Final Diagnosis -- Motor Neuron Disease with Basophilic Inclusions




Motor neuron disease (MND) is associated with a number of intracellular inclusion bodies within surviving motor neurons. In both sporadic and familial MND, Bunina bodies, skein-like inclusions and hyaline inclusions, some of which resemble Lewy bodies, may be seen (1). In Guam-type MND (2), post encephalitis lethargica-related MND (3) and occasional cases of familial MND with mutations in the SOD-1 gene (4), neurofibrillary tangles have been demonstrated. In addition, there have been a few reports (mainly in young individuals) of MND with basophilic cytoplasmic inclusions (5-11). MND with basophilic inclusions appears to be a distinctive histopathological subtype, characterized by circumscribed intraneuronal basophilic inclusions within motor neurons, but also widely distributed within the cerebral cortex, basal ganglia, brainstem and cerebellar nuclei. Unlike the more common MND-inclusions, these basophilic inclusions are largely negative for ubiquitin, although a few show speckled immunoreactivity. Most reported cases presented with rapidly progressive motor weakness, predominantly in young women (5-8). These cases (5-8), together with ours, have a mean age at onset of 19 years and mean disease duration of 12 months (excluding ventilated cases). In addition, there have been three further reports of MND with basophilic inclusions in Japanese men (9-11), who despite having similar pathology, had an mean age of onset of 47 years and duration of illness of about 7 years (excluding a ventilated case). Most cases have presented with purely motor features, although a minority of cases have autonomic dysfunction or dementia. None of the reported cases have had a family history of MND.


  1. Lowe J (1994). New pathological findings in amyotrophic lateral sclerosis. J Neurol Sci 124: 38-51.
  2. Hirano A, Malamud N, Elizan TS, Kurland LT (1966). Amyotrophic lateral sclerosis and Parkinsonism-dementia complex on Guam. Further pathologic studies. Arch Neurol 15: 35-51.
  3. McMenemy WH, Barnard RO, Jellinek EH (1967). Spinal amyotrophy. A late sequel of epidemic encephalitits (von Economo). Rev Roum Neurol 4: 251-259.
  4. Orrell RW, King AW, Hilton DA, Cambell MJ, Lane RJM, deBelleroche JS (1995). Familial amyotrophic lateral sclerosis with a point mutation of SOD-1: intrafamilial heterogeneity of disease duration, associated with neurofibrllary tangle pathology. J Neurol Neurosurg Psychiatry 59(3): 266-270.
  5. Berry RG, Chambers RA, Duckett S, Terrero R (1969). Clinicopathological study of juvenile amyotrophic lateral sclerosis. Neurology 19(3): 312.
  6. Nelson JS, Prensky AL (1972). Sporadic juvenile amyotrophic lateral sclerosis. Arch Neurol 27: 300-306.
  7. Matsumo S, Kusaka H, Murakami N, Hashizume Y, Okazaki H, Hirano A (1992). Basophilic inclusions in sporadic juvenile amyotrophic lateral sclerosis: an immunocytochemical and ultrastructural study. Acta Neuropathol 83: 579-583.
  8. Oda M, Akagawa N, Tabuchi Y, Tanabe H (1978). A sporadic case of amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions. Acta Neuropathol 44: 211-216.
  9. Kusaka H, Matsumo S, Imai T (1990). An adult-onset case of sporadic motor neuron disease with basophilic inclusions. Acta Neuropathol 80: 660-665.
  10. Kusaka H, Matsumo S, Imai T (1990). Adult-onset case of sporadic motor neuron disease with basophilic intraneuronal inclusion bodies. Clin Neuropathol 12(4): 215-218.
  11. Mizutani T, Sakamaki S, Tsuchiya N, Kamei S, Kohzu H, Horiuchi R, Ida M, Shiozawa R, Takasu T (1992). Amyotrophic lateral sclerosis with opthalmoplegia and multisystem degeneration in patients on long-term use of respirators. Acta Neuropathol 84: 372-377.

Case IndexCME Case StudiesFeedbackHome