[Bulbar-onset amyotrophic lateral sclerosis (ALS) with isolated agraphia]

We reported the two cases with bulbar-onset ALS showing isolated agraphia without overt dementia and aphasia. Patient 1 was a 69-year-old man and patient 2 was an 81-year-old woman, and both were right-handed. Each patient developed dysarthria as an initial symptom followed by dysphagia, and neurological examinations showed atrophy and fasciculation of the tongue with upper and lower motor-neuron involvement of the extremities. These characteristic features with electromyographic evidence including widespread acute and chronic denervation led to a diagnosis of bulbar-onset ALS. Around 1 year after the onset of ALS, dysarthria was mild enough to allow oral communication enabling the determination that aphasia was absent with well preserved confrontation naming, repetition, reading and comprehension. The patients were polite without abnormal behavior or character change, and their general intelligence was also well preserved with excellent scores on the Mini Mental State Examination (30 and 27 points for patients 1 and 2, respectively) and Frontal Assessment Battery (16 points for each patient). However, spontaneous writing and dictation revealed abundant writing errors characterized by omission of kana letters and paragraphia of kana and kanji letters in both patients. Some syntactic errors were also observed in writing but in spoken language. A letter-number effect on writing errors was observed in patient 1. Copying of letters or words was intact and structure and orientation of written letters was well preserved, indicating the absence of constructional, apraxic or spatial feature of agraphia. Single photon emission computed tomography demonstrated reduced uptake in the bilateral frontotemporal lobes, predominantly in the left hemisphere, with less evident alternation in magnetic resonance imaging. Our results suggest that patients with bulbar-onset ALS may develop isolated agraphia as a single-domain cognitive impairment, preceding the clinical manifestation of aphasia or dementia. We speculate that the main responsible region might be the posterior part of the middle and inferior frontal gyri including Exner's writing center and Broca's area beyond the primary motor cortex.