[Amyotrophic lateral sclerosis with dementia (ALSD)].

Area of Science:

• Neurology
• Neuroscience
• Pathology

Context:

• Alpers-Huttenlocher syndrome (ALSD) is characterized by distinct mental and behavioral changes, often preceding severe motor neuron deficits.
• Cerebral SPECT, particularly 3D-Single SPECT (3D-SSP), is a valuable diagnostic tool for ALSD, revealing consistent reductions in prefrontal blood flow.

Purpose:

• To detail the characteristic neuropathological findings in ALSD, including cerebral cortex degeneration and neuronal inclusions.
• To highlight the diagnostic utility of Cerebral SPECT in identifying ALSD.
• To explore the relationship between ALSD and other neurodegenerative conditions like motor neuron disease-inclusion dementia.

Summary:

• Neuropathological examination of ALSD patients shows degeneration in the medial temporal pole cortex, amygdala, and other regions, with characteristic ubiquitinated inclusions in dentate gyrus neurons.
• Motor neuron pathology in ALSD resembles classic ALS but features more prominent Bunina bodies and less pyramidal tract involvement; substantia nigra degeneration occurs without Lewy bodies.
• Cerebral SPECT imaging, especially 3D-SSP, effectively diagnoses ALSD by detecting significant blood flow reductions in the prefrontal cortex.

Impact:

• Findings expand the understanding of ALSD's neuropathology and diagnostic markers.
• The study suggests ALSD may encompass a broader spectrum of clinical presentations, including upper motor neuron-dominant forms.
• This research aids in differentiating ALSD from other neurodegenerative diseases and informs potential therapeutic strategies.