Infections of NervousSystem

Bacterial Infections• ACUTE PURULENT MENINGITISBacteria may gain access to the ventriculo-

subarachnoid space by way of the blood or as a metastasis from infection of the heart, lung, or other viscera.

• The classic triad of fever, neck stiffness, and altered mental status occurs in less than half of all patients,

• but 95% have at least two of four symptoms of fever,

neck stiffness, altered mental status, and headache.

• Hemophilus influenzae,Streptococcus pneumoniae

,Neisseria meningitides,Group B streptococcus,Listeria monocytogenes

• Complications and SequelaeAn inflammatory process in the meninges and its

blood vessels (i.e., convulsions, cranial nerve palsies, focal cerebral lesions, damage to the spinal cord or nerve roots, hydrocephalus)

• Tuberculous MeningitisTuberculous meningitis is always secondary to

tuberculosis elsewhere in the body .• The onset is usually subacute, with headache,

vomiting, fever. • Anorexia, loss of weight, and abdominal pain

may be present.• With progress of the disease, patients become

stuporous or comatose. • Blindness and signs of damage to other cranial

nerves may appear, or there may be convulsive seizures or focal neurologic signs.

• Papilledema, cranial nerve palsies, and focal neurologic signs are common in late stages of the disease.

• Pott's disease is a presentation of extrapulmonary TB that affects the spine.

• Brain AbscessIt arises most commonly from direct extension

of cranial infections (mastoid, teeth, paranasal sinuses, ear, or osteomyelitis of the skull), infections after fracture of the skull or neurosurgical procedures, spread via intracerebral veins, or as hematogenous metastases from infection elsewhere in the body.

Brain abscess is almost never a consequence of bacterial meningitis, except in infants.

• The symptoms of brain abscess are those of any expanding lesion in the brain, and a nonlocalizing headache is the most common symptom.

• Edema of surrounding brain tissue may rapidly increase ICP .

• Seizures, focal or generalized, are common with abscess.

• Focal signs, including altered mental status and hemiparesis, are seen in approximately 50% of patients, depending on abscess location.

• Cerebral Subdural EmpyemaSubdural empyema may result from the direct

extension of infection from the middle ear, the nasal sinuses, or the meninges.

Chills, fever, and severe headache are common initial symptoms of intracranial involvement.

Neck stiffness is present. With progression of the infection, the patient lapses into a confused, somnolent, or comatose state.

Thrombophlebitis of the cortical veins is manifested by generalized convulsions and by the appearance of focal neurologic signs .

In the late stages, the ICP is increased and papilledema may occur.

• Spinal Epidural Abscess• Spinal epidural abscess is a collection of purulent material located

outside the dura mater within the spinal canal.• Infections of the spinal epidural space are accompanied by fever,

headache, back pain, weakness of the lower extremities, and finally, complete paraplegia.

• Infective EndocarditisNeurologic complications of infective endocarditis may be the first

manifestation of the underlying intracardiac infection.

Cerebral infarcts, less often, hemorrhagic, are most common.

Intracranial hemorrhages caused by mycotic aneurysms, brain abscess,

and meningitis also are frequent.

These complications presumably result from emboli of infective material from the heart.

• Inflammatory arteritis also has been implicated as a cause.

• An encephalopathy, may occur and may be related to microemboli, vasculitis, toxic effects of medications, or metabolic derangements .

• Seizures may occur in association with any of the cerebral complications.

• Leprosy• Leprosy (Hansen disease) is a chronic disease that results

from infection by Mycobacterium leprae, which has a predilection for the skin and the peripheral nerves.

• Although any of the peripheral nerves may be affected, the disease has a predilection for the ulnar, great auricular, posterior tibial, common peroneal, and cranial nerves V and VII.

• Brucellosis• Cases have been reported with meningitis and,

sometimes, with accompanying cranial nerve paresis, meningoencephalitis, meningomyelitis, optic neuritis, and peripheral neuritis.

Brain abscesses also have been reported. • Mycoplasma pneumoniae InfectionA variety of neurologic conditions has been described :

meningitis, encephalitis, postinfectious leukoencephalitis, acute cerebellar ataxia, transverse myelitis, ascending polyneuritis, radiculopathy, cranial neuropathy, and acute psychosis.

The most common appears to be meningitis or meningoencephalitis.

• Legionella InfectionPneumonia is the most typical systemic

manifestation of infection. Upper respiratory infection, and gastrointestinal disease may also occur.

Several neurologic conditions have been described: acute encephalomyelitis, severe cerebellar ataxia, chorea, and peripheral neuropathy.

Viral Infections

• CNS Viral Syndromes• Acute viral infections of the nervous

system may manifest clinically in three forms: viral (aseptic) meningitis, encephalitis, or myelitis.

• Most epidemic forms of meningitis, encephalitis, or myelitis are caused by infection with enteroviruses or arboviruses.

• Poliomyelitis• Acute anterior poliomyelitis is an acute,

generalized disease caused by poliovirus infection. • It is characterized by destruction of motor neurons

in the spinal cord, brain, and brain stem and by the appearance of a flaccid paralysis of the muscles innervated by the affected neurons.

• Mumps• Mumps is a disease caused by a paramyxovirus .• Mild meningitis or encephalitis in a small

percentage of patients.• Other neurologic complications of mumps include

encephalomyelitis, myelitis, and peripheral neuritis.

• Measles• Measles virus causes a wide spectrum of

neurologic disease ranging from subclinical involvement and acute measles encephalitis , to chronic subacute sclerosing panencephalitis (SSPE).

• Rabies• Rabies is an acute viral disease of the CNS that

is transmitted to humans by the bite. • It is characterized by a variable incubation

period, restlessness, hyperesthesia, convulsions, laryngeal spasms, widespread paralysis, and almost invariably death.

• Herpes Simplex Encephalitis• Early diagnosis is decisive because there is

effective antiviral treatment.• The most common early manifestations are

fever, headache, and altered consciousness and personality .

• Onset is most often abrupt and may be ushered in by major motor or focal seizures.

• Mental deficits include confusion and personality changes varying from withdrawal to agitation with hallucinations.

• A progressive course ensues within hours to several days, with an increasing impairment of consciousness and the development of focal neurologic signs.

• Focal signs, such as hemiplegia, hemisensory loss, focal seizures, and ataxia, are considered distinguishing features of herpes encephalitis.

• EEG and MRI are the most likely diagnostic studies to be abnormal at onset and during the first week of infection.

• Herpes Zoster• Herpes zoster (shingles) is a viral disease that

produces inflammatory lesions in the posterior root ganglia and is characterized clinically by pain and a skin eruption in the distribution of the affected ganglia.

• Involvement of motor roots or the CNS occurs in a small percentage of patients.

• The virus of herpes zoster is VZV, the causative agent of chickenpox (varicella).

• The CNS complications (acute cerebellar ataxia, encephalitis, myelitis, meningitis) of varicella are thought to occur by a postinfectious autoimmune mechanism .

• Herpes zoster is primarily an infection of the spinal ganglia, but the cranial ganglia are affected in about 20% of patients.

• The thoracic, lumbar, cervical, and sacral segments are involved in descending order of frequency. Involvement is almost always unilateral.

• The initial symptom is usually a neuralgic pain or dysesthesia in the distribution of the affected root.

• The pain is followed in 3 to 4 days by reddening of the skin and the appearance of clusters of vesicles in part of the area supplied by the affected roots.

• Complications • Signs of involvement of the tracts of the spinal cord in

the form of a transverse or ascending myelitis have occurred.

• Mental confusion, ataxia, and focal cerebral symptoms have been attributed to involvement of the brain by VZV (herpes zoster encephalitis).

• Polyneuritis of the so-called “infectious or Guillain-Barré type” has been reported as a sequela of herpes zoster.

• Involvement of the anterior roots may result in zoster paresis.

• A more recently recognized complication of ophthalmic zoster is acute contralateral hemiplegia .(An arteritis or vasculopathy)

• ACUTE DISSEMINATED ENCEPHALOMYELITIS• ADEM may occur in the course of various infections,

particularly the acute exanthematous diseases of childhood, and following vaccinations; thus, ADEM is also known by the terms peri- or postinfectious encephalomyelitis (PIEM) and postvaccinal encephalomyelitis.

• The list of diseases is probably not yet complete, but it includes measles, rubella, varicella, smallpox, mumps, influenza, parainfluenza, infectious mononucleosis, typhoid, mycoplasmal infections.

• Additionally, vaccination against measles, mumps, rubella, influenza, and rabies may trigger these signs and symptoms.

• Because there is no specific diagnostic test, the diagnosis of ADEM, PIEM, or postvaccinal encephalomyelitis should be considered when neurologic signs develop 4 to 21 days following onset of acute exanthems, an upper respiratory tract infection, or after vaccination.

• CHRONIC VIRAL INFECTIONS• These include SSPE, PRP, progressive multifocal

leukoencephalopathy (PML), human T-cell lymphotropic virus (HTLV)-associated myelopathy (HAM) or tropical spastic para paresis (TSP), and AIDS.

• In SSPE, a chronic inflammatory disease is caused by a defect in the production of measles virus, which results in a cell-associated infection.

• It is characterized by progressive dementia, incoordination, ataxia, myoclonic jerks, and other focal neurologic signs.

• Progressive Rubella Panencephalitis• PRP usually occurs in the second decade of life,

beginning with dementia similar to that of SSPE. Cerebellar ataxia, however, is more prominent.

TSP• HTLV is a retrovirus that causes adult T-cell leukemia and

a chronic progressive myelopathy .• Onset is usually gradual, with weakness of one leg

followed in several months by weakness of the other leg. • Other complaints include

numbness and dysesthesia, bladder dysfunction, and impotence.

• Examination reveals spastic paraparesis with overactive tendon reflexes (legs more than arms) and Babinski signs.

• Progressive Multifocal Leukoencephalopathy• PML is a rare subacute demyelinating disease

caused by an opportunistic papovavirus.(JC virus ) • It occurs in patients with defective cell-mediated

immunity.• They have also occurred in patients with

carcinoma or sarcoidosis and in those immunosuppressed therapeutically and recently in MS patients treated with natalizumab.

• Onset is subacute to chronic with focal or multifocal signs (hemiplegia, sensory abnormalities, field cuts, and other focal signs of lesions in the cerebral hemispheres).

AIDS

• The neurologic syndromes in early HIV infection are indistinguishable from disorders that occur with infection by other viruses .

• These include aseptic meningitis, reversible encephalopathy, leukoencephalitis, seizures, transverse myelitis, cranial and peripheral neuropathy (Bell palsy, Guillain-Barré syndrome), polymyositis.

• The course is typically self-limited, and patients often experience full neurologic recovery.

• CSF abnormalities (pleocytosis up to 200 cells and oligoclonal bands) differentiate HIV syndromes from postinfectious disorders.

• Tests for HIV antibody may be negative, because these syndromes may precede or accompany seroconversion, and the tests must be repeated in several weeks.

• If acute HIV infection is strongly suspected, p24 antigen and viral load assay should be considered if serology is negative.

• In chronic HIV infection, neurologic disorders may accompany systemic HIV disease or secondary disorders .

• DementiaHIV-associated dementia is an insidiously

progressive subcortical dementia. Early symptoms include apathy, social

withdrawal, diminished libido, slow thinking, poor concentration, and forgetfulness.

Psychiatric syndromes, such as psychosis, depression, or mania, are sometimes profound and may be the first manifestation of HIV infection.

• Stroke• Stroke syndromes occur in 0.5% to 8% of

patients in clinical studies.• Stroke syndromes may follow secondary

infections or neoplasms, such as cryptococcus, toxoplasmosis, TB, herpes zoster, CMV, syphilis, lymphoma, or Kaposi sarcoma.

• Other causes include HIV-related vasculitis, cardiogenic emboli, thrombogenic conditions such as hyperviscosity, disseminated intravascular coagulation, and lupus anticoagulant.

• Seizures• Seizures may occur at any stage of HIV

infection and can be focal or generalized.• Leukoencephalopathy• Leukoencephalopathies in acute or chronic

HIV infection include acute fulminating and fatal leukoencephalitis; multifocal vacuolar leukoencephalopathy presenting as rapid dementia; and a relapsing-remitting leukoencephalitis that may simulate multiple sclerosis.

Movement Disorders • Movement disorders in patients with HIV

infection are most often extrapyramidal side effects of medications, including antiemetic and antipsychotic drugs.

• HIV itself can involve the basal ganglia and spinal cord and cause asterixis, myoclonus and, rarely, parkinsonism.

• Myelopathy • Chronic progressive myelopathy, an AIDS-

defining illness, is characterized by progressive spastic paraparesis, ataxia, and bowel and bladder dysfunction.

• Diagnosis of HIV myelopathy requires exclusion of cord compression, cord ischemia, secondary infections, HTLV 1 and nutritional deficiency. MRI may show gadolinium-enhancing lesions consistent with myelitis.

• Motor Neuron Disease • Several cases of an amyotrophic lateral

sclerosis (ALS)-like illness have been reported as the initial neurologic syndrome in patients with unrecognized HIV infection.

• Peripheral Neuropathy • Peripheral and autonomic neuropathies occur

in otherwise asymptomatic HIV-infected patients, especially those with progressive disease.

• Clinical syndromes include distal sensorimotor polyneuropathy (DSPN), mononeuritis multiplex, chronic inflammatory demyelinating polyneuropathy (CIDP), and ganglioneuritis.

• DSPN is the most common neurologic manifestation of HIV infection, and the frequency increases with advancing disease.

• Symptoms include painful burning dysesthesias that are often confined to the soles of the feet. Signs include stocking-glove sensory loss, mild muscle wasting and weakness, and loss of ankle jerks.

• Myopathy Myopathy is uncommon.

• OPPORTUNISTIC INFECTIONS• PML can be the initial AIDS-defining illness. Prognosis is

generally poor, with death occurring in 4 to 6 months. • The diagnosis should be suspected in patients with

focal signs who have hypodense nonenhancing lesions without mass effect on CT, or hyperintense lesions on MRI, that mainly affect white matter.

• Varicella Zoster Virus• In severely immunosuppressed patients, the infection

may not remain confined to the dorsal root ganglion and dermatomal skin segment.

• Instead, dissemination can occur causing pneumonia, diffuse rash, visceral involvement, myelitis, and encephalitis.

• Herpes Simplex Viruses• H. simplex is neurotropic and a sporadic cause

of encephalitis in both normal and immunosuppressed patients.

• Cytomegalovirus• Retinitis is the most common consequence of

CMV infection.• CMV can also cause a severe

polyradiculopathy with rapid development of flaccid paraplegia, urinary retention, and pain radiating into lumbar and sacral root distributions.

• Cryptococcosis• Cryptococcal infection, the most common

cause of meningitis in AIDS, was a presenting illness in 25% to 50% of AIDS patients in older clinical series.

• The incidence of cryptococcal infection has been dramatically reduced by current antiretroviral regimens and prophylaxis.

• Meningeal signs may be mild or absent even in the presence of headache and altered mental status.

• Toxoplasmosis• For many years, toxoplasmosis was the most

common cause of brain mass lesions in patients with AIDS and a frequent cause of death.

• Today, Toxoplasma gondii accounts for less than 2% of AIDS deaths in the United States.

• Neurologic symptoms are referable to the sites of mass lesions. With multiple lesions, the clinical picture may appear nonfocal with seizures and signs of increased ICP.

• CT and MR scans demonstrate ring-enhancing or nodular lesions with marked surrounding edema.

• Syphilis• Progression from primary syphilis (painless

chancre) to later stages is typically more rapid in HIV-infected patients who are immunodeficient.

• Early neurosyphilis, which occurs in 1.5% of AIDS patients, may be asymptomatic or present with uveitis, meningitis, stroke (often involving the middle cerebral artery territory), myelitis, or mass lesion (gumma).

• Syndromes of early neurosyphilis are more common than late syndromes (general paresis and tabes dorsalis).

• TB• The most common presentation is meningitis, which

may be chronic or fulminant, followed by tuberculomas.

• Meningitis preferentially involves the basilar meninges and is associated with hydrocephalus, multiple cranial neuropathies, and increased risk of stroke.

• NEOPLASMS• Lymphoma • Clinical signs are nonspecific and include focal

neurologic signs, seizures, cranial neuropathy, and headache. CT may be normal or show hypodense lesions as well as single or multiple lesions with patchy or nodular enhancement.

Fungal Infections• Cryptococcosis• Cryptococcus neoformans is the most common fungal infection

affecting the nervous system.

• Cryptococcus typically causes chronic meningitis, which begins insidiously with malaise, fever, photophobia, and meningismus.

• As the illness evolves, headache becomes increasingly prominent, and generalized seizures and altered mental status, including psychosis, occur.

• Increased ICP develops, causing obtundation and, eventually, herniation.

• Focal deficits reflect either development of a mass lesion or cerebral infarction resulting from basilar meningeal exudates.

Neurosyphilis• Neurosyphilis comprises several different syndromes that

result from infection of the brain, meninges, or spinal cord by Treponema pallidum .

• It is not known how much damage is caused by direct effects of the organism and how much by autoimmune mechanisms.

• The three most common forms of neurosyphilis are asymptomatic, meningeal, and vascular.

• Often, the meninges and cerebral vessels are affected together, in meningovascular neurosyphilis. The once prominent parenchymal forms, including general paresis (dementia paralytica) and tabes dorsalis, are rarely seen now.

• Asymptomatic Neurosyphilis• This diagnosis depends entirely on the serologic

findings in blood and CSF. • If the WBC count is more than 5 cells, the

disorder could be called “asymptomatic meningeal syphilis,” and there may be meningeal enhancement on MRI.

• Meningeal Neurosyphilis • This syndrome is seen within a year of the

primary infection. The clinical manifestations are those of any acute viral or aseptic meningitis: malaise, fever, stiff neck, and headache.

• Cerebrovascular Neurosyphilis • Cerebral infarct syndromes of syphilis are

similar to those of other more common causes; the diagnosis rests on typical findings in blood and CSF.

• Patients are younger than those with atherosclerosis and are more likely to have risk factors for venereal disease.

• Meningovascular Syphilis of the Spinal Cord • Conventional symptoms and signs of transverse

myelitis (meningomyelitis) usually affect both sensory and motor pathways, as well as bladder control.

• Gumma • This mass lesion, an avascular granuloma, is now

rarely seen but was found attached to the dura and was considered a localized form of meningeal syphilis.

• Tabes Dorsalis • Tabes dorsalis, also called progressive locomotor

ataxia, is manifested by lancinating or lightning-like pains, progressive ataxia, loss of tendon reflexes, loss of proprioception, dysfunction of sphincters, and impaired sexual function in men. The chief signs are loss of tendon reflexes at the knees and ankles, impaired vibratory and position sense in the legs, and abnormal pupils .

Lyme Disease• The spirochete has some characteristics of treponemes, but

it is classified among the Borreliae (Borrelia burgdorferi).• Meningeal symptoms and signs constitute the major

features of the neurologic illness, with headache and stiff neck principal.

• Radiculitis or radiculoneuritis, multiple or isolated, is common and may cause severe root pain or focal or generalized weakness. Radiculoneuritis may take the form of a Guillain-Barré-like syndrome, but the CSF shows pleocytosis.

• Cranial nerves (usually the seventh nerve) are frequently involved. The facial palsy is usually bilateral. Polyneuritis or mononeuritis multiplex may also occur.

• The combination of meningitis, radiculitis, and neuritis without fever occurs in virtually no other circumstance.

• If appropriate history of tick exposure and ECM(erythema chronicum migrans) is obtained, the diagnosis is assured.

Parasitic Infections• Cysticercosis• Cysticercosis is the result of encystment of the

larvae of Taenia solium, the pork tapeworm, in the tissues. The infestation is acquired by ingestion of the ova.

• CNS involvement occurs in 50% to 70% of all cases. Virtually all symptomatic patients have CNS involvement. It is the most common parasitic infection of the CNS.

• Clinical manifestations may be divided into four basic types, depending on anatomic site: parenchymal, subarachnoid (or meningitic), intraventricular, and spinal

• The most common presenting manifestations are seizures, increased ICP with headaches and papilledema, and meningitis.

• Echinococcosis (Hydatid Cysts)• The brain is involved in about 2% of the cases, and

neurologic symptoms may develop in patients with cysts in the skull or spine.

• The signs and symptoms that develop with enlarging cysts in the brain are similar to those of a tumor in the affected region. Seizures and increased ICP may also occur.

• Toxoplasmosis• The infection, which has a predilection for the

CNS and the eye, may be congenital with encephalitis and chorioretinitis;

• may cause meningoencephalitis during acquired primary infection in the immunocompetent host;

• and may cause mass lesions (granulomas, abscesses), encephalitis, and chorioretinitis in the immunocompromised host.

Prion Diseases

• CREUTZFELDT-JAKOB DISEASE• The clinical features include the gradual onset of

dementia in middle or late life, but occasionally in young adults.

• The most frequently seen signs, aside from dementia, are those of pyramidal tract disease (i.e., weakness and stiffness of the limbs with accompanying reflex changes), extrapyramidal signs (tremor, rigidity, dysarthria, and slowness of movement), and myoclonus, which is often stimulus sensitive.

• the immunoassay for the 14-3-3 protein is a highly supportive diagnostic test.

• (EEG) may also be of diagnostic value because periodic complexes of spike or slow wave activity.

• Increased signal intensity on T2-weighted, FLAIR and DWI magnetic resonance imaging has been seen primarily in the basal ganglia.

• In typical cases (e.g., dementia, myoclonus, periodic EEG, abnormal MRI), the diagnosis may be made clinically.