LEWY BODY PATHOLOGY

 

 

A group of closely related neurodegenerative diseases characterised by the formation of intracytoplasmic neuronal inclusions, the lewy body.

 

 

1.         Idiopathic Parkinson's disease

           

Macroscopical appearances

In typical cases the only macroscopical abnormality is the pallor of the pigmented nuclei of the brainstem: the substantia nigra and locus coeruleus. Usually there is no diffuse atrophy, the presence of this indicates Alzheimer's disease or diffuse lewy body diaease.

 

 

Microscopical appearances

The following are the histological features:

 

a.                  The hallmark lesion of idiopathic Parkinson's disease is the Lewy body. These are intracytoplasmic neuronal inclusions which are intensely eosinophilic with routine haematoxylineosin stain. They occur in the pigmented nuclei of the brainstem: in the substantia nigra and locus coeruleus, as well as in the motor nucleus of the vagus, in the nucleus basalis of Meynert, in the spinal cord and in sympathetic ganglia. Their structure and composition vary in different parts of brain; in the brainstem they have a clearly defined halo which is usually absent from the cortical inclusions. Ultrastructurally they are chiefly composed of filaments with greatest central density known as the core.

b.                  Immuoocytocbemically, they share epitopes with phosphorylated and non-phosphorylated neurofilament subunits, tubulin, microtubule-associated protein 1 and 2, and they positively immunostain with ubiqiutin.

c.                  Neuronal loss occurs in the substantia nigra and locus coeruleus, as a consequence there is extraneuronal pigment in the neuropil and in macrophages. In severe cases, this neuronal loss is accompanied by astrocytosis, best demonstrated by immunocytochemistry for glial fibrillary acidic protein (GFAP). Neuronal loss also occurs elsewhere, including the nucleus basalis of Meynert.

d.                  Changes in the globus pallidus and putamen are less severe and less constant than those in the pigmented nuclei of the brainstem.

 

 

2.         Diffuse Lewy body disease

 

Lewy bodies have been noted in the cortex, resulting in the definition of diffuse lewy body disease. They usually occur in large numbers in the parahippocampal gyrus, cingulate and insular cortices, but also throughout the neocortex, well in excess of the occasional cortical inclusions in idiopathic Parkinson's disease. This diffuse distribution of lewy bodies is often associated neuropathologically with Alzheimer type changes, mainly with plaque formation, and clinically with dementia. Cortical Lewy bodies are more difficult to discern than the brainstem inclusions, since they usually lack the distinct peripheral halo. They are most often seen in the deeper, 5th and 6th cortical layers, but also occur in layers 2 and 3.

 

As distinct from difuse Lewy body disease, a clinically and neuropathologically defined form of Lewy body dementia has been described recently in the elderly: senile dementia of the Lewy body type. Clinically these cases do not fulfill the diagnostic criteria of either Alzheimer's or Parkinson's disease. Neuropathology shows Lewy body formation and selective neuronal loss in the brainstem and other subcortical nuclei, and Lewy bodies in the neocortex and limbic cortex, but at a frequency well below that reported for diffuse Lewy body disease. Senile plaques are common, whilst tangles are rare; the plaques tend to be the diffuse type without neuritic component. These cases are similar to those reported as Lewy body variant of AIzheimer's disease, characterised by cortical and subcortical Lewy bodies, senile plaque formation and spongiform vacuolation of the temporal cortex.