Atypical Motor Neuron Disease variants: Still a diagnostic challenge in Neurology.

Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

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

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.

Finger extension weakness and downbeat nystagmus motor neuron disease syndrome: A novel motor neuron disorder?

INTRODUCTION: Disturbances of eye movements are infrequently encountered in motor neuron diseases (MNDs) or motor neuropathies, and there is no known syndrome that combines progressive muscle weakness with downbeat nystagmus. METHODS: To describe the core clinical features of a syndrome of MND associated with downbeat nystagmus, clinical features were collected from 6 patients. RESULTS: All patients had slowly progressive muscle weakness and wasting in combination with downbeat nystagmus, which was clinically most obvious in downward and lateral gaze. Onset was in the second to fourth decade with finger extension weakness, progressing to other distal and sometimes more proximal muscles. Visual complaints were not always present. Electrodiagnostic testing showed signs of regional motor axonal loss in all patients. DISCUSSION: The etiology of this syndrome remains elusive. Because finger extension weakness and downbeat nystagmus are the discriminating clinical features of this MND, we propose the name FEWDON-MND syndrome. Muscle Nerve 56: 1164-1168, 2017.