NEUROPATHOLOGY- DISEASES OF THE MYELIN SHEATH

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I. DISEASES OF MYELIN REPRESENT A HETEROGENEOUS GROUP OF DISORDERS
II. DYSMYELINATING DISEASES (LEUKODYSTROPHIES)
III. DEMYELINATING DISEASE

VOCABULARY TERMS
Terms you should be familiar with:

Dysmyelinating
Leukodystrophy
Demyelinating
Multiple sclerosis
Central pontine myelinolysis
Progressive Multifocal Leukoencephalopathy
Metachromatic Leukodystrophy
Krabbe's disease
Schilder's disease
Alexander's disease
Gamma globulin
Oligoclonal bands
Perivenous encephalomyelitis
Post vaccinal
Post infectious
Experimental Allergic Encephalomyelitis

OBJECTIVES: The objectives of this hour are to distinguish between dysmyelinating and demyelinating diseases, to consider briefly some of the dysmyelinating diseases, to recognize that multiple sclerosis is the most important demyelinating disease, and to consider its clinical, epidemiologic, pathologic and therapeutic features.

I. DISEASES OF MYELIN REPRESENT A HETEROGENEOUS GROUP OF DISORDERS

The myelin sheath of the central (and sometimes peripheral) nervous system bears the brunt of the pathologic process while other neural structures are relatively spared. Using this operational definition, one should not (e.g.) consider the involvement of subcortical white matter in an infarct or contusion as a disease of myelin. Diseases of myelin can be divided into two broad groups:

• Dysmyelinatin- Profound disturbance in the formation and preservation of myelin so that its proper functioning is never established. These disorders are also termed leukodystrophies, and almost all of them manifest themselves early in life and are genetically determined.
  
  
• Demyelinating- The myelin sheath, once properly formed and funcioning, is destrotyed by a disease process. The most common disease in this category is multiple sclerosis. Other examples include:
  
  
  • Central pontine myelinolysis
  • Progressive multifocal leukoencephalopathy
  • Subacute combined degeneration of the spinal cord

II. DYSMYELINATING DISEASES (LEUKODYSTROPHIES)

• Metachromatic Leukodystrophy
  
  
  • Most common of these disorders
  • Autosomal recessive disorder
  • Both central and peripheral white matter involved
  • Predominantly a disease of infancy, but juvenile and adult forms do exist
  • Course is progressive, usually fatal in a few years
  • Pathology is diffuse, confluent loss of myelin that is most advanced in the cerebrum.
  • Due to inborn error of metabolism in which arylsulfatase A, although present, is enzymatically inactive. Leads to breakdown of myelin and the accumulation of sulfatide-rich lipids that appear as small globules of metachromatic material in the white matter.
    
    
• Krabbe's Disease
  
  
  • Usually appears in early months of life and progresses to death in one to two years
  • Autosomal recessive caused by a deficiency of galactocerebroside, B-galactosidase
  • Expressed histologically by the presence of perivascular aggregates of globoid cells
    
    
• Schilder's Disease (sudanophilic leukodystrophy)- Most of these cases represent an X-linked recessive entity, adrenoleukodystrophy, that cojoins an inborn error of lipids in the adrenals and a disturbance in the preservation of myelin.
  
  
  • Clinical symptoms (motor, sensory and cognitive) develop in the first decade and progress insidiously.
  • The central nervous system is depleted of myelin, and the peripheral nervous system to a lesser degree.
    
    
• Alexander's Disease- characterized pathologically by lack of formation of myelin and innumerable Rosenthal fibers.

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III. DEMYELINATING DISEASE

• Multiple Sclerosis
  
  
  • Clinical Course
    • The main clinical feature is the dissemination of signs and symptoms in time and space. The lesion can occur anywhere in the white matter of the CNS, almost at random, resulting in a variable clinical presentation. Diplopia, numbness or weakness of an extremity, and monocular blindness are common initial symptoms. Largely a disease of young adults.
    • Clinical course variable but marked by exacerbations (attacks followed by remissions. Each cycle generally leaves further neurologic deficit. May involve motor, sensory, cerebellar functioning, etc., often in bizarre patterns.
    • Important variant is progressive, non-remittent spinal multiple sclerosis. Predominately in patients over forty.
    • No specific diagnostic tests. The CSF often shows elevated gamma globulin and oligoclonal bands. Both are valuable but not pathognomonic. Other helpful tests include MRI and CT scans, and evoked potentials.
  • Pathology
    • Multiple plaques- these are sharply delineated, irregular zones of total demyelination with initial preservation of axons. The plaque follows no pattern of vascular or anatomic distribution. They are most numerous in the white matter of the cerebrum (periventricular), brain stem, cerebellum and spinal cord (peripheral regions).
    • Within the plaque, initially axons are preserved. Microglial cells proliferate and phagocytize the myelin debris. Later, a glial scar forms.
  • Etiology
    • Epidemiologists have shown a wide range in the incidence of the disease. The frequency is "latitude related" and this geographic relationship pertains to the individual's global location prior to the age of 15
    • Two main hypotheses concerning etiology:
      • Viral: epidemiologic data compatible with this hypothesis. Viral particles have been identified, but transmission experiments have been negative.
      • Autoimmune: based on similarity to experimental allergic encephalomyelitis. There are, however, significant differences between the human disease and the animal model.
        
        
• Perivenous Encephalomyelitis
  
  
  • Post vaccinal.
  • Post infectious.
  • Experimental allergic encephalomyelitis.

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[ Introduction and Objectives | Basic Reactions of the CNS | Vascular Disease | Trauma to the CNS | Alcohol and the CNS | Infections of the CNS | Tumors of the CNS | Diseases of the Myelin Sheath | Spinal Cord Disease | Muscle Disease | Congenital Anomalies of the CNS | Neuropathology of AIDS | Degenerative Diseases of the CNS | Dementia and Related Issues | Unconventional Transmissible Agent (Prion) Diseases ]

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