Agraphia in intellectually normal Japanese patients with ALS: omission of kana letters

To investigate the occurrence of a writing defect, omission of kana letters (OKL), in intellectually normal Japanese patients with amyotrophic lateral sclerosis (ALS), and define the neuroimaging profile of OKL. Sixteen Japanese adults (10 men and 6 women), similar in age (mean 62.9 +/- 9.9 years) and level of education (mean 12.6 +/- 2.13 years), with early-stage, classical ALS (mean duration 15.9 +/- 5.45 months) were investigated, including tests of motor function and ALS progression; intellectual function including writing ability; and neuroimaging, with follow-up of 1 year. Main outcome measures were as follows: Raven's Colored Progressive Matrices (RCPM: intellect and psychomotor speed); one-minute verbal fluency measurement; paired associate word-learning test (PAWLT); Western Aphasia Battery (WAB); moraic segmentation test; magnetic resonance imaging (MRI); and (123)I-isopropyl amphetamine ((123)I-IMP) or (99m)Tc-ethylcysteinate dimmer (ECD) single photon emission tomography (SPECT). Three patients (18.8%) showed OKL (WAB), with disturbance in moraic segmentation. One patient showed decreased blood flow to the bilateral frontal lobes by (123)I-IMP-SPECT. Patients with OKL did not differ significantly from those without in the RCPM (intellect), RCPM (time), verbal fluency, or PAWLT (p = 0.10, 0.84, 0.63, 0.55). Although motor dysfunction and weakness progressed during follow-up, none developed symptoms of dementia. The OKL may develop as a relatively early cognitive symptom in intellectually normal Japanese patients with classical ALS. The neuroimaging profile of OKL remains uncertain.