title: TAR DNA-binding protein 43 pathology in a case clinically diagnosed with facial-onset sensory and motor neuronopathy syndrome: an autopsied case report and a review of the literature.
abstract: We report an autopsy case of a 48-year-old female clinically diagnosed with facial-onset sensory and motor neuronopathy (FOSMN) syndrome with TAR DNA-binding protein 43 (TDP-43) pathology. She developed paresthesia involving her whole face, right upper extremity and the right side of her upper trunk, followed by dysphagia, dysarthria, muscle atrophy and weakness with fasciculation in both upper extremities. Her symptoms showed a marked cranial and right-sided dominancy. She had anti-sulfoglucuronyl paragloboside (SGPG) IgG and anti-myelin-associated glycoprotein (MAG) IgG, and repeatedly showed limited response to immunotherapies. Her disease was essentially progressive, culminating in death due to respiratory failure three and a half years after onset. The autopsy revealed severe degeneration of the nuclei of the right trigeminal nerve and right facial nerve and widespread TDP-43-positive glial inclusions in the brainstem tegmentum. Neurons in the hypoglossal nerve nuclei were also shrunken and lost, with TDP-43-positive neuronal inclusions. Neuronal loss and gliosis in the anterior horn, predominantly in the cervical cord, were prominent with TDP-43-positive skein-like inclusions. Bilateral ventral roots were obviously atrophic. Spinal tract degeneration was also prominent in the ventral columns, essentially sparing the anterior corticospinal tracts at the cervical cord level. Additionally there was severe myelin pallor in the right spinal trigeminal tract and right fasciculus cuneatus of the cervical cord. The right spinal root ganglion showed numerous Nageotte's nodules and focal lymphocytic infiltration. The present case manifested FOSMN syndrome clinically, while the pathological findings suggested a motor neuron disease like TDP-43 proteinopathy and a possible involvement of immune-mediated neuropathy.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Sonoda
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Takahisa
authors.initials: T
authors.lastname: Tateishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamasaki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Sakae
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: Toru
authors.initials: T
authors.lastname: Iwaki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001933:Brain Stem / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015417:Hereditary Sensory and Motor Neuropathy / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D004268:DNA-Binding Proteins
keywords: Amyotrophic lateral sclerosis (ALS); Anti-myelin-associated glycoprotein (MAG) antibody; Anti-sulfoglucuronyl paragloboside (SGPG) antibody; Degeneration; Facial-onset sensory and motor neuronopathy (FOSMN) syndrome; Immune-mediated neuropathy; TAR DNA-binding protein 43 (TDP-43)