European Journal of Neurology 2014, 21: 1233–1241
doi:10.1111/ene.12465
Revisiting the spectrum of lower motor neuron diseases with snake eyes appearance on magnetic resonance imaging M.-V. Lebouteuxa, J. Franquesb, R. Guillevinc, E. Delmontd, T. Lenglete,f, P. Bedeg, C. Desnuelled, J. Pougetb, H. Pascal-Mousselardh and P.-F. Pradate,i a
Service de Neurologie, HIA du Val de Gr^ ace, Paris; bCentre de R ef erence des Maladies Neuromusculaires et de la SLA, APHM, c e de Poitiers, Poitier; dPole Neurosciences Cliniques, Centre de R ef erence La Timone, Marseille; Service de Radiologie, CHU et Universit epartement des Maladies du Syst eme Nerveux, AP-HP, Maladies Neuromusculaires et SLA, H^ opital Archet 1, CHU de Nice, Nice; eD epartement de Neurophysiologie, AP-HP, Groupe Hospitalier Piti e-Salp^ etri ere, Paris, Groupe Hospitalier Piti e-Salp^ etri ere, Paris; fD France; gAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; hService es, UPMC Univ Paris 06, INSERM, CNRS, d’orthop edie, Groupe Hospitalier Piti e-Salp^ etri ere, Paris; and iSorbonne Universit Laboratoire d’Imagerie, Biom edicale, Paris, France
Keywords:
lower motor neuron disease, MRI, physical activity, ‘snake eyes’ sign Received 2 January 2014 Accepted 7 April 2014
Background and purpose: The ‘snake eyes’ sign refers to bilateral hyperintensities of the anterior horns on axial spinal cord imaging. Based on sporadic reports, it has been associated with a range of lower motor neuron (LMN) syndromes, such as spondylotic amyotrophy and Hirayama disease, as well as spinal cord infarction. The objective of our study was to comprehensively characterize the full diagnostic spectrum of LMN syndromes with this radiological clue and discuss potential aetiological factors. Methods: A large patient cohort with snake eyes sign and upper limb LMN degeneration was recruited from three French neuromuscular units. Patients underwent detailed electrophysiological, radiological, clinical and anamnestic profiling. Results: Twenty-nine patients were ascertained and followed up for 9.5 8.6 years. The majority of the patients were male (86.2%) with a mean age of 37.3 14.4 years. Symptoms were bilateral in most cases (86.2%). Patients with predominantly proximal and distal deficits were equally represented (44.8% and 55.2%, respectively). A history of preceding trauma or intense physical activity was confirmed in 58.6% of the cases; 27.6% of the patients were given an initial clinical diagnosis of amyotrophic lateral sclerosis (ALS), and 51.7% were originally suspected to have multifocal motor neuropathy. None of the patients developed ALS on longitudinal follow-up. Conclusion: The snake eyes sign on magnetic resonance imaging is associated with a wide spectrum of neurological conditions and is more common in young men with a history of strenuous activity or antecedent trauma. The recognition of this syndrome is crucial as many of these patients are initially misdiagnosed with ALS.
Introduction The ‘snake eyes’ sign, or ‘owl’s eye’ sign, refers to bilateral hyperintensities of the anterior horns on axial spinal cord magnetic resonance imaging (MRI). It has been described in pure upper limb lower motor neuron (LMN) syndromes. However, this radiological clue has been mostly reported by Correspondence: Pierre-Francois Pradat, MD, PhD, Departement des Maladies du Systeme Nerveux, Groupe Hospitalier PitieSalp^etriere, 47 83 Boulevard de l’H^ opital, 75651 Paris, France (tel.: +33 1 42 16 24 71; fax: +33 1 44 24 32 69; e-mail: [email protected]).
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
sporadic case reports and the full clinical spectrum has not been comprehensively characterized in larger patient cohorts. Traditionally, this clinico-radiological entity has been most commonly associated with cervical spondylosis, spinal cord infarction and Hirayama disease. Anterior horn high signal has also been noted in post-vaccination poliomyelitis [1], West Nile virus encephalitis [2,3], enterovirus [4], dengue myelitis [5], HIV myelitis [6], tick-borne encephalomyelitis [7] and varicella zoster virus [8]. It has also been reported in neuromyelitis optica (Devic’s disease) [9], paraneoplastic myelopathies [10] and Hopkins
1233
1234
M.-V. Lebouteux et al.
syndrome [11]. A wide range of ischaemic mechanisms have been linked to the snake eyes sign, including sickle cell disease [12], decompression sickness [13], cocaine use [14], ‘steal’ syndromes secondary to arteriovenous malformations [15] and vasculitis [16,17], and also iatrogenic effects, such as intraoperative complications [18] or central-line insertion [19]. The snake eyes sign has been observed at cervical [3,7–12,14,19], thoracic [6,15–18], both cervical and thoracic levels [1,4] and along the entire spinal cord [2,5,13]. It is important to distinguish the snake eyes sign from tract-specific changes in corticospinal tracts (suggestive of paraneoplastic myelopathy, B12/copper deficiency etc.) by its location within anterior horn cells. Whilst an abundance of single case reports have emerged, there has been no systematic analysis of the full spectrum of clinical patterns associated with snake eyes in larger cohorts. Our objective was therefore to characterize the natural history, demographic, clinical and risk profile of these patients.
Methods A retrospective study was conducted of patients recruited from three large French neuromuscular units in Marseille, Paris and Nice. These departments are specialist tertiary referral centres for motor neuron diseases and utilize standardized diagnostic pathways and investigations according to French [20,21] and European guidelines [22]. Patients in these centres are followed up at regular intervals, every 3– 6 months. Patients with atypical motor neuron diseases, including patients with abnormal radiological signs, are systematically recorded. The neurologists and radiologists of these centres were asked to identify patients with snake eyes signs. Based on the review of medical records, patients were selected according to a specific inclusion criterion, described below. Patients were then contacted by phone to be interviewed for exercise habits, lifestyle and history of preceding trauma. This study was approved by the local ethics board according to the French regulations. Inclusion criteria
Inclusion criteria included the presence of snake eyes sign defined by bilateral hyperintensities of the anterior horns on axial MRI and clinical and electrophysiological evidence of LMN degeneration in the upper limbs. Exclusion criteria included sensory, cranial nerve, upper motor neuron, sphincter or cerebellar symptoms or a history of poliomyelitis.
Evaluations and investigations
Detailed clinical and demographic data, including family history, were carefully recorded. Information on exercise habits, lifestyle (sedentary versus regular physical activity) and history of preceding trauma prior to symptom onset was specifically sought. Data on the natural history and progression of symptoms were also collected. Patients were diagnosed with Hirayama disease if they presented with distal upper limb weakness and atrophy following an insidious onset in the second or third decade of their life followed by a spontaneous plateauing of their symptoms [23]. Spondylotic and spinal cord changes were systematically assessed by an experienced radiologist and orthopaedic surgeon. The diagnosis of spondylotic myelopathy was based on the absence of perispinal cerebrospinal fluid ventrally or dorsally, as well as evidence of high signal, cord deformity or compression. Cervical spinal cord imaging included T1* and T2* weighted MR sequences in all patients with both sagittal and axial reconstructions. In order to rule out confounding artefacts, the detection of the high signal was required on at least two contiguous axial slices or both axial and coronal slices. A comprehensive electrophysiological assessment was undertaken in all patients including sensory and motor nerve conduction in all four limbs. Needle electromyography (EMG) was performed on distal and proximal muscles of each limb and in one bulbar muscle [24]. A diagnosis of ‘LMN syndrome restricted to the upper limbs’ was made if the combination of the following findings were established: (i) evidence of chronic neurogenic changes (reduced number of motor units, large amplitude and long duration motor unit potentials), abnormal spontaneous activity (including fibrillations, positive sharp waves or fasciculation potentials) in wasted muscles, without lower limb or bulbar denervation; (ii) reduced compound muscle action potentials in the affected limbs with normal motor conduction studies, absence of conduction block, temporal dispersion or significant conduction slowing; (iii) normal sensory nerve conduction studies. All participating patients were screened and negative for a uniform set of blood tests including erythrocyte sedimentation rate, C-reactive protein, complete blood count, serum protein electrophoresis with immunofixation, calcium, thyroid and parathyroid hormone profiles, anti-GM1 antibodies, poliovirus antibodies and HIV serology. Additionally, DNA analysis for Kennedy’s disease in male patients and SMN1-linked spinal muscular atrophy was also carried out in patients with proximal symmetrical weakness.
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Motor neuron disease with snake eyes sign
Statistics
A non-parametric Mann–Whitney test was used for continuous data and a chi-squared test for categorical data. Analysis was performed using XLSTAT.
Results A total of 29 patients were included in this study with a mean follow-up of 9.5 8.6 years. Based on physical examination, 51.7% of the patients were thought to have a ‘likely’ diagnosis of multifocal motor neuropathy (MMN) and 27.6% were suspected to have amyotrophic lateral sclerosis (ALS) before their full diagnostic work-up was completed. However, on follow-up none of these patients developed ALS, 10.3% of the patients were ultimately diagnosed with Hirayama disease and 27.6% with cervical canal stenosis. In the remaining cases (62.1%), no specific aetiology was found, and the patients were eventually diagnosed with an idiopathic LMN syndrome associated with a snake eyes sign. The demographic and clinical profiles of the patients are summarized in Table 1. Demography, risk profile and clinical features
Mean age of symptom onset was 37.3 14.4 years and the majority of the patients were male (86.2%). 65.2% of the patients had a non-sedentary job requiring regular physical activity, such as carrying heavy loads. Either a single traumatic event (fall, car accident, cervical or head trauma) or a period of intense physical activity (military training, weight lifting or bodybuilding) preceded the onset of the deficit by L C5 C6, symmetrical C7 C4 C7 C7
Proximal, R > L Proximal, symmetrical Triceps, R > L Proximal, symmetrical Distal, L > R Distal, symmetrical
Proximal, symmetrical
C5 C6 symmetrical
C5 C6 C7 L C6 Th1, symmetrical C8, L > R
C8 Th1, R > L C8 Th1, L > R
Distal, R > L Distal, L > R Proximal L Distal, symmetrical Distal, L > R
C8 Th1 R
Distal R
C8 Th1 R C7 C8 Th1, R > L
C5 C6 C7, R > L
Proximal, R > L Distal R Distal, R > L
C5 C6 L
Proximal L
C8 Th1, R > L
Distal, R > L
C8 Th1, symmetrical C6, symmetrical C8 Th1, L > R R Th1, symmetrical C6 C7 C8, symmetrical C6 C7, L > R R>L C8, symmetrical C6 C7, R > L C8 Th1, R > L
C7 C5 C7 C7 C8 C5 C5 C7 C7 C5 C7
Distal, symmetrical Proximal, symmetrical Distal, L > R Proximal, R Distal, symmetrical Distal, symmetrical Proximal, L > R Triceps, R > L Distal, symmetrical Proximal, R > L Distal, R > L
C8 Th1, R>L C5, symmetrical C8 Th1, L > R C8, symmetrical
ENMG levels involved
Pattern of weakness
to to to to
C7 C4 C7 C6
C6 to C8 C3 to C4 C5 to C7 C6 C6 to C7 C3 to C6 C2 to C4 C3 to C7 C5 to C7 C3 to C6 C4 to C7 Cervical stenosis C3 to C6 Cervical stenosis C3 to C4 Cervical stenosis C3 to C6 Cervical stenosis C4 to C5 C6 Cervical stenosis C7 Cervical stenosis C6 to C8 C7 to T1 Cervical stenosis C6 C5 to C6 C6 to C7 Cervical stenosis C5 to C6
C4 C2 C4 C4
C3 to C5 C3 to C5
MRI high signal
ENMG, electroneuromyography; MRI, magnetic resonance imaging; ALS, amyotrophic lateral sclerosis; MMN, multifocal motor neuropathy with conduction blocks.
Gender
Patient
Age at symptom onset
Table 1 Individual patient data, demographic and clinical characteristics
None
ALS ALS MMN
MMN MMN
MMN
MMN MMN
MMN
MMN
MMN
ALS ALS ALS None (fulfilled criteria for Hirayama) ALS ALS Hirayama None MMN MMN Hirayama MMN MMN MMN MMN
ALS None
Provisional initial diagnosis
1236 M.-V. Lebouteux et al.
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Motor neuron disease with snake eyes sign
1237
Table 2 Clinical and demographic profile of patients. When percentages are shown, the absolute values are in parentheses
All patients Sample size, % n = 29 (100) Age at onset 37.3 14.4 (years, mean SD) Follow up 9.5 8.6 (years, mean SD) Male, % 86.2 Profession with intense 65.2 (15/23a) physical activity, % Preceding trauma or intense 58.6 (17) physical exercise, % Cervical canal stenosis, % 27.6 (8) Hirayama disease, % 10.3 (3) Bilateral clinical 86.2 (25) presentation, % ENMG: number of metameric levels with neurogenic changes, % 1 6.9 (2) 2 55.2 (16) 3 34.5 (10) 4 3.5 (1) MRI: number of vertebral levels with T2 hyperintensities, % 1 13.8 (4) 2 27.6 (8) 3 31 (9) 4 24.1 (7) 5 3 (1) Time to stabilization, plateauing of 5.5 6.4 symptoms (years, mean SD) Initial clinical diagnosis, % ALS 27.6 (8) MMN 51.7 (15) Hirayama 6.9 (2) Unknown 13.8 (4)
Patients with proximal presentation
Patients with distal presentation
P value
n = 13 (44.8) 33.4 10.8
n = 16 (55.2) 40.6 16.4
0.227
7.2 4.1
11.2 10.7
0.567
75 46.1 (6/13a)
0.052 0.029
61.5 (8)
56.2 (9)
0.774
15.4 (2) 0 (0) 84.6 (11)
37.5 (6) 18.7 (3) 87.5 (14)
0.185 0.099 0.823
15.4 (2) 46.1 (6) 38.5 (5) 0 (0)
0 (0) 62.5 (10) 31.2 (5) 6.2 (1)
0.103 0.379 0.684 0.359
15.4 (2) 23 (3) 30.8 (4) 23 (3) 8 (1) 4.7 3.6
12.5 (2) 31.2 (5) 31.2 (5) 25 (4) 0 (0) 6.1 7.9
0.822 0.624 0.977 0.904 0.259 0.875
38.5 (5) 30.8 (4) 0 (0) 23 (3)
18.7 68.7 12.5 6.2
0.237 0.041 0.186 0.191
100 90 (9/10a)
(3) (11) (2) (1)
ENMG, electroneuromyography; MRI, magnetic resonance imaging; ALS, amyotrophic lateral sclerosis; MMN, multifocal motor neuropathy with conduction blocks. aThe percentage is calculated based on the number of patients for whom the information was available. P values are in bold when they reach statistical significance (
doi:10.1111/ene.12465
Revisiting the spectrum of lower motor neuron diseases with snake eyes appearance on magnetic resonance imaging M.-V. Lebouteuxa, J. Franquesb, R. Guillevinc, E. Delmontd, T. Lenglete,f, P. Bedeg, C. Desnuelled, J. Pougetb, H. Pascal-Mousselardh and P.-F. Pradate,i a
Service de Neurologie, HIA du Val de Gr^ ace, Paris; bCentre de R ef erence des Maladies Neuromusculaires et de la SLA, APHM, c e de Poitiers, Poitier; dPole Neurosciences Cliniques, Centre de R ef erence La Timone, Marseille; Service de Radiologie, CHU et Universit epartement des Maladies du Syst eme Nerveux, AP-HP, Maladies Neuromusculaires et SLA, H^ opital Archet 1, CHU de Nice, Nice; eD epartement de Neurophysiologie, AP-HP, Groupe Hospitalier Piti e-Salp^ etri ere, Paris, Groupe Hospitalier Piti e-Salp^ etri ere, Paris; fD France; gAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; hService es, UPMC Univ Paris 06, INSERM, CNRS, d’orthop edie, Groupe Hospitalier Piti e-Salp^ etri ere, Paris; and iSorbonne Universit Laboratoire d’Imagerie, Biom edicale, Paris, France
Keywords:
lower motor neuron disease, MRI, physical activity, ‘snake eyes’ sign Received 2 January 2014 Accepted 7 April 2014
Background and purpose: The ‘snake eyes’ sign refers to bilateral hyperintensities of the anterior horns on axial spinal cord imaging. Based on sporadic reports, it has been associated with a range of lower motor neuron (LMN) syndromes, such as spondylotic amyotrophy and Hirayama disease, as well as spinal cord infarction. The objective of our study was to comprehensively characterize the full diagnostic spectrum of LMN syndromes with this radiological clue and discuss potential aetiological factors. Methods: A large patient cohort with snake eyes sign and upper limb LMN degeneration was recruited from three French neuromuscular units. Patients underwent detailed electrophysiological, radiological, clinical and anamnestic profiling. Results: Twenty-nine patients were ascertained and followed up for 9.5 8.6 years. The majority of the patients were male (86.2%) with a mean age of 37.3 14.4 years. Symptoms were bilateral in most cases (86.2%). Patients with predominantly proximal and distal deficits were equally represented (44.8% and 55.2%, respectively). A history of preceding trauma or intense physical activity was confirmed in 58.6% of the cases; 27.6% of the patients were given an initial clinical diagnosis of amyotrophic lateral sclerosis (ALS), and 51.7% were originally suspected to have multifocal motor neuropathy. None of the patients developed ALS on longitudinal follow-up. Conclusion: The snake eyes sign on magnetic resonance imaging is associated with a wide spectrum of neurological conditions and is more common in young men with a history of strenuous activity or antecedent trauma. The recognition of this syndrome is crucial as many of these patients are initially misdiagnosed with ALS.
Introduction The ‘snake eyes’ sign, or ‘owl’s eye’ sign, refers to bilateral hyperintensities of the anterior horns on axial spinal cord magnetic resonance imaging (MRI). It has been described in pure upper limb lower motor neuron (LMN) syndromes. However, this radiological clue has been mostly reported by Correspondence: Pierre-Francois Pradat, MD, PhD, Departement des Maladies du Systeme Nerveux, Groupe Hospitalier PitieSalp^etriere, 47 83 Boulevard de l’H^ opital, 75651 Paris, France (tel.: +33 1 42 16 24 71; fax: +33 1 44 24 32 69; e-mail: [email protected]).
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
sporadic case reports and the full clinical spectrum has not been comprehensively characterized in larger patient cohorts. Traditionally, this clinico-radiological entity has been most commonly associated with cervical spondylosis, spinal cord infarction and Hirayama disease. Anterior horn high signal has also been noted in post-vaccination poliomyelitis [1], West Nile virus encephalitis [2,3], enterovirus [4], dengue myelitis [5], HIV myelitis [6], tick-borne encephalomyelitis [7] and varicella zoster virus [8]. It has also been reported in neuromyelitis optica (Devic’s disease) [9], paraneoplastic myelopathies [10] and Hopkins
1233
1234
M.-V. Lebouteux et al.
syndrome [11]. A wide range of ischaemic mechanisms have been linked to the snake eyes sign, including sickle cell disease [12], decompression sickness [13], cocaine use [14], ‘steal’ syndromes secondary to arteriovenous malformations [15] and vasculitis [16,17], and also iatrogenic effects, such as intraoperative complications [18] or central-line insertion [19]. The snake eyes sign has been observed at cervical [3,7–12,14,19], thoracic [6,15–18], both cervical and thoracic levels [1,4] and along the entire spinal cord [2,5,13]. It is important to distinguish the snake eyes sign from tract-specific changes in corticospinal tracts (suggestive of paraneoplastic myelopathy, B12/copper deficiency etc.) by its location within anterior horn cells. Whilst an abundance of single case reports have emerged, there has been no systematic analysis of the full spectrum of clinical patterns associated with snake eyes in larger cohorts. Our objective was therefore to characterize the natural history, demographic, clinical and risk profile of these patients.
Methods A retrospective study was conducted of patients recruited from three large French neuromuscular units in Marseille, Paris and Nice. These departments are specialist tertiary referral centres for motor neuron diseases and utilize standardized diagnostic pathways and investigations according to French [20,21] and European guidelines [22]. Patients in these centres are followed up at regular intervals, every 3– 6 months. Patients with atypical motor neuron diseases, including patients with abnormal radiological signs, are systematically recorded. The neurologists and radiologists of these centres were asked to identify patients with snake eyes signs. Based on the review of medical records, patients were selected according to a specific inclusion criterion, described below. Patients were then contacted by phone to be interviewed for exercise habits, lifestyle and history of preceding trauma. This study was approved by the local ethics board according to the French regulations. Inclusion criteria
Inclusion criteria included the presence of snake eyes sign defined by bilateral hyperintensities of the anterior horns on axial MRI and clinical and electrophysiological evidence of LMN degeneration in the upper limbs. Exclusion criteria included sensory, cranial nerve, upper motor neuron, sphincter or cerebellar symptoms or a history of poliomyelitis.
Evaluations and investigations
Detailed clinical and demographic data, including family history, were carefully recorded. Information on exercise habits, lifestyle (sedentary versus regular physical activity) and history of preceding trauma prior to symptom onset was specifically sought. Data on the natural history and progression of symptoms were also collected. Patients were diagnosed with Hirayama disease if they presented with distal upper limb weakness and atrophy following an insidious onset in the second or third decade of their life followed by a spontaneous plateauing of their symptoms [23]. Spondylotic and spinal cord changes were systematically assessed by an experienced radiologist and orthopaedic surgeon. The diagnosis of spondylotic myelopathy was based on the absence of perispinal cerebrospinal fluid ventrally or dorsally, as well as evidence of high signal, cord deformity or compression. Cervical spinal cord imaging included T1* and T2* weighted MR sequences in all patients with both sagittal and axial reconstructions. In order to rule out confounding artefacts, the detection of the high signal was required on at least two contiguous axial slices or both axial and coronal slices. A comprehensive electrophysiological assessment was undertaken in all patients including sensory and motor nerve conduction in all four limbs. Needle electromyography (EMG) was performed on distal and proximal muscles of each limb and in one bulbar muscle [24]. A diagnosis of ‘LMN syndrome restricted to the upper limbs’ was made if the combination of the following findings were established: (i) evidence of chronic neurogenic changes (reduced number of motor units, large amplitude and long duration motor unit potentials), abnormal spontaneous activity (including fibrillations, positive sharp waves or fasciculation potentials) in wasted muscles, without lower limb or bulbar denervation; (ii) reduced compound muscle action potentials in the affected limbs with normal motor conduction studies, absence of conduction block, temporal dispersion or significant conduction slowing; (iii) normal sensory nerve conduction studies. All participating patients were screened and negative for a uniform set of blood tests including erythrocyte sedimentation rate, C-reactive protein, complete blood count, serum protein electrophoresis with immunofixation, calcium, thyroid and parathyroid hormone profiles, anti-GM1 antibodies, poliovirus antibodies and HIV serology. Additionally, DNA analysis for Kennedy’s disease in male patients and SMN1-linked spinal muscular atrophy was also carried out in patients with proximal symmetrical weakness.
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Motor neuron disease with snake eyes sign
Statistics
A non-parametric Mann–Whitney test was used for continuous data and a chi-squared test for categorical data. Analysis was performed using XLSTAT.
Results A total of 29 patients were included in this study with a mean follow-up of 9.5 8.6 years. Based on physical examination, 51.7% of the patients were thought to have a ‘likely’ diagnosis of multifocal motor neuropathy (MMN) and 27.6% were suspected to have amyotrophic lateral sclerosis (ALS) before their full diagnostic work-up was completed. However, on follow-up none of these patients developed ALS, 10.3% of the patients were ultimately diagnosed with Hirayama disease and 27.6% with cervical canal stenosis. In the remaining cases (62.1%), no specific aetiology was found, and the patients were eventually diagnosed with an idiopathic LMN syndrome associated with a snake eyes sign. The demographic and clinical profiles of the patients are summarized in Table 1. Demography, risk profile and clinical features
Mean age of symptom onset was 37.3 14.4 years and the majority of the patients were male (86.2%). 65.2% of the patients had a non-sedentary job requiring regular physical activity, such as carrying heavy loads. Either a single traumatic event (fall, car accident, cervical or head trauma) or a period of intense physical activity (military training, weight lifting or bodybuilding) preceded the onset of the deficit by L C5 C6, symmetrical C7 C4 C7 C7
Proximal, R > L Proximal, symmetrical Triceps, R > L Proximal, symmetrical Distal, L > R Distal, symmetrical
Proximal, symmetrical
C5 C6 symmetrical
C5 C6 C7 L C6 Th1, symmetrical C8, L > R
C8 Th1, R > L C8 Th1, L > R
Distal, R > L Distal, L > R Proximal L Distal, symmetrical Distal, L > R
C8 Th1 R
Distal R
C8 Th1 R C7 C8 Th1, R > L
C5 C6 C7, R > L
Proximal, R > L Distal R Distal, R > L
C5 C6 L
Proximal L
C8 Th1, R > L
Distal, R > L
C8 Th1, symmetrical C6, symmetrical C8 Th1, L > R R Th1, symmetrical C6 C7 C8, symmetrical C6 C7, L > R R>L C8, symmetrical C6 C7, R > L C8 Th1, R > L
C7 C5 C7 C7 C8 C5 C5 C7 C7 C5 C7
Distal, symmetrical Proximal, symmetrical Distal, L > R Proximal, R Distal, symmetrical Distal, symmetrical Proximal, L > R Triceps, R > L Distal, symmetrical Proximal, R > L Distal, R > L
C8 Th1, R>L C5, symmetrical C8 Th1, L > R C8, symmetrical
ENMG levels involved
Pattern of weakness
to to to to
C7 C4 C7 C6
C6 to C8 C3 to C4 C5 to C7 C6 C6 to C7 C3 to C6 C2 to C4 C3 to C7 C5 to C7 C3 to C6 C4 to C7 Cervical stenosis C3 to C6 Cervical stenosis C3 to C4 Cervical stenosis C3 to C6 Cervical stenosis C4 to C5 C6 Cervical stenosis C7 Cervical stenosis C6 to C8 C7 to T1 Cervical stenosis C6 C5 to C6 C6 to C7 Cervical stenosis C5 to C6
C4 C2 C4 C4
C3 to C5 C3 to C5
MRI high signal
ENMG, electroneuromyography; MRI, magnetic resonance imaging; ALS, amyotrophic lateral sclerosis; MMN, multifocal motor neuropathy with conduction blocks.
Gender
Patient
Age at symptom onset
Table 1 Individual patient data, demographic and clinical characteristics
None
ALS ALS MMN
MMN MMN
MMN
MMN MMN
MMN
MMN
MMN
ALS ALS ALS None (fulfilled criteria for Hirayama) ALS ALS Hirayama None MMN MMN Hirayama MMN MMN MMN MMN
ALS None
Provisional initial diagnosis
1236 M.-V. Lebouteux et al.
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Motor neuron disease with snake eyes sign
1237
Table 2 Clinical and demographic profile of patients. When percentages are shown, the absolute values are in parentheses
All patients Sample size, % n = 29 (100) Age at onset 37.3 14.4 (years, mean SD) Follow up 9.5 8.6 (years, mean SD) Male, % 86.2 Profession with intense 65.2 (15/23a) physical activity, % Preceding trauma or intense 58.6 (17) physical exercise, % Cervical canal stenosis, % 27.6 (8) Hirayama disease, % 10.3 (3) Bilateral clinical 86.2 (25) presentation, % ENMG: number of metameric levels with neurogenic changes, % 1 6.9 (2) 2 55.2 (16) 3 34.5 (10) 4 3.5 (1) MRI: number of vertebral levels with T2 hyperintensities, % 1 13.8 (4) 2 27.6 (8) 3 31 (9) 4 24.1 (7) 5 3 (1) Time to stabilization, plateauing of 5.5 6.4 symptoms (years, mean SD) Initial clinical diagnosis, % ALS 27.6 (8) MMN 51.7 (15) Hirayama 6.9 (2) Unknown 13.8 (4)
Patients with proximal presentation
Patients with distal presentation
P value
n = 13 (44.8) 33.4 10.8
n = 16 (55.2) 40.6 16.4
0.227
7.2 4.1
11.2 10.7
0.567
75 46.1 (6/13a)
0.052 0.029
61.5 (8)
56.2 (9)
0.774
15.4 (2) 0 (0) 84.6 (11)
37.5 (6) 18.7 (3) 87.5 (14)
0.185 0.099 0.823
15.4 (2) 46.1 (6) 38.5 (5) 0 (0)
0 (0) 62.5 (10) 31.2 (5) 6.2 (1)
0.103 0.379 0.684 0.359
15.4 (2) 23 (3) 30.8 (4) 23 (3) 8 (1) 4.7 3.6
12.5 (2) 31.2 (5) 31.2 (5) 25 (4) 0 (0) 6.1 7.9
0.822 0.624 0.977 0.904 0.259 0.875
38.5 (5) 30.8 (4) 0 (0) 23 (3)
18.7 68.7 12.5 6.2
0.237 0.041 0.186 0.191
100 90 (9/10a)
(3) (11) (2) (1)
ENMG, electroneuromyography; MRI, magnetic resonance imaging; ALS, amyotrophic lateral sclerosis; MMN, multifocal motor neuropathy with conduction blocks. aThe percentage is calculated based on the number of patients for whom the information was available. P values are in bold when they reach statistical significance (
