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Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection
Journal of the Neurological Sciences 359 (2015) 4–7
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Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection Deepti Vibha a,⁎, Madhuri Behari b,1, Vinay Goyal b,1, Garima Shukla b,1, Rohit Bhatia b,1, Achal Kumar Srivastava b,1, Vivekanandhan S. c,1 a b c
Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, Room number 707, Ansari Nagar, New Delhi 110029, India Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Department of Neuro-biochemistry, All India Institute of Medical Sciences, New Delhi, India
a r t i c l e
i n f o
Article history: Received 2 September 2015 Received in revised form 30 September 2015 Accepted 11 October 2015 Available online 18 October 2015 Keywords: Amyotrophy Monomelic Clinical features Viral infection Electrophysiology MRI
a b s t r a c t Objectives: The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. Methods: Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. Results: 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n = 107/109) and had involvement of upper limbs (83.5%; n = 91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. Conclusions: Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA. © 2015 Elsevier B.V. All rights reserved.
1. Introduction Monomelic Amyotrophy (MMA) is a neurological disorder with insidious onset wasting and weakness of one limb progressively worsening during two to four years [1]. It becomes more or less stable, although progressive course has also been described [2]. Upper motor neurons signs are characteristically absent. The cause of MMA and its relation to other anterior horn cell disorders, like amyotrophic lateral sclerosis (ALS), is poorly understood [3,4]. Though labeled as “benign” because of a non-progressive course, it leads to morbidity and disability in young patients. Therefore it warrants research in terms of etiology and also possible treatment. The disorder remains poorly understood in terms of a unifying causal hypothesis. The possible mechanisms seem to be mechanical compression [5,6], preceding viral infection [7,8] and genetic [9,10]. Viruses have been known to selectively affect the anterior horn cells especially the poliovirus [11], the West Nile virus [12,13], and HIV [8, 14]. Attempts to detect poliovirus, enteroviruses of the polio type, echo virus, or Coxsackie virus in ALS spinal cord have had conflicting results [15,16,17], but none have been studied in MMA. There is also ⁎ Corresponding author. E-mail address: [email protected] (D. Vibha). 1 These authors contributed equally to the manuscript.
http://dx.doi.org/10.1016/j.jns.2015.10.026 0022-510X/© 2015 Elsevier B.V. All rights reserved.
no evidence of MMA being more common in Japanese Encephalitis (JE) endemic areas, although both the diseases have a common geographical distribution. We aimed to describe the clinical characteristics, electrophysiology and MRI features in patients of MMA and conduct serum viral assays to explore any persistent viral activity in these patients against age and sex matched healthy controls. 2. Methods 2.1. Subjects and controls All consecutive patients of monomelic amyotrophy (MMA) seen in Neurology department between April 2013 and March 2014 were included in the study. The diagnosis was based on clinical history of insidious onset focal wasting and weakness with evidence of lower motor neuron (LMN) involvement on neurological examination (weakness, atrophy or fasciculations) without sensory findings. There have been several attempts to unify the nomenclature of sporadic adult-onset Lower Motor Neuron Disease (LMND) [3,18,19]. We followed the criteria proposed by Gourie-Devi et al. [18] which was as follows: (1) clinical evidence of wasting and weakness confined to one limb (EMG evidence of denervation in the opposite limb was not a reason for exclusion); (2) progressive course, or initial progression followed
D. Vibha et al. / Journal of the Neurological Sciences 359 (2015) 4–7
5
by stationary course; and (3) no evidence of a compressive lesion of the spinal cord. The diagnosis was always substantiated by electrophysiological evidence of LMN involvement on needle electromyography (EMG) examination, which was localized to the segment clinically affected. Exclusion criteria were: (i) familial history of lower motor neuron disease (LMND); (ii) deletion in the SMN1 gene or an expansion of CAG-repeats (N40) in the androgen receptor gene; (iii) history of diseases that may mimic LMND (acute poliomyelitis, spinal radiculopathy, diabetic amyotrophy, thyrotoxicosis or hyperparathyroidism); (iv) clinical signs of UMN involvement [pseudobulbar symptoms, brisk jaw jerk, hyperreflexia or extensor plantar response]; (v) objective sensory signs on neurological examination; (vi) tracheostomy or intermittent ventilatory assistance; (vii) structural lesions (tumors, intervertebral disk herniation, vascular lesions, syringomyelia) on MRI or myelography of the spinal cord; and (viii) motor conduction block on extensive standardized nerve conduction studies [20]. MRI brain was done in cases to look for evidence of any imaging changes suggestive of old/ subclinical viral encephalitis. The patients were followed up at six months and one year. An equal number of age (±2 years) and sex matched controls were taken for blood viral assays comparison in non-diseased population. These were patients with primary headache/backache who were presenting to Neurology outpatient clinics and had consented for the study. The study was approved by the Institute Ethics committee. Informed written consent was taken from all the participants.
Table 1 Characteristics of the participants.
2.2. Laboratory analysis
by the patients themselves (86%; n = 94/109). A history of cold paresis or exacerbation of symptoms in the winter/cold exposure was present in 82.6% (n = 90/109) of patients..
The following laboratory tests were performed: erythrocyte sedimentation rate, hemoglobin, hematocrit, blood sugar, thyroid stimulating hormone, serum immunelectrophoresis with immunofixation, phosphate, calcium (plus, if elevated, parathyroid hormone). These tests were done to exclude mimics of sporadic LMND (diabetic amyotrophy, thyrotoxicosis, hyperparathyroidism, neuropathy with monoclonal gammopathy). Serum IgM anti-GM1 antibodies were not done as routine in all patients as a previous study done from our institute earlier failed to show any association [21]. For the purpose of the study, ELISA for IgG of the following viruses was studied: Japanese E, West Nile Virus, Poliovirus 1, 2 and 3, HIV 1 and 2. Although West Nile Virus. The descriptive analysis of the demographic, clinical and investigation details were done using SPPS 22 version. 3. Results 3.1. Demographic characteristics (Table 1) In the recruitment period from April 2013 to March 2014, 109 cases and 109 age and sex matched controls were included. None of the patients refused consent. The patients were predominantly males (98.2%; n = 107/109) and most of them had involvement of upper limbs (83.5%; n = 91/109). Mean age of the patients was 23.5 ± 6.8 years and the duration of disease varied from one to twenty years. Since our hospital is a tertiary care center in North India, all our patients were from this part of the country. A majority of them were involved in manual work (43.1%; n = 47/109) closely followed by students (34.9%; n = 38/109). 3.2. Clinical features (Table 1) Almost one-third ((33%; n = 36/109) gave history of fever in the preceding three months, although they could not be corroborated by medical records and none were associated with pain in the affected limb. Wasting or thinning was the most common symptom at onset (67.9%; n = 74/109), rather than weakness, which was noted mostly
Demographic (n = 109) Age (years (mean ± SD)) Duration (years (median (range))) Sex (male (n (%))) Limb affected (n (%)) Upper limb Lower limb Side effected (n (%)) Right Left Both Occupation (n (%)) Student Manual worker (farmer, laborer) Sedentary work (office work, unemployed) Clinical symptoms and signs Preceding fever (n (%)) First symptom (n (%)) Wasting Weakness Others MMSE (mean ± SD) Cold paresis (n (%)) Reflexes (n (%)) Hypoactive Normal Hyperactive
23.5 ± 6.8 2 (1–20) 107 (98.2) 91 (83.5) 18 (16.5) 72 (66.1) 35 (32.1) 2 (1.8) 38 (34.9) 47 (43.1) 24 (22.0) 36 (33.0) 74(67.9) 28(25.7) 7 (6.7) 29.1 ± 2.3 90 (82.6) 79 (72.5) 30 (27.5) 0
3.3. Examination and clinical signs Majority of patients had upper limb involvement (83.5%; n = 91/ 109) and all except two patients had bilateral involvement. In 83.5% (n = 76/91) of patients with upper extremity involvement, there were associated neurogenic tremors or minipolymyoclonus.. 3.4. Investigations (Table 2) All patients underwent electrophysiology studies (EPS) and MRI of the spine and brain to exclude other disorders that may mimic MMA. 26 (23.8%) of the patients with clinically unilateral involvement had bilateral neurogenic changes in the EMG. Five (19.2%) out of these patients progressed clinically, during one year follow up. In the MRI study, brain examination was normal in all the patients. The MRI of the cervical spine was assessed for any abnormality. Localized atrophy was defined as a decrease in cord size in comparison to the normal cord above and below the affected level. Sagittal images suggesting atrophy were verified on the appropriate contiguous axial sections. Note was also made of any T2 hyperintensity in the anterior cervical cord [22]. In the MRI cervical spine, 13.8% of the patients had cord hyperintensities, while 18.3% had atrophy. However, a majority of
Table 2 Investigation findings of the patients. Electrophysiology studies (EPS) Segments involved (n (%)) Upper cervical Lower cervical Both involved Lumbosacral segments MRI cervical spine (n (%)) Normal Cord atrophy Cord signal change
12 (11.0) 67 (61.5) 16 (14.7) 14 (12.8) 74 (67.9) 20 (18.3) 15 (13.8)
6
D. Vibha et al. / Journal of the Neurological Sciences 359 (2015) 4–7
patients had a normal study (67.9%). None of the patients with lower limb affected showed any abnormality in imaging. Our study also did serological assays of Japanese E, West Nile Virus, Poliovirus 1, 2 and 3, HIV 1 and 2 with age and sex matched controls. None of the cases or controls had positive serological assays.
4. Discussion The classical features of MMA consist of atrophy and weakness affecting predominantly the distal muscles of a single limb [5]. The onset in usually in the late second or early third decade with progression from one to four years [1]. Our study looked at the role of persistent serological activity of viruses which have predilection to anterior horn cell (AHC), as a putative association with MMA. Although we found that up to one-third of the patients gave history of preceding fever in the past three months, none of the cases had positive serology for any of the viruses tested. Earlier studies do show the possible association of viral infection [8,12,23], which could not be observed in our study. Serological diagnosis of persistent viral activity in the serum may not be the most robust way to demonstrate association, but may be the first step towards it, short of more invasive investigations, like a Cerebrospinal Fluid (CSF) assay. Similar diagnostic tests are useful in persistent viral activity in Subacute sclerosing panencephalitis (SSPE) [24]. Our study could not find any evidence of persistent viral activity in patients of MMA. The male preponderance and duration of symptoms have been similar as compared to previous studies [3,25]. The phenomenon of cold paresis was observed in 82.6% of the patients which is more as reported in earlier studies [25,26]. The phenomenon of cold paresis is not exclusive to MMA but has been reported extensively in patients of Multifocal Motor Neuropathy and chronic inflammatory neuropathies [27]. These findings are supposed to be a result of increased sensitivity of reinnervated muscle fibers to develop depolarizing conduction block in cold. All the patients with upper limb distal involvement had minipolymyoclonus, even though only 39.6% of them gave history of fasciculations. This was also one symptom which was most amenable to satisfactory medical treatment by institution of beta blockers. The deep tendon jerks (DTJ) were hypoactive in 72.5% patients and normal in the rest. Although hyperactive DTJs have been reported rarely [28] and upto 18% of patients [25], we did not find it in any of the 109 patients, during initial evaluation or at follow up. Another notable finding was bilateral neurogenic involvement in the electromyography when the clinical involvement was unilateral in 26 (23.8%) of patients. The MRI of the spine was done in all patients to exclude compression. MMA has been thought to be a flexion myelopathy of the lower cervical cord [29], and stabilization or even improvement has been described with cervical collar, cervical decompression and fusion [30, 31]. The number of patients in such studies was too small to draw any conclusions. In our series, 66% of the patients had normal MRI, and only 16.5% showed focal cord atrophy, suggesting that this hypothesis might not account for all the cases of MMA. The cord signal change or “snake eye appearance” was seen in 13.8% of patients, but is not specific or characteristic of MMA and has been reported in anterior spinal cord infarction, cervical spondylotic amyotrophy due to compressive myelopathy [32]. To conclude, patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA.
Acknowledgments We acknowledge the funding provided by All India Institute of Medical Sciences (AIIMS), Intramural Research Grant (A-167).
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Ramalingaiah, Monomelic amyotrophy: clinical profile and natural history of 279 cases seen over 35 years (1976–2010), Amyotroph. Lateral Scler. Front. Degener 15 (2014) 457–465, http://dx.doi.org/10.3109/21678421.2014.903976. [26] K. Tashiro, S. Kikuchi, Y. Itoyama, Y. Tokumaru, G. Sobue, E. Mukai, et al., Nationwide survey of juvenile muscular atrophy of distal upper extremity (Hirayama disease) in Japan, Amyotroph. Lateral Scler. Off. Publ. World Fed. Neurol. Res. Group Mot. Neuron Dis. 7 (2006) 38–45, http://dx.doi.org/10. 1080/14660820500396877. [27] D.C.G. Straver, J.-T.H. van Asseldonk, N.C. Notermans, J.H.J. Wokke, L.H. van den Berg, H. Franssen, Cold paresis in multifocal motor neuropathy, J. Neurol. 258 (2011) 212–217, http://dx.doi.org/10.1007/s00415-010-5712-3. [28] S.D. Yoo, H.-S. Kim, D.H. Yun, D.H. Kim, J. Chon, S.A. Lee, et al., Monomelic amyotrophy (Hirayama disease) with upper motor neuron signs: a case report, Ann. Rehabil. 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Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection Deepti Vibha a,⁎, Madhuri Behari b,1, Vinay Goyal b,1, Garima Shukla b,1, Rohit Bhatia b,1, Achal Kumar Srivastava b,1, Vivekanandhan S. c,1 a b c
Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, Room number 707, Ansari Nagar, New Delhi 110029, India Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Department of Neuro-biochemistry, All India Institute of Medical Sciences, New Delhi, India
a r t i c l e
i n f o
Article history: Received 2 September 2015 Received in revised form 30 September 2015 Accepted 11 October 2015 Available online 18 October 2015 Keywords: Amyotrophy Monomelic Clinical features Viral infection Electrophysiology MRI
a b s t r a c t Objectives: The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. Methods: Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. Results: 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n = 107/109) and had involvement of upper limbs (83.5%; n = 91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. Conclusions: Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA. © 2015 Elsevier B.V. All rights reserved.
1. Introduction Monomelic Amyotrophy (MMA) is a neurological disorder with insidious onset wasting and weakness of one limb progressively worsening during two to four years [1]. It becomes more or less stable, although progressive course has also been described [2]. Upper motor neurons signs are characteristically absent. The cause of MMA and its relation to other anterior horn cell disorders, like amyotrophic lateral sclerosis (ALS), is poorly understood [3,4]. Though labeled as “benign” because of a non-progressive course, it leads to morbidity and disability in young patients. Therefore it warrants research in terms of etiology and also possible treatment. The disorder remains poorly understood in terms of a unifying causal hypothesis. The possible mechanisms seem to be mechanical compression [5,6], preceding viral infection [7,8] and genetic [9,10]. Viruses have been known to selectively affect the anterior horn cells especially the poliovirus [11], the West Nile virus [12,13], and HIV [8, 14]. Attempts to detect poliovirus, enteroviruses of the polio type, echo virus, or Coxsackie virus in ALS spinal cord have had conflicting results [15,16,17], but none have been studied in MMA. There is also ⁎ Corresponding author. E-mail address: [email protected] (D. Vibha). 1 These authors contributed equally to the manuscript.
http://dx.doi.org/10.1016/j.jns.2015.10.026 0022-510X/© 2015 Elsevier B.V. All rights reserved.
no evidence of MMA being more common in Japanese Encephalitis (JE) endemic areas, although both the diseases have a common geographical distribution. We aimed to describe the clinical characteristics, electrophysiology and MRI features in patients of MMA and conduct serum viral assays to explore any persistent viral activity in these patients against age and sex matched healthy controls. 2. Methods 2.1. Subjects and controls All consecutive patients of monomelic amyotrophy (MMA) seen in Neurology department between April 2013 and March 2014 were included in the study. The diagnosis was based on clinical history of insidious onset focal wasting and weakness with evidence of lower motor neuron (LMN) involvement on neurological examination (weakness, atrophy or fasciculations) without sensory findings. There have been several attempts to unify the nomenclature of sporadic adult-onset Lower Motor Neuron Disease (LMND) [3,18,19]. We followed the criteria proposed by Gourie-Devi et al. [18] which was as follows: (1) clinical evidence of wasting and weakness confined to one limb (EMG evidence of denervation in the opposite limb was not a reason for exclusion); (2) progressive course, or initial progression followed
D. Vibha et al. / Journal of the Neurological Sciences 359 (2015) 4–7
5
by stationary course; and (3) no evidence of a compressive lesion of the spinal cord. The diagnosis was always substantiated by electrophysiological evidence of LMN involvement on needle electromyography (EMG) examination, which was localized to the segment clinically affected. Exclusion criteria were: (i) familial history of lower motor neuron disease (LMND); (ii) deletion in the SMN1 gene or an expansion of CAG-repeats (N40) in the androgen receptor gene; (iii) history of diseases that may mimic LMND (acute poliomyelitis, spinal radiculopathy, diabetic amyotrophy, thyrotoxicosis or hyperparathyroidism); (iv) clinical signs of UMN involvement [pseudobulbar symptoms, brisk jaw jerk, hyperreflexia or extensor plantar response]; (v) objective sensory signs on neurological examination; (vi) tracheostomy or intermittent ventilatory assistance; (vii) structural lesions (tumors, intervertebral disk herniation, vascular lesions, syringomyelia) on MRI or myelography of the spinal cord; and (viii) motor conduction block on extensive standardized nerve conduction studies [20]. MRI brain was done in cases to look for evidence of any imaging changes suggestive of old/ subclinical viral encephalitis. The patients were followed up at six months and one year. An equal number of age (±2 years) and sex matched controls were taken for blood viral assays comparison in non-diseased population. These were patients with primary headache/backache who were presenting to Neurology outpatient clinics and had consented for the study. The study was approved by the Institute Ethics committee. Informed written consent was taken from all the participants.
Table 1 Characteristics of the participants.
2.2. Laboratory analysis
by the patients themselves (86%; n = 94/109). A history of cold paresis or exacerbation of symptoms in the winter/cold exposure was present in 82.6% (n = 90/109) of patients..
The following laboratory tests were performed: erythrocyte sedimentation rate, hemoglobin, hematocrit, blood sugar, thyroid stimulating hormone, serum immunelectrophoresis with immunofixation, phosphate, calcium (plus, if elevated, parathyroid hormone). These tests were done to exclude mimics of sporadic LMND (diabetic amyotrophy, thyrotoxicosis, hyperparathyroidism, neuropathy with monoclonal gammopathy). Serum IgM anti-GM1 antibodies were not done as routine in all patients as a previous study done from our institute earlier failed to show any association [21]. For the purpose of the study, ELISA for IgG of the following viruses was studied: Japanese E, West Nile Virus, Poliovirus 1, 2 and 3, HIV 1 and 2. Although West Nile Virus. The descriptive analysis of the demographic, clinical and investigation details were done using SPPS 22 version. 3. Results 3.1. Demographic characteristics (Table 1) In the recruitment period from April 2013 to March 2014, 109 cases and 109 age and sex matched controls were included. None of the patients refused consent. The patients were predominantly males (98.2%; n = 107/109) and most of them had involvement of upper limbs (83.5%; n = 91/109). Mean age of the patients was 23.5 ± 6.8 years and the duration of disease varied from one to twenty years. Since our hospital is a tertiary care center in North India, all our patients were from this part of the country. A majority of them were involved in manual work (43.1%; n = 47/109) closely followed by students (34.9%; n = 38/109). 3.2. Clinical features (Table 1) Almost one-third ((33%; n = 36/109) gave history of fever in the preceding three months, although they could not be corroborated by medical records and none were associated with pain in the affected limb. Wasting or thinning was the most common symptom at onset (67.9%; n = 74/109), rather than weakness, which was noted mostly
Demographic (n = 109) Age (years (mean ± SD)) Duration (years (median (range))) Sex (male (n (%))) Limb affected (n (%)) Upper limb Lower limb Side effected (n (%)) Right Left Both Occupation (n (%)) Student Manual worker (farmer, laborer) Sedentary work (office work, unemployed) Clinical symptoms and signs Preceding fever (n (%)) First symptom (n (%)) Wasting Weakness Others MMSE (mean ± SD) Cold paresis (n (%)) Reflexes (n (%)) Hypoactive Normal Hyperactive
23.5 ± 6.8 2 (1–20) 107 (98.2) 91 (83.5) 18 (16.5) 72 (66.1) 35 (32.1) 2 (1.8) 38 (34.9) 47 (43.1) 24 (22.0) 36 (33.0) 74(67.9) 28(25.7) 7 (6.7) 29.1 ± 2.3 90 (82.6) 79 (72.5) 30 (27.5) 0
3.3. Examination and clinical signs Majority of patients had upper limb involvement (83.5%; n = 91/ 109) and all except two patients had bilateral involvement. In 83.5% (n = 76/91) of patients with upper extremity involvement, there were associated neurogenic tremors or minipolymyoclonus.. 3.4. Investigations (Table 2) All patients underwent electrophysiology studies (EPS) and MRI of the spine and brain to exclude other disorders that may mimic MMA. 26 (23.8%) of the patients with clinically unilateral involvement had bilateral neurogenic changes in the EMG. Five (19.2%) out of these patients progressed clinically, during one year follow up. In the MRI study, brain examination was normal in all the patients. The MRI of the cervical spine was assessed for any abnormality. Localized atrophy was defined as a decrease in cord size in comparison to the normal cord above and below the affected level. Sagittal images suggesting atrophy were verified on the appropriate contiguous axial sections. Note was also made of any T2 hyperintensity in the anterior cervical cord [22]. In the MRI cervical spine, 13.8% of the patients had cord hyperintensities, while 18.3% had atrophy. However, a majority of
Table 2 Investigation findings of the patients. Electrophysiology studies (EPS) Segments involved (n (%)) Upper cervical Lower cervical Both involved Lumbosacral segments MRI cervical spine (n (%)) Normal Cord atrophy Cord signal change
12 (11.0) 67 (61.5) 16 (14.7) 14 (12.8) 74 (67.9) 20 (18.3) 15 (13.8)
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patients had a normal study (67.9%). None of the patients with lower limb affected showed any abnormality in imaging. Our study also did serological assays of Japanese E, West Nile Virus, Poliovirus 1, 2 and 3, HIV 1 and 2 with age and sex matched controls. None of the cases or controls had positive serological assays.
4. Discussion The classical features of MMA consist of atrophy and weakness affecting predominantly the distal muscles of a single limb [5]. The onset in usually in the late second or early third decade with progression from one to four years [1]. Our study looked at the role of persistent serological activity of viruses which have predilection to anterior horn cell (AHC), as a putative association with MMA. Although we found that up to one-third of the patients gave history of preceding fever in the past three months, none of the cases had positive serology for any of the viruses tested. Earlier studies do show the possible association of viral infection [8,12,23], which could not be observed in our study. Serological diagnosis of persistent viral activity in the serum may not be the most robust way to demonstrate association, but may be the first step towards it, short of more invasive investigations, like a Cerebrospinal Fluid (CSF) assay. Similar diagnostic tests are useful in persistent viral activity in Subacute sclerosing panencephalitis (SSPE) [24]. Our study could not find any evidence of persistent viral activity in patients of MMA. The male preponderance and duration of symptoms have been similar as compared to previous studies [3,25]. The phenomenon of cold paresis was observed in 82.6% of the patients which is more as reported in earlier studies [25,26]. The phenomenon of cold paresis is not exclusive to MMA but has been reported extensively in patients of Multifocal Motor Neuropathy and chronic inflammatory neuropathies [27]. These findings are supposed to be a result of increased sensitivity of reinnervated muscle fibers to develop depolarizing conduction block in cold. All the patients with upper limb distal involvement had minipolymyoclonus, even though only 39.6% of them gave history of fasciculations. This was also one symptom which was most amenable to satisfactory medical treatment by institution of beta blockers. The deep tendon jerks (DTJ) were hypoactive in 72.5% patients and normal in the rest. Although hyperactive DTJs have been reported rarely [28] and upto 18% of patients [25], we did not find it in any of the 109 patients, during initial evaluation or at follow up. Another notable finding was bilateral neurogenic involvement in the electromyography when the clinical involvement was unilateral in 26 (23.8%) of patients. The MRI of the spine was done in all patients to exclude compression. MMA has been thought to be a flexion myelopathy of the lower cervical cord [29], and stabilization or even improvement has been described with cervical collar, cervical decompression and fusion [30, 31]. The number of patients in such studies was too small to draw any conclusions. In our series, 66% of the patients had normal MRI, and only 16.5% showed focal cord atrophy, suggesting that this hypothesis might not account for all the cases of MMA. The cord signal change or “snake eye appearance” was seen in 13.8% of patients, but is not specific or characteristic of MMA and has been reported in anterior spinal cord infarction, cervical spondylotic amyotrophy due to compressive myelopathy [32]. To conclude, patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA.
Acknowledgments We acknowledge the funding provided by All India Institute of Medical Sciences (AIIMS), Intramural Research Grant (A-167).
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