for seminar

1. INFECTIONS OF THE NERVOUS
SYSTEM

2. two broad categories
• those primarily involving the meninges (meningitis)
• Confined to the parenchyma (encephalitis)
• Meninges Covering of the brain and spinal cord Three layers –
 
Dura –Arachnoid –Pia 

3. • Bacterial infections – bacterial meningitis, tuberculosis, leprosy,
neurosyphilis, brain abscess,listeriosis
• Viral infections – viral meningitis , herpes simplex encephalitis, rabies
,poliomyelitis, progressive multifocal encephalopathy
• Fungal –cryptococcal meningitis
• Parasites- neurocysticercocis
• Protozoal – toxoplasmosis

4. • Bacterial infections reach the intracranial structures by
• one of two pathways, either by hematogenous spread or
• by extension from cranial structures adjacent to the brain
• (ears, paranasal sinuses, osteomyelitic foci in the skull,
• penetrating cranial or congenital sinus tracts) (see Durand
• et al; Thigpen et al). Some infections are iatrogenic, being
• introduced in the course of cerebral or spinal surgery,
• the placement of a ventriculoperitoneal shunt, or, rarely,
• by a lumbar puncture needle

5. • With hematogenous spread of infection, usually a
• single type of virulent bacterium gains entry to the cranial
• cavity. In the adult, the most common spontaneous
• or community-acquired pathogenic organisms are pneumococcus
• (Streptococcus pneumoniae), meningococcus
• (Neisseria meningitidis), group B streptococcus, Listeria
• monocytogenes, and staphylococcus; in the neonate, Escherichia
• coli and group B streptococcus; in the infant and
• unvaccinated child, Haemophilus influenzae.

6. • Infections
• that follow neurosurgery or the insertion of a cranial
• appliance are usually staphylococcal or due to anaerobic gram-
negative organisms; a small number is a result of mixed flora,
including anaerobic ones, or one of the enteric organisms.

7. ACUTE BACTERIAL MENINGITIS
• The immediate effect of bacteria or other microorganisms in the
subarachnoid space is to cause an inflammatory reaction in the pia
and arachnoid as well as in the cerebrospinal fluid (CSF). Infection also
reaches the ventricles, either directly from the choroid plexuses or by
reflux through the foramina of Magendie and Luschka

8. • I.
• Acute meningeal inflammation:
• A.
• Pure pia-arachnoiditis: headache, stiff neck, Kernig and Brudzinski signs.
• B.
• Subpial encephalopathy: confusion, stupor, coma, and convulsions. Cerebral infarction
because of cortical vein thrombosis may underlie these symptoms in some cases.
• C.
• Inflammatory or vascular involvement of cranial nerve roots: ocular palsies, facial
weakness, and deafness are the main signs. Deafness may also be caused by middle ear
infection, by extension of meningeal infection to the inner ear, or by toxic effects of
antimicrobial agents.

9. • D.
• Thrombosis of meningeal veins: focal seizures, focal cerebral defects such
as hemiparesis, aphasia (rarely prominent), most often after the first week.
• E.
• Ependymitis, choroidal plexitis: it is doubtful if there are any recognizable
clinical effects.
• F.
• Cerebellar or cerebral hemisphere herniation: caused by swelling causing
upper cervical cord compression with quadriplegia or signs of midbrain–
third-nerve compression.

10. • Subacute and chronic forms of meningitis:
• A.
• Hydrocephalus: at first caused by purulent exudate around the base of the brain,
later by meningeal fibrosis, and rarely by aqueductal stenosis.
• B.
• Subdural effusion: impaired alertness in a child, refusal to eat, vomiting,
immobility, bulging fontanels, and persistence of fever despite clearing of CSF.
• C.
• Venous or arterial infarction: unilateral or bilateral hemiplegia, decorticate or
decerebrate rigidity, cortical blindness, stupor, or coma with or without seizures.
Deep infarcts may occur from an infectious vasculitis at the base of the brain.

11. • Late effects or sequelae:
• A.
• Meningeal fibrosis around optic nerves or around spinal cord and roots: blindness and
optic atrophy, spastic paraparesis with sensory loss in the lower segments of the body
(opticochiasmatic arachnoiditis and meningomyelitis, respectively).
• B.
• Chronic meningoencephalitis with hydrocephalus: dementia, stupor or coma, and
paralysis (e.g., general paralysis of the insane). If lumbosacral posterior roots are
chronically damaged, a tabetic syndrome results. Deep infarcts.
• C.
• Persistent hydrocephalus in the child: blindness, arrest of mental activity, bilateral
spastic hemiplegia.

12. Pathogenesis
• The most common meningeal pathogens are normal inhabitants of
the nasopharynx. the entry of bacteria into the subarachnoid space is
facilitated by disruption of the blood–CSF barrier by trauma,
circulating endotoxins, or an initial viral infection of the meninges.
• Avenues other than the bloodstream by which bacteria can gain
access to the meninges include congenital neuroectodermal defects;
craniotomy and spinal operative sites; diseases of the middle ear and
paranasal sinuses, particularly perilymphatic fistulas; skull fractures

13. • The isolation of anaerobic streptococci, Bacteroides, Actinomyces, or
a mixture of microorganisms from the CSF should suggest the
possibility of a brain abscess with associated meningitis.

14. Clinical Features
• The early clinical effects of acute bacterial meningitis are fever,
headache, usually severe, and stiffness of the neck (resistance to
passive movement on forward bending), and less often initially,
generalized convulsions and a disorder of consciousness (i.e.,
confusion, drowsiness, stupor, and coma).

15. • Flexion at the hip and knee in response to forward flexion of the neck
(Brudzinski sign) and resistance to completely extending the legs with
the hips flexed (Kernig sign) also indicate meningitis but are less
consistently elicitable.

16. • Meningococcal meningitis should be suspected when the evolution is
extremely rapid (delirium and stupor may supervene in a matter of
hours), when the onset is attended by a petechial or purpuric rash
Because a petechial rash accompanies approximately 50 percent of
meningococcal infections, its presence dictates immediate institution
of antibiotic therapy, even though a similar rash may be observed
with certain viral infections
• Pneumococcal meningitis is often preceded by an infection in the
lungs, ears, sinuses, or heart valves

17. Spinal Fluid Examination
• The spinal fluid pressure is consistently elevated (above 180 mm H2O)
in cases of bacterial meningitis
• A pleocytosis in the spinal fluid is diagnostic of meningitis. The
number of leukocytes ranges from 250 to 100,000/mm3, but the
usual number is from 1,000 to 10,000. Occasionally, in pneumococcal
and influenzal meningitis, the CSF may contain a large number of
bacteria but few, if any, neutrophils for the first few hours. Cell counts
of more than 50,000/mm3 raise the possibility of a brain abscess
having ruptured into a ventricle

18. • The protein content is higher than 45 mg/dL in more than 90 percent
of the cases; in most cases, it falls in the range of 100 to 500 mg/dL.
The glucose content is diminished (hypoglycorrhachia), usually to a
concentration less than 40 mg/dL or less than 40 percent of the blood
glucose concentration (measured concomitantly or within the
previous hour), provided that the latter is less than 250 mg/dL. The
Gram stain of the spinal fluid sediment permits the identification of
the causative agent in most cases of bacterial meningitis;
pneumococci and H. influenzae are identified more readily than
meningococci.

19. • A rise in total LDH
• activity is consistently observed in patients with bacterial
• meningitisLevels of lactic acid in the CSF (determined by either gas
• chromatography or enzymatic analysis) are also elevated
• in both bacterial and fungal meningitides (

20. Prognosis and Sequelae of Meningitis
• Untreated, bacterial meningitis is usually fatal. The mortality rate of
treated H. influenzae and meningococcal meningitis has remained
approximately 5 percent for many years; in pneumococcal meningitis,
the rate is considerably higher (approximately 15%),

21. • EMPIRIC THERAPY OF BACTERIAL MENINGITIS
• AGE OF PATIENT
• ANTIMICROBIAL THERAPYa
• 0–4 wk
• Cefotaxime plus ampicillin
• 4–12 wk
• Third-generation cephalosporin plus ampicillin (plus dexamethasone)
• 3 mo–18 y
• Third-generation cephalosporin plus vancomycin (± ampicillin)
• 18–50 y
• Third-generation cephalosporin plus vancomycin (± ampicillin)
• >50 y
• Third-generation cephalosporin plus vancomycin plus ampicillin
• Immunocompromised state
• Vancomycin plus ampicillin and ceftazidime
• Basilar skull fracture
• Third-generation cephalosporin plus vancomycin
• Head trauma; neurosurgery
• Vancomycin plus ceftazidime
• CSF shunt
• Vancomycin plus ceftazidime
• aFor all ages from 3 months onward, an alternative treatment is meropenem

22. ENCEPHALITIS DUE TO BACTERIAL
INFECTIONS
• Three common
• ones are Mycoplasma pneumoniae, L. monocytogenes, and
• Legionnaire disease

23. VIRAL ENCEPHALITIS AND MENINGITIS
• Viruses gain entrance to the body by various routes.
• Mumps, measles, and VZV enter via the respiratory passages.
• Polioviruses and other enteroviruses enter by the
• oral–intestinal route, and HSV enters mainly via the oral
• or genital mucosal route
• The fetus may be infected transplacentally by
• rubella virus, CMV, and HIV. In Another pathway of infection is along peripheral
• nerves; centripetal movement of the virus is accomplished
• by the retrograde axoplasmic transport system. HSV, VZV,
• and rabies virus utilize this peripheral nerve pathway

24. Acute Aseptic Meningitis
”aseptic”
• because bacterial cultures were negative. the most common are
• from enterovirus—mainly echovirus and Coxsackie virus.
• HIV may present
• as acute, self-limited aseptic meningitis with an infectious
• mononucleosis-like clinical picture.
• The clinical syndrome of aseptic meningitis primarily
• consists of fever, headache, signs of meningeal irritation,
• and a predominantly lymphocytic pleocytosis in the spinal
• fluid with normal glucose. Stiffness of the neck and spine on forward bending attests
• to the presence of meningeal irritation (meningismus),

25. • The
• childhood exanthems associated with meningitis and
• encephalitis (varicella, rubella, mumps) produce wellknown
• eruptions and other characteristic signs

26. FUNGAL INFECTIONS OF THE
NERVOUS SYSTEM
• Fungal infections of the CNS may arise without obvious predisposing
cause, but they typically complicate some other disease process that
suppresses immune function, such as HIV, cancer chemotherapy,
organ transplantation, severe burns, leukemia, lymphoma or other
malignancy, diabetes, rheumatologic disease, or prolonged
corticosteroid therapy. They are referred to as opportunistic

27. • Fungal meningitis develops insidiously, generally over a period of
several days or weeks, similar to tuberculous meningitis; The spinal
fluid changes in fungal meningitis are also like those of tuberculous
meningitis. Pressure is elevated to a varying extent, pleocytosis is
moderate and lymphocytes predominate. Exceptionally, in acute
cases, a pleocytosis above 1,000/mm3 and a predominant
polymorphonuclear response are observedThe 1,3-beta-D-glucan
serum assay, which detects a cell wall component present in many
types of fungi, is abnormal in patients with several different forms of
fungal infection. It has been shown to be useful in testing CSF

28. • Cryptococcosis is one of the more frequent fungal infections of the CNS, and it occurs in both normal and
immunocompromised hosts. The causative organism is usually Cryptococcus neoformans
• The pathologic changes are those of granulomatous meningitis; in addition, there may be small granulomas
and cysts within the cerebral cortex and sometimes larger granulomas and cystic nodules deep in the brain
(cryptococcomas).
• Treatment In patients without HIV, this consists of
• intravenous administration of amphotericin B or liposomal
• Amphotericin
• in patients with HIV. The recommended
• treatment in these circumstances is amphotericin supplemented
• by flucytosine for 2 weeks. Subsequently,
• fluconazole, an oral triazole antifungal agent, is given
• (or less preferably, oral itraconazole), for up to 1 year or
• indefinitely to prevent relaps

29. • Candidiasis is probably the most frequent opportunistic
• fungus infection
• Aspergillosis
• In most instances, this infection has presented as a chronic
• sinusitis (particularly sphenoidal), with osteomyelitis at the
• base of the skull or as a complication of otitis and mastoiditis.
• Cranial nerves adjacent to the infected bone or sinus
• may be involved.

30. • Mucormycosis- The cerebral infection begins in the nasal turbinates
and paranasal sinuses and spreads from there along infected vessels
to the retroorbital tissues and cavernous sinus (where it results in
proptosis, ophthalmoplegia, and edema of the lids and retina) and
then to the adjacent brain, causing hemorrhagic infarction
• Coccidioidomycosis, Histoplasmosis, Blastomycosis, and
Actinomycosis

31. INFECTIONS CAUSED BY RICKETTSIAS,
PROTOZOA
• Toxoplasmosis
• This disease is caused by Toxoplasma gondii, a tiny (2- to
• 5-μm), obligate, intracellular parasite which it involves the brain in
patients
• with HIV. Several modes of transmission of the late-acquired
• form have been described—eating raw beef, handling
• uncooked mutton (in Western Europe), and, most often,
• contact with cat feces, the cat being the natural host of
• Toxoplasma

32. active infection—fever, rash, seizures,
plenomegaly—may be present at birth. More often,
etinitis, hydrocephalus or microcephaly, cerebralcalcifications, and
motor retardation are the major
tationsThe rim-enhancing
lesion or multiple lesions of toxoplasmosis also
found incidentally on cerebral imaging studies
ent Patients with a presumptive diagnosis of cerebral toxoplasmosis are
with oral sulfadiazine
ally, then 4 to 6 g daily) and pyrimethamine (200 mg initially, then 50 to 100
y)

33. • Amebic Meningoencephalitis- Acanthamoeba and Balamuthia. Naegleria is
acquired by swimming in ponds or lakes where there is warm fresh water.
These are rare but lethal illnesses usually abrupt, with severe headache, fever,
nausea and vomiting, and stiff neck. The course is inexorably progressive—
with seizures, increasing stupor and coma, and focal neurologic signs—and
the outcome is practically always fatal, usually within a week of onset.
• Malaria-The main one of concern here is cerebral malaria, which complicates
approximately 2 percent of cases of falciparum malaria-
• This is a rapidly fatal disease characterized by headache, seizures, and coma,
with diffuse cerebral edema and only very rarely by focal features such as
hemiplegia, aphasia, hemianopia, or cerebellar ataxia

34. • The CSF may be under increased
• pressure and sometimes contains a few white blood cells,
• and the glucose content is normal
• Trypanosomiasis- There are two types; the African
• type (“sleeping sickness”) is caused by Trypanosoma brucei,
• rhodesiense, and gambiense and is transmitted by several
• species of the tsetse fly. The second type is Chagas
• disease, predominantly seen in South America

35. • The infection begins with a chancre at the site of inoculation
• and localized lymphadenopathy. Posterior cervical
• adenopathy is a characteristic feature of subsequent CNS
• infection (Winterbottom sign); another sign of neurologic
• interest is pronounced pain at sites of minor injury (called
• Kerandel hyperesthesia

36. SUBACUTE AND CHRONIC
FORMS OF MENINGITIS
• Tuberculous Meningitis-Tuberculous meningitis is usually caused by the acid-fast
• organism Mycobacterium tuberculosis and, exceptionally,
• by Mycobacterium bovis,
• The two stages in the pathogenesis
• of tuberculous meningitis include a bacterial seeding
• of the meninges and subpial regions of the brain with the
• formation of tubercles, followed by the rupture of one or
• more of the tubercles and the discharge of bacteria into the
• subarachnoid space (Rich).

37. • Small, discrete white tubercles are scattered over the
• base of the cerebral hemispheres and, to a lesser degree,
• on the convexitiesThere may be multiple small
• abscesses or a more uniform exudate in the leptomeninges
• The CSF is usually under increased pressure and contains between 50
and 500 white cells per cubic millimeter, rarely more. Early in the
disease, there may be a more-or-less-equal number of
polymorphonuclear leukocytes and lymphocytes, but after several
days lymphocytes predominate in the majority of cases

38. • The protein content of the CSF is always elevated, between 100 and
200 mg/dL Glucose is reduced to levels below 40 mg/dL but rarely to
the very low
• .
• Tuberculoma- These are tumor-like masses of tuberculous granulation
• tissue, most often multiple but also occurring singly, that
• form in the parenchyma of the brain and range from 2 to
• 12 mm in diamete

39. • Neurosyphilis-Syphilis is caused by Treponema pallidum, a slender,
spiral, motile organism. The initial event in the neurosyphilitic
infection is meningitis, which is clinically apparent in approximately 25
percent of all cases of syphilis
• The treponeme usually invades the CNS within 3 to 18 months of
inoculation with the organism.
• Usually, the meningitis is asymptomatic and can be discovered only by
lumbar puncture

40. • All forms of neurosyphilis begin as meningitis (and
• meningeal inflammation) are the invariable accompaniment
• of all forms of neurosyphilis. The early clinical
• syndromes are aseptic meningitis and meningovascular
• syphilis; the late (secondary) ones are vascular syphilis
• (1 to 12 years), followed even later by tertiary syphilis,
• general paresis, tabes dorsalis, optic atrophy, or subacute
• myelitis (Ropper). In all cases of tertiary neurosyphilis,
• the pathologic sequence results from chronic syphilitic
• meningitis and subpial recruitment of microglia and other
• inflammatory cell

41. • The CSF abnormalities
• consist of (1) a pleocytosis of up to 100 cells/mm3, sometimes
• higher, mostly lymphocytes and a few plasma cells
• and other mononuclear cells (the counts may be lower in
• patients with HIV and those with leukopenia); (2) elevation
• of the total protein, from 40 to 200 mg/dL; The glucose content
• is usually normal. Serologic diagnosis of syphilis (Fig. 31-5; See Ropper)
• This depends on the demonstration of one of two types of
• antibodies: nontreponemal (reagin, RPR) antibodies and
• specific treponemal antibodies. The timing of appearance
• and persistence of these various tests changes over time
• and bears on the sensitivity of each during the progressive
• phases of neurosyphilis

42. • Tabetic Neurosyphilis (Tabes Dorsalis)-usually develops 15 to 20 years
after the onset of the infection.
• The major symptoms are lightning pains, ataxia, and urinary incontinence;
the chief signs are absent tendon reflexes at knee and ankle, impaired
vibratory and position sense in feet and legs, and a Romberg sign
• The pupils are abnormal in more than 90 percent of cases, usually the
Argyll Robertson type (see Chap. 13). Optic atrophy is frequent. The
lancinating or lightning pains (present in more than 90 percent of cases)
are, as their name implies, sharp, stabbing, and brief, like a flash of
lightning

43. EPIDURAL AND SUBDURAL
CRANIAL INFECTION
• Subdural Empyema
• Subdural empyema is an intracranial (sometimes intraspinal) purulent
process between the inner surface of the dura and the outer surface
of the arachnoid that occurs mainly in children and is increasingly
infrequent as various bacterial infections are treated earlier in their
course. The infection usually originates in the frontal or ethmoid or,
less often, the sphenoid sinuses and in the middle ear and mastoid
cells. General malaise, fever, and headache—at first localized, then
severe and generalized and associated with vomiting are the first
indications of intracranial spread.

44. • The usual CSF findings are increased pressure, pleocytosis in the range
of 50 to 1,000/mm3, a predominance of polymorphonuclear cells,
elevated protein content (75 to
• 300 mg/dL), and normal glucose values.
• Treatment Most subdural empyemas, by the time they
• are recognized clinically, require drainage through multiple
• burr holes, or through a craniotomy

48. BRAIN ABSCESS
• With the exception of a small proportion of cases (approximately
• 10%) in which infection is introduced from the
• outside (compound fractures of the skull, intracranial
• operation, bullet wounds), brain abscess is secondary to
• bacteremia and a bacterial focus elsewhere in the body. Otogenic and rhinogenic
abscesses reach the nervous system
• by direct extension, in which the bone of the middle
• ear or nasal sinuses becomes the seat of an osteomyelitis,
• with penetration of the dura and leptomeninges, infection
• may spread along the major intracranial veins

49. • Metastatic abscesses from hematogenous spread are
• usually situated in the distal territory of the middle cerebral
• arterieThe most common organisms causing bacterial cerebral
abscess are virulent streptococci, many of which are anaerobic or
microaerophilicStaphylococci also commonly cause brain abscess, but
pneumococci, meningococci, and H. influenzae rarely do

50. • Headache is probably the most frequent initial symptom
• of an intracranial abscess
• Other early
• symptoms, roughly in order of their frequency, are drowsiness
• and confusion; focal or generalized seizures; and focal
• motor, sensory, or speech disorders.

51. • Although lumbar puncture is generally not recommended
• given the risk of herniation with a mass lesion, if
• performed in the early stages of abscess formation, the CSF
• pressure tends to be moderately increased; and there is a
• mild to moderate pleocytosis with 10 to 80 percent neutrophils;
• and the protein content is modestly elevated, rarely
• more than 100 mg/dL. Glucose values are not lowered,
• and the CSF is sterile unless there is concomitant bacterial
• meningitis.