Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies

Objectives-To describe the neuropathological features of clinical syndromes associated with tomacula or focal myelin swellings in sural nerve biospies and to discuss possible common aetiopathological pathways leading to their formation in this group of neuropathies. Methods-Fifty two patients with sural nerve biopsies reported to show tomac ula or focal myelin swellings were reviewed, Light and electron microscopy were performed, and tomacula were analysed on teased fibre studies. Molecul ar genetic studies were performed on those patients who were available for genetic testing. Results-Thirty seven patients were diagnosed with hereditary neuropathy wit h Liability to pressure palsies (HNPP), four with hereditary motor and sens ory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1) , four with HMSN with myelin outfolding (CMT4B), three with IgM paraprotein emic neuropathy, three with chronic inflammatory demyelinating polyneuropat hy (CIDP), and one with HMSN III (CMT3). Conclusions-Most of these syndromes were shown to be related to genetic or immunological defects of myelin components such as peripheral myelin protei n 22 (PMP22), myelin protein zero (P0), or myelin associated glycoprotein ( MAG). These proteins share the HNK-1 epitope which has been implicated in c ell adhesion processes. Impaired myelin maintenance may therefore contribut e to the formation of tomacula and subsequent demyelination.