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

Abstract

ABSTACT 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

Preserved eye movements in adults with spinal muscular atrophy

“…We conclude that extraocular muscle function is very likely spared in adult SMA patients. Despite the fact that our measurements are based only on 15 patients, the present quantitative oculomotor data corroborate the clinical experience that neuro-ophthalmic symptoms in SMA are not common and, if present, should prompt suspicion for an alternative neuromuscular disorder, perhaps from the category of myopathies with gaze impairments and muscle atrophy (myotonic dystrophy type I 8,30 or congenital myopathies 33 ) and motor neuron disorders with ocular motility abnormalities (end-stage amyotrophic lateral sclerosis, 16 finger extension weakness, and downbeat nystagmus motor neuron disease syndrome 18 ). Nonetheless, larger patient samples with varying constellations of symptoms and more severe disease will be needed to draw final conclusions.…”

“…Some abnormalities have been attributed to peripheral neuromuscular impairment, whereas others are thought to reflect supra-or infratentorial brain dysfunction. [16][17][18][19][20] In SMA, in addition to case reports of oculomotor abnormalities from the pre-genetic era, there is also anecdotal histological evidence of ballooned neurons contained epitopes of phosphorylated neurofilament and ubiquitin in the oculomotor and trochlear nuclei of the brainstem. 21 Nonetheless, postmortem studies in larger case series established a severe motor neuron loss in all ventral roots and caudal brainstem motor nuclei, with the exception of the third, fourth, and sixth nerve motor nuclei, 22 much like the pathological pattern reported in other motor neuron disorders, such as amyotrophic lateral sclerosis 23 and Kennedy disease.…”

“…Oculomotor abnormalities have been reported in various motor neuron disorders, even if these are not considered typical for these conditions. Some abnormalities have been attributed to peripheral neuromuscular impairment, whereas others are thought to reflect supra‐ or infratentorial brain dysfunction 16‐20 . In SMA, in addition to case reports of oculomotor abnormalities from the pre‐genetic era, there is also anecdotal histological evidence of ballooned neurons contained epitopes of phosphorylated neurofilament and ubiquitin in the oculomotor and trochlear nuclei of the brainstem 21 …”

Clinical spectrum of glutamic acid decarboxylase antibodies in a Taiwanese population

“…Another patient with downbeat nystagmus motor neuron disease syndrome also had positive serum GAD‐abs. A trial using plasma exchange and intravenous immunoglobulins transiently improved the symptoms of weakness but did not alter the disease course . These observations provide some hints that antigens released from degenerating neurons may trigger immunological responses.…”

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.…”