Laboratory for Ultrastructural Neuropathology (LUN)
1. Definition, aims and objectives of LUN.
One of the main aims of ultrastructural neuropathology is to examine particular cell and tissue abnormalities in neurological disorders by electron microscopy (EM). It is also a traditionally pursued investigation of our laboratory focussing on diagnostic EM as well as on research topics. We have outlined optimal processing procedures and specific analytical criteria regarding the use of extracerebral tissues in neurometabolic storage disorders. Brain tissue, peripheral nerves and skeletal muscles but even other tissues including neurons or Schwann cells are investigated to demonstrate specific ultrastructural patterns such as structural abnormalities and diagnostic inclusions which are typical of a disease.
Diagnostic electron microscopy
The laboratory is performing diagnostic electron microscopy (EM) of extracerebral tissue biopsies to provide accurate ultrastructural diagnoses in hereditary neurological disorders affecting children as well as adult patients. Lesions or particular structures are first searched by light microscopy on semithin resin sections of conventionally processed specimens. Ultrathin sections from selected areas are examined by EM and the findings are described in a detailed histopathological report. Ultrastructural identification and characterization of histopathological alterations are often mandatory to orientate further biochemical and molecular genetic studies in several metabolic storage disorders, peripheral neuropathies and skeletal muscular diseases.
Yearly, biopsies obtained from more than 100 patients with a neurological disease are analysed by EM. Further EM from earlier biopsies in unresolved diagnostics or according to genetic molecular results are also carried out.
Research topics
Hereditary neurological diseases are seldom but mostly diversified. We demonstrated that carefully described EM findings and subtle features may be highly effective for research purposes. For example, in neuromuscular disorders use of immunohistochemistry along with EM is mostly useful in congenital myopathies to orientate further genetic molecular studies. Moreover, this approach allowed us to contribute successfully to the unravelling and identification of the basic genetic defect in 3 congenital myopathies (myosin storage myopathy, cap disease and Mallory body-like myopathy). These results were achieved through international multi-disciplinary collaborations.
To date, biopsy results are also retrospectively reviewed for research purposes to characterize disease patterns more accurately and to enhance the knowledge in the pathogenesis of structural or developmental lesions. Postmortem brain samples are also investigated for correlative histopathological studies and to define more precisely on structural details.
In this postgenomic area we are particularly interested to focus on genotype/ phenotype correlations between specific mutations and morphological features to revise and redefine phenotypes such as in Charcot-Marie-Tooth disease, a hereditary peripheral neuropathy. These objectives are integrated in multi-disciplinary research projects and publications.