Preferential involvement of the basolateral limbic circuit in an amyotrophic lateral sclerosis patient.

Sirs, In this report, we describe a patient of amyotrophic lateral sclerosis (ALS) with dementia (ALSD) unusually presenting with personality changes or social misconduct which led to an initial diagnosis of Pick’s disease (PiD) 5 years prior to the appearance of motor neuron signs. Accentuated degeneration in the basolateral limbic circuit plausibly explains these initial manifestations [1]. A 46-year-old woman presented with progressive social misconduct, auditory and persecutory hallucination and abnormal sexual behaviors, which led to an initial clinical diagnosis of PiD or schizophrenia by a group of psychiatrists several years later. After progressive worsening of these symptoms, she became mute. She then gradually exhibited weakness and atrophy of the upper limbs after age 51. Needle electromyography showed lower motor neuron involvement and she was diagnosed as suspected ALS. Computed tomography of the brain demonstrated moderate atrophy in the fronto-temporal lobes. Single photon emission computed tomography showed a decreased uptake of the tracer not only in these atrophic areas but also in the bilateral basalganglia and thalami. She died of respiratory failure at age 53. The brain weighed 1160 g and macroscopically showed moderate atrophy of the fronto-temporal cortices, hypopigmentation of the substantia nigra and mild atrophy of the spinal cord and anterior roots. Microscopic investigation demonstrated degeneration of lower motor neurons with Bunina bodies. Upper motor neurons were mostly preserved. Spongiotic changes in layers II-III of the fronto-temporal cortices was accentuated in the orbital gyrus, mediodorsal-ventral temporal tip, and entorhinal region (Fig. 1a and b). Neuronal loss and gliosis were mild to moderate in the medio-dorsal (MD) nucleus of the thalamus (Fig. 1c), caudate nucleus and accumbens. Involvement of the amygdala was moderate to severe. Cytoplasmic inclusions (CI) in neurons immunopositive for ubiquitin and TDP-43 were present in the dentate granular cells, superficial small neurons in the fronto-temporal cortices, striatum, amygdala, and MD nucleus of the thalamus (Fig. 1d). The ubiquitin-positive CI in the striatum exhibited eosinophilia with H&E staining which had been thought to be invisible by H&E. There were few neurofibrillary tangles and amyloid senile plaques. Pick bodies were absent. Presence of Bunina bodies and cortical lesions with the CI confirmed ALSD. Although extramotor involvement in ALSD could be variable, this case is characterized by a unique distribution of the lesions, found in the orbital gyrus, temporal pole, amygdala, and MD nucleus of the thalamus. These structures are collectively grouped as basolateral limbic circuit [1] based on their anatomical