Supranuclear Opthalmoplegia, Neck Dorsiflexion, and Midbrain Tegmentum Atrophy Associated with Brainstem Pathology of Alzheimer’s disease

It has been well known that Alzheimer’s disease affect brainstem [1-4], however, clinical manifestations caused by brainstem involvement have not been elucidated. We encountered 2 cases presented supranuclear ophthalmoplegia, neck dorsiflexion, and midbrain tegmentum atrophy associated with brainstem pathology of Alzheimer’s disease.

Clinical summary: Case 1 [5]. A 75-year-old man developed 9 years course of l-dopa nonresponsive parkinsonism, supranuclear ophthalmoplegia, and neck dorsiflexion at the terminal stage. MRI revealed atrophy of the midbrain tegmentum.

Case 2 [6]. An 85-year-old man developed 9 years course of l-dopa responsive parkinsonism and subsequent dementia, followed by supranuclear ophthalmoplegia, neck dorsiflexion, and dementia. MRI revealed midbrain tegmentum and medial temporal lobe atrophy.

Neuropathological findings: Case1. Cortical atrophy was moderate in frontal and temporal lobes. The substantia nigra and locus coeruleus were depigmented. Gliosis was observed in midbrain tegmentum. Abundant senile plaques were detected cerebral cortex (Braak C). Small senile plaques were remarkably detected in colliculi. Neurofibrillary tangles were positive for both 3R and 4R tau with the predominance of 3R tau. They were abundant in cerebral cortex (Braak VI), and frequent in colliculi. Lewy bodies were abundant in amygdala but scarce in midbrain tegmentum.

Case 2. Substantia nigra showed thin but depigmentation was mild. Locus coeruleus showed depigmentation. Microscopic findings demonstrated pure Alzheimer’s disease (tangle pathology: Braak V, plaque pathology: Braak C) with 3R dominant neurofibrillary tangles in substantia nigra, near riMLF, and superior colliculus. Senile plaques were observed in superior colliculus. Neither Lewy body nor α-synuclein positive material were observed.

Alzheimer’s pathology affects brainstem, which can cause supranuclear opthalmoplegia, neck dorsiflexion, and atrophy of midbrain tegmentum.

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