Distinctive clinicopathological features of 2 large families with amyotrophic lateral sclerosis having L106V mutation in SOD1 gene

Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: Multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions

“…A review of the literature confirmed that most autopsied FALS patients with SOD1 gene mutations showed degeneration in Clarke's nucleus, the posterior spinocerebellar tract and dorsal columns, with a variety of combinations of the degenerative lesions and their extent (Supplementary Table). Observation of affected siblings suggested that protracted disease duration was related to development of more severe and more widespread degenerative lesions, which might have been the case in the present autopsied patient who survived 11 years with the support of artificial ventilation for the final 5 years before death. However, it still remains unknown why most FALS patients with SOD1 gene mutations manifest pure motor neuron disease despite the presence of evident degeneration in the non‐motor systems related to proprioceptive sense; pallhypesthesia was reported in only a few patients with G37R, G72S, and L106V mutations in the SOD1 gene.…”

“…Generally, patients with such widespread degeneration had a longer disease duration than those without, although the substantia nigra and reticular formation of the brainstem could be affected even in patients with relatively shorter disease duration. Again, from observations of affected siblings, it could be considered that such widespread degeneration involving many regions of the CNS might be associated with protracted disease duration. On the other hand, however, in FALS with an H46R SOD1 gene mutation, the pathological picture has been reported to be that of classical FALS despite the extremely long disease duration (17–47 years) .…”

“…We also conducted a careful review of the clinical features of all the affected members of the proband's family. Here we report the results obtained, along with a literature review of autopsy cases of FALS with SOD1 gene mutations …”

Non‐motor manifestations in ALS patients with tracheostomy and invasive ventilation

“…Voiding difficulty is partly attributed to weakness of the pelvic or abdominal wall muscles, but a neurogenic mechanism may contribute to bladder dysfunction with disease progression. Some patients with superoxide dismutase‐1 gene variants have a neurogenic or atonic bladder . All of these signs may have an association with ALS pathogenesis.…”

“…Some patients with superoxide dismutase-1 gene variants have a neurogenic or atonic bladder. [28][29][30]50 All of these signs may have an association with ALS pathogenesis.…”