Facial Onset Sensory and Motor Neuronopathy: A Neurodegenerative TDP-43 Proteinopathy? (IN9-1.010)

Abstract

Objective: We report clinical, electrophysiologic and pathologic features of five new cases of facial onset sensory and motor neuronopathy or FOSMN syndrome. An autopsy performed in one case identified TDP-43 cytoplasmic inclusions.

Background Vucic et al. described four adult males in 2006 with facial sensory loss gradually spreading to cervical and brachial dermatomes associated with LMN weakness of cranio-bulbar and upper extremity (UE) distribution. Autopsy in one case suggested a neurodegenerative process affecting motoneurons and sensory ganglia.

Design/Methods: A retrospective review of patients referred to Mayo Clinic from 2004 to 2011 identified five males who met the clinical features of FOSMN.

Results: The age of onset ranged from 55 to 63 years. The presenting symptoms often years after onset, were facial numbness (5), associated with loss of taste (1), dysphagia (3), and masseter weakness (2). Sensory loss spread to scalp, neck, upper torso and distal UEs. Patients developed facial, masseter, bulbar, neck flexor/extensor and LMN weakness of UEs. Two patients died of respiratory failure 6 and 9 years after onset. Electrodiagnostic studies revealed prolonged to absent trigeminal blink R1 responses, reduced sensory nerve action potentials in UEs, and chronic denervation mainly in cranial and cervical regions. CSF protein elevation (4) ranged from 46 to 96 mg/dL. Brain and cervical MR images were normal. Biopsies of greater auricular and transverse cervical nerves revealed low grade axonal degeneration. A patient aged 65 who died 6 years after onset, came to autopsy. Neuronal loss and gliosis with TDP-43 positive cytoplasmic neuronal and glial inclusions were present in hyploglossal nucleus and cervical motoneurons. Alpha-synuclein positive inclusions were found in substantia nigra, pigmented brainstem nuclei and mesial temporal lobe suggestive of incidental Lewy body disease.

Conclusions: FOSMN syndrome joins sporadic ALS, frontotemporal lobar degeneration (FTLD-U) and other neurodegenerative disorders as a TDP-43 proteinopathy.

Disclosure: Dr. Bosch has nothing to disclose. Dr. Tracy has nothing to disclose. Dr. Goodman has nothing to disclose. Dr. Dyck has nothing to disclose. Dr. Toro has nothing to disclose. Dr. Giannini has nothing to disclose.