CENTRAL NERVOUS SYSTEM :

Inflammatory and Demyelinating Diseases

 

References:

Kumar, Cotran and Robbins, 6th Edition, pg. 726-731; 736-737

Rubin and Farber, 2nd Edition, pg. 1405-1425

Cotran, Kumar and Collins, 6th Edition, pg.1314-1329

To view a web site with additional examples of these diseases:

http://www.sun.ac.za/anatpath/neuro_path/studlec1.html

In a clinical consideration of a possible infectious disease process of the nervous system, it is important to characterize the disorder relative to:

The anatomic compartment. Leptomeningitis induces headache, stiff neck, and increased cells and protein in the cerebrospinal fluid. Cerebritis characteristically produce a neurologic deficit, dysfunction, or seizure.

The duration of symptoms. Virulent pathogens are rapidly symptomatic and may cause death. Other pathogens may cause symptoms over months or years.

The age of the patient. Newborns are affected by toxoplasmosis and E. coli meningitis. Young children may contract H. influenza meningitis. Adult infections are diverse.

The biological state of the host. Immunosuppression either therapeutically or by AIDS enhances the likelihood of cryptococcal meningitis or parenchymal infections by toxoplasmosis, Progressive Multifocal Leucoencephalopathy, Cytomegalovirus or herpetic encephalitis. Uncontrolled diabetes renders the patient vulnerable to mucormycosis.

NEUTROPHILIC REACTION

BACTERIAL MENINGITIS

Clinical presentation is with headache, vomiting, fever and stiff neck. Seizures common in children.

Inflammation of the subarachnoid space causes cervical rigidity manifest by pain in knee when hip is flexed (Kernig sign) and flexion of knee and hip when neck is flexed (Babinski’s sign). In untreated cases, delirium gives way to stupor, coma and death.

Inflammatory cells (polymorphonuclear leucocytes) and bacteria are present in the CSF. CSF changes vary with the nature and extent of infection and with the immunological competence of the host.

Specific bacteria vary with the age of the host. May be a complication of middle ear infection in children

  1. Escherichia coli infects neonates.

  2. Hemophilus influenza infects infants and toddlers.

  3. Streptococcus pneumonia infects adults and elderly; increased incidence with basal skull fracture.

  4. Neisseria meningitidis causes epidemic meningitis in adults, frequently causes petechial rash and DIC with adrenal hemorrhage (Waterhouse-Friderickson syndrome).

Cerebral abscess: Cerebritis Æ necrosis Æ abscess Æ swelling and pressure necrosis Æ extension

 GRANULOMATOUS REACTIONS

TUBERCULOUS MENINGITIS AND TUBERCULOMA

Organisms gain access to CNS via the blood stream

Basal meningitis

Parenchymal involvement - tuberculoma which may present as tumor.

TB of spine causes Pott’s disease

Caseating granulomas

Giant cells

Acid fast bacteria

Fatal in 4-6 weeks if untreated

SARCOIDOSIS very rare

CRYPTOCOCCAL MENINGITIS

Indolent infection in an immunocompromised host

Causes graunlomatous meningitis but may have minimal tissue reaction

Encapsulated spheres 5-15 m diameter

India ink on CSF for diagnosis

PLASMACELLULAR REACTION

SYPHILIS

1. Luetic meningovascular syphilis; obliterative endarteritis with plasma cells in meninges

2. Tabes dorsalis; inflammatory processes damages dorsal root ganglia with transynaptic degeneration of posterior columns and loss of position, vibration sense

3. Luetic dementia; loss of neurons, microglia and nodular ependymitis

4. CSF serology reverts to negative

LYMPHOCYTIC/MICROGLIAL

A. VIRAL ENCEPHALOMYELITIS

1. Viral meningitis

  1. Usually benign illness of children and young adults

  2. Coxsackie B virus

  3. Arbovirus.

  4. CSF shows lymphocytosis

2. Viral encephalitis

  1. Arboviridiae

  2. Transmitted by mosquitoes and ticks

  3. Clinical features vary with virus

  4. Pathology varies from mild meningitis to severe encephalitis

3. Inclusion forming viruses

  1. Rabies – Negri bodies

  2. Herpes

  3. Cytomegalovirus

  4. Measles - Subacute Sclerosing Panencephalitis (SSPE)

  5. JC virus - Progressive Multifocal Leucoencephalopathy (PML)

4. Rabies

  1. Rhabdovirus - enveloped ssRNA virus

  2. Transmitted by saliva from bite of infected animal

  3. Reservoir in dogs, wolves, skunks foxes and bats

  4. Latent period 10 to 90 days

  5. Peripheral nerve to spinal cord and brain, encephalitis

  6. Destruction of brain stem neurons causes "hydrophobia"

  7. Kills 50,000 annually in endemic areas

5. Herpes virus

  1. Herpes Simplex Virus type 1 (HSV-1) causes "cold sores"; resides latently in the Gasserian ganglia

  2. Herpes encephalitis is a fulminant necrotizing infection localized to temporal lobes

  3. HSV-2 infects infants via the birth canal

  4. Cytomegalovirus - causes encephalitis in utero; important cause of encephalitis in immunocompromised adults, i.e. AIDS.

6. Subacute Sclerosing Panencephalitis (SSPE)

  1. Persistent measles virus infection

  2. Rare complication in live vaccine recipients

  3. CSF contains elevated measles virus antibody titer

7. Progressive multifocal leucoencephalopathy (PML)

  1. JC virus, Papovaviridiae

  2. Immunocompromised host, esp. AIDS (1-3%)

  3. Dementia, weakness and ataxia

  4. Death in 6 months

  5. Virus infects oligodendroglia and causes demyelination

8. Poliomyelitis

  1. Enterovirus - small, non-enveloped single-stranded RNA virus

  2. Spread by fecal-oral route

  3. Viral binding site on lower motor neurons

  4. Fever, malaise, headache, meningitis, paralysis

  5. Mortality 5-25% with death from respiratory failure

  6. Chromatolysis and neuronophagia

  7. Vaccines have largely eliminated the disease

9. AIDS Encephalopathy

  1. 50% of AIDS patients have encephalopathy.

  2. AIDS dementia complex

  3. Macrophages and microglia are infected by HIV-1

  4. Vacuolar myelopathy--spinal cord

10. AIDS opportunistic infections

a) Bacteria

Mycobacterium avium intracellulare, Mycobacterium tuberculosis, Neurosyphyllis – rare

b) Viruses

Cytomegalovirus – very common infects neurons, glia, ependyma; Progressive Multifocal Leucoencephaolpathy, Herpes simplex, Herpes zoster – radiculopathy, Epstein Barr virus – B cell CNS lymphoma

c) Fungus

Cryptococcus neoformans – very common, Coccidiodes immitis – Southwest USHistoplasma capsulatum – Mississippi , Aspergillus fumigatus – very common, Zygomycetes (mucormycosis), Candida sp.

 

d) Parasites

Toxoplama gondii – very common often treated empirically, Acanthomoeba

SPONGIFORM ENCEPHALOPATHY (PRION DISEASE)

Proteinaceous infectious particle

Kuru - cannibalism

Creutzfeldt-Jakob disease – sporadic

Pitutary hormone extracts

"Mad Cow" Disease – new variant CJD

 

DEMYELINATING DISEASES

AUTOIMMUNE

Multiple sclerosis - Clinical

Age of onset is usually 20-40 years. MS has an acute onset

Symptoms are disseminated "in space and time". Sensory, motor, and visual problems

The duration is quite variable, usually over many years.

Risk factors include living in northern latitudes, HLA-A3, B7, and DW2, relative affluence.

Multiple Sclerosis - Pathology

The characteristic pathologic lesion is the MS plaque, a well-circumscribed area of demyelination with relative preservation of axons.

Grossly, the plaque appears as a discrete greyish area in the white matter. A characteristic location is adjacent to the frontal horns of the lateral ventricles. Spinal cord involvement is common and may cause bladder and bowel problems. The plaques are visualized with magnetic resonance imaging (MRI).

Microscopically, there is loss of myelin with preservation of axons. There is microglial proliferation and phagocytosis. Plaques are characteristically perivenular.

Viral infections and disorders of immune regulation have been suggested as a cause.

IDIOPATHIC Central pontine myelinolysis

Caused by rapid correction of hyponatremia

Alcoholics

Debilitated patients

PERIPHERAL NEUROPATHY

NUTRITIONAL and METABOLIC NEUROPATHIES

Diabetes, Thiamine deficiency, Pyridoxine deficiency, Alcoholism,Renal failure

TOXIC NEUROPATHIES

Lead, Arsenic, Cisplatin, Vincristine, Organic solvents

INFLAMMATORY NEUROPATHIES

Guillain-Barré syndrome, Chronic inflammatory demyelinating neuropathy, Vasculitic neuropathy, Leprosy, Sarcoidosis

HEREDITARY NEUROPATHIES

Hereditary motor and sensory neuropathies (Charcot-Marie-Tooth disease, Refsum’s disease, Dejerine-Sottas disease); Hereditary sensory neuropathies; Leukodystrophies

MISCELLANEOUS

Amyloid neuropathy, Paraneoplastic neuropathies, Neuropathies associated with immunoglobulin abnormalities

ALL NEUROPATHIES RESULT IN NEUROGENIC ATROPHY OF MUSCLE