Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND)

Abstract

Atypical motor neurone disease (MND) represents a challenging and expanding group of neurodegenerative disorders involving the upper or lower motor neurones, and rarely both. Neuro-ophthalmological disturbances such as gaze-evoked downbeat nystagmus are extremely rare in the context of typical and atypical MND. Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND) syndrome has been recently recognised as a distinct syndromic phenotype of MND, with a characteristic clinical picture. We describe a 63-year-old woman with long-standing lower motor neurone involvement of the upper limbs, who on examination had gaze-evoked downbeat nystagmus. After extensive negative investigation for secondary causes of MND and downbeat nystagmus, we diagnosed FEWDON-MND syndrome.

Update on Nystagmus and Other Ocular Oscillations

“… 28 While DBN is typically observed in dysfunction of the lower cerebellum, the association of DBN with motor neuron diseases indicates the need to look for neuromuscular disorders in patients with this type of nystagmus. 38 39 40 SCA38 is characterized by DBN, intermittent strabismus, and hearing loss in addition to gait ataxia, and is associated with lower total scores on the Scale for the Assessment and Rating of Ataxia (SARA) and higher levels of docosahexaenoic acid, which should also be validated for DBN. 41 There are rare cases of DBN being observed during attacks of Meniere's disease, which are probably due to asymmetry in the vertical VOR or saccular dysfunction.…”

Nystagmus Characteristics in Finger Extension Weakness and Downbeat Nystagmus Motor Neuron Disease (FEWDON-MND)

“…Sensory symptoms and pain are always absent. Of the 11 patients described in the literature, 5 present with downbeat nystagmus without oscillopsia, diplopia, or other neuro-ophthalmological disturbances (1,2,4), including our case report. The last 2 cases described by Micieli et al (5) experienced oscillopsia.…”

“…Motor neuron diseases (MNDs) are rarely associated with disturbances of eye movements, especially with nystagmus. The first 3 reports of a motor neuronopathy related to simultaneous downbeat nystagmus were presented in 2006 by Thakore et al (1), followed by 3 other additional cases described in 2017 (2); 4 reports by Anagnostou et al in 2018 (3) and Pinto et al in 2019 (4), respectively; and 2 cases by Micieli et al 2019 (5). These findings confirmed a new clinical disease entity characterized by distal upper extremity extensor muscle weakness due to a MND associated with downbeat nystagmus: the FEWDON-MND.…”

“…The differential diagnosis includes clinical conditions marked by the presence of long-standing/slow progressive muscular weakness of the upper limbs, comprising degenerative forms (atypical variant of MND/ALS, slowly progressive familiar ALS, non-5q adult-onset spinal muscular atrophies, late-onset distal hereditary motor neuronopathy, and postpolio syndrome) or autoimmune disorders (multifocal motor neuropathy with conduction block) (4). Conversely, the remaining causes of downbeat nystagmus—without cerebellar ataxia—should be ruled out (immune-mediated syndromes, demyelinating diseases of the central nervous system, drug toxicity, neuroinfectious causes, degenerative disorders, vascular compromise, congenital malformations, and idiopathic forms) (4), as well as the rare congenital downbeat nystagmus which presents a characteristic form of vertical nystagmus enhanced by fixation.…”

“…Generally, the patients develop muscular weakness between the age of 16 and 40 years, starting in the extensor groups of the distal upper extremity and evolving with contralateral limb failing in the same muscle unit, before affecting other proximal muscular groups of the upper limbs. Afterward, the lower limbs can also be involved and gait disturbances appear (1,2,4). The most affected muscles are generally atrophic with apparent fasciculations, suggesting the involvement of lower motor neurons.…”