2. 2
CNS infections
By
Dr Muhammad Saleem Laghari
MBBS(KEMU), MCPS, FCPS (Paed)
Gold Medalist FCPS-I
Associate Professor
Department of pediatrics
SMC,RYK
4. 4
Case Scenario
A 2 years old boy presented with history of
fever, irritability & vomiting. Examination
revealed semiconscious child having temp.102F0
decrebrate posturing .Rest of systemic
examination unremarkable.
Q - write 3 differential diagnosis.
6. 6
Case Scenario
A 7 year old boy brought to emergency with
high grade fever, headache for 2 days &
projectile vomiting since morning. Examination
revealed semiconscious child with positive neck
stiffness.
1- What is the most likely diagnosis?
2- Write 3 relevant investigations to reach final
diagnosis.
3- Write steps in the management of this case.
7. 7
Key:
1- Acute – pyogenic meningitis
2- (i) CSF examination & culture (after fundoscopy)
(ii) CBC
(iii) Blood culture
3- Steps of Treatment
a. General Supportive Measures
Maintain I/V line, Monitor vitals, Fluids balance, IOP
record, Control of fever.
b. Specific treatment
(i) Either combination of B. Penicillin + Chloramphenicol or
(ii)Vancomycin + Cefotaxime / Ceftriaxone
(iii)Duration of Treatment: 7 – 10 days
c. Steroids: Dexamethasone 0.6 mg/kg/day in 2 – 4 divided doses for
2- 4 days
d.Monitor and treatment of complications.
8. 8
Case Scenario
8 year old girl presented to emergency department
with complaint of progressive loss of weight & low
grade fever for 2 months, lethargy, off & on
headache & vomiting for 2 weeks and now
unconsciousness for last 5 days. Examination
revealed unconscious, emaciated girl having 10 Kg
weight. No BCG scar. CNS examination revealed
right sided uncrossed hemiplegia. Her grand father
died 2 months back.
1- What is most likely diagnosis?
2- Mention 4 investigations to reach final diagnosis?
3- Write 4 steps of treatment of above disease?
9. 9
Key:
1- TBM
2- (i) CSF examination & Culture
(ii) CBC + ESR
(iii) Chest X-ray
(iv) Mantoux test
(v) CT Scan Brain
3- (i) General measures
(ii) Anti tuberculosis treatment (INH, PZA,
Rifampicin, Streptomycin)
(iii) Corticosteroids
(iv) Monitor & treatment of complication
(v) Follow up
34. 34
Incidence
Most serious complication of tuberculosis.
TBM complicates 1 of every 200 primary infections.
It is not reported in infants below 4 months of age.
The maximum risk of TBM is within 6 months of
primary infection.
The highest incidence is recorded below 5 years of age.
35. 35
Pathogenesis
TMB is always a secondary lesion with primary
usually in the lungs.
Meningitis results from the formation of a
metastatic caseous lesion (seeding of the bacilli)
in the cerebral cortex, meninges and choroid
plexus during the process of initial occult
lympho-hematogenous spread of the primary
infection.
36. 36
Within a short period of time, caseous foci form on the
surface of brain (Rich’s foci). They increase in size and
discharge bacilli in the CSF (subarachnoid space).
A thick, gelatinous exudate may infiltrate the cortical or
meningeal blood vessels, producing
inflammation, obstruction, or infarction. Most
commonly involved site is the brain stem causing
frequent involvement of 3rd, 6th, and 7th cranial nerves.
Basal cisterns are obstructed causing communicating
hydrocephalus. Accompany-ing inflammation may
cause cerebral edema.
37. 37
Clinical features
In a classical case, onset is insidious but may be
fulminant in certain cases.
A more rapid progression of the disease may occur in
young infants in whom symptoms develop for only
several days before the onset of acute
hydrocephalus, brain infarction, or seizures.
Classically, the onset is gradual (over several weeks).
History of measles may precede the onset of TBM.
The clinical manifestations may be divided into 3 stages
and each stage lasts approximately 1 week. There may
be considerable overlap of the 3 stages.
38. 38
Stage-1 (Prodromal stage).
(lasts for 1-2 weeks)
Initial symptoms are non-specific.
The child becomes listless or irritable, loses
interest in play, have
fever, anorexia, vomiting, constipation and
weight loss.
Some children may complain of headache and
drowsiness.
There are no focal neurologic signs.
There may be loss of or stagnation of the
developmental milestones.
39. 39
Stage – 2
Onset of 2nd stage is more abrupt.
During this stage, signs of meningeal irritation (neck
stiffness) appear with increased CSF pressure. Positive
kerning and Brudzinski signs develop with increased
tendon jerks and extensor plantar responses. There may
be generalized hypertonia.
Headache is the cardinal symptoms in the 2nd week of
illness in older children. Fever is constant and headache
is severe, persistent and often occipital.
Vomiting and constipation may become severe.
Exudate develops at the base of brain involving cranial
nerves and brain stem.
40. 40
Abducent nerve paralysis is common.
Oculomotor lesion causes internal squint. Facial
palsy is also common.
Some children may have disorientation, and
speech and movement disorders.
In infants anterior fontanelle may be bulging
and sutures become separated with “crackpot”
sign.
In older children, papilledema develops. Head
circumference starts enlarging rapidly.
41. 41
Choroid tubercles may be seen.
Child is semiconscious and may shriek loud
noises and develops convulsions.
All the above clinical features are due to the
development of hydrocephalus and increased
intracanial pressure along with meningeal
irritation.
42. 42
Stage – 3
Child rapidly becomes comatose during 3rd week.
He is emaciated with scybalous masses in the
abdomen.
Child starts getting high-grade irregular fever and
convulsions.
There may be hemiplegia or paraplegia.
With extreme neck stiffness opisthotonus develops
with decerebrate rigidity and pupil becomes dilated
and fixed.
There is deterioration of the vital signs especially
hypertension.
Death may occur if treatment is started late during
this stage.
Tache-cerebrale is sometimes seen in children.
44. 44
Management
General measures
1. Careful record of vital signs
2. Daily monitoring of the complications
3. Phenobarbitone: Dose 5mg/kg/day to control
convulsions.
4. Antipyretics: Paracetamol
5. corticosteroids
45. 45
6. Pyridoxine 10mg daily to prevent polyneuritis.
7. Feeding: Give tube feeding according to the
requirement.
8. Bed sores: Change posture every two hours to
prevent bed sores.
9. Care of comatose patient
10. Care of bowel and bladder.
11. It is also important to screen to screen the
family members for tuberculosis and treat the
infected persons.
48. 48
Prognosis
It depends upon two factors:
1. Age of the patient
2. Stage of the disease at which treatment is started.
Without treatment it is invariably fatal.
In stage-1, 100% cure rate is expected.
Even with optimal therapy mortality ranges from 30-
50% and incidence of neurologic squelae is 75-80%
especially in stage-3. there may be
blindness, deafness, paraplegia, mental retardation and
diabetes inspidus.
Infants and young children have poor prognosis as
compared to older children.
51. 51
It results in marked cerebral dysfunction and
early loss of consciousness.
It is usually caused by viruses e.g.
influenza, herpes simplex but brain tissue is also
involved as part of bacterial meningitis (e.g.
tuberculous meningoencephalitis, etc.)
Sometimes features of encephalitis occur after
few days of known viral infection or vaccination
and it is then called “Postinfectious” encephalitis.
Neuro-logic manifestations suggestive of
encephalitis but occurring in the absence of
inflammation indicate encephalopathy.
General Consideration
52. 52
Etiology.
Encephalitis is mainly caused by viruses.
It is caused by direct viral infection of the brain
via a hematogenous or neuronal route.
Arboviruses and enteroviruses are most
commonly responsible for epidemics of acute
encephalitis.
Herpes simplex is the most common cause of
sporadic encephalitis.
Varicella virus commonly causes cerebellar
ataxia.
54. 54
Pathophysiology.
Following ingestion or mosquito bite, the virus
infects several organs, where it multiples
causing a systemic febrile illness.
CNS is involved in the secondary viraemia if the
virus continues to multiply in the primary organs.
The neurologic damage occurs either (1) by
direct invasion and destruction of neural tissues
by actively multiplying viruses, (2) or by reaction
of the patient tissues to antigens of the virus.
55. 55
Pathology.
The brain is swollen with marked vascular
congestion, and initial polymorph response is
followed by mononuclear, lymphocyte and
plasma cells infiltration. There is degeneration of
the neuronal cells and interanuclear inclusion
bodies may be present.
Certain viruses appear to have an affinity for
invading certain parts of the brain, e.g. herpes
simplex for fronto-temporal lobe, mumps virus is
often associated with transverse
myelitis, chickenpox for cerebellum.
56. 56
Clinical Features.
All viruses, which cause encephalitis, can
also cause meningitis. Encephalitic picture
may predominate or a combined picture of
meningo-encephalitis may occur if
meninges are also inflamed. The clinical
features are extremely variable.
A sudden onset of high fever and
headache are the first signs of the illness.
57. 57
Features of encephalitis `
Most Common causes
Herpes
Measles
Chicken Pox
Polio.
Clinical features
Fever
Disturbed
Consciousness
Convulsion
Focal neurologic signs
Encephalitis; Direct invasion of gray matter by infectious agent.
Post-infectious; Delayed immunologicaly mediated demyelination.
Encephalopathy: Encephalitis like illness without fever or aseptic
meningitis (inflammation) is called encephalopathy and is due to
toxic or metabolic causes.
58. 58
Signs of central nervous system involvement
occur early which vary from mild drowsiness to
deep coma.
Headache, fever, irritability, mental confusion or
abnormal behavior may be marked.
Headache is common in older children whereas
infants may have gross irritability and feeding
difficulty.
Focal neurological signs may occur, cranial
verve palsies (squint or facial palsy)
speech, disturbances (aphasia), spastic palsies
(hemiplegia, tetraplegia), cerebellar
disturbances (ataxia) and abnormalities or
various reflexes.
Meningeal infammation may produce neck
rigidity and stiffness of back.
59. 59
some children may present with abnormal
behavior screaming spells, irritability,
confusion, tremors and stupor, muscle
weakness and occasionally paralysis may
occur.
Spastic paraplegia with loss of bowel and
bladder control indicates spinal cord
involvement.
Sensory disturbances may be present in
some. Respiratory irregularities and visual
disturbances may occur.
Occasionally myocarditis and hypotension
may complicate the picture.
60. 60
The clinical features usually do
not point to a specific viral
etiology but some types of
encephalitis present distinct
clinical features e.g. Herpes
simplex, since it is treatable it
is described further.
61. 61
Herpes Simplex Encephalitis.
Type-1:
infants and children typically present with
fever, vomiting, and lethargy and proceed to
coma and focal fits.
It usually produces features of a space-
occupying lesion in the temporal lobe like
hemiparesis, focal fits and raised intracranial
pressure tentorial herniation, papilledema and
decerebrate posturing may occur.
CSF examination may show xanthochromia and
in some cases RBSs. Cell count varies between
50-5000, CSF protein is normal or moderately
elevated with normal glucose.
62. 62
Type-2:
Herpes virus type 2 causes
encephalitis in the newborn following
vaginal delivery. Virus is acquired from
maternal birth canal and results in typical
vesicular skin eruptions and encephalitis.
63. 63
Chicken Pox Encephalitis. (1 in 1000-5000).
Occurs 4 – 6 days after the rash but it can
produce the rash in some. CSF shows
10 – 15 cells/mm3 with polys initially and
lymphos later. Protein is normal or
moderately elevated with normal glucose.
64. 64
Measles Encephalitis.
(1 in 600-1000 with a high mortality rate)
It usually develops 2 days to 2 weeks after the
appearance of rash, rarely even before. Spinal
cord involvement with paraplegia and neurologic
bladder may occur with inappropriate ADH
secretion. CSF reveals lymphocytic pleocytosis
of 20 – 250 cells with slightly raised protein and
normal glucose.
65. 65
Polio – Encephalitis.
Occurs in 1 – 5 percent of patients showing
neurological manifestation of polio infection.
Drowsiness, irritability, coarse tremors, coma
and fits indicated encephalitis in addition to the
usual symptoms of paresis of limbs or brain
stem involvement.
Although sensory deficits are rare but these can
occur in the presence of transverse myelitis or
following involvement of the posterior hours of
the gray mater.
CSF shows mild pleocytosis of 50 – 200
cells, initially polys and later lymphos. Protein in
CSF is moderately elevated and glucose normal.
Polio-encephalitis should always be considered
in differential diagnosis, as it is common here.
66. 66
Mumps
Mumps is commonly associated with
aseptic meningitis, which occurs 2 – 3
days after the onset of parotitis, but
encephalitis occurs 7 – 10 days later with
frequent convulsions and coma. Diagnosis
is confirmed by virus isolation, serological
methods and fluorescent antibody
techniques
67. 67
Lymphocytic Choriomeningitis.
This virus is thought to be transmitted to
man by the inhalation or ingestion of dried
mica excreta. After incubation period of 1
week there is malaise, headache and
myalgia usually lasting 1 – 2 weeks. It is
followed by meningo-encephalitis.
68. 68
Slow Viral Diseases
Slow Viral Diseases are manifested
months to years after the viral infection.
Slow CNS infection is due to prions (Small
protein-aceous particles). There is
dementia, poor congnitive functions, and
behavior changes. Most common viruses
causing such type of disease are measles
(subacute sclerosing panencephalitis or
SSPE), rubella, HIV and HSV.
69. 69
Diagnosis.
Diagnosis is essentially clinical and by
exclusion of diseases such as
meningitis, cerebral malaria,
brain tumor, heat stroke
and lead encephalopathy.
70. 70
1- Lumber Puncture.
Cerebrospinal fluid should be examined to
exclude bacterial and tuberculous meningitis. In
viral encephalitis CSF is generally clear. In viral
encephalitis CSF is generally clear, leukocyte
count varies from 10 – 5000 cells with
polymorph initially and lymphocytes later. There
is moderate elevation of protein with normal
glucose.
2- Antibody titer.
Serologic testing should be done twice 15 days
apart or demonstrate rising titer (4 fold or more)
71. 71
3- Virus Isolation.
Viruses can be isolated from blood, CSF, faces
and throat swabs.
4- Brain CT Scan/MRI brain.
These are helpful in localizing the process as in
focal necrotizing encephalitis (Herpes simplex).
5- Brain Biopsy.
The diagnosis is established and confirmed by
brain biopsy. It is only indicated in cases, which
are suspected to be having herpes encephalitis
because specific antiviral chemotherapy is
available. Virus is then identified by immuno-
flouresecent technique from brain biopsy.
72. 72
6- EEG.
infection of the brain causes very
marked disorganization of the EEG with
the development of large amplitude, slow
waves. In herpes encephalitis there are
large amplitude, slow waves at rate of
2 – 4 / Sec and these waves recur after
every 2 sec on a background of very slow
activity in the temporal region.
7- Blood Counts.
these are done as routine to rule out
bacterial infections.
75. 75
Management.
1- Nursing Care.
Nursing a comatose child
monitoring vital functions,
frequent suctioning of airways,
change of posture every ½-1 hours to avoid pressure sores
and positional deformity.
Attention should be paid to oral hygiene, eye care, and
abdominal distension from bladder enlargement (urinary
retention) and bowel care (ileus or severe constipation).
2- Anticonvulsants.
Inj. Diazepam 0.2mg/kg I/V or
Inj. Paraldehyde 0.15ml/kg PR.
Once convulsions are controlled give phenobarbitone 5-8
mg/kg/day orally to prevent further convulsions.
76. 76
3- Cerebral Edema:
Raised intra-cranial pressure and cerebral
edema is present in most cases even
without any evidence of papilledema and
should be treated.
(i). dexamethasone.
(ii). Mannitol
4. Antiviral Drugs.
For herpes simplex virus
infections, acyclovir is the treatment of
choice.
77. 77
5-Intravenous Fluids.
Maintain fluid and electrolyte balance.
Fluids should be restricted to 60% of the
daily requirement and do not give dextrose
water or 0.18% saline which results in
cerebral edema.
6-Nutrition.
Calories required are given through
nasogastric tube in the from of liquid and
semisolid diets e.g. milk, juices, soup, egg,
etc.
78. 78
7-Antibiotics.
Should be given until bacterial etiology is ruled
out by blood and CSF examination.
8-Antipyretics.
High fever should be controlled by antipyretics
or tepid water sponging.
79. 79
Progonsis.
Most patients survive and some may have
residual focal defects.
Mortality varies from 10-50%.
The outcome is particularly poor in herpes
simplex encephalitis (mortality rate > 70%)
while better in enteroviral encephalitis.
Encephalitis is usually severe in children >
1 year of age and in those presenting with
coma.
81. 81
Definition
It is a severe form of malaria caused by
Plasmodium falciparum, manifesting as
coma (GCS <11)
convulsions, and/or
hemoglobinuria.
OR
Malaria with coma persisting for >30
min after a seizure.
82. 82
Etiology
Plasmodium falciparum is transmitted from:
1. Bites of previously infected female
anopheles mosquitoes.
2. Transfusion of infected blood.
3. Organ transplant and by hypodermic
needles.
83. 83
Epidemiology
The infection is usually much more severe in
young children.
A and B blood groups are more protective
than O groups.
Hemoglobin E and C are also more protective.
Fetal hemoglobin, sickle cell trait and G6PD
deficiency have lesser tendency of plasmodium
falciparum infection.
Malnutrition is protective as immunity is
decreased.
84. 84
Pathophysiology
First the Plasmodium falciparum enters the red
blood cells.
After 8 – 18 hours, these cells become increasingly
sticky and tend to adhere to the endothelial lining of
blood sinuses and vessels especially when the
circulation is slow. The fixed cells are unable to
come back to the general circulation.
As more cells adhere, flow within the vessels is
progressively impeded and occlusion or even
rupture may occur.
The symptoms depend on the site and extent of the
occlusion of the blood vessels. The lungs, brain and
intestinal tract are usually more affected.
The parasites keep maturing in the infected cells
even when they are fixed to the endothelium or
85. 85
The release of merozoites, where the
circulation is slowed, facilitates the
invasion of nearby red blood cells.
Plasmodium falciparum invades all
erythrocytes irrespective of age and so
parasitemia in a non-immune child may
be very heavy.
One schizont yields 8 – 32
merozoites, the highest of all the
species.
86. 86
Pathology
When the parasitized red blood cells attach to
the endothelium of venules and capillaries, the
inflammatory process start around them. There
is hemorrhage and necrosis around these
vessels.
All these lead to the blockage of vessels by
parasitized red blood cells. Fibrin thrombi may
also form in the arterioles and capillaries giving
a picture of DIC. The same process in the
brain lead to the cerebral edema.
87. 87
The immunofourescence has shown the
deposition of plasmodium falciparum antigen
and antibody complex in capillaries. There are
two suggested ways to explain:
ICAM (Intercellular Adhesion Molecule)
medicated increased adherence of RBC’s to
the endothelium of cerebral vessels.
NO (Nitric oxide) mediated increased fragility
and destruction of cerebral matter.
88. 88
Clinical Features
The characteristic adult pattern of cerebral malaria is
not present in children especially under 5 years of
age.
The clinical signs and symptoms usually start
after 8-15 days of infection. Initially there are
behavior changes like anorexia, fretfulness, unusual
crying, drowsiness, or disturbance of sleep.
Fever may be absent or increase gradually for 1-2
days or the onset may be sudden with high-grade
temperature with or without prodromal chill.
The complaints include
headache, nausea, generalized aching, particularly of
the back.
When the spleen has enlarged quickly and is
89. 89
Cerebral symptoms are evidenced by convulsions
or coma. The neurologic signs in infants and
children are those of increased intracranial pressure
and symmetric upper motor neuron and brainstem
disturbances such as disconjugate gaze and
decerebrate and decorticate postures.
There is severe pallor and splenomegaly (or
hepatosplenomegaly; liver may only be enlarged at
times).
The classic picture of a child with high-grade fever
who is unconscious and convulsing cannot be
mistaken.
There is no neck rigidity (except abnormal
posturing).
90. 90
Diagnosis
1. CBC
Leucopenia is variable.
Monocytosis is common.
Anemia
Reticulocyte count increased.
2. Thick and thin blood film: (most specific test)
Initially ring forms are seen and after 10 days
crescents (gametocytes) are seen.
Up to 20 % of RBC’s may be infected.
Negative if antimalarials are given.
3. CSF:
Usually normal if no associated meningitis
91. 91
4. Serum electrolytes.
5. Blood sugar: hypoglycemia.
6. Detection of parasitic antigen:
a. ICT – Malaria
b. DNA / RNA are detected with
probes.
7. Serological tests: Not very specific but
species specific antibodies can be
detected.
92. 92
Management
Supportive treatment
Anemia
Give blood transfusion if hemoglobin <6 gm %. (Pack
cells 10 mlkg).
Hypoglycemia:
Give 50 % glucose bolus I/V stat and then regular
glucose supplements with 10 % dextrose water.
Renal Failure:
Increase hydration
May require dialysis.
Decrease the dose of anti-malarial to 1/3.
93. 93
Convulsions:
Diazepam 0.3 – 0.5 mg IV slow;
Phenobarbitone (10 mg/kg PO/NG tube stat, then
maintenance dose 5 mg/kg/day in 2 divided doses).
Paraldehyde (0. 15 ml/kg P/R).
Lowering of high temperature.
Tepid sponging or paracetamol orally by N/G tube.
Fluids:
5% dextrose saline 20-40ml/kg in 30 minutes or dextran
75%.
Late shift to 5% dextrose 1/5 saline.
Total fluid 100-150 ml/kg/day.
94. 94
Specific Treatment.
Start IV anti-malarial and then shift to oral when the
patient becomes conscious.
1 injection quinine dihydrochloride (300 mg/1 ml vial).
20 mg/kg IV stat, then 10 mg/kg IV-8 hourly for 7 days (1
mg in 1 ml of 5% dextrose water over 2-4 hours.
8.3 mg quinine base = 10 mg quinine dihydrochloride.
Injection Artemethrine:
It is also use in these days
Dose 3.2 mg/kg IM stat then 1.6 mg/kg/day for 2 days.
2 Injection Choloroquine dihydrochloride: (200 mg/5ml
vial)
5 mg/kg in 10 ml/kg of isotonic saline in 3-4 hours, then
repeat same dose at 6 hours, then give 5mg/kg daily for 3
days.
95. 95
Quinine Sulphate:
10 mg/kg/dose – 8 hourly for 4-7 days PO.
Chloroquin phosphate / hydrochlorosuin
sulphate:
10 mg/kg stat
Then 10 mg/kg next day
Then 5 mg/kg next day
Injection chloroquin dihydrochloride:
(200 mg/5ml vial)
5 mg/kg in 10 ml/kg of isotonic saline in
3-4 hours, then repeat same dose at 6
hours, then give 5mg/kg daily for 3 days.
96. 96
Differential Diagnosis.
Febrile Fits: Age 6 months – 6 years, patient is
arousable, CSF clear.
Pyogenic meningitis: Toxic ill patient. Signs of
meningeal irritation positive. CSF is turbid and
abnormal.
Viral encephalitis: Anemia, coagulo-pathy and
malarial parasite is absent. CSF may be normal with
increased proteins and pleocytosis.
SOL: Increased ICP evidenced by
vomiting, headache, diplopia and papill-edema..
Localizing signs and cranial nerve palsies are present.
Malarial parasite is absent. MRI/CT scan confirm.
97. 97
Hepatic coma: Deep jaundice and less
anemia. Liver is usually smaller. LFT’s gross
abnormality. Coagulation defects. Decreased
serum proteins and especially serum
albumin. Malarial parasite is negative.
Hypoglycemic coma: Afebrile, cold and
sweating. Jaundice, anemia, bleeding and MP
are absent. Serum sugar is <40 mg%.
Uremia: H/o preceding
edema, diarrhea, and vomiting.
Hematuria, dysuria and recurrent abdominal
pain. H/O previous UTI or renal stones.
98. 98
Criteria for cerebral malaria diagnosis
CNS:
Unarousable or coma > 6 hours.
Focal or generalized fits.
Posture
(opisthotonic, decerebrate, decorticate).
Conjugate deviation of the eyes.
Retinal hemorrhages.
Renal:
Urine output < 400 ml/day.
Serum creatinine > 3 mg%.
99. 99
Prognosis
Mortality of cerebral malaria ranges from
10-30 %.
Death in most of the cases occur within 24
hours of admission / treatment.
Some children have a rapid and progressive
recovery, but most of the time duration of
impaired consciousness after treatment
being started ranges form few hours to
several days.
Majority of the surviving children had a full
recovery but about 10% have a permanent
neurologic deficit.
