Infections of the Nervous System

Note: Significant diseases are indicated in bold and syndromes in italics.

I. Bacteria

1. Bacterial meningitis

a. General symptoms: Only subtle behavioral changes may be apparent early in the disease course, but progression of the disease typically involves

i.    fever, headache, meningismus, photophobia, somnolence

ii.   focal neurological dysfunction (15%), particularly hearing loss

iii.  seizures (20%)

b. general diagnostic testing

i.    blood cultures identify causative pathogens in 50% of cases

ii.   cerebrospinal fluid analysis

(1) increased intracranial pressure, protein, and lactate

(2) decreased glucose

(3) pleocytosis is typically > 100 cells/μL, and > 60% neutrophils; may be lower early in disease course

Note: Local flora and sensitivity patterns require consultation with an infectious diseases expert.

(1) the initial infection is located in a parameningeal site, such as

(a) purulent sinusitis, which produces frontal lobe abscesses

(b) otitis media or mastoiditis, which produce temporal lobe or cerebellar abscesses

iii.  head injury: closed head trauma is a rare cause of abscesses except in cases that involve unrepaired cerebrospinal fluid leaks

iv.   neurosurgery, usually in cases where an air sinus has been opened

v.    idiopathic (20%)

b. common pathogens: abscesses include multiple organisms in 90%, usually Streptococcus species (50%), Bacteroides, and Enterobacteriaceae and other anaerobic bacteria

i.    abscesses from trauma also include multiple Staphylococcal species

ii.   abscesses in infants often include Gram-negative bacteria

c. symptoms: headache, nausea, and somnolence caused by increased intracranial pressure focal neurological injury

i.    increased intracranial pressure may enlarge the head circumference in infants

ii.   fever occurs in only 50% because the infection is isolated

d. diagnostic testing: ultimately requires tissue therapy

(1) early cerebritis (stage I): exhibits poorly demarcated ring enhancement that does not wash out and parenchymal edema

(2) late cerebritis (stage II): exhibits a developing necrotic center

(3) early encapsulation (stage III): exhibits a vascularized, necrotic center

(4) late encapsulation (stage IV): exhibits a thin collagen capsule that enhances but then washes out; gliosis develops around capsule

ii.   diagnosis requires tissue biopsy

iii.  blood cultures are rarely helpful; avoid lumbar puncture due to herniation risk

e. treatment

i.    medical treatment: most effective in neuroimaging stages I–II, before the development of an abscess capsule

(1) empiric therapy: vancomycin third-generation cephalosporin metronidazole or chloramphenicol

(2) glucocorticoids prevent fibrous encapsulation but also reduce penetration of antibiotics, therefore use only in patients who are clinically deteriorating

ii.   surgical drainage in cases with mass effect, elevated intracranial pressure, poor neurological condition, or proximity of the abscess to a ventricle (i.e., to prevent ventriculitis)

3. Bacterial encephalitis: an uncommon form of bacterial infection in the brain

a. Bartonella henselae/cat scratch disease

i.    pathophysiology: a Gram-negative bacillus transmitted by scratches from a colonized cat and possibly by cat fleas

ii.   symptoms: fever; lymphadenopathy proximal to the scratch; encephalitis with seizures develops in only 1% of infected patients

(1) may also cause myelitis and/or radiculitis in conjunction with angiomatous skin lesions that are similar to Kaposi’s sarcoma in the immunosuppressed

iii.  diagnostic testing: B. henselae enzyme linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR); cerebrospinal fluid is normal in 70% and otherwise shows only a mild lymphocytosis; cultures are unrevealing

iv.   treatment: gentamicin or trimethoprim-sulfamethoxazole (TMP-SMX)

v.    prognosis: complete recovery in the immunocompetent

c. symptoms (neurological): neurological symptom from

i.    meningitis, which has a relatively high rate of cranial neuropathy (25%, particularly CN VI > III, IV, VII) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) due to its preference for the basal meninges

(1) seizures, focal deficits (15%), and hydrocephalus may also occur

d. diagnostic testing: the diagnosis of tuberculosis infection in the brain is supported by identifying tuberculosis elsewhere in the body

i.    for meningitis: cerebrospinal fluid demonstrates increased protein, low glucose, and a lymphocytic pleocytosis; immunosuppressed patients may not exhibit the pleocytosis

(1) elevated total protein levels (> 100 mg/dL, often > 1000) may form a web-like coagulant that is very characteristic of tuberculosis meningitis {Froin’s syndrome}; removal of the coagulant leaves a supernatant with a very low protein level

(2) cerebrospinal fluid smear is positive in only 30%; acid-fast bacilli cultures are positive in 70%, but take 8 weeks to complete

(3) M. tuberculosis PCR is positive in 75%

(4) neuroimaging may demonstrate skull base meningeal enhancement

ii.   for tuberculoma

(1) neuroimaging demonstrates one or more ring-enhancing lesion (s), either high or low density

(2) tissue biopsy is required if the diagnosis of systemic tuberculosis cannot be made

e. treatment

i.    medical treatment: isoniazid + rifampin + pyrazinamide ± ethambutol or streptomycin, typically continued for 6–9 months; optimal drug regimen depends upon local resistance patterns

(1) may consolidate into a two-drug regimen if the patient is clinically improved after 2 months on the four-drug regimen; continue the two-drug regimen for 10 more months

(2) vitamin B6 supplementation is necessary to prevent isoniazid neuropathy

(3) glucocorticoids can be used to control tissue edema or Froin’s syndrome that can obstruct the arachnoid granulations and cause communicating hydrocephalus

ii.   surgical treatment

(1) cerebrospinal fluid shunting for any signs of hydrocephalus

(2) excision for tuberculomas that are causing symptomatic mass effect despite glucocorticoid therapy

f. prognosis: uniformly fatal within 6 weeks if untreated; 20% mortality in the immunocompetent, 30% mortality in immunosuppressed

2. Mycobacterium leprae/leprosy

a. pathophysiology: M. leprae is spread between persons by infected droplets, and it grows best at temperatures a few degrees below human body temperature; preferentially infects in the epineurium and perineurium of nerves of the extremities

i.    tuberculous leprosy (in patients with strong cell-mediated immunity): a few skin nodules develop that are associated regions of sensory loss; palpable nerve hypertrophy

ii.   indeterminate leprosy: a single hypopigmented patch that has sensory loss

(1) progresses to either tuberculous or lepromatous forms depending upon the effectiveness of the patient’s cell-mediated immunity

iii.  lepromatous leprosy (in patients with poor cell-mediated immunity): multiple skin nodules with cartilage erosion in the nose and ears {leo-nine face deformity}; distal small-fiber sensory loss in the extremities, nose, and ears with palpable nerve hypertrophy

(1) skin nodules are not initially associated with sensory loss, as they are in the tuberculous form of leprosy

(2) weakness and arthropathy develop late in the disease course

c. diagnostic testing

i.    identifying bacterial particles in macrophages in skin biopsies, nasal mucosa, or nerve biopsies

ii.   lepromin skin test is useful for distinguishing between lepromatous and tuberculous forms of the disease, but is not useful in diagnosis because it is commonly negative in the lepromatous form

d. treatment: dapsone + clofazimine + rifampin; treat for 1 year in patients with indeterminate or tuberculous forms, or for 2 years in patients with lepromatous form

i.    treatment often induces an erythema nodosum-like reaction upon initiation

III. Spirochetes

1. Lyme disease

b. epidemiology: common in New England, Minnesota–Wisconsin, and the Pacific Northwest

c. symptoms: 50% of infections are asymptomatic

i.    stage 1 (acute infection): localized erythema migrans

ii.   stage 2 (within weeks): nonspecific flu-like symptoms or meningitis; heart block and myocarditis; arthritis

iii.  stage 3 (within months): mild sensory polyneuropathy; subtle cognitive disturbances occur in 5% of cases {Lyme encephalitis}

(1) radiculoneuritis is prominent only with B. afzelii or B. garinii infection, which cause Lyme disease in Europe

iv.   “chronic” Lyme disease: similar to chronic fatigue syndrome and fibromyalgia, however, there is no clear evidence for its existence as a distinct disease entity

d. diagnostic testing: cerebrospinal fluid B. burgdorferi ELISA and Western blotting, or else positive blood serology in the presence of a consistent clinical syndrome

i.    serum or cerebrospinal fluid Borrelia PCR is not sufficiently reliable

i.    prior to development of neurological symptoms: doxycycline for 14–21 days

ii.   with neurological symptoms: third-generation cephalosporin IV for 2–4 weeks

iii.  prophylaxis with the Lyme disease vaccine, an OspA adjuvant

(1) single-dose doxycycline may prevent infection it administered within 72 hours of a tick bite

2. Syphilis: Caused by Treponema pallidum

a. primary syphilis: the only symptom is a painless chancre that is acquired by contact with an actively infected site on another person (i.e., another chancre, mucous membrane or skin rash, condyloma lata)

i.    may exhibit asymptomatic central nervous system infection as documented by pleocytosis of the presence of spirochetes on dark field microscopy

Figure 11–1 Stages of syphilis.