serotypes 1/2a, 1/2b, and 4.
1. Neonatal listeriosis: Two clinical presentations: early-onset and late-onset neonatal disease
2. In 🤰: affects both mother and fetus.
3. Adults: bacteremia and meningitis
66
Clinical manifestations of listeriosis in pregnant mothers
```
Affects both mother and fetus.
1. Fetal complications:
• abortion,
• preterm delivery ➡️ early onset disease
2. Maternal complications,
• flu-like symptoms
• bacteremia
• meningitis
```
67
Clinical manifestations of listeriosis in adults
It produces manifestations such as bacteremia and meningitis in elderly individuals (>60 years)
• Common risk factor is immunosuppression (steroid therapy, HIV, diabetes, malignancy)
• Listeria can cause meningitis in kidney transplanted patients 1-month after the transplantation
• It also causes gastroenteritis following consumption
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Treatment of listeriosis
Meningitis:
Ampicillin DoC, given for 2–3 weeks in combination with gentamicin for synergistic effect
• Cotrimoxazole is given for patients with penicillin allergy
• In febrile gastroenteritis, Amoxicillin is recommended in immunocompromised, elderly or 🤰
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Chronic meningitis
Persistence of signs and symptoms as well as the CSF abnormality for >4 weeks
70
Bacterial agents of chronic meningitis
1. Partially treated pyogenic meningitis
2. Parameningeal infections (e.g. otitis media)
3. Mycobacterium tuberculosis
4. Borrelia burgdorferi (Lyme disease)
5. Treponema pallidum (tertiary syphilis)
71
Chronic bacterial meningitis
| clinical manifestations
1. Persistent headache and neck or back pain/stiffness
2. Hydrocephalus
3. Cranial neuropathies:
Leads to facial weakness, diminished vision, papilledema, optic atrophy, hearing loss
4. Myelopathy or radiculopathy: Leads to arm or leg weakness or numbness, urinary retention/incontinence
5. Changes in the personality such as altered mental status—drowsiness, inattention, disorientation, and memory loss.
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Mycobacterium tuberculosis Infections of CNS
Tuberculosis of the CNS accounts for ~5% of extrapulmonary
cases. It is seen most often in young children but also develops in adults, especially those infected with HIV. It presents in two clinical forms: tuberculous meningitis and tuberculoma.
73
Tuberculous Meningitis (TBM) basics
TBM results from the hematogenous spread of primary or post-primary pulmonary TB.
Typically, the disease evolves over 1–2 weeks or longer, which differentiates it from bacterial meningitis
74
```
Tuberculous Meningitis (TBM)
Clinical Features
```
1. Headache, slight mental changes, low-grade 🤒 , malaise, night sweat, anorexia, and irritability.
2. Evolve acutely with severe headache, confusion, lethargy, altered sensorium, and neck rigidity
3. Cranial nerves paresis (ocular nerves) is common.
4. Stroke (cerebral arteritis)
5. Coma, with hydrocephalus and intracranial hypertension.
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Tuberculous Meningitis (TBM) lab diagnosis
```
1. CSF analysis:
🔼 TLC (lymphocytic)
Protein 100-800 mg/dL
🔽 glucose
2. Cobweb 🕸 coagulum
3. Acid fast staining
4. CSF culture: slow but gold standard
5. GeneXpert assay: preferred
6. Imaging: hydrocephalus
Other TB lesions in half
```
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Cobweb coagulum
In Tuberculous Meningitis (TBM) when CSF is kept in a tube for 12 hours, a coagulum forms in the form of a cobweb due to higher fibrin content in the fluid
Acid-fast staining of cobweb may give better yield as TB bacilli may be trapped in it. However, the strands may be mistaken as fungi
77
Tuberculous Meningitis (TBM)
Acid-fast staining of CSF
Direct smear of CSF sediment may reveal bacilli. However, sensitivity is very low and may require repeated lumbar punctures to increase the yield
Acid-fast staining of cobweb may give better yield as TB bacilli may be trapped in it. However, the strands may be mistaken as fungi
78
```
Tuberculous Meningitis (TBM)
culture of CSF
```
Culture of CSF is diagnostic in up to 80% of cases and remains as the gold standard test.
However, culture is time consuming, takes 4–8 weeks by Lowenstein-Jensen medium and 2-3 weeks by automated liquid culture, such as Mycobacteria Growth Indicator Tube (MGIT)
79
Treatment of Tuberculous meningitis
If unrecognized, TBM is invariably fatal.
• Treatment should be initiated immediately upon a ➕ GeneXpert MTB/RIF result (though a ➖ result does not exclude TB)
• It responds well to anti-tubercular therapy, if started early.
• However, neurologic sequelae may occur, if Rx is delayed
• Adjunctive glucocorticoids will reduce the CSF pressure, resulting in faster resolution.
80
Tuberculoma (or Tuberculous Granulomas)
Uncommon manifestation of tubercular infection of CNS
• Space-occupying lesions (firm nodule with central caseous necrosis)
• Usually causes seizures and focal signs.
• CT or MRI reveals contrast-enhanced ring lesions, but biopsy is necessary to diagnose and differentiate it from malignancies
81
Neuroborreliosis (Lyme Disease)
| basics and manifestations
By Borrelia burgdorferi through tick bite.
Apart from cutaneous lesions and arthritis it may present with various CNS infections after several weeks or months:
1. Meningitis
2. Subtle encephalitic signs
3. Cranial neuritis (including bilateral facial palsy)
4. Radiculoneuropathy
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Neuroborreliosis (Lyme Disease)
| CSF findings
1. Elevated lymphocytes (~100 cells/μL)
2. Elevated protein levels
3. Normal or slightly low glucose level
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Meningopolyneuritis
| Bannwarth’s syndrome [of Neuroborreliosis (Lyme Disease)]
Seen in cases of neuroborreliosis (Lyme disease) from Europe and Asia, which presents as radicular pain with CSF pleocytosis, without meningeal or encephalitic signs
84
Neuroborreliosis (Lyme Disease)
| treatment
IV ceftriaxone for 14–28 days is recommended for neuroborreliosis.
Alternatively IV cefotaxime or IV penicillin G can be given
85
Neurosyphilis
| basics
Neurosyphilis is a type of tertiary form of syphilis, which develops in about 10% of untreated patients
Invasion of CNS occurs early within first few weeks of infection, which is followed by decades of asymptomatic period.
86
Neurosyphilis
| clinical manifestations
```
1. Asymptomatic neurosyphilis:
25-40% of cases
2. Meningeal syphilis:
Chronic meningitis
3. Meningovascular syphilis:
Vasculitis of arteries leading to embolic stroke
4. General paresis of insane:
5. Tabes dorsalis: late manifestation
Demyelination of the posterior columns such as ataxia, foot drop, paresthesia, bladder disturbances and impotence
```
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General paresis of insane
```
It is a late manifestation of Neurosyphilis
Features of parenchymal damage such as defects in:
P. Personality
A. Affect,
R. Reflexes (hyperactive)
E. Eye (e.g. Argyll Robertson pupils)
S. Sensorium (illusions, delusions,…)
I. Intellect (recent memory loss)
S. Speech
```
88
Neurosyphilis
| lab diagnosis
```
1. CSF analysis:
• 🔼 lymphocytes (>5/μL)
• 🔼 protein level (>45 mg/dL)
2. CSF VDRL test
High specificity but less sensitivity
3. FTA-ABS test (fluorescent treponemal antibody absorption)
4. PCR based tests: high sensitivity
```
89
CSF VDRL test
• Venereal disease research laboratory (VDRL) is a nontreponemal test, detects antibodies against a nonspecific cardiolipin antigen derived from bovine heart
• It is highly specific and, when reactive, is considered diagnostic of neurosyphilis. But, it has low sensitivity
📝 : other nontreponemal test like RPR (rapid plasma reagin) test can’t be performed on CSF ➡️ shouldn’t be used in substitution of VDRL for neurosyphilis
90
FTA-ABS test (fluorescent treponemal antibody
| absorption test) for neurosyphilis
It is reactive far more often than the CSF VDRL test in all stages of syphilis, but reactivity may reflect passive transfer of serum antibody into the CSF.
A nonreactive FTA-ABS test on CSF however may be used to rule out asymptomatic neurosyphilis
91
Treatment of neurosyphilis
• Aqueous crystalline or procaine penicillin G is given for 10–14 days for neurosyphilis or in cases of abnormal CSF in any stage.
• Consider re-treatment if non-treponemal titres in CSF do not decrease by four-folds within 2 years of completion of treatment
📝: In patients with penicillin allergy, desensitization to penicillin has to be done, following which penicillin is administered.
