What is Neuropathology?

Neuropathology means a study of the diverse ways in which the neurons, neuroglia, connective tissues, blood vessels, meninges, and peripheral nerves react toward disease and traumatic causes.  By tradition, neuropathologists, as well as neurologist, have been concerned with skeletal muscle, because of locomotor dysfunction, with eye and inner ear, and with the pituitary and pineal glands.  In certain neurotropic diseases, those diseases which have a selective affinity for the nervous tissue, the degenerative changes in the neurons may be pathognomonic, especially when topographic distribution is also considered.  Topographic distribution refers to a particular region or regions within brain and spinal cord.  There are occasions in which the degenerative changes involving the neurons may be less evident than the inflammatory reaction and cellular (glial) proliferation.  At one time the inflammatory reaction and the glial proliferation was a source of confusion for it led to the belief it was the primary process.  Neuroglial proliferation is almost always a reaction to degeneration of neurons, axis cylinders or mylen sheaths, however, it may also be a simultaneous reaction to the same underlying cause of the neurodegenerative process.  

As the main signs and symptoms of neurologic diseases are due to destruction of neurons in specified centers or nuclei, their study is of paramount inportance.  Thus, an equally important component of the study of neurotropic diseases is the neuroanatomic location, topography, of the lesion. The two component studies are complementary, degenerative changes in neurons and the associate inflammatory and glial proliferation and the neuroanatomic location of the lesions.  Thus, any study of a nervous disease is incomplete, shallow at best, if attention is directed to one component.

Historically, neuropathology as a discipline has a diverse background, with foundational roots in pathology, anatomy, neurology, neurosurgery and psychiatry.  In 1906, Santiago Ramón ŷ Cajal, along with the Italian scientist Camillo Golgi were awarded the Nobe Prize in Physiology and Medicine for their work on the structure of the nervous system.

 Santiago Ramón ŷ Cajal (1853-1934) was a Spanish pathogists, histologist and neuroscientist.  His pioneering work on the microscopic structure of the brain has led to his being referred to as the father of modern neuroscience.  He made several major contributions to neuroanatomy.  He discovered the axonal growth cone, and demonstrated experimentally that the relationship between nerve cells was not continuous but contiguous.  This provided definitive evidence for what would later be known as the "neuron doctrine", now widely considered the foundation of modern neuroscience.  He provided descriptions of cell types associated with neural structures, and produced excellent depictions of structures and their connectivity.  He discovered a new type of cell, which was subsequently named after him, the interstitial cell of Cajal, which is found in the gastrointestinal tract.  This cell mediates neurotransmissions from motor neurons to the smooth muscle cells of the gastrointestinal tract.  An astroid 117413 Ramonycajal is named in his hornor.    

 

Santiago Ramón ŷ Cajal

Santiago Ramón ŷ Cajal

                                                                                                                                                                                                                                   

 

Camillo Golgi (1843-1926) was an Italian physician, biologist, pathologist, and scientist.  He spent much of his career studying the central nervous system.  While working as chief medical officer in a psychiatric hospital, he experimented with metal impregnation of nervous tissue, using mainly silver (silver staining).  He discovered a method of staining nervous tissue that would stain a limited number of cells at random in their entirety.  This enabled him to view the paths of nerve cells in the brain for the first time.  He called his discovery the "black reaction", which later received  his name (Golgi stain).  He also discovered a tendon sensory organ, which bears his name, "Golgi receptor".  He identified an intracellular organelle found in most eukaryotic cells, which is part of the endomembrane system that packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destinations.  These membrane-bound vesicles are referred to as the Golgi apparatus or Golgi complex.   The work and discoveries of Cajal and Golgi are reflective of the genesis and nature of neuropathology as a subject, rooted in general pathology, but having seminal links with basic and clinical neurosciences.

 

Camillo Golgi

Camillo Golgi

 

Both World War I and II, with their impact on Europe, had at least one positive effect in they brought together the different practices of neuropathology.  Neuropathologist trained in different ways and from different backgrounds, some of whom were forced to leave mainland Europe and move to Britain or the United States, began to work together.  An early example of this partnership and collaboration between those trained in Germany and those trained in Great Britain is seen in the work of Alfred Meyer and Elizabeth Beck.  Both were refugees from Germany: Alfred Meyer trained in psychiatry and Elizabeth Beck in neuroanatomical technique.

Alfred Meyer (1895-1990) was a German-born British neuropathologist.  As a prominent member of the British Neuropathological Society, his contribution is remembered in a biennial memorial lecture.  His most significant work was on the anatomical aspects of frontal leucotomy (prefrontal lobotomy), and the nature of the structural abnormalities in the brain associated with temporal lobe epilepsy.  Meyer was born in Krefeld.  His successful early career was threatened by the rise of the Nazis, and he escaped to Britian in 1933, beginning work at the Maudsley Hospital, London.  His study of frontal leucotomy led to a classic book on the subject with Elizabeth Beck, published in 1954; and he undertook pioneering work on the pathology of epilepsy while professor of neuropathology at the Institute of Psychiatry.  This lecture is delivered every second year by a distinguished speaker, invited to present the lecture at one of the annual meetings of the Society.

 

Alfred Meyer

Alfred Meyer

 

 

In Britain there were two individuals who were important to the emergence of neuropathology as a specialty in the 20th century, Godwin Greenfield and Dorothy Russell.

Godwin Greenfield (1884-1958)is considered by some to be the architect of British neuropathology, as well as, the father of neuropathology.  He served as the pathologist to the National Hospital, Queen Square, London for the major period of his life and worked on various subjects, such as, cerebrospinal fluid, intracranial tumors, cerebellar ataxias, dystrophia myotonica, disseminated sclerosis, and subacute combined degeneration of the spinal cord,  Greenfield wrote several books: "Pathology of the Nervous System" with Sir edward Farquhar Buzzard (1871-1945), London, 1921; "The Cerebro-Spinal Fluid in Clinical Diagnosis" with E.A. Carmichael, London, 1925.  Greenfield published the first detailed textbook in neuropathology in 1958, Greenfield's Neuropathology, which is now in its ninth edition.  After his retirement he visited the National Institute of Neurological Diseases in Bethesda, Maryand on several occasions, dying their from a myocardial infarction.

Godwin Greenfield

Godwin Greenfield

Dorothy Russell (1895-1983), one of the leading figures in the history of British neuropathology.  She served as the Professor of Morbid Anatomy at the London Hospital Medical College. Like Greenfield, she did much to establish neuropathology as a specialty, as well as having a profound and lasting influence on the development and practice of neuropathology throughout the world.  Her training was in general histopathology, but the formation of a neurosurgical unit at London Hospital, led by Hugh Cairns, encouraged Dr. Russell to take up neuropathology.  The year after Greenfield's Neuropathology was published, Russell and Rubinstein published 'Pathology of Tumours of the Nervous System', which was intended to be an accompanying volume.

Dorothy Russell

Dorothy Russell

What is Forensic Neuropathology?

There is a subspecilty within neuropathology referred to as Forensic Neuropathology.  Forensic Neuropathology is that subdivision of neuropathology, which focuses on the morbidity and mortality of traumatic injuries to the brain, spinal cord and peripheral nerves.  It is the very nature of Forensic Pathology that a significant percentage of forensic cases involve the central and peripheral nervous systems.  It is because of this involvement in Forensic Pathology that it is essential the Forensic Pathologists have a thorough understanding of neuropathology.  Should the Forensic Pathologist not have that level of expertise, they should enlist the aid of a neuropathologist, especially one who has expertise in traumatic lesions affecting the nervous system.  The use of such expertise will greatly enhance justice and avoid the tragic conviction of the innocent.  As stated in the 'Practice Guidelines' of the Police Advisory Board in Forensic Pathology of the British Home Office: "The evidence should be objective: speculation should be avoided, unwarranted conclusions can never be defended."