CNS Block

Year 2, CENTRAL NERVOUS SYSTEM BLOCK - PATHOLOGY

1. Cellular aspects of nervous system injury  
 
Objectives:
The student should:
- Understand the role of the different constituents of Central nervous system (CNS) cells in the disease status.
- Understand the “injury” concept.
- Explain the basic pathological descriptive terms used in CNS cellular injury.
- Correlate the different patterns of cellular injury with some important clinical examples.
-Understand the concept of reaction of neurons, astrocytes and other glial cells to injury.
- Recognize the axonal injury in both CNS and Peripheral nervous system as well as the consequences and the pathological findings.
 
Background:
The central nervous system cells are unique in many pathological aspects. A good example is the CNS cellular reaction to injury. 
The response of the CNS to hypoxia, ischemia, infarction or to hemorrhage and the pattern of injury in accordance with the onset, the type and the duration of the insult is unique to this system, hence the importance of recognizing these different aspects.

Key principles to be discussed:
-The definition of and an example for each of the following terms:
- Markers of CNS Neuronal Injury: Acute neuronal injury, red neurons, intracellular inclusions and dystrophic neuritis.
- Cerebral edema, definition and types.
- Marker of Axonal injury: CNS - spheroids and central chromatolysis, Peripheral nervous system- Wallerian degeneration and segmental demyelination.
-  Marker of Astrocytes reaction to injury: gemistocytic astrocytes, fibrillary astrocytes, Rosenthal fibers and Corpora amylacea.
- Other cells reaction to injury: Oligodendrocytes, Ependymal and Microglia (microglial nodules and neuronphagia).
               
Take home messages:
- The cellular constituents of the nervous system respond in different ways to various forms of injury.
  
Key words:
Cellular injury, neurons, glial cells, diffuse axonal injury, oligodendrocytes, ependymal cells, microglia, neuronophagia, acute neuronal injury, red neurons, spheroids, central chromatolysis,  dystrophic neuritis, gemistocytic astrocytes, fibrillary astrocytes, Rosenthal fibers, Wallerian degeneration, segmental demyelination and corpora amylacea.

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2. Pathology of brain tumors – Two lectures
 
Objectives:
Upon completion of this lecture, students should be able to:
- Appreciate how the anatomy of the skull and the spinal column influences the prognosis of both benign and malignant primary CNS tumors.
- List the principal clinicopathological features of some of the main types of tumors that can arise within the central and the peripheral nervous systems.
 
Background:
CNS tumors exhibit unique characteristics that make them different from tumors of the other body sites. Also childhood CNS tumors differ from those in adults, both in histologic subtypes and locations. Although histological classification and grading play a major rule in predicting the outcome a CNS tumor, the anatomic site of the neoplasm can have lethal consequences irrespective of histologic classification.
 
Key principles to be discussed:
- CNS tumors incidence and classification, with special consideration of the general differences between the pediatric and the adult population
- The unique characteristics that set CNS tumors apart from neoplastic processes elsewhere in the body
- The incidence, common clinical presentation, location, macroscopic appearances, microscopic features, pattern of spread and prognosis of the following neoplasms will be explained and discussed (within the context of the recommended textbook):
- Astrocytic neoplasms: Pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma and gliobastoma
- Oligodendroglioma
- Ependymoma
- Medulloblastoma
- Meningioma
- Metastatic tumours
- Peripheral nerve sheath tumours: schwannoma and neurofibroma
Key principles to be covered by self-directed learning:
- The inheritance pattern and the main features of:

  • Type 1 Neurofibromatosis 
  • Type 2 Neurofibromatosis 

 
Take home messages:
- Histologic distinction between benign and malignant lesions may be more subtle in comparison to other body systems. 
- Even low-grade or benign tumors can have a poor clinical outcome depending on their location.
- The most aggressive and poorly differentiated glial tumor is glioblastoma; it contains anaplastic astrocytes and shows striking vascular abnormalities.
- Metastatic spread of brain tumors to other regions of the body is rare, but the brain is not comparably protected against spread of tumors from elsewhere. 
 
Key words:
CNS tumors, astrocytoma,glioblastoma,oligodendroglioma, ependymoma,  medulloblastoma, meningioma, metastatic tumours, peripheral nerve sheath tumours, schwannoma, neurofibroma and neurofibromatosis.

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3. Pathology and pathogenesis of multiple sclerosis
 
Objectives:
The student should:
- Appreciate the critical role of myelin in maintaining the integrity of the CNS system.
- Understand the pathogenesis and the clinic-pathological features of multiple sclerosis as the classical and the commonest example of CNS demyelinating diseases.
 
Background:
In general, diseases involving myelin are separated into two broad groups. Demyelinating diseases of the CNS are acquired conditions that are classically represented by multiple sclerosis. Other processes that can cause this type of disease include viral infection, drugs and other toxic agents. 
When myelin is not formed properly or has abnormal turnover kinetics, the resulting diseases are referred to as”dysmyelinating”. These are associated with mutations affecting the proteins required for the formation of normal myelin or in mutations that affect the synthesis or degradation of myelin lipids. 
 
Key principles to be discussed:
- Myelin function
- The differences between CNS and PNS Myelin
- Primary Demyelinating disease classification
- Multiple sclerosis:  definition, epidemiology, pathogenesis and clinicopathological features; with special emphasis on CSF analysis findings, morphology and distribution of MS plaques.
 
Take home messages:
- In view of the critical role of myelin in nerve conduction;  diseases of myelin can lead to widespread and severe neurologic deficits.
- Diseases of myelin can be grouped into demyelinating diseases (in which normal myelin is broken down for inappropriate reasons-often by inflammatory processes), and dysmyelinating diseases (which are metabolic disorders that include the leukodystrophies in which the underlying structure of the myelin is abnormal or its turnover is abnormal).
- Multiple sclerosis, an autoimmune demyelinating disease, is the most common disorder of myelin, affecting young adults often with a relapsing-remitting course and eventual progressive accumulation of neurologic deficits.
- Other less common forms of immune-mediated demyelination often follow infections and are more acute illnesses.
 
Key words:
Multipsle sclerosis, demyelination, dysmyelination, leukodystrophy, plaques, T cell-mediated delayed type hypersensitivity, oligoclonal bands and optic neuritis.

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Further reading (Prescribed book):
Vinay Kumar, MBBS, MD, FRCPath, Abul K. Abbas, MBBS and Jon C. Aster, MD, PhD, Robbins Basic Pathology, 10th Edition