CNS Infection mbbs.pptx. ooooooooooooooo

Lecture Outline: infections of the central nervous system
Bacterial infections
• Tuberculosis
• Leprosy
• Neurosyphilis
• Lysteriosis
• Bacterial meningitis
•Brain abscess
Viral infections
• Viral
meningitis
• Herpes
simplex
encephalitis
• Rabies
• Poliomyelitis
• Progressive
multifocal
leukoenceph
alopathy
Protozoal infections
•Toxoplasmosis
Fungal infections
•Cryptococcal meningitis
Parasites
• Neurocysticercosis
CT: Neurocysticercosis

Bacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS.
⚫
⚫ Meningitis: Inflammation of meninges. Bacterial infection involving the leptomeninges
within the subarachnoid space.
Infection of leptomeninges
⚫ Skull or backbone fractures
⚫ Medical procedures
⚫ Along peripheral nerves
⚫ Blood or lymph
⚫ Encephalitis: Inflammation of the brain.

•Depending on the duration of symptoms, meningitis may be classified as
acute or chronic:
•Acute meningitis evolution of symptoms within hours to several days, Acute
meningitis (<1 d) is almost always a bacterial infection. Expedient diagnosis is
essential.
•Patients with acute bacterial meningitis may decompensate very quickly and
so they require emergency care, including antimicrobial therapy, ideally
within 30 minutes of emergency department (ED) presentation.
•Chronic meningitis has an onset and duration of weeks to months. The
duration of symptoms of chronic meningitis is characteristically at least 4
weeks.
•Most bacterial meningitis is not acute. Approximately 75% of patients with
bacterial meningitis present subacutely with symptoms beginning several
days prior.
•Chronic symptoms lasting longer than 1 week suggest meningitis caused by
some viruses as well as tuberculosis, syphilis, fungi (especially cryptococci).

•Three major pathways exist by which an infectious agent bacteria, virus, fungus, or
parasites gain access to the CNS
•From this site, the organism invades the submucosa by circumventing host defenses (eg,
physical barriers, local immunity, phagocytes/macrophages) and gains access to the CNS
by (1) invasion of the bloodstream (ie, bacteremia, viremia, fungemia, parasitemia) and
subsequent hematogenous seeding of the CNS, which is the most common mode of
spread for most agents (eg, meningococcal, cryptococcal, syphilitic, and pneumococcal
meningitis); (2) a retrograde neuronal (ie, olfactory and peripheral nerves) pathway or (3)
direct contiguous spread (ie, sinusitis, otitis media, congenital malformations, trauma,
direct inoculation during intracranial manipulation).
•Bacteria from the maternal genital tract colonize the neonate after rupture of
membranes, and specific bacteria, such as group B streptococci (GBS), enteric gram-
negative rods, and Listeria monocytogenes, can reach the fetus transplacentally and
cause infection
•Once pathogens enter the subarachnoid space, an intense host inflammatory response
is triggered by lipoteichoic acid and other bacterial cell wall products produced as a result
of bacterial lysis. This response is mediated by the stimulation of macrophage-equivalent
brain cells that produce cytokines and other inflammatory mediators. This resultant
cytokine activation then initiates several processes that ultimately cause damage in the
subarachnoid space, culminating in neuronal injury and apoptosis.

•Mortality/Morbidity
•Morbidity and mortality depend on pathogen, patient's age and condition, and severity of acute illness.
•Despite advances in care for patients with bacterial meningitis, the overall case fatality remains steady at
approximately 10-30%.
•Bacterial meningitis was uniformly fatal before the antimicrobial era. With the advent of antimicrobial
therapy, the overall mortality rate from bacterial meningitis has decreased but remains alarmingly high
approximately 25%.
•Among the common causes of acute bacterial meningitis, the highest mortality rate is observed with
pneumococcus. The reported mortality rates for each specific organism are 19-26% for S pneumoniae
meningitis,
• 3-6% for H influenzae meningitis,
•3-13% for N meningitides meningitis
Sex
•Male infants have a higher incidence of gram-negative neonatal meningitis male-to-female ratio is
3:1.
Age
•Very young individuals (infants and young children) and elderly individuals (>60 y) are more predisposed
to the infection.
•Newborns are at highest risk for acute bacterial meningitis. After the first month of life, the peak
incidence is in infants aged 3-8 months.

The classic presentation of meningitis includes the triad fever, sever neck stiffness/rigidity, called
meningismus, and change in mental status (eg, lethargy, confusion, irritability, delirium, and coma)
Signs of meningeal irritation are observed in only approximately 50% of patients with bacterial meningitis,
and their absence certainly does not rule out meningitis.
• Kernig sign: flex patients hip to a 90° angle and then attempting passively straighten the leg at the
knee produces pain in the hamstrings and resistance to further extension. Should present bilaterally to
support the meningitis diagnosis.
•Brudzinski sign: is positive if the patients hips and knees flex automatically when the examiner flexes the
patients neck while the patient is supine.
• Nuchal rigidity: Resistance to passive flexion of the neck is also a sign.
•Headache-Exacerbation of existing headache by repeated horizontal movement of the head, at a rate of 2-
3 times per second, may also suggest meningeal irritation.
•Cranial nerve palsies may be observed as a result of increased ICP or the presence of exudates
encasing the nerve roots.
• Nuchal rigidity (generally not present in children <1 y or in patients with altered mental status)
• Fever and chills
• Photophobia
• Vomiting
• Prodromal upper respiratory infection (URI) symptoms (viral and bacterial)
• Seizures (30-40% in children, 20-30% in adults)
•Papilledema is present in only one third of meningitis patients with increased ICP; it takes at least
several hours to develop.

Brudzinski Sign of Meningitis:

Kernig’s Sign of Meningitis:

Systemic findings upon physical examination may provide clues to the etiology.
o Skin findings range from a nonspecific blanching, erythematous, maculopapular
rash to a petechial or purpuric rash, most characteristic of meningococcal meningitis.
Commonly affects the trunk and extremities.
Symptoms in infants
Cardinal signs of meningitis (eg, fever, vomiting, stiff neck) are rarely present. For
neonatal meningitis, these signs are the exception, rather than the rule.
• Lethargy and/or change in level of alertness
• Poor feeding and/or vomiting
• Respiratory distress
• Bulging fontanelle
• Paradoxic irritability (ie, quiet when stationary, cries when held)
• High-pitched cry
• Hypotonia
•Approximately 6% of affected infants and children show signs of disseminated
intravascular coagulopathy and endotoxic shock. These signs are indicative of a poor
prognosis.

Meningitis is caused by the following pathogens in each age group:
•Beyond the neonatal period, the 3 most common organisms that
cause acute bacterial meningitis are Streptococcus pneumoniae,
Neisseria meningitidis, and Haemophilus influenzae type b (Hib).
•Neonates - Group B or D streptococci, Escherichia coli, and L
monocytogenes
•Infants and children -H influenzae (48%), S pneumoniae (13%), and N
meningitidis
•Adults -S pneumoniae, (30-50%), H influenzae (1-3%), N
meningitidis (10-35%), gram-negative bacilli (1-10%), staphylococci
(5-15%), streptococci (5%), and Listeria species (5%)

Etiology of neonatal meningitis
oBacteria are often acquired from the maternal vaginal flora.
oEarly onset group B streptococcal meningitis occurs during the first 7 days of life, a
consequence of maternal colonization and the absence of protective antibody in the
neonate; it is often associated with obstetric complications. The disease is seen most
often in premature or low birth weight babies. Pathogens are acquired before or
during the birth process.
Etiology of meningitis in infants and children:
In children older than 4 weeks, S pneumoniae and N meningitidis are the most
common etiologic agents. H influenzae type b has essentially disappeared in
countries where the conjugate vaccine is routinely used.
oMost deaths occur within 24 hours of hospital admission in patients who have
features associated with poor prognosis (eg, hypotension, shock, neutropenia,
extremes of ages, petechiae and purpura of <12 h duration, disseminated
intravascular coagulopathy, acidosis, presence of organism in WBC on peripheral
smear, low erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP],
serogroup C disease).

S pneumoniae meningitis
oS pneumoniae are lancet-shaped, gram-positive diplococcic, 84 serotypes.
oIt is a common colonizer of the human nasopharynx (5-10% of healthy adults and
20-40% of healthy children).
oPresently, it is the most common bacterial cause of meningitis, accounting for
47%
of cases.
oChildren of any age may be affected, but incidence and severity are highest in very
young and elderly persons.

N meningitidis meningitis
oN meningitis is a gram-negative diplococcus that is carried in the
nasopharynx of otherwise healthy individuals. It initiates invasion by
penetrating the airway epithelial surface.
oPresently, it is the leading cause of bacterial meningitis in children
and young adults, accounting for 59% of cases.
oMost cases occur in infants aged 6-12 months; a second lower peak
occurs among adolescents. A petechial or purpuric rash frequently is
seen.
oMost deaths occur within 24 hours of hospital admission in patients
who have features associated with poor prognosis (eg, hypotension,
shock, neutropenia, extremes of ages, petechiae and purpura of <12 h
duration, disseminated intravascular coagulopathy, acidosis, presence
of organism in WBC on peripheral smear, low erythrocyte
sedimentation rate [ESR] or C-reactive protein [CRP], serogroup C
disease).

H influenzae type b meningitis
oH influenzae type b is a gram-negative rod frequently found as part of
the normal flora in the upper respiratory tract.
oH influenzae meningitis occurs primarily in children who have not
been immunized with H influenzae type b vaccine, with 80-90% of the
cases occurring in children aged 1 month to 3 years
oIts isolation in adults suggests the presence of an underlying
medical disorder, including paranasal sinusitis, otitis media,
alcoholism, CSF leak following head trauma.
oSince the implementation of the HIB vaccine, the carriage rates for
the B strain have decreased from 2-4% to less than 1%
oCurrent mortality rates are less than 5%. Most fatalities occur
during the first few days of the illness.
oIt can spread from one individual to another by airborne droplets or
direct contact with secretions.

General guidelines
The cornerstone in the diagnosis of meningitis is examination of the
CSF.
Bacterial meningitis is a medical emergency. A firm diagnosis is usually
made when bacteria are isolated from the cerebrospinal fluid (CSF)
and evidence of meningeal inflammation is demonstrated by increased
pleocytosis, elevated protein level, and low glucose level in the CSF.
Measure the opening pressure and send the fluid for cell count (and
differential count), chemistry (ie, CSF glucose and protein), and
microbiology (ie, Gram stain and cultures).The opening pressure of CSF
should be measured in older children. Similarly, the color of the CSF
(eg, turbid, clear, bloody) should be recorded.

The bacterial meningitis score :
Positive cerebrospinal fluid Gram stain
CSF absolute neutrophil count greater than or equal
to 1000 cells/mcL
CSF protein greater than or equal to 80 mg/dL
Peripheral blood absolute neutrophil count greater
than or equal to 10000 cells/mcL
History of seizure before or at the time of
presentation

The opening pressure (reference range is 80-200 mm H2O) may be elevated,
suggesting some form of increased ICP from cerebral edema.
•If the spinal fluid is not crystal clear, administer treatment immediately without
waiting for the results of CSF tests.
•CT scan of the brain may be performed prior to lumbar puncture in some patient
groups with a higher risk of herniation.
•A lumbar puncture (LP) may be contraindicated in some of the following conditions
brain abscess, brain tumors or other cause of raised intracranial pressure, and
occasionally infection at the lumbar puncture site-
•Risk of cerebral herniation complicating lumbar puncture performed to diagnose
acute bacterial meningitis. perform CT examinations performed before a lumbar
puncture. An LP “removes the stopper from below, thus adding to the effects of the
compression from above.”
Infants and children
Many children receive antibiotics before definitive diagnosis is made. As a rule, a few
doses of oral antimicrobial agents, or even a single injection of an antibiotic, do not
significantly alter CSF findings, including bacterial cultures, especially in patients with H
influenzae type b disease.

•Examination of the CSF in patients with acute bacterial meningitis reveals
the characteristic neutrophilic pleocytosis (usually hundreds to a few
thousand, with >80% PMN cells). In some cases of L monocytogenes
meningitis (25-30%), a lymphocytic predominance may occur. Low CSF WBC
count (<20 cells/µL) in the presence of a high bacterial load suggests a poor
prognosis.
•The opening pressure (reference range is 80-200 mm H2O) may be
elevated, suggesting some form of increased ICP from cerebral edema.
•The CSF glucose (reference range is 40-70 mg/dL) is less than 40 mg/dL in
60% of patients. Obtain a simultaneous blood glucose determination for
comparison purposes. Some patients may have elevated blood sugar levels as
a result of underlying diabetes mellitus, and the predictive value of the CSF
and blood sugar ratio may not be accurate in these circumstances.
• The CSF protein (reference range is 20-50 mg/dL) is usually elevated.

Bacterial Meningitis Viral Meningitis* Fungal Meningitis**
Pressure
5-15 cm H2 O
Increased Normal or mildly increased Normal or mildly increased in TB. May
be increased in fungal. AIDS patients
with cryptococcal meningitis have
increased risk of blindness, death
unless maintained at <30 cm.
Cell count
preterm: 0-
25
term: 0-22
>6 months: 0-
5
mononuclear
cells/mm3
No cell count result can exclude
bacterial meningitis. Typically
thousands of PMNs, but may be less
dramatic or even normal (classically, in
very early meningococcal meningitis
and in extremely ill neonates).
Lymphocytosis with normal CSF
chemistries seen in 15-25%, especially
when cell counts <1000 or if partially
treated. Approximately 90% of patients
with ventriculoperitoneal shunts have
CSF WBC count >100 cells/mm3 are
infected; CSF glucose usually normal,
and organisms are less pathogenic. Cell
count and chemistries normalize slowly
(over days) with antibiotics.
Usually <500 cells, nearly 100%
mononuclear. Up to 48 hours, significant
PMN pleocytosis may be
indistinguishable from early bacterial
meningitis; this is particularly true with
eastern equine encephalitis. Presence
of nontraumatic RBCs in 80% of HSV
meningoencephalitis, although 10%
have normal CSF results
Hundreds of mononuclear
cells
Micro
no organisms
Gram stain 80% effective.
Inadequate decolorization may
mistake H influenzae for gram-
positive cocci.
Pretreatment with antibiotics may
affect stain uptake, causing gram-
positive organisms to appear gram
negative and decrease culture yield
on average 20%.
No organism India ink 80-90% effective for fungi;
AFB stain 40% effective for TB
(increase yield by staining supernate
from at least 5 cc CSF)
Glucose
euglycemia: >50% serum
hyperglycemia: >30% serum wait 4 h
after glucose load
Decreased Normal Sometimes decreased. Aside from
fulminant bacterial meningitis, the
lowest levels of CSF glucose are seen
in TB, primary amebic
Table 1. Comparison of CSF Findings by Type of Organism

•CSF Gram stain permits rapid identification of the bacterial cause in 60-90% of
patients with bacterial meningitis. The presence of bacteria is 100% specific, but the
sensitivity for detection is variable. The likelihood of detection is higher in the presence
of a higher bacterial concentration and diminishes with prior antibiotic use.
•CSF bacterial cultures yield the bacterial cause in 70-85% of cases. The yield
diminishes significantly in patients who have received antimicrobial therapy. In these
cases, some experts advocate the use of a CSF bacterial antigen assay. This is a latex
agglutination technique that can detect the antigens of HIB, S pneumoniae, N
meningitidis, E coli K1, and S agalactiae. Its theoretical advantage is the detection of
the bacterial antigens even after microbial killing, as is observed following antibacterial
therapy. Others, however, have shown that it may not be better than the Gram stain. It
is specific (a positive result indicates a diagnosis of bacterial meningitis), but a negative
finding on bacterial antigen test does not rule out meningitis (50-95% sensitivity).
•Obtain blood cultures and appropriate cultures from possible sites of infection.
Obtain these promptly and prior to the administration of an antibacterial agent. The
utility of these cultures is most evident in cases when the performance of a lumbar
puncture is delayed by the need for head imaging (risk for herniation in a patient with
focal neurologic deficit or coma) and when antimicrobial therapy is rightfully initiated
before the lumbar puncture and neuroimaging tests.

Acute viral meningitis
•The CSF picture of acute viral meningitis is different from the CSF picture of
bacterial meningitis.
• The opening pressure is usually within the reference range.
•The CSF cell count is usually in the few hundreds (100-1000 cells/µL) with a
predominance of lymphocytes. Some cases of echovirus, mumps, and HSV meningitis
may produce a neutrophilic picture early in the course of disease.
•The CSF glucose level is usually within the reference range, but some cases of
LCM, HSV, mumps, and polio may cause low CSF glucose levels.
• CSF protein levels may be within the reference range but are usually elevated.
• PCR assay
Cryptococcal meningitis
•The definitive diagnosis usually relies on the demonstration of the specific fungal
pathogen in the CSF.
•The CSF is characterized by a lymphocytic pleocytosis (10-200 lymphocytes), a
reduced glucose level, and an elevated protein level.
• The CSF opening pressure may be elevated at times, suggesting increased ICP.
•The CSF picture of other fungal meningitis is similar to the CSF picture of
cryptococcal meningitis, usually with lymphocytic pleocytosis.

Tuberculosis meningitis
•The CSF of patients with tuberculosis meningitis is characterized by a
predominantly lymphocytic pleocytosis, usually in the hundreds.
• The opening CSF pressure is usually elevated.
•A characteristic hypoglycorrhagia (glucose <40 mg/dL) is present, and the protein
level is usually elevated, especially if a CSF block is present.
•The demonstration of the acid-fast bacilli in the CSF is difficult and usually requires a
large volume of CSF.
•Meningeal biopsy, with the demonstration of caseating granulomas and acid-fast
bacilli on the smear, may prove useful because it has a higher yield than the CSF acid-
fast bacilli smear.
•The culture for Mycobacterium usually takes several weeks and may delay
definitive diagnosis.
• PCR
•The need for mycobacterial growth in cultures remains because this offers the
advantage of performing drug susceptibility assays.

Lumbar puncture
oElevated opening pressure correlates with increased risk of
morbidity and mortality in bacterial and fungal meningitis.
o Take tube #1 to chemistry lab for glucose and protein.
oTake tube #2 to hematology lab for cell count with
differential.
oTake tube #3 to microbiology and immunology lab for Gram
stain, bacterial culture, acid-fast bacillus (AFB) stain and
tuberculosis (TB) cultures, India ink stain and fungal cultures, CIE,
VDRL, and cryptococcal antigen, if indicated.
oHold tube #4 for repeat cell count with differential, if needed
(or for other subsequent studies not initially ordered).
oResearch correlates CSF cytokines in children with bacterial
meningitis.

Neonatal
Initiate treatment as soon as bacterial meningitis is suspected.
Ideally, blood and cerebrospinal fluid (CSF) cultures should be
obtained before antibiotics are administered.
Fluid and electrolyte management
By prescribing the correct type and volume of fluid, the risk of
development of brain edema can be minimized. The child should
receive fluids sufficient to maintain systolic blood pressure at
around 80 mm Hg, urinary output of 500 mL/m2/d, and adequate
tissue perfusion. Although care to avoid SIADH is important,
underhydrating the patient and risk of decreased cerebral
perfusion are equally concerning as well.

Traditionally, initial antimicrobial treatment consists of ampicillin
and an aminoglycoside combination (ampicillin and cefotaxime
also appropriate).As per the 2004 Infectious Diseases Society of
America (IDSA) practice guidelines for bacterial meningitis, the
combination of vancomycin and either ceftriaxone or cefotaxime
is recommended for those with suspected bacterial meningitis,
with targeted therapy based upon susceptibilities of isolated
pathogens. This combination provides adequate coverage for
most penicillin-resistant pneumococci and beta-lactamase
resistant H influenzaetype b.
Once the pathogen has been identified and antimicrobial
susceptibilities determined, the antibiotics may be modified for
optimal targetted treatment.

One of the major contributors to the morbidity
associated with bacterial meningitis is the severity of
inflammation. Decreased inflammation, reduction in
cerebral edema and intracranial pressure, and lessening
brain damage with use of dexamethasone.As a result,
the IDSA guidelines recommend the use of adjunctive
dexamethasone in cases of H influenzae type b
meningitis to be initiated 10-20 minutes prior to or at
least concomitant with the first antimicrobial dose at
0.15 mg/kg q6h for 2-4 days.

Bacteria Susceptibility Antibiotic(s)
Duration
(Days)
S pneumoniae Penicillin MIC <0.1 mg/L Penicillin G 10-14
MIC 0.1-1 mg/L Ceftriaxone or cefotaxime
MIC >2 mg/L Ceftriaxone or cefotaxime
Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime
plus vancomycin or
rifampin
H influenzae Beta-lactamase-negative Ampicillin 7
Beta-lactamase-positive Ceftriaxone or cefotaxime
N meningitidis ... Penicillin G or ampicillin 7
L monocytogenes ... Ampicillin or penicillin G
plus an aminoglycoside
14-21
S agalactiae ... Penicillin G plus an
aminoglycoside, if
warranted
14-21
Enterobacteriaceae ... Ceftriaxone or cefotaxime
plus an aminoglycoside
21
P aeruginosa ... Ceftazidime plus
an
21
Table.Specific Antibiotics and Duration of Therapy for Patients With Acute Bacterial Meningitis

•Neurosyphilis is caused by the bacteria spirochaete Treponema pallidum.
•Infects the brain and spinal cord.
•Occurs in persons with untreated syphilis 10 - 20 years after they are first
infected.
Incidence
•Before the advent of antibiotics, typically 25-35%
Neurosyphilis in HIV
• Neurosyphilis is now most common in patients with HIV infection.
•In the AIDS population up to 1-3% of patients are positive to cerebrospinal
fluid (CSF) Veneral Disease Research Laboratory (VDRL) tests. Without
therapy, 5-10% of patients develop clinical evidence of neurosyphilis.
•The classically described time intervals from infection to symptom onset of
20 and 25-30 years for, respectively, general paresis and tabes dorsalis
appear to be shortened in HIV-infected patients.

.
•The CNS manifestations of syphilis can be broadly classified into meningeal and parenchymal. Meningeal
manifestations range from the acute and more subtle and chronic forms of meningitis and
meningoencephalitis up to the formation of circumscribed masses. These gummas are composed, similarly
to those in all other sites in the body, of granulation tissue surrounded by mononuclear epithelial and
fibroblastic cells and, intracranially, usually located over the cerebral convexities, adherent to both dura and
brain parenchyma.
•Parenchymal manifestations include two types of vasculitis, respectively Heubner's and Nissl's endarteritis,
the former affecting large and medium-sized arteries with resultant irregular luminal narrowing and ectasia,
the latter primarily involving small vessels in which a luminal narrowing occurs as a consequence of intense
proliferation of endothelial and adventitial cells. Vascular neurosyphilis may present with focal neurological
deficits as a consequence of arterial occlusion.

•CSF examination: An abnormal leukocyte cell count, protein
level, or glucose level
•Demonstrated reactivity to Venereal Disease Research
Laboratory (VDRL) antibody test
Other tests include:
•Fluorescent treponemal antibody absorption
•Rapid plasma reagin
•Treponema pallidum particle
agglutination assay
•Cerebral angiogram
•Head CT or MRI scan
Imaging findings include meningeal enhancement and
small infarcts or foci of ischaemia with a predilection for
the basal ganglia and the middle cerebral artery regions,
revealed in the subacute phase by areas of contrast
enhancement. Cerebral atrophy is a frequent
accompaniment. Gummas are visible as mass lesions, with
nodular or ring enhancement, at the brain surface.

•Syphilitic meningitis. Acute syphilitic meningitis usually occurs within the first few weeks to
the first few years of infection; 10% of cases are diagnosed at the time of the secondary-stage
syphilis rash. Patients present with headache, stiff neck, nausea, and vomiting, meningeal
irritation, Argyll Robertson pupil (miotic pupil not reactive to light but reactive to
accommodation is pathognomonic), and cranial nerve abnormalities, especially the optic
nerve, facial nerve and the vestibulocochlear nerve. Rarely, it affects the spine instead of the
brain, causing focal muscle weakness or sensory loss.
•Meningovascular syphilis occurs 10 or more years (average, 7 years) after the primary
syphilis infection. Meningovascular syphilis can be associated with prodromal symptoms
lasting weeks to months before focal deficits are identifiable. Prodromal symptoms include
unilateral numbness, paresthesias, upper or lower extremity weakness, headache, vertigo,
insomnia, and psychiatric abnormalities such as personality changes. The focal deficits initially
are intermittent or progress slowly over a few days-seizures and paraplegia. However, it can
also present as an infectious arteritis and cause an ischemic stroke. Angiography may be able
to demonstrate areas of narrowing in the blood vessels or total occlusion.

•General paresis (dementia paralytica) is a severe manifestation of neurosyphilis. It is a chronic
dementia that ultimately results in death in as little as 2-3 years. General paresis can occur between 3-30
years after infection, mostly in patients >40 years. Other clinical signs include: delusions, alterations of
personality, memory loss and speech difficulties, and associated with a general hypereflexitivity and with
the Argyll Robertson pupil. Pathology: General paresis appears to be the result of diffuse parenchymal
damage associated with chronic meningoencephalitis. Imaging of the brain usually shows atrophy. Direct
spirochete invasion of the neural tissue causing neuronal degeneration, astrocytic proliferation, and
meningitis. Resultant degenerative and sclerotic changes produce a thickened dura matter, chronic
subdural hematoma, cortical cell atrophy, and astrocyte proliferation. The frontal lobes are
disproportionately affected.
General paresis pathology

•Tabes dorsalis Clinical signs include vision loss, loss of reflexes and loss of sense of vibration, spastic gait,
and impaired balance, pains in the limbs or abdomen, failure of muscle coordination, and bladder
disturbances and is the reflection of a myelopathy characterized by atrophic, degenerated, and
demyelinated dorsal nerve roots and posterior spinal columns. Tabes dorsalis can occur anywhere from 5
-50 years after initial syphilis infection, usually in persons aged 25-40. Both direct invasion by the spirochete
and an immunologenic reaction may occur, producing degenerative and sclerotic changes in the posterior
nerve root fibres of the spinal cord, spinal ganglia cells, long fibers of the posterior columns of the spinal
cord, optic nerves and oculomotor nuclei.
•Gumma A soft, non-cancerous growth resulting from the tertiary stage of syphilis. It is a form of
granuloma.

•Meningovascular syphilis responds promptly to treatment with penicillin G. Treatment of
general paresis and tabes dorsalis is far less successful. iv or sc for 10 - 14 days. Combined with
Oral Probenecid x4/day.
•Non-pregnant individuals who have severe allergic reactions to penicillin may be effectively
treated with oral tetracycline or doxycycline.
•Ceftriaxone may be considered as an alternative therapy.
•Follow-up includes clinical evaluation (blood tests and lumbar punctures for CSF fluid analysis)
at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after
treatment.
Prognosis
This is considered a life-threatening complication of syphilis. Prognosis can change based on the
type of neurosyphilis and how early in the course of the disease people with neurosyphilis get
diagnosed and treated. Individuals with asymptomatic neurosyphilis or meningeal neurosyphilis
usually return to normal health. People with meningovascular syphilis, general paresis, or tabes
dorsalis usually do not return to normal health, although they improve.
Ceftriaxone

Viral Meningitis
• Viral meningitis is inflammation of the leptomeninges as a manifestation
of CNS infection. Viral meningitis syn. aseptic meningitis.
• In uncomplicated viral meningitis, the clinical course is usually self-
limited, with complete recovery in 7-10 days. However, when the viral
pathogen causes a more involved meningoencephalitis or
meningomyelitis, the course can be significantly more protracted.
• Partially untreated bacterial meningitis in particular can present
similarly to viral meningitis-devastating outcomes if misdiagnosed.
Causes
• Enteroviruses account for more than 85% of all cases of viral
meningitis.
• Herpes family viruses: HSV-1, HSV-2, VZV, EBV, CMV, and human
herpesvirus 6 collectively cause approximately 4% of cases of viral
meningitis, with HSV-2 being the most common offender.
• Lymphocytic choriomeningitis virus
• Adenovirus
• Measles

Viral Meningitis
Pathophysiology
• Viral pathogens may gain access to the CNS via 2 main
routes: hematogenous or neural.
• Multiple host defenses (local and systemic immune
responses, skin and mucosal barriers, and the blood-
brain barrier) prevent viral inoculum from causing
clinically significant infection.
Mortality/Morbidity
• Excluding the neonatal period, the mortality rate
associated with viral meningitis is less than 1%; the
morbidity rate is also low.

Viral Meningitis-Clinical Manifestations
•
•
• The classically taught triad of meningitis consists of fever, nuchal
rigidity, and altered mental status.
Upon presentation, most patients report fever, headache, irritability,
nausea, vomiting, stiff neck, rash, or fatigue within the past 18-36 hours.
Nuchal rigidity or other signs of meningeal irritation (Brudzinski or
Kernig sign) may be seen in more than half of patients but is generally
less severe than in bacterial meningitis. Pediatric patients, especially
neonates, tend not to exhibit nuchal rigidity on examination.
• The neonate may exhibit hypotonia, irritability, and poor feeding.
• Some viruses cause rapid onset of the above symptoms, while others
manifest as nonspecific viral prodromes, such as malaise, myalgia, and
upper respiratory symptoms. In many cases, symptoms have a biphasic
pattern; the nonspecific flu-like symptoms and low-grade fever precede
neurologic symptoms by approximately 48 hours. With the onset of
neck stiffness and headache, the fever usually returns.

Viral Meningitis-Clinical Manifestations
•
•
• Headache is common and is characteristically severe.
• Photophobia is relatively common but may be mild. Phonophobia may
also be present.
• Seizures occur occasionally and are usually from the fever, although the
involvement of brain parenchyma (encephalitis) should be considered.
• Other signs of specific viral infection can aid in diagnosis:
• Pharyngitis and pleurodynia in enteroviral infections
• Skin manifestations, such as zoster eruption in VZV, maculopapular rash
from measles and enteroviruses, vesicular eruption by herpes simplex,
and herpangina in coxsackievirus A infections.
Pharyngitis, lymphadenopathy, and splenomegaly suggest Epstein-Barr
virus infection.
Immunodeficiency and pneumonia should suggest adenovirus,
cytomegalovirus , or HIV as the causative agent.
• Parotitis and orchitis can occur with mumps
• Gastroenteritis and rash occur with most enteroviral
infections.

Viral Meningitis-Diagnosis
• CT scan usually is performed prior to LP to rule out intracranial
hematoma, mass effect, or obstructive hydrocephalus.
• PCR testing for viral DNA.
• The following are some CSF characteristics used to support the diagnosis
of viral meningitis:
• Cells: Pleocytosis with WBC counts in the range of 50 to >1000 x 109/L
of blood has been reported in viral meningitis. Mononuclear cell
predominance is the rule, but PMNs may comprise the majority of cells
in the first 12-24 hours; the cell count usually is then dominated by
lymphocytes in the classic CSF pattern of viral meningitis. This helps to
distinguish viral from bacterial meningitis, which has a much higher cell
count and a predominance of PMNs in the cell differential; this is by no
means an absolute rule, however.
• Protein: CSF protein level usually is only slightly elevated, but can range
from being normal to as high as 200 mg/dL.
• Glucose: Normal in most cases.
• Culture, Gram stain, and acid-fast stain

Viral Meningitis-Treatment
• Mostly supportive-Rest, hydration, antipyretics, and pain or
anti-inflammatory medications. The most important decision
is whether to initiate antimicrobial therapy empirically for
bacterial meningitis while waiting for the cause to be
identified. Patients with signs and symptoms of
meningoencephalitis should receive acyclovir early to
possibly curtail HSV encephalitis.
• Enteroviruses and HSV are both capable of causing viral
septic shock in newborns and infants. In these young
patients, broad-spectrum antibacterial coverage and
acyclovir should be instituted as soon as the diagnosis is
suspected.
• Seizures should be treated immediately with IV
anticonvulsants such as lorazepam, phenytoin, midazolam,
or a barbiturate.

T1-weighted MRI of brain demonstrates
diffuse enhancement of the meninges in
viral meningoencephalitis.

Herpes Simplex Encephalitis
Herpes simplex encephalitis (HSE) occurs as 2 distinct entities:
• In children older than 3 months and adults, oral herpes, HSV-1
is responsible for virtually all cases.
• In neonates, the usual cause is herpes simplex virus type 2
(HSV-2), genital herpes which is acquired at the time of
delivery.
Frequency
• Herpes simplex encephalitis is the most common cause of
sporadic lethal encephalitis, occurring in about 1 person per
250,000-500,000 population per year.
Mortality/Morbidity
• Before the availability of IV acyclovir the mortality rate of
herpes simplex encephalitis in untreated patients is 70%.

Herpes Simplex Encephalitis-Pathophysiology
• Brain infection is thought to occur by means of direct neuronal
transmission of the virus from a peripheral site to the brain via the
trigeminal or olfactory nerve. The herpes virus preferentially
involves the temporal lobe and orbital surfaces of the frontal
lobes. Herpes viruses cause a hemorrhagic necrosis and
inflammatory infiltrates.

Destruction of inferior frontal and anterior
temporal lobes – necrotizing
inflammation

Herpes Simplex Encephalitis-Clinical Manifestations
• Herpes simplex encephalitis (HSE) is an acute or subacute illness, causing both
general and focal signs of cerebral dysfunction:
• Fever (90%)
• Headache (81%)
• Psychiatric symptoms (71%)
• Seizures (67%)
• Vomiting (46%)
• Focal weakness (33%)
• Memory loss (24%)
• Alteration of consciousness
(97%)
• Hemiparesis (38%)
• Cranial nerve defects (32%)
• Visual field loss (14%)
• Papilledema (14%)

Herpes Simplex Encephalitis-Diagnosis
• No pathognomonic clinical findings reliably distinguish HSE from other neurological disorders with
similar presentations (eg, non-HSV encephalitis, brain abscess, tumor). Confirmation of the
diagnosis depends on the identification of HSV in the CSF by means of a polymerase chain reaction
(PCR) or on the identification of HSV in brain tissue by means of brain biopsy. The diagnosis of HSE
should be considered in any patient with a progressively deteriorating level of consciousness, fever,
abnormal CSF findings, and focal neurological abnormalities in the absence of any other causes.
Serologic analysis
• Serologic evaluation of blood or CSF may be useful for retrospective diagnosis, but it has no role in
the acute diagnosis and treatment of patients.
CSF analysis
• Patients with herpes simplex encephalitis (HSE) typically have mononuclear pleocytosis of 10-500
WBCs/µL (average, 100 WBCs/µL).
• As a result of the hemorrhagic nature of the underlying pathologic process, the RBC count may be
elevated (10-500 RBCs/µL).
• Protein levels are elevated to the range 60-700 mg/dL (average, 100 mg/dL).
• Glucose values may be normal or mildly decreased (30-40 mg/dL).
• In about 5-10% of patients, especially children, initial CSF results may be normal.
• However, on serial examinations, the cell counts and protein values increase.
• Viral cultures of CSF are rarely positive and should not be relied on to confirm the diagnosis.
Polymerase chain reaction
• PCR analysis of CSF for the detection of HSV DNA has virtually replaced brain biopsy as the criterion
standard for diagnosis.

Herpes Simplex Encephalitis-Treatment
•
• Empiric treatment of patients with suspected HSE is recommended pending
confirmation of the diagnosis because acyclovir, the drug of choice, is relatively
nontoxic and because the prognosis for untreated HSE is poor.
The treatment of choice for herpes simplex encephalitis (HSE) is acyclovir.
Through a series of in vivo reactions catalyzed by viral and host cellular
enzymes, acyclovir is converted to acyclovir triphosphate, a potent inhibitor of
HSV DNA polymerase, without which viral replication cannot occur. Human
cells are not affected.
• Acyclovir has relatively few serious adverse effects. The drug is excreted by the
kidney, and the dose should be reduced in patients with renal dysfunction.
Crystal-induced nephropathy may occur if the maximum solubility of free drug
is exceeded. Risk factors for this are intravenous administration, rapid infusion,
dehydration, concurrent use of nephrotoxic drugs, underlying renal disease,
and high doses. The risk of renal toxicity is reduced by adequately hydrating
the patient (eg, 1 mL fluid per day for each 1 mg/d of acyclovir).
• Gastrointestinal disturbances, headache, and rash are among the more
frequent adverse reactions. Acyclovir is considered appropriate for serious
infections during pregnancy.
• Since most relapses occur within 3 months of completing an initial course of

Herpes Simplex Encephalitis-Neuroimaging
• Typically, T2-weighted MRI reveals hyperintensity corresponding to edematous
changes in the temporal lobes, inferior frontal lobes, and insula, with a
predilection for the medial temporal lobes. Foci of hemorrhage occasionally
can be observed on MRI.
T2–weighted MRI image in a 62-year-old
woman with confusion and herpes
encephalitis shows T2 hyperintensity
involving the right temporal lobe.

Top Image: Axial diffusion-weighted image reveals
restricted diffusion in the left medial temporal lobe
consistent with herpes encephalitis. This patient
also had a positive result on polymerase chain
reaction assay for herpes simplex virus, which is
both sensitive and specific. In addition, the patient
had periodic lateralized epileptiform discharges on
electroencephalogram, which supports the
diagnosis of herpes encephalitis.
Bottom Image: Coronal T2-weighted image reveals
hyperintensity in the left temporal lobe (arrows) in
a distribution similar to the restricted diffusion
abnormality seen in the previous image. This
finding is typical for herpes encephalitis. In
patients with HHV6 infection, one series noted that
in addition to mesial temporal lobe abnormality,
abnormal T2 hyperintensity has been seen in the
insular and inferior frontal region, which may
suggest the diagnosis. There are felt to be 2 typical
imaging appearances: one seen in older adults
involves T2 hyperintensity confined to the medial
temporal lobe; in young adults, a more varied
pattern has been described that includes foci of
restricted diffusion with an otherwise normal
magnetic resonance, diffuse cortical necrosis, or
small focal regions of abnormal T2 hyperintensity.

Poliomyelitis
•
• Greek polio (gray) and myelon (marrow, indicating the spinal cord)
• Humans are the only know reservoir for poliovirus, a member of the
Picoviridae, enterovirus group.
Poliovirus transmission now primarily occurs in the Indian subcontinent, the
Eastern Mediterranean and Africa.
• Person-to-person spread occurs predominantly via the fecal-oral route.
• Poliovirus is highly infectious and may be present in the stool up to 6 weeks;
seroconversion in susceptible household contacts of children is nearly 100%
and for adults >90%.
• Enhanced potency trivalent oral poliovirus vaccine (OPV) containing attenuated
strains of all 3 serotypes of poliovirus. Effective immunity (99% after 3 doses).

Poliomyelitis-clinical manifestations
• Incubation period 6-20 days.
• 95% of all polio infections are asymptomatic even though infected persons shed virus in stool and
are contagious.
• Abortive Poliomyelitis- Occurs in 4-8% of infections. Minor illness, no CNS infection, complete
recovery in one week. Sore throat, fever, nausea, vomiting, abdominal pain, constipation-influenza
like illness indistiguisable from other enteric viral illnesses.
• Nonparalytic aseptic meningitis- Usually occurring several days after a prodrome similar to minor
illness. Symptoms stiff neck, leg and back, deep muscle pain, and sometimes areas of hyperesthesia
(increased sensation) and paresthesia (altered sensation), typically last 2-10 days followed by
complete recovery.

Poliomyelitis-clinical manifestations
Three types of paralytic polio are described:
• Spinal polio (79%) asymmetric paralysis usually involving the legs
• Bulbar polio (2%) weakness of the mucles innervated by cranial nerves
• Bulbospinal polio (19%) combination
• Postpolio Syndrome-Occurs 30-40 years after paralytic poliomyelitis, when patients note seemingly
increased weakness.
• Flaccid paralysis-Occurs in <1% of polio infections. Paralytic symptons typically begin 1-10 days
after the prodromal symptoms. Initially sever muscle aches and spasms are seen with significant
menigumus and a Kerning sign. Evolves into a flaccid paralysis with diminished muscle stretch
reflexes. No sensory or cognitive loss occurs. Weakness and paralysis present 12 months after onset
is usually permanent.
⚫
⚫
⚫
Diagnosis
Poliovirus isolation from the pharynx or stool. Neutralizing Ab present early at high levels. CSF
shows increased WBC and protein.
Differential diagnosis-Asymmetric weakness distribution and CSF findings help to differentiate it
from Gullain-Barre syndrome
⚫ Treatment
⚫ Physical therapy is the most important part of treatment of paralytic polio during convalescence.
The ideal strategy with polio is clearly to prevent it by immunization against poliovirus.

Poliomyelitis
Pathophysiology
The virus enters via the oral
route and multiplies in the
intestinal mucosa lymphoid
tissues in the pharynx, it is
usually present in the throat
and stool before clinical
onset. Within 1 week of
clinical onset little virus
exists in the throat, but it
continues to be excreted in
the stool for several weeks.
The virus invades the local
lymphoid tissue, enters the
blood stream and then
infects the CNS. Viral
replication in the anterior
horn cells of the spinal cord
and the brainstem motor
neuron cells results in cell
destruction and paralysis.

Rabies Virus (Rhabdovirus)
Introduction
⚫ Rabies is a viral disease that causes acute encephalitis. It is zoonotic, most commonly by a bite
from an infected animal. The rabies virus travels to the brain by following the peripheral nerves.
The incubation period of the disease is usually a few months in humans, depending on the
distance the virus must travel to reach the central nervous system. Once the rabies virus reaches
the central nervous system and symptoms begin to show, the infection is effectively untreatable
and usually fatal within days.

Diagnosis
⚫ Demonstration of anti-rabies glycoprotein Ab in serum or CSF.
Prognosis
⚫ In unvaccinated humans, rabies is almost invariably fatal if post-exposure
prophylaxis is not administered prior to the onset of severe symptoms. Death
ordinarily occurs within three to five days after the onset of symptoms due to
cardiac or respiratory failure.
Incidence
• Rabies is common in Asia, especially in India, where up to 50,000 die each year.
Some parts of America and Africa, have it. Greenland and many countries in
Europe have rabies in their animal populations. Although most of Scandinavia,
as well as Japan, Australia and New Zealand are practically Rabies-Free!
Rabies Virus (Rhabdovirus)

In the unvaccinated individual rabies evolves in three stages:
⚫ The Prodomal Phase - the lead up over a period of 2 -3 days. The patient may have a fever,
vomiting and loss of appetite, anxiety, often with pain and parenthesias at the bite site. The
autonomic nervous system is affected, this manifests itself as copious salivation and sadness.
⚫ The Anger Stage-The patient will appear restless and irritable and display signs of aggression. May
appear disorientated and may develop seizures. This stage lasts for about 2 - 4 days.
⚫ The Paralytic Stage- Two to 10 days after the prodrome, the encephalitic form presents with
agitation, autonomic instability, delirium, seizures, rigidity, severe pharynx spasms, stridor,
hydrophobia and aerophobia. The paralytic (20%) form presents with progressive paralysis until
death. Paralysis develops, usually beginning at the wound site. The production of large quantities of
saliva and tears coupled with an inability to speak or swallow are typical during the later stages of
the disease, in which the patient has difficulty swallowing because the throat and jaw become
slowly paralyzed. Hydrophobia- shows panic when presented with liquids to drink, and cannot
quench his or her thirst.
Rabies Virus (Rhabdovirus)-Signs and symptoms
Patient with rabies, 1959

Treatment after exposure, known as post-exposure prophylaxis (PEP), is highly successful in
preventing the disease if administered promptly, generally within ten days of infection.
Thoroughly washing the wound as soon as possible with soap and water for approximately
five minutes is very effective at reducing the number of viral particles. If available, a virucidal
antiseptic such as povidone-iodine, iodine tincture, aqueous iodine solution or alcohol
(ethanol) should be applied after washing. Exposed mucous membranes such as eyes, nose
or mouth should be flushed well with water.
One dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a
fourteen day period. The immunoglobulin dose should not exceed 20 units per kilogram
body
weight. As much as possible of this dose should be infiltrated around the bites, with the
remainder being given by deep intramuscular injection at a site distant from the
vaccination site. The first
dose of rabies vaccine is given as soon as possible after exposure, with additional doses on
days three, seven and fourteen after the first. Patients who have previously received
pre-exposure
vaccination do not receive the immunoglobulin, only the post-exposure vaccinations on day
0 and 2.
Rabies Virus (Rhabdovirus)-Treatment

Brain and spine Tuberculosis
• Tuberculous meningitis: tuberculosis infection of the meninges. It is the most common
form of CNS tuberculosis.
• Causative agent: Mycobacterium tuberculosis is an aerobic gram-positive rod.
• CNS tuberculosis most commonly occurs in those infected with HIV and those from
South East Asia where TB is still endemic
Frequency
The World Health Organization (WHO) estimates that one third of the world's population is
infected by M. tuberculosis.
Clinical Manifestations
Tuberculous meningitis progresses rapidly with headache, fever, tremor, and cranial nerve
deficts (esp CN-IV palsy). Focal neurological deficits may include monoplegia,
hemiplegia, aphasia, and tetraparesis. Vasculitis with resultant thrombosis and
hemorrhagic infarction may develop in vessels . Visual findings-Papilledema is the most
common visual effect of TBM.
• The clinical picture in primary spinal meningitis is often characterized by myelopathy,
with radicular pain and progressive paraplegia or tetraplegia.

Brain and spine Tuberculosis-Pathophysiology
Diagnosis
• Diagnosis of TB meningitis is made by analysing
cerebrospinal fluid collected by lumbar puncture. A
spider-web clot in the collected CSF is characteristic of
TB meningitis, but is a rare finding.
• Culture for M. tuberculosis takes 2 weeks. More than
half of cases of TB meningitis cannot be confirmed
microbiologically, and these patients are treated on the
basis of clinical suspicion only before the diagnosis is
confirmed.
• PCR

Brain and spine Tuberculosis
Treatment
• The treatment of TB meningitis is isoniazid, rifampicin,
pyrazinamide and ethambutol for two months, followed by
isoniazid and rifampicin alone for a further ten months.
Corticosteroids are always used in the first six weeks of treatment
when cerebral edema, subarachnoid block, or both occur.
• Treatment must be started as soon as there is a reasonable
suspicion of the diagnosis. Treatment must not be delayed while
waiting for confirmation of the diagnosis.
Mortality/Morbidity
• Death follows within weeks in untreated CNS tuberculosis.
Mortality is greatest at the extremes of age 20% at <5 years of age
and 60% at>50 years or if illness has been present more than 2
months (80%)

Tuberculous meningitis -Clinical Manifestations
• Tuberculous meningitis progresses rapidly with headache, fever,
meningismus, and cranial nerve deficts (esp CN-IV palsy). Focal
cerebral or cerebellar deficts are followed by altered sensorium
and coma.
Visual findings
• Papilledema is the most common visual effect of TBM. In children,
papilledema may progress to primary optic atrophy and blindness
resulting from direct involvement of the optic nerves and chiasma
by basal exudates (ie, opticochiasmatic arachnoiditis).
• In adults, papilledema may progress more commonly to
secondary optic atrophy, provided the patient survives long
enough.
• Apart from papilledema, fundus examination occasionally reveals
a retinal tuberculoma or a small grayish-white choroidal nodule,
highly suggestive of TB. These lesions are believed to be more
common in miliary TB than in other forms of TB.

Neurologic findings
• Cranial neuropathies, most often involving CN VI, may be noted. CNs III,
IV, VII, and, less commonly, CNs II, VIII, X, XI, and XII, also may be
affected.
• Focal neurological deficits may include monoplegia, hemiplegia, aphasia,
and tetraparesis.
• Tremor is the most common movement disorder seen in the course of
TBM. In a smaller percentage of patients, abnormal movements,
including choreoathetosis and hemiballismus, have been observed,
more so in children than adults. In addition, myoclonus and cerebellar
dysfunction have been observed. Deep vascular lesions are more
common among patients with movement disorders.
• Vasculitis with resultant thrombosis and hemorrhagic infarction may
develop in vessels that traverse the basilar or spinal exudate or lie
within the brain substance. Eventually, fibrinoid degeneration within
small arteries and veins produces aneurysms, multiple thrombi, and
focal hemorrhages, alone or in combination.
Tuberculous meningitis-Clinical Manifestations

Tuberculous meningitis-Pathophysiology
• Many of the symptoms, signs, and sequelae of tuberculous meningitis (TBM) are the
result of an immunologically directed inflammatory reaction to the infection. The
development of TBM is a 2-step process. M. tuberculosis bacilli enter the host by droplet
inhalation, the initial point of infection being the alveolar macrophages. Localized
infection escalates within the lungs, with dissemination to the regional lymph nodes to
produce the primary complex. During this stage, a short but significant bacteremia is
present that can seed tubercle bacilli to other organs in the body.
• In persons who develop TBM, bacilli seed to the meninges or brain parenchyma,
resulting in the formation of small subpial or subependymal foci of metastatic caseous
lesions. These are termed Rich foci, after the original pathologic studies of Rich and
McCordick.
• The second step in the development of TBM is an increase in size of a Rich focus until it
ruptures into the subarachnoid space. The location of the expanding tubercle (ie, Rich
focus) determines the type of CNS involvement. Tubercles rupturing into the
subarachnoid space cause meningitis. Those deeper in the brain or spinal cord
parenchyma cause tuberculomas or abscesses. While an abscess or hematoma can
rupture into the ventricle, a Rich focus does not.
• A thick gelatinous exudate infiltrates the cortical or meningeal blood vessels, producing
inflammation, obstruction, or infarction. Basal meningitis accounts for the frequent
dysfunction of cranial nerves (CNs) III, VI, and VII, eventually leading to obstructive
hydrocephalus from obstruction of basilar cisterns. Subsequent neurological pathology
is produced by 3 general processes: adhesion formation, obliterative vasculitis, and
encephalitis or myelitis.

T1 w MRI IMAGE
Tuberculoma is the round gray mass in the left corpus callosum. The red
meninges on the right are consistent with irritation and probable
meningeal reaction to tuberculosis.
Tuberculomas are conglomerate caseous foci within the substance of the brain.
Under conditions of poor host resistance, this process may result in focal areas
of cerebritis or frank abscess formation, but the usual course is coalescence of
caseous foci and fibrous encapsulation (ie, tuberculoma).
Tuberculous meningitis-Pathophysiology

Tuberculous spinal meningitis-Clinical manifestions
• Tuberculous spinal meningitis may manifest as an acute,
subacute, or chronic form.
• The clinical picture in primary spinal meningitis is often
characterized by myelopathy, with progressive ascending
paralysis, eventually resulting in basal meningitis and associated
sequelae.
• In some cases with acute onset, in addition to variable
constitutional symptoms, patients develop acute paraplegia with
sensory deficits and urinary retention. The clinical picture often
mimics transverse myelitis or Guillain-Barré syndrome.
• The subacute form is often dominated by myeloradiculopathy,
with radicular pain and progressive paraplegia or tetraplegia.
• A less virulent chronic form might mimic a very slowly progressive
spinal cord compression or a nonspecific arachnoiditis.
• The dorsal cord seems to be affected most commonly, followed

T2-weighted magnetic resonance image
of the thoracic spinal cord of a patient
with 2 hyperintense intramedullary
tuberculomas.
Brain and spine Tuberculosis-Neuroimaging

•
• In the tuberculous process, the spinal meninges may be involved, owing to the
spread of infection from intracranial meningitis, primary spinal meningitis in
isolation as a result of a tuberculous focus on the surface of the cord rupturing
into the subarachnoid space, or transdural extension of infection from caries of
the spine.
Pathologically, a gross granulomatous exudate fills the subarachnoid space and
extends over several segments. Vasculitis involving arteries and veins occurs,
sometimes resulting in ischemic spinal cord infarction.
• The earliest lesion in the vertebra is invariably due to hematogenous spread,
often involving the body of the vertebra near an intervertebral disk. The
intervertebral disk is almost always involved with the spread of the disease to
the adjacent vertebra and eventually along the anterior or posterior
longitudinal ligaments or through the end plate. Soon, a cold abscess develops,
either as a paraspinal abscess in the dorsal and lumbar regions or as a
retropharyngeal abscess in the cervical region. As the disease progresses,
increasing decalcification and erosion result in progressive collapse of the bone
and destruction of intervertebral disks, involving as many as 3-10 vertebrae in
one lesion, resulting in kyphosis. The abscess may rupture intraspinally,
resulting in primary spinal meningitis, hyperplastic peripachymeningitis,
intraspinal abscess, or tuberculoma.
Tuberculous spinal meningitis -Pathophysiology

Tuberculous spondylitis-Clinical manifestions
•
•
• Tuberculous spondylitis is also known as Pott disease or spinal caries.
• In regions where the disease is endemic, such as Asia and Africa, this condition
still accounts for 30-50% of all cases of compressive myelopathy resulting in
paraplegia. Spinal TB also accounts for approximately 50% of all bone and joint
TB cases.
In the lumbar region, tuberculous spondylitis may result in a psoas abscess that
often calcifies.
It usually runs a subacute or a chronic course, with back pain and fever and
variable neurological deficits.
• Spondylitis can also result in various symptoms, including local and radicular
pain, limb motor and sensory loss, and sphincter disturbances.
• Eventually, complete spinal cord compression with paraplegia, the most
dreaded complication, may supervene.

Brain and spine Tuberculosis-Diagnosis
•
• Diagnosis of TB meningitis is made by analyzing cerebrospinal fluid
collected by lumbar puncture. The CSF usually has a high protein, low
glucose and a raised number of lymphocytes. Acid-fast bacilli are
sometimes seen on a CSF smear, but more commonly, M.
tuberculosis is grown in culture. A spider-web clot in the collected
CSF is characteristic of TB meningitis, but is a rare finding.
• Culture for M tuberculosis; takes 2 weeks (50-80% of known cases
of TBM yield positive results). More than half of cases of TB
meningitis cannot be confirmed microbiologically, and these patients
are treated on the basis of clinical suspicion only before the
diagnosis is confirmed..
Polymerase chain reaction (PCR): Results imply that PCR can provide
a rapid and reliable diagnosis of TBM, although false-negative results
potentially occur in samples containing very few organisms.
• Differential diagnosis: Cryptococcal antigen and herpes antigen
testing; Syphilis serology

T2-weighted magnetic resonance image
of a patient with a tuberculoma in the
right parietal lobe.
Brain and spine Tuberculosis-Neuroimaging

Brain and spine Tuberculosis-Treatment
• The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and
ethambutol for two months, followed by isoniazid and rifampicin alone for a
further ten months. Corticosteroids are always used in the first six weeks of
treatment when cerebral edema, subarachnoid block, or both occur.
• Treatment must be started as soon as there is a reasonable suspicion of the
diagnosis. Treatment must not be delayed while waiting for confirmation of the
diagnosis.
Surgical Care
• Hydrocephalus occurs as a complication in about a third of patients with TB
meningitis and will require placement of a ventriculoperitoneal shunt.
• Mortality/Morbidity
• Death follows within weeks in untreated CNS tuberculosis. Mortality is greatest
at the extremes of age 20% at <5 years of age and 60% at>50 years or if illness
has been present more than 2 months (80%)

Progressive multifocal leukoencephalopathy
• PML is caused by reactivation of the endemic JC papovavirus
(polyomavirus). As many as 90% of healthy individuals have
serum antibodies to this virus, but less than 10% show any
evidence of ongoing viral replication.
• Progressive multifocal leukoencephalopathy (PML) occurs
almost exclusively in AIDS patients.
• As many as 90% of healthy individuals have serum antibodies to
this virus, but less than 10% show any evidence of ongoing viral
replication.
• At present, PML develops in as many as 5% of all patients with
AIDS-PML is an AIDS-defining illness.

Pathology
• Multiple demyelinative lesions are generally
located in the cerebral white matter. Spinal cord
involvement is rare.
This sliced fixed brain shows multiple
isolated or confluent gray demyelinative
foci. Atrophy may be present.

Progressive multifocal leukoencephalopathy-
Pathology-demyelinative foci

Mortality/Morbidity
• In the pre-HAART (Highly Active Antiretroviral therapy- three to four
anti-virals taken in combination) era, the prognosis of PML was dismal,
with death occurring within 4-6 months after diagnosis.
Clinical Manifestations
• Present with rapidly progressive focal symptoms including behavioral,
speech, cognitive impairment, hemiparesis, and visual impairment.
Focal signs tend to be related to posterior brain (eg, occipital lobes).
• Late in the course abnormalities may progress to quadriparesis, cortical
blindness, profound dementia and coma.
Diagnosis
• PCR
• Brain biopsy has a sensitivity of 74-92% and a specificity of 92-100%.
• CSF cell count and chemistry usually normal

Contrast-enhanced T1-weighted MRI
demonstrates a hypointense lesion
predominantly in a subcortical, left
frontoparietal location. Note the
characteristic absence of enhancement
and lack of mass effect.
PML-Neuroimaging

Fluid-attenuated inversion recovery
(FLAIR) MRI shows a PML lesion with
improved contrast after the suppression
of cerebrospinal fluid signal intensity.
PML-Neuroimaging

Nonenhanced CT of the head shows a
hypoattenuating lesion in the
subcortical white matter. Note the
characteristic scalloped lateral margin.
PML-Neuroimaging

Fluid-attenuated inversion recovery (FLAIR) images in a patient with HIV infection presenting with visual
defects, aphasia, and balance problems. Patchy, confluent, and hyperintense lesions are seen in the left
occipitotemporoparietal lobes in the subcortical and periventricular white matter. The patient's clinical
and radiologic features suggested progressive multifocal leukodystrophy, though cerebrospinal fluid
results for the JC virus were negative.
PML-Neuroimaging

Neuro-Cyptococcosis
⚫ Cryptococcal meningitis -a leading cause of infectious morbidity and mortality in patients with AIDS.
Among AIDS/HIV subjects, cryptococcal meningitis is the second (1st
being tuberculous meningitis) most
common cause of opportunistic neuro-infection. Cryptococcal meningitis occurs in non-HIV patients
who are immunodeficient due to diabetes, cancer, solid organ transplants, chemotherapeutic drugs,
hematological malignancies etc and rarely in healthy individuals with no obvious predisposing factors.
⚫ Cryptococcal meningitis is the most common form of fungal meningitis and is caused by Cryptococcus
neoformans . C. neoformans is Soil fungus associated with pigeon and chicken droppings. Seroypes A
and D and AD hybrids are globally responsible for 98% of all cryptococcal infections in patients with
AIDS.
Cryptococcus neoformans

Neuro-Cyptococcosis-Pathogenesis
⚫ The fungus enters the human body through inhalation into the lungs. In the alveoli, the yeasts come
into contact with alveolar macrophages, which elicit an inflammatory response. This pulmonary
infection is often asymptomatic but the organism may disseminate to other organs depending on the
immune status of the individual. The cerebrospinal fluid is an ideal site for infection as it lacks
complements and immunoglobulins.

Neuro-Cyptococcosis-Clinical manifestations
⚫ Cryptococcal meningitis commonly presents as chronic or subacute
meningitis. Patients often present with severe unbearable headache with
or without fever that is often severe enough to interfere with day-to-day
activities. Headache may be accompanied by vomiting and at times, there
can be transient visual obscurations due to raised intracranial tension. In
some instances, severe headache almost mimics headache associated with
subarachnoid hemorrhage. The exact mechanism for such severe headache
is not known, but it may due to meningeal involvement / raised intracranial
tension / or sino-venous thrombosis. Seizures are seen in < 8% of cases.
Examination is usually unremarkable except for papilledema. Neck stiffness
is seen in only 30% of the cases. One third of the patients can have
disseminated infection with the involvement of the lungs, kidney or skin. A
careful search for cutaneous cryptococcal lesions can be rewarding in some
cases of suspected cryptococcal meningitis. Cranial neuropathies,
especially of the lower cranial nerves, affecting one or more cranial nerves
(II, VII, VIII, IX, X, XII) occur in isolated cases secondary to basal
arachnoiditis or due to hydrocephalus.

Neuro-Cyptococcosis-Pathology
Opaque thick fibrotic CSF obstruction - hydrocephalus. Gelatinous
material within the subarachnoid space and small cysts within the
parenchyma ("soap bubbles“) Specially in the basal ganglia.

The nature and duration of treatment for cryptococcal infection is based on the immunity
of the host and anatomic sites of involvement. For immunocompetent individuals with
cryptococcal meningitis, the standard therapy consists of amphotericin B 0.7-1.0
mg/kg/day along with 5- flucytosine 100 mg/kg/day for 6-10 weeks. An alternative to this
regimen is amphotericin B
0.7-1.0 mg/kg/day plus 5-flucytosine 100 mg/kg/day for two weeks, followed by
fluconazole 400mg/day for a minimum of ten weeks. Fluconazole "consolidation"
therapy may be
continued for as long as 6-12 months, depending on the clinical status of the patient.
For patients with HIV infection and cryptococcal meningitis, induction therapy with
amphotericin B
0.7-1.0 mg/kg/day plus 5-flucytosine 100 mg/kg/day is given for two weeks,
followed by fluconazole 400mg/day for a minimum of ten weeks. After ten weeks
of therapy, the
fluconazole dosage may be reduced to 200 mg/day, depending on the clinical
status of the
patient. Fluconazole should be continued for life or at least up to the time the CD4+
count reaches 350/cmm.
Neuro-Cyptococcosis-Treatment

Elevated intracranial pressure occurs in up to 75% of the patients with cryptococcal
meningitis and is an important contributor to mortality and morbidity. Treated
aggressively-percutaneous lumbar drainage or ventriculoperitoneal shunting or
acetazolamide. In patients with normal baseline opening pressure (< 200 mm H 2 O), a
repeat lumbar puncture should be performed two weeks after the initiation of therapy
to exclude elevated pressure and to evaluate culture status.
Prognosis
The majority of the patients with cryptococcal meningitis improve with adequate
therapy. Mortality is seen in about 10% of the cases while morbidity is unusual.
Mortality is more common in HIV-positive individuals.
Neuro-Cyptococcosis-Treatment

T2 MRI Multicystic form of cerebral cryptococcosis:
lesions in basal ganglia and cerebellum
Neuro-Cyptococcosis-Neuroimaging

T2 W MRI Small cystic lesions in basal ganglia

CNS cryptococcosis: brain MRI findings (A) Axial T2 sequence showing bilateral
pseudocysts as hyperintensities (arrowheads) predominantly involving the basal
ganglia. The pseudocysts are thick walled and septated with a proteinaceous content
depicted by their relative hyperintensity compared to CSF. (B) Post-gadolinium MRI
sequences showing little to no enhancement of the cysts or surrounding parenchyma.

Nocardiosis
Nocardiosis is an acute, subacute, or chronic infectious disease that occurs in
cutaneous, pulmonary, and disseminated forms. Disseminated nocardiosis may
involve the brain or meninges, usually from a pulmonary focus. Most persons
with disseminated nocardiosis have underlying immunocompromising disease
or are receiving immunosuppressive therapy.
Pathophysiology
Members of the genus Nocardia are aerobic actinomycetes that are ubiquitous
saprophytes in soil, decaying organic matter, and water. Nocardia asteroides is
responsible for most cases of Nocardia disease among humans.
High-power microscopic appearance of Nocardia.

Nocardiosis
Diagnosis
Brain biopsy is the most reliable diagnostic technique if the
diagnosis cannot be made by evaluation of pulmonary or skin lesion.

Nocardiosis-Clinical manifestations
•CNS nocardiosis is detected in 20-40% of disseminated nocardial infections. CNS
nocardiosis manifests as a slowly progressive mass lesion, with a host of
specific neurologic findings related to the specific location of the abscess.
•In two thirds of patients with CNS nocardiosis, clinical findings indicate abscess
with or without meningitis, including fever, headache, stiff neck, altered
consciousness and/or altered mental status, personality changes, or various
localizing neurologic findings.
Brain MRI
scan in a
patient with
nocardial
brain
abscess.

Nocardiosis-Treatment
atient
s
Sulfonamides have long been the first-line antimicrobial therapy for
nocardiosis. Among the sulfonamides, sulfadiazine is generally preferred
because of its CNS and CSF penetration.
Alternative parenteral therapies include meropenem, third-generation
cephalosporins (cefotaxime or ceftriaxone), and , alone or in combination.
Meropenem plus amikacin (synthetic aminoglycoside) may be the preferred
regimen.
Surgery-Needle aspiration or surgical excision needed in
most. Relapse common
Mortality/Morbidity
•Cure rates with appropriate therapy are approximately 100% in skin and soft-
tissue infections.
•Ninety percent of pleuropulmonary infections can be cured with appropriate
therapy.
•The cure rate in disseminated nocardiosis falls to 63%, while only half
of p with brain abscess can be cured with therapy.
sulfadiazine meropenem amikacin

⚫
⚫
⚫
⚫ Listeriosis is a bacterial infection caused by a gram-positive, motile bacterium, Listeria
monocytogenes. Listeriosis is relatively rare and occurs primarily in newborn infants, elderly
patients, and patients who are immunocompromised.
Epidemiology
Incidence in 2004–2005 was 2.5–3 cases per million population, where pregnant women
accounted for 30% of all cases. Of all nonperinatal infections, 70% occur in
immunocompromised patients.
Etiology
Listeria monocytogenes is ubiquitous in the environment. The main route of acquisition of
Listeria is through the ingestion of contaminated food products. Listeria has been isolated
from raw meat, dairy products, vegetables, and seafood. Soft cheeses, unpasteurized milk and
unpasteurised pâté are potential dangers.
Diagnosis
In CNS infection cases, Listeria monocytogenes can often be cultured from the blood, and
always cultured from the CSF. There are no reliable serological or stool tests.
Listeriosis

There are four distinct clinical syndromes:
⚫
⚫ Infection in pregnancy: Listeria can proliferate asymptomatically in the vagina and uterus. If
the mother becomes symptomatic, it is usually in the third trimester. Symptoms include fever,
myalgias, arthralgias and headache. Miscarriage, stillbirth and preterm labor are complications
of this infection. Symptoms last 7-10 days.
Neonatal infection (granulomatosis infantisepticum): There are two forms. One, an early-
onset sepsis, with Listeria acquired in utero, results in premature birth. Listeria can be isolated
in the placenta, blood, meconium, nose, ears, and throat. Another, late-onset meningitis is
acquired through vaginal transmission, although it also has been reported with caesarean
deliveries.
⚫ Central nervous system (CNS) infection: Listeria has a predilection for the brain parenchyma,
especially the brain stem, and the meninges. It can cause cranial nerve palsies, encephalitis,
meningitis, meningoencephalitis and abscesses. Mental status changes are common.
Symptoms of meningitis are headache, stiff neck, confusion, loss of balance, and convulsions.
Seizures occur in at least 25% of patients.
⚫ Gastroenteritis: L. monocytogenes can produce food-borne diarrheal disease, which typically is
noninvasive. The median incubation period is 21 days, with diarrhea lasting anywhere from 1–
3 days. Patients present with fever, muscle aches, gastrointestinal nausea or diarrhea,
headache, stiff neck, confusion, loss of balance, or convulsions.
Listeriosis-Clinical manifestations

⚫ Treatment
Bacteremia should be treated for 2 weeks, meningitis for 3 weeks, and brain
abscess for at least 6 weeks. Ampicillin generally is considered antibiotic of choice;
gentamicin is added frequently for its synergistic effects. Overall mortality rate is 20–
30%; of all pregnancy-related cases, 22% resulted in fetal loss or neonatal death, but
mothers usually survive.
Listeriosis

⚫Cysticercosis, is an infection which results from the ingestion of the
eggs of the pork tapeworm, Taenia solium. The eggs are usually
found in fecally-contaminated water or food. Autoinfection as a
result of the entry of eggs into stomach due to retroperistalsis or as
a result of accidental ingestion of eggs from the host's own feces
due to contaminated hands is also possible. The incubation period
ranges from months to over ten years. Neurocysticercosis, is when
the brain or spinal cord is affected by the larval stage of T. solium
(cysticercus) , neurocysticercosis is the most common helminthic
(tapeworm) infestation to affect the CNS worldwide and is the
prime cause of acquired epilepsy.
Neurocysticercosis
T. Solium adult worm stage

In the case of cysticerci in the brain parenchyma, four major stages have been
classified:
⚫
⚫
⚫ In stage 1, immature cysts appear within 1–4 weeks during which the oncosphere
lodges to the brain and finally expands into a cyst. It is mainly asymptomatic,
although flu-like illness, rare seizures, rare increased intracranial pressure from
massive infestation has been recorded.
In stage 2, the cysticerci become mature and viable about 2 months after egg
ingestion. The cyst possesses a protoscolex with the cyst bladder and causes no or
minimal surrounding inflammation or edema. The cysticerci also down-regulate host
cellular immunity. Stage 2 cysts are also asymptomatic, and can persist for more
than 10 years.
⚫ Stage 3 is typified by colloid or degenerating cysts with thick cystic fluid, thickened
capsule, and appear two to 10+ years after the cyst becomes mature. The cyst no
longer prevents a host immune response and its antigens leak from the bladder
wall. The intense inflammation is provoked around the degenerating cyst. Most
patients bearing stage 3 develop clinical signs and symptoms such as seizures,
occasional focal neurological signs, headaches, nausea, vomiting, lethargy from
increased intracranial pressure and altered mental status.
At stage 4, the cyst is calcified. The surrounding inflammation drops since the dead
cyst no longer produces foreign antigens. Common clinical features includes
persistent non-provoked seizures although most of the patients are asymptomatic.
Neurocysticercosis-Pathophysiology

Incidence
⚫ NCC is endemic in Central and South America, sub-Saharan Africa, and in
some regions of the Far East, including the Indian subcontinent, Indonesia,
and China, reaching an incidence of 3.6% in some regions. It is rare in
Eastern and Central Europe, in North America (with the exception of
Mexico), and in Australia, Japan, and New Zealand, as well as in Israel and
in the Muslim countries of Africa and Asia. NCC is the most common
parasitic infection of the CNS. Approximately 2.5 million people
worldwide carry the adult tapeworm, and many more are infected with
cysticerci.
⚫ Race Subcutaneous cysticercosis is more common in Asian populations than
in other peoples of other areas of endemic disease.
⚫ Age Peak incidence is between ages 30 and 40 years.
Morbidity
⚫ The racemose form of NCC, which appears macroscopically as groups of
cysticerci, often in clusters that resemble bunches of grapes, located in the
subarachnoid space, is associated with poor prognosis and elevated
mortality rate (over 20%).
Neurocysticercosis

⚫ In meningeal cysticercosis, cysticerci often do not develop into typical cysts, and become racemose, lacking
a scolex and becoming lobes in thin-walled bladders. These cysts increase and slowly leak their antigen into
the subarachnoid CSF producing meningitis and can further develop into arachnoiditis, which may lead to
obstructive hydrocephalus, cranial nerve involvement, intracranial hypertension, arterial thrombosis and
stroke. In intraventricular cysticercosis, the cysts occur in the lateral, third or fourth ventricles which may be
asymptomatic or if they block the flow of CSF, they may cause increased intracranial pressure. Because the
larvae are relatively large, they may lodge in the subarachnoid space, ventricles, or brain tissue. Cysts in the
subarachnoid space may result in chronic meningitis, cysts in the ventricular system may lead to obstruction
hydrocephalus, and cysts in the cerebrum may mimic brain tumors.
Neurocysticercosis-Pathophysiology

NCC is a pleomorphic disease, although it sometimes produces no clinical manifestation. This pleomorphism is
due to variations in the locations of the lesions, the number of parasites, and the host's immune response.
⚫ •Many patients are asymptomatic; others report vague symptoms such as headache or dizziness.
⚫ •The onset of symptoms is usually subacute to chronic, with the exception of seizures, which present in an
acute fashion. Patients may present with the following:
Epilepsy
⚫
⚫
⚫
Epilepsy is the most common presentation (70%) and is also a complication of the disease.
NCC is the leading cause of adult-onset epilepsy and is probably one of the most frequent causes of
childhood epilepsy in the world.
Seizures secondary to NCC may be generalized or partial. Simple and complex partial seizures may be
associated with the presence of a single lesion. Generalized seizures are usually tonic-clonic; this is thought
to be related to the presence of multiple lesions. However, irritation of focal cortical tissue by one of the
lesions most probably leads to focal onset with secondary generalization. Myoclonic seizures also have been
described.
Headache
⚫
⚫ Chronic headaches associated with nausea and vomiting (simulating migraines)
⚫ Headaches associated with intracranial hypertension and indicative of hydrocephalus
⚫ Intracranial hypertension
⚫ Most often, intracranial hypertension is due to obstruction of cerebrospinal fluid (CSF) circulation caused by
basal or ventricular cysticercosis. It may also result from large cysts displacing midline structures, granular
ependymitis, arachnoiditis, or the so-called cysticercotic encephalitis caused by the inflammatory response
to a massive infestation of cerebral parenchyma with cysticerci.
These patients may have seizures and deterioration of their mental status, mainly due to the host's
inflammatory reaction as an exaggerated response to the massive infestation.
Neurocysticercosis-Clinical Manifestations

Strokes
⚫ Ischemic cerebrovascular complications of NCC include lacunar infarcts and large cerebral infarcts due to occlusion or vascular
damage.
⚫ Hemorrhage also can occur, and has been reported as a result of rupture of mycotic aneurysms of the basilar artery.
⚫ Strokes may be responsible for the following signs and symptoms: paresis or plegias, involuntary movements, gait
disturbances, or paresthesias.
Neuropsychiatric disturbances
• These range from poor performance on neuropsychological tests to severe dementia.
• These symptoms appear to be related more to the presence of intracranial hypertension than to the number or location of
parasites in the brain.
Diplopia: This is a result of intracranial hypertension or arachnoiditis producing entrapment or compression of cranial nerves III,
IV, or VI.
Hydrocephalus
⚫ Ten to thirty percent of patients with NCC develop communicating hydrocephalus due to inflammation and fibrosis of the
arachnoid villi or inflammatory reaction to the meninges and subsequent occlusion of the foramina of Luschka and Magendie.
⚫ Noncommunicating hydrocephalus may be a consequence of intraventricular cysts.
⚫ Other forms of neurocysticercosis
Intrasellar neurocysticercosis: Patients present with ophthalmologic and endocrinologic manifestations mimicking those of
pituitary tumors.
Spinal NCC: This is rare. Spinal NCC may be either intramedullary or extramedullary. The latter is the most frequent and is
responsible of symptoms of spinal dysfunction such as radicular pain, weakness, and paresthesias. Intramedullary
presentation may cause paraparesis, sensory deficits with a level, and sphincter disturbances.
Ocular cysticercosis: This occurs most commonly in the subretinal space. Patients may present with decreased visual acuity, visual
field defects, or monocular blindness.
Neurocysticercosis-Clinical Manifestations

Neurocysticercosis-Neuroimaging
CT scans showing different
phases of
neurocysticercosis.Top left:
CT scan showing many
calcifications and active
cysts with scolices in both
hemispheres.Top right: T1-
weighted MRI showing 2
active cysts with the scolex
in their interior (vesicular
phase).Bottom left:
Postcontrast CT scan
showing a ring-enhancing
cyst (colloidal phase) on
left.Bottom right: Proton
density-weighted MRI
showing a thick capsule with
adjacent scolex and
perilesional edema (colloidal
phase).

Neurocysticercosis-Neuroimaging
Neuroimaging in neurocysticercosis. Cysticercotic encephalitis.Left:
Contrast-enhanced CT scan showing multiple, small, nodular, and annular
areas of abnormal enhancement in brain parenchyma.Right: Gadolinium-
enhanced T1-weighted MRI showing hyperintense lesions.

Antihelminthic drugs (Albendazole or praziquantel) and corticosteroids or
surgery. Surgical treatment includes direct excision of ventricular cysts, shunting
procedures, and removal of cysts via endoscopy. In the case of brain
parenchymal cysticercosis, treatment depends on the stage of cyst development.
In immature cyst stage (stage 1), high-dose corticosteroids are administered to
reduce the edema but antihelminthic drugs have been found to be harmful.
Vesicular or viable cysts (stage 2) are often asymptomatic, and usually are not
treated with antihelminthic drugs, while surgical removal of the cyst, along with
albendazole is indicated in the colloid cyst stage (stage 3). No antihelminthic
treatment is administered in dead calcified cysts stage (stage 4).
Neurocysticercosis-Management and Therapy

Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii.
Up to one third of the world's human population is estimated to carry a Toxoplasma
infection.
Clinical manifestations
Four major T. gondii clinical syndromes occur: congenital, ocular, lymphadenopathic, and
severe neurologic or disseminated diseases.
Acute toxoplasmosis
During acute toxoplasmosis, symptoms are often influenza-like: swollen lymph nodes, or
muscle aches and pains that last for a month or more. Rarely, a patient with a fully
functioning immune system may develop eye damage or nasal lesions from
toxoplasmosis. After the first few weeks of infection have passed, the parasite rarely
causes any symptoms in otherwise healthy adults. However, subjects with HIV/.AIDS or
those who are pregnant, may become seriously ill. Infants infected via placental
transmission may be born with either of these problems, or with nasal malformations.
Acute toxoplasma infection can leads to psychotic symptoms similar to schizophrenia.
Latent toxoplasmosis
In most immunocompetent patients, the infection enters a latent phase, during which only
bradyzoites are present, forming cysts in nervous and muscle tissue. Occurs in 50% of
immunocompromised patients. Diffuse encephalitis, meningoencephalitis, or focal
cerebral
mass lesions are common presentations in patients with AIDS or HIV with toxoplasmosis.

Toxoplasmosis-Transmission
Toxoplasma eggs are shed in cat feces. After their
release in the soil, these eggs require 24 hours to
become infectious. Cats excrete the pathogen in their
faeces for a number of weeks after contracting the
disease, generally by eating an infected rodent.
Intermediate hosts (dogs, rodents, food animals, and
humans) become contaminated by ingesting
Toxoplasma eggs. In the soil, the eggs can remain
infectious for more than 1 year. Ingestion of raw or
partly cooked meat, especially pork, lamb, or venison
containing Toxoplasma cysts. Infection prevalence in
countries where undercooked meat is traditionally
eaten has been related to this transmission method.
Oocysts may also be ingested during hand-to-mouth
contact after handling undercooked meat, or from
using knives, utensils, or cutting boards contaminated
by raw meat.
Pregnancy precautions
Congenital toxoplasmosis is a special form in which an
unborn child is infected via the placenta. A positive
antibody titer indicates previous exposure and
immunity and largely ensures the unborn baby's safety.
A simple blood draw at the first pre-natal doctor visit
can determine whether or not the woman has had
previous exposure and therefore whether or not she is
at risk.

Toxoplasmosis
Diagnosis
The indirect fluorescent Ab test measuring IgG Ab is the most widely used diagnostic
tool. Detection of T. gondii in human blood samples may be also achieved by using the
PCR.
Treatment
Acute
•Pyrimethamine (antimalarial) 4-6 weeks
•Sulfadiazine -in combination with pyrimethamine.
•Clindamycin
•Cotrimoxazole or spiramycin-used for pregnant womenP
ty
or
i
m
pe
ret
h
va
em
ni
n
te
the infection of
their child.
Latent
•In latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics
do not reach the bradyzoites in sufficient concentration.
•Atovaquone - used to kill Toxoplasma cysts in AIDS patients.
•Clindamycin - in combination with atovaquone
spiramycin
Atovaquone
Clindamycin

Toxoplasmosis-Pathology
CNS toxoplasmosis, which has a propensity for involvement of the
basal ganglia.

⚫ T2-weighted coronal magnetic
resonance image at the level of the
insulae in a patient with human
immunodeficiency virus infection and
central nervous system toxoplasmosis.
The image shows large, bilateral
hyperintense lesions (almost
symmetrically placed on either side of
the third ventricle and/or lateral
ventricle) (arrows). Note the slight
mass effect on the right lateral
ventricle (V).
Toxoplasmosis-Neuroimaging

⚫ T1-weighted axial brain magnetic
resonance image at the level of the
basal ganglia in a 24-year-old man with
human immunodeficiency virus
infection. The image shows
hypointense lesions in the region of the
thalami (arrows) caused by
toxoplasmosis.

⚫ T1-weighted gadolinium-enhanced
magnetic resonance image at the level
of the fourth ventricle in a 32-year-old
patient with human immunodeficiency
virus infection. The image shows a
peripheral, right frontoparietal ring-
enhancing lesion (arrow). The patient
presented with a solitary space-
occupying lesion, which was confirmed
to be secondary to toxoplasmosis.

⚫ T1-weighted axial gadolinium-enhanced magnetic resonance images at 2 levels through the
basal ganglia (same patient as in the previous image). These images show 2 complex, ring-
enhancing lesions in the basal ganglia on the right, with surrounding notable white matter
edema. This appearance is typical of central nervous system toxoplasmosis, which has the
propensity for involvement of the basal ganglia.

Prion Related Diseases
Disease Host Mechanism
Kuru Human Cannibalism
Sporadic CJD Human Spontaneous PrPC to PrPSc
conversion or somatic mutation
Iatrogenic CJD Human Infection from prion-containing
material
Familial CJD Human Mutations in the PrP gene
vCJD Human Infection from BSE
GSS Human Mutations in the PrP gene
FFI Human D178N mutation in the PrP
gene, with M129 polymorphism
Sporadic fatal insomnia Human Spontaneous PrPC to PrPSc
conversion or somatic mutation
Scrapie Sheep Infection in susceptible sheep
BSE Cattle Infection from contaminated
food
•The prion diseases are a large group of related neurodegenerative conditions, which affect both
animals and humans.
•Prion diseases are unique in that they can be inherited, they can occur sporadically, or they can be
infectious.
• These diseases all have long incubation periods but are typically rapidly progressive once clinical
symptoms begin.
Table. Prion-Related Diseases, Hosts, and Mechanism of Transmission

The infectious agent in the prion disease is composed mainly or entirely of an
abnormal conformation of a host-encoded glycoprotein called the prion protein. PrPC is a
glycosylphosphatidylinositol-anchored cell-surface glycoprotein. PrP is found in most
tissues of the body but is expressed at highest levels in the CNS, in particular in neurons.
The replication of prions involves the recruitment of the normally expressed prion protein,
which has mainly an alpha-helical structure, into a disease-specific conformation that is
rich in beta-sheet, initiating a self-perpetuating vicious cycle. A unifying feature of all the
prionoses is their neuropathology. These illnesses tend to affect the gray matter,
producing neuronal loss affecting the cerebral hemispheres and cerebellum, gliosis, and
characteristic spongiform change. In approximately 10% of patients with CJD, amyloid is
present in the cerebellum or in the cerebral hemispheres.
Prion Related Diseases-Pathophysiology
Prion-related diseases. Spongiform
change in prion disease. This section
shows mild parenchymal vacuolation and
prominent reactive astrocytosis.

Transmission
Prion diseases are transmitted naturally by peripheral routes, either orally or
transcutaneously
•Spread of prions to the CNS via lymphoid organs or hematogenic.
•Prion diseases may spread by iatrogenic means. Hence, take care not to reuse EEG
and/or electromyography (EMG) needles, surgical instruments that have been exposed
to a patient with prion disease. The prion agent is remarkably resistant to inactivation;
hence, routine sterilization procedures, such as autoclaving, are ineffective.
•Ten percent of cases of CJD are familial, with an autosomal dominant pattern of
inheritance linked to mutations in the PrP gene.
Frequency
The most common prion disease is CJD, with a uniform incidence of approximately 1 case
per million population internationally.
Familial forms of prion diseases, such as GSS and fatal familial insomnia (FFI), are much
more rare. As of February 2006, 159 cases of definite or probable vCJD have been
reported in the
United Kingdom of which 153 persons have died.
Mortality/Morbidity
Prion-related diseases are relentlessly progressive and invariably lead to
death. The mean duration of sporadic CJD is 8 months.
vCJD has a slightly longer course, with a mean duration of 14 months.
Familial CJD has a mean duration of 26 months, while GSS has the longest course, about
60 months.
Age
The mean age of onset of sporadic CJD is 62 years.
vCJD occurs in younger patients, with a mean age of onset of 28 years.
Prion Related Diseases

CJD
By far the most common human prion disease is CJD, accounting for about 85% of all
human prion disease. Clinically, CJD is characterized by a rapidly progressive dementia
associated with myoclonic jerks, as well as a variable constellation of pyramidal,
extrapyramidal, and cerebellar signs. The EEG findings typically show distinctive changes
of high-voltage slow (1-2 Hz) and sharp wave complexes on an increasingly slow and low-
voltage background.
• Sporadic CJD is characterized by a rapidly progressive multifocal neurological
dysfunction, myoclonic jerks, a terminal state of global severe cognitive
impairment, and death in about 8 months.
•About 40% of patients with sporadic CJD present with rapidly progressive cognitive
impairment, 40% with cerebellar dysfunction, and the remaining 20% with a
combination of both.
•The clinical picture rapidly expands to include behavioral abnormalities, higher
cortical
dysfunction, cortical visual abnormalities, cerebellar dysfunction, and both
pyramidal and extrapyramidal signs.
•Almost all patients with sporadic CJD develop myoclonic jerks that involve either
the
entire body or a limb. These myoclonic jerks can occur spontaneously or
can be precipitated by auditory or tactile stimulation.
Variant Creutzfeldt-Jakob disease (vCJD)
A recent epidemic of a new prionosis has occurred; BSE has led to more then 160,000
cattle deaths in the United Kingdom. This new disease is thought to be caused by
Prion Related Diseases-Clinical Manifestations

Imaging Studies
MRI is an important imaging test. MRI may show hyperintense signals in the cortical
ribbon, basal ganglia, and the thalamus on diffusion-weighted images (DWI) and fluid-
attenuated inversion recovery (FLAIR) images. Two characteristic radiological signs have
been described. The "hockey stick" sign, which refers to increased signal in the
putamen and head of the caudate nucleus resembling a hockey stick, and the "pulvinar"
sign, which corresponds to a usually bilaterally increased signal in the pulvinar
thalamic nuclei. The latter sign has been found especially in patients with vCJD.
Other Tests
•Perform an EEG.
During the course of sporadic CJD, most patients develop a characteristic picture on EEG
with periodic or pseudoperiodic paroxysms of sharp waves or spikes on a slow
background. These
periodic complexes have a sensitivity and specificity of 67% and 87% respectively on a
single EEG. However, if repeated recordings are obtained, more then 90% of patients
show periodic
EEG abnormalities.
0.5-1 Hz periodic sharp waves focally or diffusely.
oIn vCJD, EEG does not show the typical changes observed in sporadic CJD, and
findings often are normal.
Perform lumbar puncture (LP) in all suspected cases.
Check the opening pressure.
Evaluate the cerebrospinal fluid (CSF) for cell count, protein, glucose, bacterial cultures,
viral cultures, VDRL, cryptococcal antigen, and acid-fast bacilli (AFB).
CSF is typically normal in sporadic CJD, although the CSF protein may be elevated slightly
Prion Related Diseases -Diagnosis

Shows characteristic signal changes of an MRI taken from a
patient with sporadic CJD, using diffusion-weighted imaging
(DWI). An abnormal signal is shown in both the basal ganglia
(red arrows) and the cortical ribbon (yellow arrow).

Alzheimer Disease
Cortical Basal Ganglionic
Degeneration Dementia in Motor
Neuron Disease Frontal and
Temporal Lobe Dementia Herpes
Simplex Encephalitis
HIV-1 Encephalopathy and AIDS Dementia
Complex Hydrocephalus
Inherited Metabolic
Disorders Multi-infarct
Dementia Multiple System
Atrophy Nonherpes viral
encephalitis Diffuse Lewy
body disease Chronic
meningitis
Dementia as a paraneoplastic
syndrome Familial myoclonic
dementia
Lithium poisoning
Treatment
All prion diseases are fatal; no effective treatment is available. Patients are
Prion Related Diseases-Differential Diagnoses

Kuru
Several different forms of prion disease exist. The first human prionosis to be described is
called kuru. This is an illness of the Fore people living in the highlands of New Guinea that is
thought to be linked to ritualistic cannibalism. Presumably, this illness originated with the
consumption of an initial patient with sporadic CJD. Kuru was once the major cause of death
among Fore women. Women had a greater tendency than men to develop kuru because it was
part of the ritual cannibalism for women to eat the brains (and neural tissue has the highest
dose of PrPSc). However, the disease has virtually disappeared with the end of cannibalistic
rituals. Similar to scrapie, patients clinically present with difficulty walking and they develop
progressive signs of cerebellar dysfunction. Death occurs approximately 1 year following onset
of symptoms.
Gerstmann-Strãussler-Scheinker disease
Patients with this illness present with a slowly progressive limb and truncal ataxia, as well as
dementia.
The prominent involvement of the brainstem often leads to symptoms suggestive of
olivopontocerebellar degeneration. The pattern of inheritance is autosomal dominant and is
caused by mutations of the PrP gene. The neuropathology of GSS is remarkable in that
extensive and
invariable amyloid deposition occurs, in addition to the typical spongiform change, gliosis, and
neuronal loss. Interestingly, in several kindreds of GSS, extensive neurofibrillary tangle
(NFT)
formation is found. NFTs are an essential feature of Alzheimer disease, but are also
observed in other neurodegenerative conditions.
Another variation of autosomal dominantly inherited human prionosis has been termed prion
protein congophilic angiopathy (ie, prion protein cerebral amyloid angiopathy [PrP-CAA]),
Other Prion Related Diseases

Tetanus
Risus sardonicus is a highly characteristic, abnormal,
sustained spasm of the facial muscles that appears to
produce grinning. The name of the condition
derives from the appearance of raised eyebrows and
an open "grin" - which can appear malevolent to the
lay observer
- displayed by those suffering from these muscle
spasms.
Tetanus, is a medical condition characterized by a prolonged contraction of skeletal
muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin
produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani. Infection
generally occurs through wound contamination and often involves a cut or deep
puncture wound. As the infection progresses, muscle spasms develop in the jaw (thus
the name "lockjaw") and elsewhere in the body.
Opisthotonos (o-pis-to-ton-is)

The rough surface of rusty metal
provides a prime habitat for a C.
tetani endospore to reside, and the
metal affords a means to puncture
skin and deliver endospore into the
wound. Tetanus begins when
spores of C. tetani enter damaged
tissue. The spores transform into
rod-shaped bacteria and produce
the neurotoxin tetanospasmin (aka
tetanus toxin). It binds to the
neuromuscular junction and then
attaches to peripheral motor
neuron nerve endings. It travels
centrally up the nerve in by
retrograde axonal transport to the
anterior horn cells, where it enters
adjacent spinal inhibitory
interneurons, blocking inhibitory
neurotransmitter release to the
anterior horn cell. Damaged upper
motor neurons can no longer inhibit
lower motor neurons. This leads
Tetanus-Pathophysiology

The incubation period of tetanus may be up to several months but is usually about 8 days.
In general, the further the injury site is from the CNS, the longer the incubation period.
Generalized tetanus is the most common type of tetanus, representing about 80% of
cases. The generalized form usually presents with a descending pattern. The first sign is
trismus, or lockjaw, and the facial spasms called risus sardonicus, followed by stiffness of
the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other
symptoms include elevated temperature, sweating, elevated blood pressure, and
episodic rapid heart rate. Spasms may occur frequently and last for several minutes with
the body shaped into a characteristic form called opisthotonos. Spasms continue for up
to 4 weeks, and complete recovery may take months.
Neonatal tetanus is a form of generalized tetanus that occurs in newborns. Infants who
have not acquired passive immunity because the mother has never been immunized
are at risk. It
usually occurs through infection of the unhealed umbilical stump, particularly when the
stump is cut with a non-sterile instrument. Neonatal tetanus is common in many
developing countries
and is responsible for about 14% (215,000) of all neonatal deaths, but is very
rare in
developed countries. In neonatal tetanus, symptoms usually appear from 4 to 14 days
after birth, averaging about 7 days.
Focal tetanus is an uncommon form of the disease, in which patients have
persistent
contraction of muscles at the wound site. The contractions may persist for many weeks
before gradually subsiding. Focal tetanus is generally milder; only about 1% of cases are
fatal, but it may precede the onset of generalized tetanus.
Tetanus-Treatment-Clinical Manifestations

Mild tetanus
•Tetanus immunoglobulin IV or IM,
•metronidazole IV for 10 days, antibiotic that decreases the number of bacteria but
has no effect on the bacterial toxin.
•diazepam,
•tetanus vaccination
Severe tetanus
Severe cases will require admission to intensive care. In addition to the measures listed
above for mild tetanus:
•human tetanus immunoglobulin injected intrathecally (increases clinical improvement
from 4% to 35%)
•tracheostomy and mechanical ventilation for 3 to 4 weeks,
•magnesium, as an intravenous (IV) infusion, to prevent muscle spasm,
•diazepam as a continuous IV infusion (muscle relaxants) In extreme cases it may be
necessary to paralyze the patient with curare-like drugs and use a mechanical
ventilator.
•the autonomic effects of tetanus can be difficult to manage (alternating hyper- and
hypotension, hyperpyrexia/hypothermia) and may require IV labetalol, magnesium,
clonidine,
ornifedipine.
In order to survive a tetanus infection, the maintenance of an airway and proper nutrition
are required. An intake of 3500-4000 calories, and at least 150 g of protein per day, is
often given in liquid form through a tube directly into the stomach (Percutaneous
endoscopic gastrostomy), or through a drip into a vein (Total parenteral nutrition). This
high-caloric diet maintenance is required because of the increased metabolic strain
Tetanus-Treatment

Tetanus can be prevented by vaccination with tetanus toxoid. Adults receive a booster
vaccine every ten years, and standard care practice in many places is to give the
booster to any patient with a puncture wound who is uncertain of when he or she was
last vaccinated, or if he or she has had fewer than 3 lifetime doses of the vaccine.
Diagnosis
There are no blood tests that can be used to diagnose tetanus. The diagnosis is based on
the presentation of tetanus symptoms. The "spatula test" is a clinical test for tetanus that
involves touching the posterior pharyngeal wall with a sterile, soft-tipped instrument,
and observing the effect. A positive test result is the involuntary contraction of the jaw
(biting down on the "spatula"), and a negative test result would normally be a gag reflex
attempting to expel the foreign object.
Tetanus-Prevention

Botulism
⚫ Botulism causes flaccid paralysis of muscles. It is caused by a neurotoxin, called
botulinum toxin, produced by the bacterium Clostridium botulinum (and rarely
by C. butyricum and C. baratii). There are seven distinct neurotoxins (types A-
G) that C. botulinum produces, but types A, B, and E (and rarely F) are the most
common that produce the flaccid paralysis in humans. Botulism is not
transmitted person to person.
⚫ Food-borne botulism is caused by eating foods that contain the botulinum
neurotoxin.
⚫ Wound botulism is caused by neurotoxin produced from a wound that is
infected with the bacteria C. botulinum.
⚫ Infant botulism occurs when an infant consumes the spores of the botulinum
bacteria. The bacteria then grow in the intestines and release the neurotoxin.
⚫ Gram-positive, endospore-forming, obligate anaerobe

Botulism
⚫
⚫
⚫
⚫
⚫
Pathophysiology
botulinum toxin paralyzes the nerves so that the muscles cannot contract. This happens
when the neurotoxin enters nerve cells and eventually interferes with the release of
acetylcholine so the nerve cannot stimulate the muscle to contract. Unless the nerve
can regenerate a new axon that has no exposure to the neurotoxin, the interference at
the neuromuscular junction is permanent.
⚫ Clinical Manifestations
⚫ The classic symptoms of botulism include double vision, blurred vision, drooping eyelids,
slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Constipation
may occur. Examination may reveal that the gag reflex and the deep tendon reflexes like
the knee-jerk reflex are decreased or absent.
Infants with botulism appear lethargic, weak, and floppy, feed poorly, become
constipated, and have a weak cry and poor muscle tone. In infants, constipation is often
the first symptom to occur.
These are all symptoms of the muscle paralysis that is caused by the neurotoxin. If
untreated, these symptoms may progress to cause paralysis in various parts of the body,
often seen as a descending paralysis of the arms, legs, trunk, and breathing muscles.
In food-borne botulism, symptoms generally begin 18-36 hours after eating a
contaminated food, but they can occur as early as six hours or as late as 10 days
afterward.

Botulism
Diagnosis
⚫ Differential diagnosis: Symptoms of other diseases, such as differential diagnosis Guillain-
Barré syndrome , and myasthenia gravis can appear similar to those of botulism.
⚫ The most direct way to confirm the diagnosis is to identify the botulinum neurotoxin in the
patient's blood, serum, or stool. This is done by injecting the patient's serum or stool into the
peritoneal cavity of mice. An equal amount of serum or stool from the patient is treated
with multivalent antitoxin and injected in other mice. If the antitoxin-treated serum- or
stool- injected mice live while those injected with untreated serum or stool die, then this is a
positive test for botulism and is called the mouse inoculation test. The bacteria can also be
isolated from the stool of people with food-borne and infant botulism, but this is not a
definitive test. However, stool cultures can help differentiate botulism from E. coli,
Salmonella, and other infectious agents.
Treatment
⚫
⚫ If diagnosed early, food-borne and wound botulism can be treated with an antitoxin that
blocks the action of neurotoxin circulating in the blood. The trivalent antitoxin (effective
against three neurotoxins: A, B, and E). The antitoxin can prevent the disorder from
worsening, but recovery still takes many weeks. Wounds should be treated, usually
surgically, to remove the source of the toxin-producing bacteria. Infant botulism: immune
globulins that can be given iv.
The respiratory failure and paralysis that occur with severe botulism may require a patient to
be on a breathing machine (ventilator) for weeks and may require intensive medical and
nursing care. After several weeks, the paralysis slowly improves as axons in the nerves are
regenerated.

•Leprosy is a chronic infectious disease of skin and peripheral nerves.
•World wide it is the most common cause of peripheral neuropathy
•Mycobacterium leprae Acid-fast rod that grows best at 30°C.
•Because of the distinct lifecycle of M. leprae, leprosy takes a very long time to manifest
itself as disease after infection. The incubation time alone can be up to 5 years for the
pathogen. It may even take up to 20 years for symptoms to appear.
•Today leprosy is seen primarily in Asia, Africa, and Latin America
•Prevalence of 1.3 million patients (70% from India)
Leprosy

Transmission by respiratory droplets and direct skin contact during close and frequent
contact. Other routes: contact with armadillos (a reservoir in Texas), infected soil and
tattooing.
Diagnosis 3 cardinal diagnositic
criteria: 1.Anesthetic skin patches
2.Thinkened nerves
3.Acid-fast bacilli in skin smears
Leprosy

1.Paucibacillary (Tuberculoid)- <5 skin lesions and or 1 nerve is involved It is
characterized by one or more hypopigmented skin macules and anaesthetic
patches, where skin sensations are lost because of damaged peripheral nerves
that have been attacked by the human host's immune cells.
2.Multibacillary (midborderline or borderline)-Borderline leprosy is of
intermediate severity and is the most common form. Skin lesions resemble
tuberculoid leprosy but are more numerous and irregular; large patches may
affect a whole limb, and peripheral nerve involvement with weakness and
loss of sensation is common.
3.Multibacillary (Lepromatous)- >5 skin lesions and/or >2 nerves involved
Multibacillary lepsory is characterized by lesions on the skin, nodules,
thickened skin, and damage to the nasal passages. Disfiguring nodules over
body; At its extreme, the loss of feeling prevents the adequate care of cuts or
burns on extremities, which may lead to gangrenous infections and eventual
amputation. Serious leprosy of the nasal passages can cause loss of the nose.
Leprosy-WHO classification criteria

•Multidrug treatment with antibiotic combination of
rifampin, dapsone, and clofazimine is highly effective.
Recurrence occurs with high bacterial loads and after 5
years of initial treatment. Severe neuronal damage
responds to oral prednisone.
•Thalidomide for severe erythema nodosum leprosum (an
inflammatory complication of leprosy that results in painful
skin lesions on the arms and legs and face) (teratogen-
child bearing women).
•Management- improve hygiene, injury prevention,
reconstructive plastic surgery (nasal reconstruction)
Leprosy-Treatment
Necrotic erythema nodosum leprosum

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